Renukaprasad Ys - Medicine - Thesis New

CLINICAL, AND BIOCHEMICAL SPECTRUM OF CHRONIC KIDNEY DISEASE IN TERTIARY CARE CENTER
BY
Dr. RENUKAPRASAD Y.S.

M.B.B.S., Dissertation submitted to the Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore.
In Partial fulfillment Of the requirements for the degree of
DOCTOR OF MEDICINE IN GENERAL MEDICINE

Under the guidance of
Dr. B.M. VISHWANATH

M.D., MRCP (UK), MRCP (IRELAND)
PROFESSOR
DEPARTMENT OF GENERAL MEDICINE J.J.M. MEDICAL COLLEGE DAVANGERE 577 004. 2012
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA
DECLARATION BY THE CANDIDATE
I hereby declare that this dissertation entitled
CLINICAL, AND
BIOCHEMICAL SPECTRUM OF CHRONIC KIDNEY DISEASE IN TERTIARY CARE CENTER is a bonafide and genuine research work carried out by me under the guidance of Dr. B.M. VISHWANATH M.D., MRCP
(UK), MRCP (IRELAND) Professor, Department of Medicine, J.J.M .Medical College, Davangere.
PLACE : DAVANGERE DATE : / /2011 (Dr. RENUKAPRASAD Y.S.)
ii
CERTIFICATE BY THE GUIDE
This is to certify that this dissertation entitled CLINICAL, AND BIOCHEMICAL SPECTRUM OF CHRONIC KIDNEY DISEASE IN TERTIARY CARE CENTER is a bonafide research work done by
Dr. RENUKAPRASAD Y.S. in partial fulfillment of the requirement for the degree of M.D. (General Medicine).
PLACE : DAVANGERE DATE : / /2011 Dr. B.M. VISHWANATH

M.D., MRCP(UK), MRCP (IRELAND)
PROFESSOR DEPARTMENT OF GENERAL MEDICINE J.J.M. MEDICAL COLLEGE DAVANGERE 577 004.
iii
ENDORSEMENT BY THE HOD, PRINCIPAL/HEAD OF THE INSTITUTION
This is to certify that this dissertation entitled CLINICAL, AND BIOCHEMICAL SPECTRUM OF CHRONIC KIDNEY DISEASE IN TERTIARY CARE CENTER is a bonafide research work done by Dr. RENUKAPRASAD Y.S. under the guidance of Dr. B.M. VISHWANATH
M.D., MRCP (UK), MRCP (IRELAND) Professor, Department of Medicine, J.J.M. Medical College, Davangere.
Dr. G. RAJASEKHARAPPA M.D., PROFESSOR AND HEAD, DEPARTMENT OF GENERAL MEDICINE, J.J.M. MEDICAL COLLEGE DAVANGERE 577 004.
Dr. H.R. CHANDRASEKHAR PRINCIPAL, J.J.M. MEDICAL COLLEGE DAVANGERE 577 004.
M.D.,
DATE :
/2011
DATE :
/2011
PLACE : DAVANGERE
PLACE : DAVANGERE
iv
COPYRIGHT Declaration by the Candidate
I hereby declare that the Rajiv Gandhi University of Health Sciences, Karnataka shall have the rights to preserve, use and disseminate this dissertation / thesis in print or electronic format for academic / research purpose.
Rajiv Gandhi University of Health Sciences, Karnataka.
ACKNOWLEDGEMENT
I take this opportunity to extend my gratitude and sincere thanks to all those who have helped me to complete this dissertation. I am extremely indebted and remain grateful forever to my guide Dr. B.M. VISHWANATH M.D., MRCP (UK), MRCP (IRELAND) Professor of Medicine, for his constant able guidance and constant encouragement in preparing this dissertation during my post-graduate course. It gives me pleasure to express my gratitude to my guide and Professor and Head of Department of Medicine Dr.G.RAJASEKHARAPPA, M.D., for his excellent guidance, encouragement and constant inspiration during my P.G. course. I owe a great sense of indebtedness to Dr. H. GURUPADAPPA M.D., Director P.G. Studies and Research, J.J.M. Medical College, Davangere, who has been a constant source of inspiration during my post graduate course. My sincere thanks and gratitude to Emeritus Professor Dr. S.M. YELI, M.D., for his excellent guidance and constant inspiration during my study period. My sincere thanks and gratitude to Emeritus Professor Dr. P.M. UPASI M.D., for his excellent guidance and constant inspiration during my study period. It gives me immense pleasure to express my deep sense of gratitude and sincere thanks to Dr.MANJUNATH ALUR, M.D., Dip.Diab.,
Dr.S.N.VISHWAKUMAR, M.D., Dr.P.E.DHANANJAYA, M.D., Dr.SRINATH .K.V. M.D., Dr.K.SRIHARSHA M.D., Dr.N.S.BRID M.D., Dr.B.D.CHAVAN M.D Dr.K.V.CHANDRASHEKAR M.D., for their guidance and encouragement during my postgraduate course. I am very much thankful to Dr.P.MALLESH, M.D., D.M (Cardio) and Dr.RAJEEV AGARAWAL, M.D., DNB(Nephro), Dr. ARPANDEV
BHATTACHARYA, D.M,(Endocrine) Dr. L. KRISHNAMURTHY D.M., (Neuro) for their encouragement and advice.
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I express my sincere thanks to Dr.B.G.KARIBASAPPA M.D., Dr.
Dr.A.P.THIPPESWAMY B.G SHIVAKUMAR.
M.D., M.D,
Dr.GURUSHANTHAPPA, M.D., Dr.S.S.SAWKAR M.D., Dr.VINAY SWAMY M.D., Dr. VINAY YELI, M.D., Dr.S.CHANDRASHEKAR, M.D., Dr
MRUTHUNJAYA C.T M.D. Dr.SURENDRA E.M., M.D., Dr. SHAH ABRAR M.D., Dr.MAHESH D M.D., M.D., Dr.U.R.RAJU M.D.,
Dr.MAHABALESHWAR MAYYA M.D., for their valuable advice during my P.G. Course. My special thanks to Superintendent and Staff of Chigateri General Hospital and Bapuji Hospital. I thank Mrs.RAJESHWARI Bio-statistician, Librarian and Staff of library of J.J.M.M.C., Davangere. My Special thanks to my friends. I extend my sincere thanks to my post-graduate colleagues and all my Friends, who had helped me in preparing this dissertation. I must give my sincere thanks to my PARENTS for their valuable support, love and constant encouragement. I thank Mr.SANJEEV KUMAR G.P. of M/s GUNDAL Computer-Center, for their meticulous computerized layout of this dissertation. My heart full thanks to all patients who formed this study group and cooperated wholeheartedly. I thank the Almighty Mr.MAHESH, Chief
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LIST OF ABBREVIATIONS USED

AIN ATN BUN CAPD CGN CKD CPN CRF CRI DN ECF ESRD GFR HD HTN K/DOQI LVH NSAID OU P.m.p PCKD PD PTH RAS rHuEPO RRT : : : : : : : : : : : : : : : : : : : : : : : : : : Acute intestinal nephritis Acute tubular necrosis Blood urea nitrogen Chronic ambulatory peritoneal dialysis Chronic glomerulonephritis Chronic kidney disease Chronic pyelonephritis Chronic renal failure Chronic renal insufficiency Diabetic nephropathy Extra cellular fluid End stage renal disease Glomerular filtration rate Hemodialysis Hypertension Kidney disease outcome quality initiative Left ventricular hypertrophy Non steroidal anti inflammatory drugs Obstructive uropathy Population per million Polycystic kidney disease Peritoneal dialysis Parathormone Renal artery stenosis Recombinant human erythropoietin Renal replacement therapy
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ABSTRACT
Background and objectives : A prospective study was carried out in 50 patients detected to have chronic renal failure to determine the aetiology, laboratory and clinical profile of these patients. Materials and Methods : 50 patients with CRF were included who fulfilled the criteria set by the National Kidney Foundations, Kidney Disease outcome quality initiative for diagnosing CRF by subjecting them to clinical assessment, laboratory analysis and ultrasonography of the abdomen and pelvis. Results : The aetiology of CRF in our patients was found to be diabetic nephropathy in 38%, Hypertensive Nephropathy in 28%, Chronic Glomerulonephritis in 24%, Obstructive Uropathy in 6%, polycystic kidney disease in 2% and chronic pyelonephritis in 2%. The abnormality in the laboratory profile of the patients were found to be Anaemia in 90%, Hypocalcemia in 46%, Hypoalbuminaemia in 34%, Hyperkalemia in 34% and Hyponatremia in 24%. The commonest clinical symptoms seen in our patients were Pedal edema in 78% and Oliguria 76%. The commonest clinical signs were Hypertension in 92% and Pallor 90%. Interpretation and conclusion : The major concern which our study highlights is the need for the prompt detection and management of renal insufficiency before the need to initiate renal replacement therapy. Our study also shows the growing incidence of CRF due to hypertension, diabetes and obstructive uropathy which emphasizes the need for the prompt detection of the above disorders to prevent renal damage. KEY WORDS :
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TABLE OF CONTENTS
PAGE NO
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
INTRODUCTION OBJECTIVES REVIEW OF LITERATURE METHODOLOGY RESULTS DISCUSSION CONCLUSION SUMMARY BIBLIOGRAPHY ANNEXURES PROFORMA MASTER CHART
LIST OF TABLES
SL.NO. TABLES PAGE
xi
LIST OF GRAPHS
SL.NO. LIST OF GRAPHS PAGE NO.
LIST OF FIGURES
LIST OF FIGURES Page No.
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INTRODUCTION
Chronic kidney disease is characterized by a decrease in glomerular filtration rate and histological evidence of reduction in nephron population. The clinical course is typically one of a progressive and unrelenting loss of nephron function ultimately leading to end stage renal disease. Kidney failure is the most visible aspect of the spectrum, but it represents only a minority of the total population affected by kidney disease. The time between initial onset of disease and development of terminal renal failure may vary considerably not only between different diseases but also in different patients with similar disease processes. The progressive nature of CKD and the ensuing ESRD is putting a substantial burden on global health resources since all modalities of treatment are expensive. There are multiple causes of kidney injury that lead to the final common pathway of ESRD, and this syndrome is characterized by hypertension, anemia, renal bone disease, nutritional impairment, neuropathy, impaired quality of life, and reduced life expectancy. Increasing evidence acquired in the past decades indicates that the adverse outcomes of CKD such as renal failure, cardiovascular disease, and premature death can be prevented or delayed by early detection of CKD. Earlier stages of CKD can be detected through laboratory testing only. Treatment of earlier stages of chronic kidney disease, as well as initiation of treatment of cardiovascular risk factors at early stages of CKD should be effective in reducing the rate of progression of CKD to ESRD.
Unfortunately, despite the evident importance of CKD there is limited data on its epidemiology within the general population, especially from developing countries like India. Two community-based studies have shown a prevalence of chronic renal failure of 0.16% 1 and 0.79% 2 . Renal failure registry data is unlikely to be representative of the broader spectrum of CKD. There is a wide variability both within and between countries in the occurrence, clinical characteristics and outcomes of patients with kidney failure and there have been substantial changes over time. Only 3% to 5% of all patients with ESRD in India get some form of renal replacement therapy. Thus, planning for prevention of CKD on a long term basis is the only practical solution for India 3 .
OBJECTIVES
The prsent study is undertaken with the following objectives: 1. To assess the cliical profile of patients with chronc renal failure at the time of presentation. 2. To assess the biochemical profile of patients with chronic renal failure. 3. To determine the aetiology of chronic renal failure wherever
possible.
REVIEW OF LITERATURE
CHRONIC KIDNEY DISEASE Chronic kidney disease represents the entire spectrum of disease that occurs following the initiation of kidney damage. The introduction of a formal definition for CKD has enabled standardize current medical communication, facilitate appropriate population based screening, and encourage timely prevention and treatment of kidney disease. DEFINITION 4 1. Kidney damage for 3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifest by either a. Pathological abnormalities; or b. Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging test. 2. GFR < 60 ml/min/1.73 m 2 for 3 months, with or without kidney damage. The GFR is considered the best measure of overall kidney function. A GFR below 60 mL/min/1.73m 2 represents loss of one half of more of the adult level of normal kidney function. patient age, sex, and body size. Normal GFR varies according to
Recommended equations for estimation of GFR using serum creatinine (pl creatinine), Age, Sex, Race and Body weight. 1) Cockcroft Gault formla 5 Estimated creatinien clerance ( )
(multiply by 0.85 for women). 2) MDRD formula (Modification of diet in renal disease study) Estimated GFR (ml/mt per 1.73 m 2 ). = 1.86 x (pl creatinine) -1.154 x (age) -0.203 Multiply by 0.742 for women Multiply by 1.21 for African Amercians. AGE, SEX, RACE DIFFERENCES : AGE: In young adults, the normal GFR is approximately 120 to 130 mL /minute / 1.73 m 2 and declines with age. 6 A decreased GFR in an elderly patient appears to be an independent predictor of adverse outcomes such as mortality and cardiovascular disease 7,8 . Because of the age-related decline in GFR, the prevalence of chronic kidney disease increases with age; approximately 17 percent of persons older than 60 years have an estimated GFR of less than 60 mL / minute /1.73 m 2 . GENDER Male gender has been recognized as an important factor in the development of CKD 9 . Gender-based genetic variability has been linked to
5
differences in BP in both black 10 and white individuals 11 . Males may be more susceptible to CKD, which would explain the higher proportion in renal replacement therapy programmes. In contrast to testosterone, l2,13 estrogens may attenuate CKD progression by lowering the cardiovascular stress response to adrenergic stimuli 14 . Chronic kidney disease is a national public health problem be set by inequities in incidence, prevalence, and complications across race/ethnicity, and socioeconomic status. SOCIOECONOMIC STATUS In U.S, geographic analyses have revealed community-level poverty was strongly associated with higher ESRD incidence but was a more powerful predictor for black than for white individuals. 15 Racially divided communities may share low-income status but often differ in wealth, community assets, exposure to heavy metals or excess ambient air particulate matter, and other variables that may influence CKD-related outcomes. 16 RACE Racial factors also have a role in the susceptibility to CKD as shown by high prevalence of CKD related to hypertension, diabetes, or both, among Africans and native Americans in USA as well as Afro-Caribbean and Asian individuals in UK. 17 In U.S, ESRD rates in minorities ranged from 1.5 to 4 times those of age-adjusted counterparts, despite similar rates for the early stages of CKD. 18
THE INCIDENCE AND PREVALENCE Chronic renal insufficiency is a major public health problem. Over the years the number of patients with end stage renal disease has steadily increased. In the United States the rate of increase has been reported as 6 -7% per year. In USA more than 80000 patients were supposed to have developed end stage renal disease in 2008 19 and more than 11% of US population had renal dysfunction (serum creatinine >1.5mg/dl) 20 . In the year 2008, approximately 205000 and 240000 patients with
ESRD were currently maintained on chronic dialysis in Japan and the United States respectively 21 . The burden to the exchequer is also quite high. The current cost for ESRD in Japan and the United States (including about 90000 transplant recipients in the United States) amounts to approximately US $ 10 and 15 billion, respectively 21 . A prospective study in the United Kingdom, there were approximately 600 patients per million population (p.m.p.) with established renal failure not requiring renal replacement treatment and an annual incidence of end stage renal failure needing dialysis of 78 p.m.p 39 . In other countries the incidence varies from as low as 4 p.m.p. in Bolivia 22 to as high as 254 p.m.p. in Puerto Rico 23 . Barsoum reported an incidence of 200 p.m.p in the Egyptian population 24 . In India studies have shown that upto 0.8% of the population may suffer from chronic kidney disease thereby putting the number at about 8 million of the 1 billion population 2 .
7
In India where the average per capita income is Rs 12,989/ - per annum and with 36% of the population below the poverty line, ours is a country, which cannot afford to treat end stage renal disease.
AETIOLOGY OF CHRONIC KIDNEY DISEASE : There are many causes of chronic renal failure for most renal diseases can eventually lead to a significant reduction in function. Not only has there been a dramatic increase in incidence of ESRD but also a relative shift in etiologies. Diabetic and hypertensive nephropathies are more frequent when compared to glomerulonephritis 25 . The causes of end stage renal failure in the elderly differ substantially from those in younger populations. The most common disorders leading to renal failure at this age are nephrosclerosis, diabetes, and obstructive uropathy although in as many as one-third it proves impossible to
identify any specific cause 26 . The influence of age on causes of chronic renal failure is illustrated by the higher prevalence of obstructive uropathy and reno -vascular disease (ischaemic renal disease) in the elderly. So also is myeloma and amyloidosis 27 . In women there is a higher prevalence of reflux and analgesic nephropathies, there is evidence of a faster rate of deterioration in male patients with polycystic disease and some forms of glomerulonephritis, which may explain the higher number of male patients treated by renal replacement therapy27 .
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Traditionally, hypertensive, and diabetic patients comprise the largest risk group for the development and progression of CRI. RENAL CAUSES 4 Glomerulonephritides These manifest as haematuria, signs of a nephrotic syndrome (tiredness, weight gain, oedema, susceptibility to infection, hyperlipidaemia), and/or hypertension. With more frequent, regular health screening, one of the most common presentations of chronic glomerulonephritis (e.g. IgA
nephropathy) is the detection of dipstix proteinuria (and/or haematuria), hypertension and/or elevated serum creatinine in an asymptomatic patient. Reflux nephropathy Usually diagnosed in childhood during investigation of urina ry infection or screening in families, it may, however, escape discovery until adult life when it is detected during investigation of urinary infection, especially in pregnancy, hypertension, or renal failure. Though often silent, there may be a history of recurrent episodes of flank pain, dysuria, fever, and rigors. CKD in adult life peaks in the twenties and thirties and is uncommon after the age of 50. Secondary chronic pyelonephritis This is the etiology in patients with CKD and a history of stone disease, obstruction, or neuropathic bladder.
Medication related Both over the counter as well as prescribed and recreational drugs are implicated in this category. Chinese herb nephropathy (caused by Aristolochia fangchi) is an example where fibrosis and tubulointerstitial changes persist for months or years after discontinuation of the toxin though slow recovery may occur on stopping. Prolonged consumption of non -steroidal antiinflammatory drugs (NSAlDs) and selective COX-2 agents has also been implicated in the etiology of CKD (analgesic nephropathy). These drugs also cause a reduction in GFR in patients with glomerulonephritis, due to inhibition of vasodilatory prostaglandins, acute interstitial nephritis, nephrotic syndrome or papillary necrosis. Angiotensin-converting enzyme (ACE) inhibitors and/or Angiotensin II Receptor Blockers may cause renal insufficiency in patients with bilateral renal artery stenosis or renal artery stenosis in a single kidney due to renal hypoperfusion. Hereditary nephritis Autosomal Dominant Polycystic Kidney Disease (APKD) is the most frequent cause of CKD in hereditary nephritis. Renal failure usually occurs in the third to fifth decade; family history is positive in ~ 75% cases. Similarly, a positive family history is usual in the rarer types of renal cystic disease such as tuberous sclerosis and medullary cystic disease. Alport's syndrome is another important hereditary nephritis characterized by progressive nephritis with haematuria and sensori-neural hearing loss.
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Infections Renal tuberculosis is a rare cause of CKD. Classically, the presentation is of dysuria, fever and sterile pyuria and is confirmed by urine culture and renal imaging (calcified renal substance). Interstitial renal tuberculosis causing renal failure with small kidneys on imaging and without the tell -tale renal calcification is diagnosed by renal biopsy or inferred from evidence of tuberculosis in other systems. Another infection associated with CKD 5 that shows a geographic variation is schistosomiasis which is an important cause in Egypt. Substance abuse Heroin-associated nephropathy (was an important cause of CKD 5 in New York) 28 SYSTEMIC DISEASES Diabetes mellitus Diabetes mellitus is the most frequent cause of renal involvement in a systemic disease. Renal involvement occurs as frequently in type II as in type I diabetes. The increasing prevalence of CKD in the developed world in particular is predominantly accounted for by type II diabetic nephropathy 29 . Hence, the need for good control of blood sugars to prevent microalbuminuria and therafter ACE inhibitors and/or ARBs to retard progression. Hypertension Long-standing 'benign' hypertension is also an important cause
of CKD, particularly in the elderly age group, but is difficult to di fferentiate
11
from occult renal diseases with secondary hypertension except by renal biopsy30 . Systemic Lupus Erythematosus (SLE) A diagnosis of SLE may be initially suspected clinically and then a renal biopsy is done to assess the severity of renal illnes s or else it is diagnosed when a renal biopsy is performed in any patient with proteinuria or abnormal urinary sediment. Therefore most patients should have one at the time of their initial assessment for renal insufficiency 30 . Amyloidosis Secondary amyloidosis is suspected when CKD complicates longstanding inflammatory diseases (like severe rheumatoid arthritis) or chronic infections (such as destructive lung tuberculosis). It presents as a nephrotic syndrome. Primary amyloidosis occurs due to the proliferation of a single clone of plasma cells in middle and old age presenting with renal insufficiency and proteinuria. In patients with plasma cell dyscrasias, renal failure may also result from myeloma cast nephropathy, light chain deposition disease or hyperviscosity syndrome 30 . Systemic vasculitis and anti-glomerular basement membrane disease: Systemic vasculitis and Anti-glomerular basement membrane disease usually present as rapidly progressive renal failure. A history of haemoptysis and dyspnoea, together with rapidly deteriorating renal function and an active urine sediment, suggest antiglomerular basement membrane disease
(Goodpasture's syndrome) but can also occur in systemic vasculitis. Other significant symptoms are of persistent sinusitis with dyspnoea, cough, and
12
haemoptysis (Wegener's disease) or only systemic symptoms (microscopic polyangitis). Thrombotic microangiopathy This thrombotic syndrome. Occupational renal diseases Occupational renal diseases causing CKD is an extremely rare entity with the exception of lead toxicity. Theses patients have hyperuricaemia, hypertension and small kidneys. The diagnosis is best made by demonstrating an increase in urinary lead excretion following an infusion of EDTA. More recently, long-term occupational or environmental exposure to relatively low levels of cadmium has been shown to cause CKD 31 . POSTRENAL CAUSES Prostatic hypertrophy This presents with obstruction of the lower urinary tract is common in elderly males and is usually symptomatic. However, 40 per cent of men over the age of 65 have some of the symptoms of hesitancy, slow and forked stream, urgency with or without urge incontinence, frequency, intermittency, nocturia, and terminal dribbling 32 . Pressure-flow measurements have shown that two-thirds of these patients have some degree of outflow obstruction and are at risk of urinary retention 33 . A useful clinical clue to serious outflow obstruction is palpation of a distended bladder after micturition (confirmed more reliably by ultrasonography before and after micturition).
13
may
occur
due
to
haemolytic or anti
uraemic phospholipids
syndrome, antibody
thrombocytopenic
purpura
Other causes of obstruction are retroperitoneal fibrosis, sloughed papillae and renal calculi renal function. inducing hydronephrosis and a deterioration of
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CLASSIFICATION
OF
CHRONIC
KIDNEY
DISEASE
BY
PATHOLOGY, AETIOLOGY AND PREVALENCE IN PATIENTS WITH END-STAGE RENAL DISEASE AS PER KIDOQI 4 Prevalence among patient with ESRD** 33%
Pathology Diabetic glomerulosclerosis
Aetiology (examples*) Diabetes Mellitus Type 1 Type 2
Glomerular Diseases (Primary or Secondary) Proliferative glomerulonephritis Mesangial proliferative glomerulonephritis Membranoprliferative glomerulonephritis Focal proliferative glomerulonephritis Diffuse proliferative glomerulonephritis Crescentic glomerulonephritis Nononflammatory glomerular diseases Minimal change disease Focal glomerular sclerosis Membranous nephropathy Fibrillary glomerular diseases Hereditary nephritis (Alport's) Vascular disease Diseases of large-size vessels Diseases of medium-size vessels Nephrosclerosis Diseases of small vessels Microangiopathy
Systemic lupus erythematosis, vasculitis, bacterial endocarditis, chronic hepatitis B or C, HIV infection
19%
Hodgkin's disease HIV infection, 19% heroin toxicity Drug toxicity, solid tumors Amyloidsis, light chain disease
Renal artery stenosis Hypertension
Sickle cell disease, hemolytic uraemic syndrome (including cyclosporin or tacrolimus toxicity)
21%
15
Tubulointerstitial diseases Tubulointerstitial nephritis Pyelonephritis Analgesic nephropathy Infection, stones NSAID Antibiotics Sarcoidosis 4%
Allergic interstitial nephritis Granulomatous interstitial nephritis Autoimmune interstitial nephritis
Uveitis
Noninflammatory tubulointerstitial diseases Reflux nephropathy Obstructive nephropathy Myeloma kidney Vesico-ureteral reflux Malignancy, prostatism, stones Multiple myeloma Cystic diseases Polycystic kidney disease Tuberous sclerosis Von hippel lindau Medullary cystic disease Autosomal dominant or recessive 6% 4%
Diseases in the transplant Chronic rejection Drug toxicity Recurrent disease Transplant glomerulopathy Cyclosporine or tacrolimus Glomerular diseases Not considered
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RISK
FACTORS
FOR CHRONIC
KIDNEY
DISEASE
AND ITS
OUTCOMES 4 Type Susceptibility factors Factors Definition that to Examples
increase Older age, family history of kidney chronic kidney disease,
susceptibility damage
reduction in kidney mass, low birth weight, racial or ethnic minority status, low income or educational level
Initiation factors
Factors
that
directly Diabetes mellitus, high blood pressure, autoimmune diseases, systemic infections, urinary
initiate kidney damage
tract infections, urinary stones, obstruction of lower urinary tract, drug toxicity Progression factors Factors that cause Higher level blood of proteinuria, level, in
worsening kidney damage higher and faster decline in poor
pressure
glycemic
control
kidney
function
after diabetes, smoking
kidney damage has started End-stage factors Factors that increase Infection, anemia, cardiovascular low serum
morbidity and mortality in factors, kidney failure
albumin level, late referral for dialysis
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SPECIFIC DIAGNOSIS A history of nephritic syndrome suggests primarily previous
glomerular disease as a cause of the CRF/ Recurrent gross hematuria may accompany IgA nephropathy or membranoproliferative glomerulonephritis. A careful personal and family history for hypertension and diabetes
mellitus should be obtained, including information on any family members in whom ESRD developed. It now appears that some families have a genetic predisposition not only for essential hypertension and diabetes mellitus but also for the development of renal disease secondary to these systemic diseases. A history of recurrent renal stones or obstructive uropathy, including prostatism, or excessive mixed analgesic intake may suggest primarily tubulointerstitial disease. The family history is also very helpful in the diagnosis of autosomal dominant polycystic kidney disease - although in about 30% a spontaneous mutation occurs - familial glomerulonephritis (Alport's syndrome), IgA nephropathy, and medullary cystic kidney disease. On physical examination, signs of hypertensive (left ventricular hypertrophy and hypertensive retinopathy) or diabetic disease (peripheral neuropathy, diabetic retinopathy) are important. Knobby, bilaterally enlarged kidneys support a diagnosis of polycystic kidney disease and a palpable bladder or large prostate suggests obstructive uropathy and is an indication for measurement of residual urinary volume after voiding. Gouty tophi and a history of gout may be relevant. Signs and symptoms of polyarteritis nodosa, systemic lupus erythematosus, Wegener's granulomatosis,
scleroderma and essential mixed cryglobulinemia should be sought because these systemic disease often involve the kidney. The findings of rheumatoid
18
arthritis are important because this disease is now the most common cause of systemic amyloidosis, which often involves the kidneys. Hepatosplenomegaly and macroglossia also suggest renal amyloidosis. LABORATORY INVESTIGATIONS After history and clinical examination, the relevant investigati ons (urine, blood, radiology and histology) are to be done to confirm the diagnosis. Urine Urinalysis and microscopy Dipstick examination of a fresh mid-stream urine sample is useful to assess the urinary pH and screen for leucocyturia, proteinuria, haemat uria, and glucosuria. The pH is usually low in CKD, unless the patient is on a very low protein diet. If the urine contains non-albumin proteinuria, then the dipstick test will be negative with the 24-hour quantification showing significant proteinuria. Microscopy of the urine sediment may and reveal erythrocytes
(dysmorphic if glomerular in origin), leucocytes
casts. Erythrocyte
casts are seen in glomerulonephritis (IgA, postinfectious, and SLE) and in cases of vasculitis. Leukocyte casts identify pyuria as coming from the kidney and are found in stone disease, tuberculosis, analgesic nephropathy and other causes of chronic interstitial nephritis. Quantitation of proteinuria (24-hours) Quantitation of proteinuria (24-hours) is used to measure proteinuria. Proteinuria is almost universal in CKD with the proteinuria in the nephrotic
19
range in conditions like diabetic nephropathy. The accuracy of the collection is checked by quantitating total urinary creatinine, which is fairly constant (range 10-14 mmol/day in females and 12-18 mmol/day in males). The degree of proteinuria can be also be "measured" by the spot urine protein/creatinine ratio and a good correlation has been shown between the two measures 34 , although the accuracy decreases at extremes of creatinine excretion (e.g. muscular men who have high and cachextic patients who and low urinary creatinine concentrations, respectively). Blood Hematology A full hemogram is important to establish the type of anaemia in a patient with CKD. A Coomb's test is done if clinically indicated to exclude autoantibody-induced haemolysis (as can occur in SLE). A peripheral blood smear may show microangiopathic haemolytic anaemia (fragmented and helmet-shaped erythrocytes and burr cells). If this occurs in combination with thrombocytopenia, it is suggestive of the haemolytic uraemic syndrome or thrombotic thrombocytopenic purpura. Biochemistry Serum creatinine concentration provides only a rough approximation of GFR as the amount excreted increases with a decline in GFR 35 . The electrolyte profile shows the presence of hyperkalemia and
severe metabolic acidosis. Blood sugar estimation and liver function tests provide information about underlying diseases such as diabetes mellitus and liver failure.
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Serology Serological tests can give additional support in the assessment of a diagnosis and underlying and C3 disease can be activity. decreased Serum in total haemolytic
complement
mesangiocapillary (including titres of
glomerulonephritis,
postinfectious
glomerulonephritis
endocarditis), cryoglobulinaemia and lupus nephritis. Elevated
serum anti-nuclear antibody and anti-double-stranded DNA support the diagnosis of lupus. In a patient with rapidly progressive renal failure with an active urine sediment, antiglomerular basement membrane antibodies confirm a diagnosis of Goodpasture's disease while Anti-Neutrophil Cytoplasmic Antibodies support a diagnosis of systemic vasculitis (Anti -proteinase 3 specific for Wegener's granulomatosis or Anti-myeloperoxidase - associated with microscopic polyangitis).
Virology Patients with CKD are commonly tested for antibodies against Human Imunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) and Hepatitis B surface antigen (HBsAg). HBsAg is associated with membranous glomerulopathy, IgA nephropathy and mixed cryoglobulinaemia. HCV infection is associated with type 1 membranoproliferative glomerulonephritis and cryoglobulinaemia. About 95 per cent of patients with mixed essential cryoglobulinaemia have evidence of HCV infection (by testing for antiHCV antibodies and HCV RNA).
21
Knowing the virology status is also important in vaccinating against Hepatitis B virus to protect against infection from dialysis and blood transfusions. Radiological investigations Renal ultrasonography is valuable in assessment of a patient of CKD. The renal size, renal cortical thickness and echogenicity can be determined. The presence of cysts and hydronephrosis can be demonstrated. If calculi are suspected, plain x-ray of the urinary tract can be done followed by intravenous urography (if renal function is normal) or non -contrast spiral computerized tomography (CT). CT with intravenous contrast and
arteriography (or magnetic resonance imaging with angiography) is required for diagnosis of classical polyarteritis nodosa and renovascular disease. However, angiogaphy renovascular disease. Role of biopsy In places where routine health checks are common place or if the patient has presents early in the course of the illness , a renal biopsy is mandatory (in most) to establish a diagnosis, to assess the extent of damage and to plan therapy. In others, it may have been deemed unnecessary because the diagnosis was established on clinical grounds, for example, in diabetes. If the kidneys are small, the hazards of the procedure are increased and have to be weighed against the small chance of finding a reversible cause. remains the 'gold standard' for diagnosing
22
STAGES OF KIDNEY DISEASE

Glomerular filtration rate (GFR) is accepted as the best index of overall kidney function in health and disease. Several stages of CKD, defined as structural abnormalities of the kidney that can lead to decreased GFR, are recognized 4,30 .
1.KIDNEY DAMAGE(GFR, 90 mL/min/1.73 m )
2
This stage is defined as the presence of structural or functional abnormalities of the kidney, initially without decreased GFR, which over time can lead to decreased GFR. 2.Mild reduction in GFR (60 to 89 mL/min/1.73 m 2 )/Early CRF At this stage, patients usually have hypertension and may have laboratory abnormalities indicative of dysfunction in other organ systems, but most are asymptomatic. If the serum creatinine level is elevated, it may be no more than borderline and of equivocal significance. 3.Moderate reduction in GFR (30 to 59 mL/min/1.73 m2)/Moderate CRF This stage is characterized primarily by the presence of azotemia, defined as the accumulation of the end products of nitrogen metabolism in the blood and expressed by an elevation in serum creatinine and serum urea nitrogen (SUN) concentrations. Erythropoietin production decreases, and laboratory abnormalities reflecting dysfunction in other organ systems are usually present. Although patients may have symptoms, they often remain remarkably asymptomatic even though their kidney function may be reduced by as much as 70%.
23
STAGES OF CKD WITH THE FREQUENCY OF COMPLICATIONS GFR (mL/min/ 1.73m 2 )
Stage
Descrption
Symptoms or signs Anaemia 4%
Chronic kideny damage with normal or increased GFR
90
Hypertension 40% 5 year mortality 19% Anaemia 4%
Mild GFR loss
60-89
Hypertension 40% 5 year mortality 19% Anemia 7%
Moderate GFR loss
30-59
Hypertension 55% 5 year mortality 24% Hyperphosphatemia 20%
Severe GFR loss
15-29
Anemia 69% Hypertension >75% 3 year mortality 14% Hyperphosphatemia 50%
Kidney failure ESRD
<15
Anemia 69% Hypertension >75% 3 year mortality 14%
4.Severe reduction in GFR (15 to 29mL/min/1.73 m 2 )/Pre-ESRD In this extremely tenuous stage of CKD, the worsening of azotemia, anaemia, and other laboratory abnormalities reflect dysfunction in several organ systems. However patients usually have mild symptoms.
24
5.Kidney failure (GFR, < 15 ml/min/1.73 m2 )/ ESRD In most cases, this level of kidney function is accompanied by a constellation of symptoms and laboratory abnormalities in several organ systems, which are collectively referred to us uremia, initiation of kidney replacement therapy (dialysis or transplantation) is typically required for treatment of comorbid conditions or complications of decreased GFR, which would otherwise increase the risk of morbidity and mortality. PATHOPHYSIOLOGY OF CHRONIC RENAL FAILURE Renal disease is often attributed to classic antibody-mediated or cellmediated immunologic renal injury. However, renal injury complicating
such common disorders as diabetes and hypertension has no apparent immunologic basis. Therefore, the pathogenesis of injury in these conditions must occur by way of nontraditional (nonimmune) pathways, Several nonimmune mechanisms of renal injury have recently been elucidated including systemic and alterations in circulating lipids, abnormal
internal hemodynamics and disordered regulation of
endogenous renal cell function 36 . An important clinical observation in patients with nonimmunologic renal disease is the invariable progression to ESRD once the baseline serum creatinine is more than 1.5 to 2.0 mg/dL, even in the absence of the original inciting event. This observation has advanced the hypothesis that nephron loss
serves to promote further nephron loss, although the mechanisms responsible for this inexorable course remain incompletely understood. It is thought that
25
adaptive changes occur in the remaining functional nephrons and promote progressive renal scarring. Studies in rats show that experimental ablation of renal mass promotes progressive loss of renal function, and the relative reduction in total renal mass correlates with the rate of progressive renal injury. Adaptive changes associated with nephron ablation have been the subject of intense investigation over the past decade. Among these "adaptations," investigated sustained changes in intraglomerular hemodynamics have been
most intensively37 .
Remnant nephrons undergo marked
increase in single nephron plasma flow (hyperperfusion), single
nephron glomerular filtration rate (hyperfiltration), and glomerular hydraulic pressure (glomerular hypertension) in response to ablation of renal mass. Glomerular hypertension, characterized by increased glomerular capillary hydrostatic pressure, appears to be of considerable importance. In fact, agents that attenuate glomerular hydraulic pressure, such as
angiotensin-converting enzyme (ACE) inhibitors and protein-restricted diets, can protect against progressive renal scarring. These observations form the basis of studies evaluating the clinical effects of sustained use of ACE inhibitors in patients with chronic renal failure. While hemodynamic factors have been extensively studied, the specific cellular and biochemical pathways that link altered glomerular
hemodynamics
with progressive renal scarring are still poorly understood.
Moreover, recent studies (3-5) have suggested that a variety of perhaps complementary mechanisms contribute to progressive renal scarring,
including proteinuria and alterations in levels of circulating lipids, hormones

26
and electrolytes. Collectively, these factors may contribute to progressive renal injury by changing the function of various resident renal cells, such as macrophages and mesangial cells 38 . Two other important concepts in understanding are the intact-nephron progression of CRF
hypothesis and the trade-off hypothesis 39 . The first nephrons behave like normal nephrons.
states that in general, adapted
Some of the failure to regulate sodium and water relates to increased solute excretion per nephron-in effect, an osmotic diuresis of the remaining nephrons that impairs sodium and water conservation, especially in states of extracellular fluid volume depletion. Thus renal concentrating ability is lost, as well as the ability of the remaining nephrons to adjust to low and high intake of sodium, water, potassium and other dietary solutes because these nephrons are functioning at maximum capacity even with normal intake of these substances. The "trade off hypothesis is to be considered together with the intact nephron hypothesis, that is the concept that adaptations arising in chronic renal failure may control one abnormality, but only in such a way as to produce other changes characteristic of the uremic syndrome. The best example is increase of parathormone secretion which is essential for
increased fractional excretion of phosphate; as the glomerular filtration rate falls, plasma phosphate is lowered by decreased tubular reabsorption. The consequence of normal plasma phosphate is then secondary
hyperparathyroidism and metastatic calcification 27,39 .
27
PATHOPHYSIOLOGY OF UREMIA Although the pathogenesis of the different uremic symptoms is not completely understood, three major mechanisms are involved: diminished excretion of electrolytes and water, reduced excretion of organic solutes and decreased hormone production 40 . Diminished excretion of electrolytes and water An important function of the healthy kidney is to excrete the electrolytes and water generated from dietary intake in order to maintain a steady state in which intake and urinary excretion are roughly equal. The conditions that cause loss of kidney function induce adaptive mechanisms that attempt to preserve the homeostatic state of electrolyte and water balance. If, for example, three quarters of nephrons have been lost, then each remaining nephron must excrete four times the amount of electrolytes and water to maintain the excretion at the same level of dietary intake 40 . However, all these compensatory mechanisms eventually fail, at
which stage the continual loss of function results in the kidney's inability to maintain balance. At this point, patients are said to have end -stage renal disease (ESRD). The number of functioning nephrons at this time is so small that urinary excretion cannot achieve a level equal to intake. Clinical manifestations include edema and hypertension (caused by retention), hyponatremia (resulting from free water sodium retention)
hyperkalemia, metabolic acidosis, hyperuricemia and hyperphosphatemia. Reduced excretion of organic solutes
28
The kidneys excrete a variety of organic solutes, the most commonly measured ones being urea and creatinine. Unlike the excretion of electrolytes and water, the excretion of urea and creatinine is not actively regulated. Thus the plasma level of these solutes begins to rise with the initial decline in GFR and increases progressively as kidney function deteriorates. Once the GFR falls below 15 mL/min/1.73m 2 , patients begin to complain of many of the manifestations. It is thought that many of these symptoms are mediated by an accumulation of uremic toxins. However, it is not yet possible to identify the toxins responsible for most uremic symptoms 41 . Although it has been postulated that urea may be an important toxin, symptoms of uremia correlate only inconsistently with the level or urea. Decreased hormone production The kidneys normally produce several hormones, including
erythropoietin and calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D. the decreased production of these two hormones plays an important role in the development of anaemia and bone disease, respectively.
29
CLINICAL ABNORMALITIES IN UREMIA 42

Fluid and electrolyte disturbances Volume expansion Hyponatremia Hyperkalemia Hyperphosphatemia Neuromuscular disturbances Fatigue Sleep disorders Headache Impaired mentation Lethargy Asterixis Muscular irritability Peripheral neuropathy Restless legs syndrome Myoclonus Seizures Coma Muscle cramps Myopathy Dermatologic disturbances Pallor Hyperpigmentation Pruritus Ecchymoses Nephrogenic fibrosing dermopathy Uremic frost
Endocrine-metabolic disturbances Secondary hyperparathyroidism Adynamic bone Vitamin D-deficient osteomalacia Carbohydrate resistance Hyperuricemia Hypertriglyceridemia Increased Lp(a) level Decreased high-density lipoprotein level Protein-energy malnutrition Impaired growth and development Infertility and sexual dysfunction Amenorrhea
Gastrointestinal disturbances Anorexia Nausea and vomiting Gastroenteritis Peptic ulcer Gastrointestinal bleeding Idiopathic ascites Peritonitis
Cardiovascular and pulmonary disturbances Arterial hypertension Congestive heart failure or pulmonary edema Pericarditis Hypertrophic or dilated cardiomyopathy Uremic lung Accelerated atherosclerosis
Hematologic and immunologic disturbances Anemia Lymphocytopenia Bleeding diathesis Increased susceptibility to infection Leukopenia Thrombocytopenia
30
CLINICAL MANIFESTATIONS OF CHRONIC KIDNEY DISEASE AND UREMIA Uremic syndrome consists of an array of complex symptoms and signs that occur when advanced kidney failure prompts the malfunction of virtually every organ system. However, the onset of uremia is slow and insidious, beginning with rather nonspecific symptoms such as malaise, weakness, insomnia and a general feeling of being unwell. Patients may lose their appetite and complain of morning nausea and vomiting. Eventually, signs and symptoms of multisystem failure are evident. Electrolyte disturbances CKD leads to a variety of disturbances in electrolytes and fluid balance. Sodium balance Sodium balance remain virtually normal until very late in the course of CKD, because the kidney can markedly increase the amount of sodium excreted per nephron by reducing tubular sodium reabsorption. Although sodium balance is maintained, the kidney loses its ability to adapt to large variations in salt intake. Indeed, intake of large amounts of sodium can easily overwhelm the excretory capacity of the failing kidney and result in fluid retention, edema, and hypertension. Likewise, if diuretics are used
overzealously, the patient may become volume-depleted, with further aggravation of the kidney failure. Wasting of sodium by the chronically diseased kidney-so-called sodium-wasting nephropathies-is rare.
31
Clinically evident edema is uncommon until the GFR fails to less than 125 mL/min/1.73m 2 . However, edema can occur at higher GFR levels in patients with glomerular disease and significant proteinuria (i.e., nephrotic syndrome) and in those with heart failure. The cornerstone of treatment of edema (and hypertension) is restriction lower than that recommended of dietary sodium to a level
for uncomplicated hypertension
(<100mEq/day; 2.3 g of sodium or 6 g of salt) 43 . If sodium restriction is not effective or not achieved, diuretics should be used 44 . Thiazide diuretics are usually ineffective if the serum creatinine level is greater than 3 mg/dL (>265 micromole/L). Thus, more potent loop diuretics are the agents of choice in patients with CKD. The initial aim is to determine the threshold dose that is effective. Patients with advanced CKD may require doses of furosemide (Lasix) as high as 400 mg per day. Lack of response to high doses of loop diuretics often is due to noncompliance with dietary sodium restriction. In such cases, a combination of a thiazide diuretic or metolazone given before the loop diuretic may induce diuresis. For maximum efficacy, the thiazide diuretic should be given 30 minutes before the loop diuretic. are Potassium-sparing diuretics of (e.g. risk Sprionolactone of inducing
[Aldactone]) hyperkalemia.
contraindicated
because
the
Potassium balance Potassium balance and plasma potassium level are also maintained until very late in CKD, mainly because of an increase in renal excretion of potassium per functioning nephron and an increase in potassium output in the stool 45 . Hyperkalemia may develop earlier in the course of CKD in patients
32
with hyporeninemic hypoaldosteronism, a complication usually seen in patients with diabetic nephropathy or tubulointerstitial disease. Hyperkalemia may occur in association with dietary indis cretion (e.g. Excessive consumption of chocolate, dried fruits, or bananas), use of potassium-containing salt substitutes, increased catabolism (as with severe intercurrent illness), metabolic acidosis. It may also be seen with the use of potassium sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, and nonsterodial anti-inflammatory drugs (NSAIDs). Hypokalemia may occasionally occur in patients with CKD, and it is sually due to gastrointestinal losses or excessive use of the cation exchange resinsodium polystyrene sulfonate 46 . Mild hyperkalemia in the range of 5 to 5.5 mEq/L is a common feature inpatients with CKD and requires dietary potassium restriction to 2 to 3 g (50 to 75 mEq) per day as well as discontinuation of any offending drug. P atients with serum potassium concentration below 6 mEq/L usually respond to a combination of a loop diuretic and low-potassium diet. Asymptomatic patients with a serum potassium level above 6 to 6.5 mEq/L can be treated with sodium polystyrene sulfonate, given orally or by colonic enema at a dose of 15 to 30 g every 6 hours with sorbitol. More marked or symptomatic hyperkalemia, particularly in the presence of electrocardiographic changes, is treated with combinations of intravenous calcium gluconate (for urgent situations) and infusions of glucose and insulin with or without bicarbonate. This therapy transiently drives potassium into the cells until excess potassium can be removed from the body.
33
The latter can be achieved with sodium polystyrene sulfonate o r diuretics at high doses. In patients with kidney failure, dialysis may be required.
Water balance The ability to concentrate or dilute urine is impaired inpatients with CKD, which makes them more susceptible to hypernatremia and
hyponatremia. Hypernatremia may occur if water consumption is not sufficient to replace fluid loss. More commonly, hyponatremia develops in patients with CKD because they either drink water or are given hypotonic fluids in excess of their ability to excrete water. To prevent hyponatermia, most patients are permitted a modest fluid intake of 1.5 L per day. Also, intravenous administration of hypotonic solutions should be avoided. Metabolic acidosis Most patients with CKD develop metabolic acidosis because of their reduced ability to excrete the hydrogen ions generated mainly from the metabolism of sulfur-containing amino acids 47,48 . As a patient's condition approaches ESRD, serum bicarbonate concentration often falls to between 12 and 20 mEq/L and the anion gap increases. A level below 10 mEq/L is unusual, because buffering of the retained hydrogen ions by intracellular buffers prevents a progressive fall in the concentration of serum bicarbonate. Treatment of metabolic acidosis appears to be justified because chronic acidemia has been associated with worsening of hyperparthyroid -induced kidney bone disease and negative calcium balance, enhanced skeletal muscle breakdown and catabolism, growth retardation in children, and probably faster
34
progression of GFR loss 49 . The goal is to maintain the serum bicarbonate level above 20 mEq/L. Sodium bicarbonate in a dose equivalent to the daily production of acid (0.5 to 1 mEq/kg body weight per day) is generally recommended. Because of the concomitant sodium load, diuretic therapy may be necessary to avoid edema and hypertension. Sodium citrate is better tolerated than sodium bicarbonate because it does not produce carbon dioxide gas in the stomach. However, sodium citrate should not be used in patients taking aluminum-containing phosphate binders, because it markedly increases aluminum absorption and increases the risk of aluminum intoxication. Calcium carbonate, which is often used as a phosphate binder, can help control acidemia as well. Hypoalbuminemia and nutritional disorders Hypoalbuminemia is highly prevalent in patients starting dialysis 50 . Its cause is multifactorial. CRI disrupts several components of protein metabolism, increasing nitrogen and essential amino acid requirements 51 . Concomitant disease, such as hepatic impairment, nephrotic syndrome, and volume overload, can contribute to hypoalbuminemia. Factors associated with socioeconomic status and access to medical care have also been implicated 50 . Using data from the US Renal Data System maintained by the Health Care Financing Administration, a recent study documented the high frequency of hypoalbuminemia in patients entering dialysis. Of 74,232 patients who began dialysis between April 1995 and June 1997 and for whom the relevant data were available, 60% had serum albumin levels below the lower normal limit for the testing laboratory and 37% had levels 3.0 g/dL. Multivariate
35
analysis showed that hypoalbuminemia was associated with female gender, black or other non-Caucasian race, nonprivate or no insurance, and diabetes. Stall et al 52 found that, even once dialysis was initiated and an "adequate" dialysis regimen was provided, many patients were not attaining acceptable levels of nutrition as evidenced by continued hypoalbuminemia and changes in body composition. The impact of hypoalbuminemia and malnutrition on overall morbidity and mortality rates has been well documented. The presence of malnutrition and level of serum albumin are both predictors of mortality in patients who begin either hemodialysis or peritoneal dialysis. 53,54 Three studies have found hypoalbuminemia to be associated with higher rates of hospitalization in ESRD patients. 55,56,57 Finally, hypoalbuminemia in renal patients appears to be a risk factor for development of pulmonary edema and infectious complications 55 . To date, however, no trails have established that there is effective treatment that either restores albumin levels to normal or reduces any of the long-term risks of hypoalbuminemia in ESRD. Recent data suggest that hypoalbuminemia may be a reflection of chronic inflammation rather than nutrition per se. Clearly, better efforts are needed to assess the degree of malnutrition and the presence of chronic inflammation during both the CRI and ESRD periods so as to develop appropriate means of early int ervention 58 . Gastrointestinal complications Anorexia, nausea, and vomiting are common in advanced kidney failure 59 . These symptoms are usually corrected by dialysis. Peptic ulcer disease as well as atrophic Similarly, angiodysplasia gastritis are known complications.
of the gastrointestinal tract, in particular the

36
colon, is relatively common and can cause severe Gastrointestinal bleeding in renal failure
and protracted is
bleeding.
exacerbated by the
underlying bleeding diathesis when uremia is advanced. However, malnutrition is a common problem in CKD patients, and nutritional support coordinated with an experienced renal dietician is an important component of management of these patients 60 . Neurological complications The function of the central and peripheral nervous systems may be disturbed in chronic renal failure. Cerebrovascular accidents of all types are common in CKD. Encephalopathy is a feature of severe uremi a and is characterized by a decline in higher mental functions, causing confusion, loss of memory, apathy, and irritability. These are often followed by motor disturbances causing myoclonic jerks, flapping tremor (asterixis), and seizures. Uraemic peripheral neuropathy is mixed motor and sensory in nature. Its presence is an indication to start dialysis. It causes paraesthesiae, including restlessness or burning feet. Autonomic nervous system dysfunction has also been described in uraemic patients and may c ause postural hypotension and impotence 61 .
37
CARDIOVASCULAR COMPLICATIONS
Patients with kidney failure are at high risk of cardiovascular mortality62 . They experience a high rate of fatal and nonfatal cardiovascular disease events prior to reaching kidney failure. 63,64 Patients in all stages of CKD are therefore considered in the "highest risk group" for development of cardiovascular disease and CKD is recognized as a cardiovascular risk equivalent. 65,66 CKD is a risk factor for cardiovascular disease and cardiovascular disease may be a risk factor for CKD. Analysis of communitybased studies including Atherosclerosis Risk in Communities Study, Cooperative Health Study, Framingham Heart Study, and the Framingham Offspring Study, CKD defined as GFR of 15 to 60 ml/min/1.73 m 2 , was an independent predictor of a composite outcome of all -cause mortality as well as fatal and nonfatal cardiovascular disease events 67 . Several studies has established urinary albumin excretion as an independent predicto r of cardiovascular outcomes 68 in CKD patients. Patients with CKD are much more likely to suffer from atherosclerosis and heart failure, resulting in cardiovascular death, than to eventually require renal replacement therapy. This is likely due in part to accelerated rates of cardiovascular disease among those with CKD. In addition, patients with CKD are more likely to present with atypical symptoms, which may delay diagnosis and adversely affect outcomes. Traditional cardiovascular risk factors, such as hypertension smoking history, diabetes mellitus, dyslipidemia and older age, are highly prevalent in CKD populations. 69,70 Patients with CKD are also more likely to have the metabolic syndrome, which could contribute to the increase in cardiovascular risk. 71,72 Increased arterial
38
stiffness is noted in patients with CKD is also a possible risk factor .Some risk factors are relatively unique to patients with moderate to severe CKD. These include retention of uremic toxins, anemia, increased calcium intake, abnormalities in bone mineral metabolism, and proteinuria. The overall absolute risk of future adverse cardiovascular events is somewhat lower with CKD patients than that observed in patients with a history of prior heart disease, but without CKD. In gener al, the risk is approximately 50 percent lower with CKD alone, although the risk increases with increasing renal dysfunction and/or severity of proteinuria. All patients with the same degree of renal dysfunction also do not have the same risk of cardiovascular disease. Thus, in addition to the evaluation for the presence of CKD, the proper assessment of overall cardiovascular risk requires an adequate assessment for the presence and severity of the other major risk factors for cardiovascular disease ISCHEMIC HEART DISEASE Ischemic heart disease most commonly results from atherosclerosis of the coronary arteries. The processes that contribute to accelerate
atherosclerosis include a dyslipidemia characterized by decreased function of lipoprotein lipase, reduced HDL-C, elevated TG, and elevated LDL-C. Both uremia and dialysis therapy markedly enhance oxidant stress through the production of proinflammatory complement fragments, cytokines, and
increased adhesion molecules in endothelial cells 74 . Endothelial dysfunction begets cardiac and arterial remodeling with resultant cardiovascular events. Potentially important in the inflammatory cascade and ensuing cardiovascular
39
mortality among kidney patients are C-reactive protein (CRP) and asymmetric dimethyl-arginine. HEART FAILURE About 40% of people starting dialysis therapy have a history of heart failure symptoms, which is a risk factor for significant morbidity and mortality in this group 75 . For those without heart failure symptoms at the commencement of dialysis, 25% will develop it within 3 years (7% per
year) 76 . Age (risk increased by 30% for every 10 years), female sex, hypertension, diabetes, conditions of atherosclerosis (CAD, cerebrovascular or peripheral vascular disease), pericarditis, and structural ca rdiac
abnormalities (left ventricular hypertrophy, clinical cardiomegaly) were all associated with heart failure. Multiple studies of patients with class II and III HF, in whom a low cardiac output state is not present, have shown decreased survival in a graded fashion related to renal impairment. Hematologic abnormalities Progressively more severe normochromic, normocytic anemia develops as the GFR & renal erythropoietin secretion decreases. In most of the patients, the hematocrit reaches about 20-25% by the time that ESRD develops. The pathogenesis of the anemia of chronic renal disease is related to: To the etiology of the renal disease To the failure of renal excreatory function To the failure of renal endocrine function. Failure of renal excreatory function leads to an increased demand for red blood cells because of shortning of red blood cells life span, impaired
40
utilization of iron, decreased responsiveness to erythropoietin & increased blood loss. Failure of renal endocrine function leads to a decreased erytliropoitic response to these demands because of impaired production of erythropoietin. A greater degree of anemic hypoxia is required to generate
the necessary amount of erythropoietin, and equilibrium between deman d & supply is first established at anemic levels 77 . Uremic coagulopathy is secondary to a defect in platelet function as well as factor VIII function. It is characterize by a prolonged bleeding time but usually normal clotting time. The platelet dysfunctio n responds to dialysis and to infusion of desmopression. Epistaxis, menorragia, bruising & parpura as well as gut bleeding may also occur. Uremic patients should be regarded as immunocompromised and infection is an important cause of death in chronic renal failure and dialysis patients. The leukocyte count, but not polymorphonuclear function is commonly normal with a normal differential, as are total immunoglobulin and complement levels. Cellular immune function is depressed, however antibody response to hepatitis B & influenza immunization, for eg., are less than in normal subjects, but protection is still indicated & feasible. Bone disease Metabolism of calcium and phosphorus is abnormal in patients with CKD and is associated with the development of bone disease. Phosphate retention occurs as GFR declines. Both hyperphosphatemia and more important, reduction in the active form of vitamin D (1,25 -
dihydroxycholecalciferol) lead to hypocalcaemia. (The active form of vitamin
41
D is normally produced by the kidney and increases calcium absorption in the intestine.) As attempts are made to normalize the serum calcium level, secondary hyperparathyroidism can develop, causing significant bone damage occur. 78,79 The spectrum of bone disease, also known as renal osteodystrophy, includes osteitis fibrosa, osteomalacia, and adynamic bone disease. The most common form is osteitis fibrosa caused by secondary hyperparathyroidism. Although initially asymptomatic, osteitis fibrosa can produce bone pain, pathologic fractures, and metastatic calcifications in its more advanced stages. The complications associated with hyperparathyroidism can be prevented or minimized by controlling hyperphosphatemia and by lowering the parathyroid hormone level 80 . Pathogenic factors in renal osteodystrophy 81 Hypocalcaemia Phosphorus retention Impaired calcaemic response to PTH Altered degradation of PTH by the kidney Disordered regulation of PTH and calcitonin Altered Vitamin D metabolism
Dyslipidemia Abnormalities of lipid metabolism appear to occur early in the course of kidney failure and are another treatable complication of CRI. Lipoprotein lipase activity falls in patients with glomerular filtration rates (GFRs) of 50 mL/min or less, and triglyceride values rise with GFRs in the range of 15
42
to30mL/min. 82,83 As kidney failure progresses, a generalized disorder of lipid metabolism becomes apparent, irrespective of the underlying cause of the kidney disease. Abnormalities include hypercholesterolemia, elevated ratio of low-to high-density lipoproteins, elevation of lipoprotein(a), and elevated chylomicron remnant level 84 . Hyperlipidemia is among the many contributors to atherosclerosis in patients with ESRD. Treatment during the CRI stage may help prevent such complications, although specific data on the benefits of such intervention are not currently available. Standard regimens for the management of
dyslipidemia can be employed in CRI, with appropriate modification of drug dosages based on the level of kidney function. Thyroid disease in ESRD ESRD is a non-thyroidal illness, which affects the thyroid hormone metabolism. Multiple other comorbid conditions that affect the thyroid hormone metabolism (diabetes mellitus, malnutrition, frequent infections) are also common in ESRD. Certain thyroid diseases occur in increasing frequency in these patients and they include goiter, thyroid nodules and thyroid cancer. Incidence of hyperthyroidism is the same as in the general population but primary hypothyroidism occurs more frequently. Incidence in literature varies from 0% in Austria to 9.5% in Michigan, where the incidence of primary hypothyroidism in the general population is 0.6-1.1%. Chronic renal failure and the skin The cutaneous manifestations of chronic renal failure include prurit us, dry flaky skin, as well as darkening and yellow pigmentation of the skin,
43
made more obvious by the pallor of anaemia. Bullous lesions in sun -exposed areas (pseudoporphyria cutanea) are occasionally seen in patients on dialysis. Proximal skin necrosis (thighs and trunk) is a consequence of ischemia resulting from calcification and occlusion of arterioles. Trophic nail changes are frequent, including brown nail arcs (half-and-half nails). Most common causes of death among patients with CKD 73
Heart failure Myocardial infarction Sepsis Withdrawal from dialysis Strokes Malignant neoplasm Other
31.2% 15.6% 11.3% 5.2% 6.4% 3.8% 26.5%
TREATMENT OF CKD Attenuation of progression Once a diagnosis of CKD is made, there are certain medical measures that can be undertaken to attenuate the progression. Blood pressure control The importance of the control of blood pressure in patients with renal disease cannot be overemphasised. Hypertension is common in patients with CKD and the rate of decline in renal function increases with increasing blood pressure1 85,86 and also reduction in blood pressure attenuates the deterioration of renal function (first convincing demonstration was in diabetic
nephropathy). 87,88
44
Two important factors contribute to the rise in blood pr essure of patients with CKD. First, most renal diseases are associated with sodium retention, which results in an increase in extracellular fluid volume and an increase in peripheral vascular resistance. Second, activation of the renin angiotensin-aldosterone system results in increased circulating angiotensin II, which in addition to being a potent vasoconstrictor, also enhances sodium retention by the kidney. Hence, the two initial steps in the treatment of hypertension in CKD should consist of a reduction in sodium intake, with or without the use of diuretics, and treatment with agents that block the effects of angiotensin II, that is, ACE inhibitors or ARBs. Other antihypertensives that are commonly prescribed are calcium channel blockers, beta adrenergi c antagonists, a-adrenoceptor blockers and diuretics. The target blood pressure in patients with CKD is 120/70 mmHg especially with proteinuria of over 1 g/day. 89,90 Regular follow-up is essential as it has been demonstrated that patient compliance, effica cy of
antihypertensive treatment, and retardation of renal failure are clearly related to the number of outpatient visits 91 . Dietary recommendations Sodium restriction In patients with CKD, the ability to excrete sodium usually is limited. Thus, a sodium-restricted diet of 6 g/day is a useful initial step in the treatment of hypertension. Determining a 24 h urinary sodium excretion can check compliance with the sodium restricted diet.
45
Sodium
depletion
may
occur
in
patients
with
CKD
due
to
tubulointerstitial disease such as pyelonephritis, interstitial nephritis or hydronephrosis. In these, sodium has to be monitored closely and often restriction is not advisable. Protein restriction The initial observations in the rat model with reduced renal mass h ad shown that protein restriction attenuated the development and progression of renal failure. Thereafter, some retrospective studies and several (but not all) randomized prospective studies confirmed that a low protein diet might have the same effect in humans. In the initial analysis of the Modification of Diet in Renal Disease (MDRD) Study, 4 (which was the largest trial to date on the effect of protein restriction on CKD in man) the effects of dietary protein restriction and blood-pressure control on the progression of CKD, the investigators reported a small beneficial effect of the low -protein diets on the course of renal function after an average follow-up period of 2.2 years. When the initial 4 months of low-protein diet were excluded from the analysis, the decline in GFR of protein-restricted patients was attenuated 92 . This secondary analysis of the MDRD trial patients also revealed a high protein intake was associated with a more rapid decline in GFR. It was calculated that each 0.2 g/kg body weight reduction in protein intake resulted in a 29 percent reduction in the rate of decline in GFR. The effect of protein restriction on the progression of CKD has been analysed in two meta-analyses. 93,94
46
Altogether, it can be concluded from these studies that protein restriction causes a modest reduction in the progression of CKD in man. It was concluded that dietary protein restriction significantly reduced the risk for renal insufficiency or death with a relative risk of 0.67 (95% confidence interval 0.50-0.89) in patients with non-diabetic renal failure and 0.56 (95% confidence interval 0.40-0.77) in patients with diabetic nephropathy. Currently, mild protein restriction to 0.6 to 0.8 grams per kg is recommended. Calorie intake is kept at 30 kcal/kg body weight/day or more. Dietary protein restriction also helps to alleviate the symptoms of uraemia in those not being considered for dialysis in addition to attempting to slow the progression of renal insufficiency without negatively jeopardizing nitrogen balance. Dietary compliance is monitored most readily by measuring the serum urea : creatinine ratio (which should be reduced by treatment) and the 24-h urinary urea excretion. produce about 150 mmol of urea. Fluid balance In CKD, the regulatory capacity of the kidney is progressively reduced. Both excretion and conservation of electrolytes and water are impaired; when sudden loads of potassium, acid, or fluid has to be handled the limitations of renal functional reserve become apparent and signs of decompensation may occur. Consequently, water and electrolyte intakes must be adapted to renal excretory capacity. In the subset of patients who are fluid overloaded, both sodium and water have to be restricted. On the other hand, in patients with conditions that For example, a 40 g protein diet should
47
predominantly affect the renal medulla (for example, interstitial nephritis and pyelonephritis), defective urinary concentrating ability is particularly common and dehydration occurs easily in patients with inadequate fl uid intake, due to persistent diuresis despite fluid deprivation. Several
mechanisms are responsible for the inability to excrete concentrated urine, including the increased solute load in remnant nephrons resulting in an osmotic diuresis, alteration of medullary interstitial solute concentrations as a result of the damaged countercurrent exchange system and impaired medullary blood flow. In addition, impaired sensitivity to antidiuretic hormone causes decreased outward water transport in the distal nephron segments. As a result of decreased concentrating capacity, urine osmolality is roughly that of plasma, approximately 300 mOsm/kg H 2 0, in patients with CKD. If the obligatory osmolar production in an adult is around 600 mOsm/kg H20, daily urine output will be roughly 2 1 per day. Fluid intake should therefore be approximately 2-3 1/day in order to ensure adequate urine flow rates and to prevent dehydration. In some patients who are 'salt losers', fluid requirements may be even greater. Potassium Patients with CKD are usually able to maintain serum potassium within normal imits until oliguria occurs or GFR is less than 5 ml/min. Preservation of normokalaemia results from an adaptive increase in potassium excretion by remnant nephrons and increased bowel loss. However, hyperkalaemia may be an early feature of renal failure in patients with hyperchloraemic metabolic acidosis and hyporeninaemic lypoaldosteronism, which occur particularly in patients with chronic tubulointerstitial nephritis and diabetic nephropathy.
48
Hyperkalaemia also complicates an acute potassium oad (e.g. blood transfusion, or medication, which interferes with potassium secretion, for example, potassium sparing diuretics, ACE inhibitors, -blockers, and NSAIDs) Foods containing high levels of potassium like nuts, chocolate, fruits, wine and fruit juice and salt substitutes (containing potassium) are particularly dangerous. Therefore a judicious restriction of potassium rich diet and monitoring of serum potassium while on ACE inhibitors and ARBs is warranted. Other medications Phosphate binders and calcitriol Skeletal abnormalities occur early in renal failure, well before
symptoms develop. 95 A variety of biochemical and radiological investigations are available to assist n the diagnosis and monitoring of renal osteodystrophy of which serum parathyroid lormone (PTH) remains the single most useful biochemical test in predicting bone listology in an individual patient. 96 In early CKD, it would appear that adynamic bone disease is the principal type of xme lesion with high turnover bone disease developing with more advanced renal failure. As renal insufficiency progresses, higher levels of PTH are necessary for normal bone remodeling. The cause of this 'skeletal resistance' to PTH in uraemia is probably multifactorial. Inhibition of osteoclastic bone resorption appears to be the central mechanism. Therefore a plasma PTH of two to three times the normal value is usually required to maintain normal bone turnover.
49
When the patient is seen in the early phases of CKD, the objective is to maintain normal bone turnover by maintaining serum calcium, phosphate, PTH and calcitriol and blood pH in the normal range. The mainstay in preventing secondary hyperparathyroidism is strict phosphorus control. Some dietary phosphate restriction is usually required once GFR is less than 50 ml/min. Care must be taken in maintaining a sufficient protein intake, however, and adequate nutrition must be maintained. Dietary restriction alone is usually inadequate in controlling serum phosphate once GFR is less than 25 ml/min. Phosphate binders are then added to reduce phosphorus absorption from the intestine. Calcium carbonate i 500 -2000mg thrice daily) is effective and probably the most widely used phosphate b inder. It must be taken with food to give optimal phosphorus binding and to reduce the risk of hypercalcaemia. If hyperphosphataemia persists despite
administration of calcium carbonate, excess dietary intake (e.g. dairy products) should be excluded and alternative phosphorus binding agents substituted. Another commonly used calcium containing binders is calcium acetate. It is a more effective binder than calcium carbonate and is less ikely to be associated with hypercalcaemia. The downside of using calcium containing phosphate binders is the risk of a positive calcium balance which in dialysis patients is associated with vascular calcification and a raised calcium x phosphate product is associated with a higher relative risk of death. In the face of hypercalcemia, other phosphate binders like sevelemar hydrochloride and lanthanum carbonate may need to replace calcium based products. Others still being evaluated include polynuclear iron preparations.
50
In some patients, aluminium-containing phosphate binders have to be resorted to. If needed, they should be used only for a limited period of time since aluminium is absorbed to a variable extent and can lead to aluminium overload, manifesting as anaemia and aluminium-mediated bone disease. In patients with lower stages of CKD, administration of l,25-(OH) 2 D3 (calcitriol) 0.25 g/day causes a rise in serum calcium, a fall in serum phosphorus and alkaline phosphatase, and retards the development of histological bone abnormalities. 97 Careful monitoring of serum calcium is required, since hypercalcaemia may accelerate the decline in renal function. Though new vitamin D metabolites are available such as 22-oxacalcitriol, paracalcitriol (19 nor-1,25 dihydroxy-vitamin D2), and doxercalciferol (1-hydroxy-vitamin D2), their benefits over conventional calcitriol and alfacalcidol remain to be
established 98 . Bone biopsy is generally reserved for patients with unusual biochemical and radiological evidence of bone disease. Treatment of anemia Anaemia is a predictable consequence of CKD and is directly related to its severity. It frequently occurs early with one study reporting a prevalence of 45% in patients with a serum creatinine 2 mg/dl 99 . Monitoring anaemia is important to determine if it becomes disproportionate to the stage of CKD. A haemoglobin of less than 6 g/dl is rarely due to CKD alone. Red cell indices should be scrutinized to detect the onset of iron, folate or vitamin B12 deficiency. Functional iron deficiency is common and should be confirmed by measurement of percentage of hypochromic red cells, serum iron, transferrin
51
and ferritin. As oral iron is often poorly tolerated, intravenous iron is now frequently administered to predialysis patients. Occult gastrointestinal bleeding is common in patients with advanced stages of CKD and is most commonly due to superficial upper gastrointestinal lesions 100 . Recombinant human erythropoietin (rhEPO) is effective in treating anaemia in adults and children with CKD both prior to and while o n dialysis. Benefits of correcting anaemia include increased quality of life, reduced morbidity and improved survival. This may be related to reduction in left ventricular mass and normalization of cardiac output with partial correction of anaemia. There is also evidence to suggest that rhEPO therapy may retard the progression of CKD and delay the onset of dialysis by as much as 6 months. 101,102 Treatment of hyperlipidemia Hyperlipidaemia is often present in patients with CKD 35 . Nonetheless, there are only a limited number of studies, usually with a small number of patients, in which the effects of treatment of hyperlipidaemia has been investigated. A meta-analysis by Freid et al showed clearly that treatment of hyperlipidaemia ameliorates the progression of CKD. 103,104 Other recommendations Obesity is clearly associated with hypertension, and reduction of body weight should be recommended to obese patients. Increasing physical exercise and reducing calorie intake may achieve this. In patients with advanced
CKD, caution must be exercised in severe calorie restriction because of the risk of catabolism.
52
Alcohol abuse can also contribute to hypertension and may also interfere with adherence to antihypertensive or other therapy. It is advisable to limit alcohol intake to less than 21 units in men and 14 units in women. In patients with CKD, it has been shown that cigarette smoking enhances the rate of progression of disease. 105,106 Thus, patients with CKD should be strongly advised to quit smoking.
INDICATIONS FOR DIALYSIS: ESTABLISHED INDICATIONS - There are a number of absolute
clinical indications to initiate maintenance dialysis . 107 These include : Pericarditis. Fluid overload or pulmonary edema refractory to diuretics Accelerated medications Progressive uremic encephalopathy or neuropathy, with signs such as confusion, asterixis, myoclonus, wrist or foot drop, or in severe cases, seizures. A clinically significant bleeding diathesis attributable to ur emia Persistent nausea and vomiting Plasma creatinine concentration above 12 mg / dL (1060 )Limol/L) or blood urea nitrogen (BUN) greater than 100 mg/dL (36 mmol/L) However, these indications are potentially life threatening and the patient is generally known to have advanced chronic renal failure. As a result, hypertension poorly responsive to antihypertensive
53
most nephrologists agree that delaying initiation of dialysis until one or more of these complications is present may put the patient at unnecessary jeopardy. RELATIVE INDICATIONS - Since an important goal of dialysis is to enhance the quality of life as well as prolong survival, it is therefore important to consider less acute indications for dialysis. These relative indications include anorexia progressing to nausea and vomiting, decreased attentiveness and cognitive tasking, depression, severe anaemia unresponsive to erythropoietin, persistent pruritus or the restless leg syndrome . 108 Unfortunately, the expression of these signs and symptoms is variable in patients with slowly progressive renal disease. The following are some of the factors that may contribute to this variability. Some patients accommodate to these symptoms and downgrade their sense of well-being as renal failure progresses. Many of the medications given to patients with chronic renal failure have side effects that mimic uremic symptoms. As examples, oral iron therapy often leads to nausea and centrally acting antihypertensive drugs can induce drowsiness independent of the degree of renal failure. On the other hand, partial correction of anaemia by erythropoietin may improve that patients sense of wellbeing without effecting the extent of uremia. These factors illustrate the need to identify more objective markers of renal failure in order to lessen the subjective component of the decision to initiate dialysis.
54
Peritoneal Dialysis (PD) Chronic ambulatory PD (CAPD) and other PD modalities may provide a less expensive means to treat patients with ESRD who require chronic regular dialysis. There are certain advantages in PD over hemod ialysis (HD), but PD has not been widely used in Japan and other countries; infact PD has been used in less than 5% of patients with ESRD. There are several medical and non-medical reasons for the same. Some patients will be placed on PD purely for medical reasons. However, when there is no particular reason to choose either HD or PD, many patients will be placed on HD. One of the main reasons is the fact that 70 to 80% of patients will not be able to be on a chronic dialysis program more than 5 year as a result of loss of peritoneal function. This is particularly true in Japan, where the majority of patients will be maintained on HD longer than 10 years. In India, CAPD is reserved as a last option for most patients of ESRD. Patients not suitable for transplantation and who can afford peritoneal dialysis are offered this modality of treatment. 109 Complications of Chronic Dialysis Although retarding the progression of chronic renal disease is crucial to the treatment of ESRD, prevention and management of various complications of chronic dialysis patients are also of critical importance in maintaining the quality of life of these patients. Although there are many complications that are particular to chronic dialysis patients, including vascular disease, peritonitis (for PD), bone disease, dialysis amyloidosis, and malnutrition, a recent proposal of the possible role of carbonyl stress as an
55
underlying biochemical mechanism for some of these complications is of particular importance. This carbonyl stress hypothesis suggests that through continuous oxidative as well as nonoxidative stresses, several carbonyl compounds will be generated in quantities so massive (compared with any other medical condition, including diabetes) that extraordinary amounts of glycation end products will accumulate, thus modifying proteins throughout the body. This is a new and attractive hypothesis with a solid scientific, experimental, and clinical basis, and thus, it warrants further investigation and development. Renal transplantation is the best option available to patients with ESRD. However, cultural and social factors have hampered the increase in renal transplantation in certain parts of the world, including India and other Asian countries. In fact, in Japan, most renal transplantation procedures have been performed with donations from a living relative, but the number never exceeded 100 per year despite having a large number of patients with ESRD 21 . A marked shortage of donor kidneys, the lack of good cadaver program, and large scale poverty have led to trafficking of organs. It is estimated that 50% to 50% of kidneys transplanted in India come from living unrelated donors 110 . The annual cost of renal replacement therapy (RRT) is more than 10 times the per capita gross national product (GNP) in most developing countries. The high cost of RRT in the non-state funded infrastructure in the developing countries poses a major challenge to proper treatment of patient having end stage renal disease.
56
METHODOLOGY
Source of data : Patients admitted in Chigateri General Hospital and Bapuji Hospital, attached to J.J.M. Medical College, Davangere, between 2009 to 2011. Method of collection of data : A minimum fifty pateints both male and female with chronic renal failure shall be included according to inclusion criteira set by National Kidney Foundation. K/DOQ1. Inclusion criteira : Patients with serum creatinine above 2mg% with abnormal findings on renal ultrasound : asymetric kidney size, small kidneys (less than 9cm) or large polycystic kidneys. Elevated serum creatinine with no improvement for more than 3 months. Uremic symptoms over three monthys with elevated serum creatinine.
Exclusion criteria : Patients below the age of 17 years were not included in this study. A detailed history and thorough physical examination was carried out in all patients. Data recorded in each patient included a ge, sex the underlying primary renal disease, clinical and biochemical features of chronic renal failure on a standard proforma. An aetiological diagnosis was made on each patient even though it could not always be confirmed by histopathology.
57
Chronic Glomerulonephritis was diagnosed in patients with history of oedema, hypertension and documented nephritic range of proteinuria. Hypertensive nephropathy was diagnosed in patients with long history of hypertension and other target organ damage. Diabetic Nephro pathy was diagnosed in patients with long history of diabetes, presence of diabetic retinopathy and proteinuria more than 500mg in 24 hours. Chronic Pyelonephritis was diagnosed on ultrasonogram when there is presence of small kidneys with irregular borders. Obstructive Uropathy, Autosomal dominant polycystic kidney disease and Obstructive nephropathy were diagnosed by ultrasonogram.
Creatinine clearance to be calculated using Cockcroft -Gault formula: ( )( ( )( ) ( ) )
Statistical analysis of data was done using standard statistical techniques.
58
RESULTS
Table 1 Age and Sex Incidence Male Number of patients 34 Mean Age 50.9 yrs Youngest Patient 17 yrs Eldest Patient 80 yrs Note : Male Female ratio : 2.12 : 1 Female 16 46.1 yrs 23 yrs 70 yrs Total 50 49.3 yrs -
Table 2 Aetiology of Chronic Renal failure Aetiology Chronic glomerulonephritis Diabetic nephropathy Hypertensive nephropathy Obstructive uropathy Polycystic disease of kidney Chronic pyelonephritis Total No.of pateints 12 19 14 3 1 1 50 Percentage 24 38 28 6 2 2 100
Graph -1 Etiology of Chronic Renal Failure
20 18 16 No.of patients 14 12 10 8 6 4 2 0 12
19
14
3 1 1
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Fable 3: Haemoglobin levels in chronic renal failure Haemoglobin (gm%) <5 5-10 >10.1 Total No.of pateints 3 42 5 50 Percentage 6 84 10 100
The above table reveals that 84% of the patients have their haemoglobin level in the range of 5-10 gm%. Only 6% of the patients have its value below 5mg%, but 10% of the patients exhibit that their haemoglobin level more than 10 mg%.
Graph - 2 Haemoglobin Levels in Chronic Renal Failure
45 40 35 No.of pateints 30 25 20 15 10 5 0 <5 3
42
5-10
>10.1
60
Table 4 Blood urea value in chronic renal failure Blood urea (mg/dl) <50 50-100 101-150 151-200 >200 Total No.of pateints 1 12 22 9 6 50 Percentage 2 24 44 18 12 100
From the table it is clear that almost 44% have their blood urea level in the range 101-250 mg/dl. Also one can see from the table that only 12% of patients have their blood urea level more than 300 mg/dl and hardly 2 % had the value below 50 mg/dl.
Graph - 3 Blood Uioa values in Chronic Renal Failure
25 20 No.of pateints 15 10 5 1 0 <50 50-100
22
12 9 6
101-150
151-200
>200
Blood urea level (mg/dl)
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Table 5 : Serum Creatinine Values in Chronic Renal Failure Serum creatinine (mg/dl) 2-5 5.1-12 >12.1 Total No.of pateints 18 31 1 50 Percentage 36 62 2 100
The above table reveals that 62% of the patients have their Serum Creatinine value in the range of 5-12 mg/dl. Only 2% of the patients have its value greater than 12.1 mg/dl; but 36% Of the patients exhibit that their serum Creatinine value in the range 2-5 mg/dl.
Graph-4 Serum Creatinine value in Chronic Renal Failure
35 30 No.of pateints 25 20 15 10 5 0 2-5 18
31
5.1-12 Serum creatinine level (mg/dl)
>12.1
62
Table 6 Creatinine Clearance in Chronic Renal Failure Creatinine clearance (ml/mt) <5 5.1-10 10.1-15 15.1-20 20.1-25 >25 Total No.of pateints 2 25 13 5 2 3 50 Percentage 4 50 26 10 4 5 100
The table shows that 50% of patients have their clcr value within the range 5.1-10 ml/mt where as 26% of them have this value in the range 10.1-15 ml/mt. Purther 10% of patients had this value in the range 15.1-20 ml/mt. Only 4% hade the value below 5 ml/mt and the same percentage of patients can be seen in the range 20.1-25 ml/mt. Only 6% of patients had creatinine clearnace >25. Graph 5: Creatinine Clearance in Chronic Renal Failure
25 25 20 No.of pateints 15 10 5 5 0 <5 5.1-10 10.1-15 15.1-20 20.1-25 >25 Creatinine clerance (ml/mt) 2 2 3 13
63
Table 7: Serum Potassium levels in Chronic Renal Failure S. Potassium (mEq/l) <3.5 3.5-5 >5 Total No.of pateints 2 31 17 50 Percentage 4 62 34 100
From the table we see that 34% patients have Hyperkalemia. 62% had the value within normal limits (3.5-5 mEq/1). Only 4% had the value less than 3.5 mEq/1.
Graph -6 Serum Potassium Levels in Chronic Renal Failure
35 30 No.of pateints 25 20 15 10 5 0 <3.5 2
31
17
3.5-5 Serum pottasium (mEq/l)
>5
64
Table 8 Serum Sodium levels in Chronic Renal Failure S. Sodium (mEq/l) <130 130-145 >145 Total No.of pateints 12 37 1 50 Percentage 24 74 2 100
From the table it appears that hyponatremia (Serum sodium level < 130 mEq/l) is present in 24% of patients. Further in 74% cases this value lies between the normal limits (130-145 mEq/l). Only 2% had the value > 145 mEq/l.
Graph-7 Serum Sodium Levels in Chronic Renal Failure
40 35 30 No.of pateints 25 20 15 10 5 0 <130 12
37
1 130-145 Serum Sodium (mEq/l) >145
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Table 9 : Serum Calcium levels in Chronic Renal Failure S. Calcium (mg/dl) <8 8-10 >10 Total No.of pateints 23 26 1 50 Percentage 46 52 2 100
Hypocalcaemia (<8 mg/dl) can be seen in 46% of cases. 52% of cases have this value within normal limits (8.10 mg/dl).
Graph-8 Serum Calcium Levels in Chronic Renal Failure
30 25 No.of pateints 20 15 10 5 0 <8 23
26
8-10 Serum Calcium (mg/dl)
>10
66
Table 10 : Serum Albumin levels in Chronic Renal Failure S. Albumin (g/dl) <3.5 3.5-5 Total No.of pateints 17 33 50 Percentage 34 66 100
Hypoalbuminemia (Serum Albumin < 3.5g/dl) can be seen in 3 4% of cases. 66% of cases have this value within normal limits (3.5 - 5 g/dl).
Graph - 9 Serum Albumin Levels in Chronic Renal Failure
33 35 30 No.of pateints 25 20 15 10 5 0 <3.5 Serum Albumin (g/dl) 3.5-5 17
67
Table 11: Kidney Size (by USG) in Chronic Renal Failure Size (cms) Normal Decreased Increased Total No.of pateints 15 32 3 50 Percentage 30 64 6 100
64% of the cases seem to have decreased kidney size and 6% appears to have an increased kidney size. Where as 30% of the patients have exhibited normal size.
Graph-10 Kidney Size (by USG) in Chronic Renal Failure
35 30 25 No.of pateints 20 15 10 5 0 Normal 15
32
Decreased
Increased
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Table 12 : Signs of Chronic Renal Failure Signs Pallor Hypertension Pedal Edema Ascites Pulmonary Edema Palpable Kidney Nail Changes Pleural Effusion Skin Changes Peripheral neuropathy No.of pateints 45 46 39 12 2 3 1 1 2 1 Percentage 90 92 78 24 4 6 2 2 4 2
The clinical examination reflects that almost 90 % of the patients had pallor, 92% reflected the.presence of hypertension and 78% had pedal edema. 24% of them had ascites and all the other signs were found to be below 6%. Graph-11 Signs of Chronic Renal Failure
50 45 40 35 30 25 20 15 10 5 0
45
46 39
No.of pateints
12 2 3 1 1 2 1
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Table 13: Symptoms of Chronic Renal Failure Symptoms Pedal edema Oliguria Breathlessness Vomiting Anorexia General Weakness Facial edema Flank pain Hematuria Abdominal distention Altered sensojium Convulsions Polyuria Dysuria No.of patients 39 38 34 23 16 13 1 5 9 11 5 2 3 1 Percentage 78 76 68 46 32 26 22 10 18 22 10 4 6 2
The presences of various symptoms observed in 50 patients are presented in the above table. We see that 78% of the cases had pedal edema followed by the most common urinary symptom Oliguria that is 76%. The Gastrointestinal symptom namely anorexia is found in 32%. 26% had general weakness and 46% were having vomiting as symptom. The numbers of cases having facial edema were 22% and 68% of the cases exhibited breathlessness as a symptom. The percentage of patients having various other symptoms can be seen from the table.
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Graph 12 : Symptosm of chronic renal failure
50 45 45 40 35 30 25 20 15 10 5 0 3 1 1 39 46
No.of pateints
12
71
Table-14: The Comparison between groups based on Serum Creatinine levels in terms of Haemoglobin, Potassium, Calcium and Albumin Levels. Group Serum No creatinine No I II III ANOVA 2-5 5.1-12 >12.1 18 31 1 % % 36 62 2 F P 8.31 2.48 7.48 1.55 5.00 2.03 0.14 NS 4.51 0.75 4.85 0.88 5.80 1.76 0.18 NS 8.14 1.10 7.94 0.89 7.60 0.55 0.58 NS 3.59 0.45 3.56 0.53 2.20 3.62 0.03 S Hb% (gm/dl) K+ S.calcium S.Alb
p>0.05 Non significant (NS), p<0.05 Significant (S) In the first group of pateints average haemoglobin level was found to be 8.31 with standard diviation of 2.48. In second group average In third group
haemoglobin level was found to be 7.48 with SD of 1.55.
average haemoglobin was 5 p value was found to be 0.14 which indicates there is insignificant decrease in haemoglobin with increase in serum creatinine. Serum potassium in first, second, and third group were 4.51 with SD of 0.75, 4.85 with SD of 0.88 and 5.8 respectively. p value was found to be 0.18 which indicates insignificant increase serum potassium with increase in serum creatinine. Serum calcium in first, second, and third group were 8.14 with SD of 1.10, 7.94 with SD of 0.89 and 7.60 respectively. with p value of 0.58
which indicates insignificant decrease in serum calcium with increse in serum creatinine.
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Serum albumin in first, second and third group were 3.5 with SD of 0.45, 3.56 with SD 0.53 and 2.2 respectively with p value of 0.03 which indicates significant decrease in serum albumin with increase in serum creatinine.
73
DISCUSSION
The present study consisted of 50 patients of CRF who were admitted to the hospital or were on regular dialysis on OPD basis. These patients fulfilled the criteria set by the National Kidney Foundations' Kidney Disease Outcome Quality Initiative for diagnosing CRF. They were studied and evaluated clinically and laboratory investigated and ultrasonography of abdomen was done. Tn our study of 50 patients there was a male : female ratio of 2.12:1. The mean age was 49.3 years. The youngest patient was 17 years of age and the oldest 80 years of age. This shows the broad variation in age in our study group highlighting the preponderance of CRF across a very large age group. Out of the 18 studies analyzed by the National Kidney Foundations K/DOQI, 17 reported that the male sex was more at risk for CRF and 14 showed mat the male sex was associated with a faster rate of progression to BSRD. Our studies showed that the prevalence of chronic kidney damage as a result of hypertension and diabetes is far lower in younger age groups than in adult patients above the age of 30 years. Our findings are similar to those reported by the National Kidney Foundations KVDOQI subgroup on children and adolescents study conducted by Fivush et al 111 . In our study an increasingly high number of patients were found to be diabetic(37%) and hypertensive(24%). This trend is similar to that reported by Dash and Agarwal in the study conducted at the All India Institute of Medical Sciences 112 .
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Lysaght et al have also demonstrated similar trends in American populations 113 . In the study conducted by Xue et al the number of patients with diabetic nephropathy was almost 50% of the study groups 114 . The aetiological data also shows the prevalence of Chronic glomerulonephritis at 23% which is concurrent with the data from other developing countries like Egypt and Bolivia. 21,24 The haemoglobin levels were below 10 gm/dl in 90% of the patients thereby emphasizing the need for correction of anaemia in patients with CRF. It is well established that anaemia develops in the course of chronic renal disease and is nearly universal in patients with chronic renal failure. Lower haemoglobin levels may result from a loss of erythropoietin synthesis on the kidneys and/or the presence of inhibitors of erythropoietin synthesis. Numerous articles describe the association of anaemia with kidney failure and describe its various causes. McGonigle, Wallin et al studied 863 patients for anaemia and found upto 90% of patients to have haemoglobin less, than 10 gm/dl 115 . They also established that erythropoietin deficiency and disorders related to its synthesis are the main cause of "anaemia in patients with CRF. These findings are consistent with our study. Furthermore they also established that the severity of anaemia is related to duration and extent of kidney damage. The lowest haemoglobin levels were found in anephric patients and those who commenced dialysis at very severely decreased levels of kidney function. Our studies showed that patients with creatinine levels above 12 mg/dl had an average haemoglobin of 5emphasizing again that greater the extent of kidney damage more the severity of the anaemia.
75
The incidence of Hyperkalemia was 34% which shows the need for the early detection and management of this dangerous complication.
Hyperkalemia is a known complication of CRF which may be precipitated in a number of conditions but certain aetiologies of CRF may be associated with more earlier and more severe disruption of potassium secretory mechanisms in the distal nephron, relative to the reduction in GFR. Most important are conditions associated with hyporeninemic hypoaldosteronism like diabetic nephropathy and renal tubular acidosis. Hyponatremia was reported at an incidence of 24% in our study which is also a known association with CKD. Hyponatremia in itself is an uncommon complication in predialysis patients, and water restriction is necessary only when hyponatremia is documented. Hypocalcemia is a known entity in patients with CRF and our studies showed the prevelance at 46%. It is known that bone disease and disorders of calcium and phosphorus metabolism develop during the course of CKD. Radiological and histologic demonstration of bone disease can be
demonstrated in nearly 40% of patients with severely decreased kidney function. Reduced levels of calcium have been described in patients with GFR less than 70 ml/ min in various studies. Histological changes in the bone have also been shown to occur at earlier stages of CKD. In a study of 176 patients with creatinine clearances of 15 to 50 ml/ min, 75% had "important histological abnormalities, with the majority having osteitis fibrosa with or without osteomalacia" as reported by Hamdy et al in their study on the effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure 116 . In another study of patients by Coen et
76
al
(Metabolic
acidosis and osteodystrophic bone disease in patients with CRF) patients with creatinine clearance of 20 to 59 ml/ min, 87% of patients had abnormal bone histology and the majority had lesions of high bone formation rate associated with hyperparathyroidism 117 . The kidney size was decreased in 64% of the patients. The normal sized kidneys in 30% of the patients is attributable to the large number of diabetic nephropathy cases in which normal kidney size is a known entity. The small hyperechoic kidneys which are characteristic of CKD were found in the patients with decreased kidney size. The serum Albumin levels were decreased in 34% of the patients and this is consistent with known studies like Koppel et al -Modification of diet in" renal disease(MDRD study group) 118 . The serum albumin is found to be lower at levels of GFR below 30 ml/min, indicating a decline in circulating protein levels or serum protein concentrations, proteinlosses or
inflammation. An acceptable goal fcr albumin level is above 4.0 mg/dl by bromocresol green method. Using data from the US Renal Data System maintained by the Health Care Financing Administration, a recent study documented the high frequency of hypoalhuminemia in patients entering dialysis. Of 74,232 patients who began dialysis between April 1995 and June 1997 and for whom the relevant data were available, 60% had serum albumin levels below the lower normal limit for the testing laboratory and 37% had levels of 3.0 g/dL. Multivariate analysis showed that hypoalbuminemia was associated with female gender, black or other non-Caucasian race, nonprivate or no insurance, and diabetes. Stall et al found that, even once dialysis was initiated and an "adequate" dialysis regimen was provided, many patients
77
were not attaining acceptable levels of nutrition as evidenced by continued hypoalbuminemia and changes in body composition. The most common symptoms in our patients were pedal oedema. (78%), oliguria (76%), breathlessness (68%), vomiting (44%) and
anorexia(32%). CNS symptoms like convulsion and altered sensorium were found in 4% and 10% of patients respectively. Decrease GFR in NHANES III patients was associated with impaired walking and lifting ability. In another subgroup in the above study, patients with decreased GFR the impairment of physical function was not significantly related to the level of kidney function, but physical impairment was 8 times worse than in the general populatio n. Dialysis patients report greater physical dysfunction than transplant recipients and diabetic dialysis and transplant patients are more likely to report physical dysfunction than those patients who do not have diabetes. Poor kidney fur. tion is also associated with lower employment in the above study. Full time employment is higher for those with decreased GFR ( mean serum creatinine 5.4 mg/dl, 69%) compared with those with kidney failure ( mean serum creatinine 13.7 mg/d , 12%). The above study also reported reduced social activity, social functioning and social interaction as a result - of the CRF symptoms. Anorexia was evidenced by almost a third (32%) of our patients. Anorexia in CRF is evidenced by decreased dietary protein intake, which are hallmarks of CRF. As limitation of protein intake reduces the accumulation of toxic substances derived from the metabolism of protein. Decreased dietary protein intake may be viewed as adaptive in patients with CKD. Thus, the overall outcome of this adaptive procedure may be the increased prevalence of protein energy malnutrition in patients with CKD.
78
The most common signs were hypertension (92%) and pallor (90%). Pedal oedema (78%) and ascites (24%). Other signs like palpable kidney, pulmonary oedema, skin and nail changes, pleural effusion etc were found in less than 10% of patients. National Kidney Foundations K/DOQI evaluated 26 studies which related blood pressure to the level of GFR decline in univariate and/or multivariate analysis. Most studies reporting mult ivariate analysis showed a significant association between elevated blood pressure, based on any measures of blood pressure, and faster rate of GFR decline. These data confirm that elevated blood pressure is associated with faster rate of GFR decline when controlling other factors. Pedal oedema arid ascites are associated with deranged biochemical parameters and the correction of the same has shown to improve outcomes.
79
CONCLUSION
We aim to spotlight the growing incidence of CRF among the population. The growing incidence of this problem is a major health hazard in our country which we can ill afford. Out of 50 patients in our study, the majority (66%) were having CRF as a result of Diabetes and Hypertension , which when detected and manage d at early stages can halt the progress to chronic kidney, disease and renal replacement therapy. Other manageable conditions like Obstructive Uropathy should also be detected and managed at an early stage to prevent irreversible kidney damage. The other complications like Anaemia, Hypocalcemia, Hyponatremia and Hyperkalemia were also present in significant numbers and emphasize the need for the detection and correction of these complications.
80
SUMMARY
In the present study, patients diagnosed with CRF admitted on receiving dialysis at Chigateri General Hospital and Bapuji Hospital attached to J.J.M. Medical College, Davangere between August 2010 and August 2011 wer included in this study. 50 consecutive pateints with CRF the aetiology, laboratory and clincal profile were studied. The study revealed that diabetic nephropathy (38%) hypertnsive nephropathy (28%) and chronic glomerulonephritis (24%) were the most common causes of CRF in our patients. The also revealed a high number of patients with anaemia, hypocalcemia and hyperkalimia. The major concern of this study to highlight the high prevalence of diabetes and hypertension as a cause for CRF and the need to initiate step for early detection and management of these conditons.
81
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ANNEXURE I PROFORMA
NAME AGE SEX RELIGION ADDRESS
: : : : :
IP.NO. D.O.A. D.O.D.
: : :
PRESENTING COMPLAINTS: Oliguria Dysuria Nocturia Polyuria Haematuria Facial oedema Pedal oedema Anorexia Vomiting Other symptoms : : : : : : : : : : Flank pain :
Abdominal distension : Altered sensorium : Convulsions Pruritis Skin rashes Bone pain Breathlessness : : : : :
Generalized weakness :
HISTORY OF PRESENTING ILLNESS:
PAST HISTORY Diabetes mellitus Hypertension Renal disease Prostatic symtoms Any other systemic illness in the past UTI Stone disease Drug history
96
PERSONAL HISTORY: Sleep Appetite Bowel Bladder Smoker/chewing tobacco Alcohol consumption
FAMILY HISTORY
GENERAL/ PHYSICAL EXAMINATION PULSE: TEMP: BUILT: CLUBBING: BP: WEIGHT: PALLOR: LYMPHADENOPATHY: RESP. RATE: JVP: ICTERUS:
OEDEMA: PEDAL / FACIAL/ GENERALIZED SYSTEMIC EXAMINATION ABDOMEN Renal Mass Renal angle Tenderness Other findings Renal. Bruit Liver Spleen Ascites
CARDIOVASCULAR SYSTEM
RESPIRATORY SYSTEM
97
CENTRAL NERVOUS SYSTEM: NEUROLOGICAL DEFICIT SENSORIUM OTHER FINDINGS INVESTIGATIONS BLOOD Hb TC DC: ESR RBS ANAfif relevant) Total protein S. Cholesterol URINE Protein: Sugar: Microscopy: LE cell(if relevant) Albumin Globulin N L E B M Urea Cratinine Sodium Potassium Calcium Chloride Phosphorus Magnesium
ULTRASOUND ABDOMEN: Liver: Gall bladder: Kidneys: Kidney Size: Parenchymal changes: Cortico medullary differentiation: Pelvicalcylelal system Bladder: Kidney Biopsy (if done): Diagnosis: (cause of Renal Failure) Dialysis: Done/ Not Done Renal Transplantation: Done/ Not Done
98
Spleen: Right
Ascites: Left

Renukaprasad Ys - Medicine - Thesis New

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CLINICAL, AND BIOCHEMICAL SPECTRUM OF CHRONIC KIDNEY DISEASE IN TERTIARY CARE CENTER

Dr. RENUKAPRASAD Y.S.

In Partial fulfillment Of the requirements for the degree of

DOCTOR OF MEDICINE IN GENERAL MEDICINE

Dr. B.M. VISHWANATH

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation entitled

PLACE : DAVANGERE DATE : / /2011 (Dr. RENUKAPRASAD Y.S.)

CERTIFICATE BY THE GUIDE

PLACE : DAVANGERE DATE : / /2011 Dr. B.M. VISHWANATH

ENDORSEMENT BY THE HOD, PRINCIPAL/HEAD OF THE INSTITUTION

COPYRIGHT Declaration by the Candidate

PLACE : DAVANGERE DATE : / /2011 (Dr. RENUKAPRASAD Y.S.)

Rajiv Gandhi University of Health Sciences, Karnataka.

I express my sincere thanks to Dr.B.G.KARIBASAPPA M.D., Dr.

Dr.A.P.THIPPESWAMY B.G SHIVAKUMAR.

PLACE : DAVANGERE DATE : / /2011 (Dr. RENUKAPRASAD Y.S.)

LIST OF ABBREVIATIONS USED

of CKD, particularly in the elderly age group, but is difficult to di fferentiate

Pathology Diabetic glomerulosclerosis

Aetiology (examples*) Diabetes Mellitus Type 1 Type 2

Renal artery stenosis Hypertension

Allergic interstitial nephritis Granulomatous interstitial nephritis Autoimmune interstitial nephritis

OUTCOMES 4 Type Susceptibility factors Factors Definition that to Examples

increase Older age, family history of kidney chronic kidney disease,

initiate kidney damage

worsening kidney damage higher and faster decline in poor

after diabetes, smoking

morbidity and mortality in factors, kidney failure

albumin level, late referral for dialysis

SPECIFIC DIAGNOSIS A history of nephritic syndrome suggests primarily previous

(dysmorphic if glomerular in origin), leucocytes

mesangiocapillary (including titres of

endocarditis), cryoglobulinaemia and lupus nephritis. Elevated

STAGES OF KIDNEY DISEASE

STAGES OF CKD WITH THE FREQUENCY OF COMPLICATIONS GFR (mL/min/ 1.73m 2 )

Symptoms or signs Anaemia 4%

Chronic kideny damage with normal or increased GFR

Hypertension 40% 5 year mortality 19% Anaemia 4%

Mild GFR loss

Hypertension 40% 5 year mortality 19% Anemia 7%

Moderate GFR loss

Hypertension 55% 5 year mortality 24% Hyperphosphatemia 20%

Severe GFR loss

Anemia 69% Hypertension >75% 3 year mortality 14% Hyperphosphatemia 50%

Kidney failure ESRD

Anemia 69% Hypertension >75% 3 year mortality 14%

internal hemodynamics and disordered regulation of

Remnant nephrons undergo marked

increase in single nephron plasma flow (hyperperfusion), single

with progressive renal scarring are still poorly understood.

including proteinuria and alterations in levels of circulating lipids, hormones

states that in general, adapted

hyperparathyroidism and metastatic calcification 27,39 .

CLINICAL ABNORMALITIES IN UREMIA 42

for uncomplicated hypertension

of the gastrointestinal tract, in particular the

dihydroxycholecalciferol) lead to hypocalcaemia. (The active form of vitamin

31.2% 15.6% 11.3% 5.2% 6.4% 3.8% 26.5%

INDICATIONS FOR DIALYSIS: ESTABLISHED INDICATIONS - There are a number of absolute

Creatinine clearance to be calculated using Cockcroft -Gault formula: ( )( ( )( ) ( ) )