INTERNAL MEDICINE POSTING
NEPHROLOGY SYSTEM
1.0 ACUTE KIDNEY INJURY
AKI is abrupt deterioration in parenchymal renal function, which is reversible over a period of days or weeks
Acute Dialysis Quality Initiative Group propose the RIFLE criteria utilising either increase in serum creatinineor decrease in urine
output
Classification
Type Cause
Prerenal -d/t impaired perfusion of
the kidney with blood
-in normal condition,
kidney is able to maintain
GFR close to normal
(autoregulation) despite
wide variation in renal
perfusion pressure and
volume status
-further depression of renal
perfusion lead to a drop in
glomerular filtration and
development of pre renal
uraemia
1. True volume depletion
-diarrhoea, vomiting,
haemorrhage
2. reduced renal perfusion
-CCF, liver cirrhosis,
nephritic syndrome, severe
hypoproteinemia
3. Renovascular disease
4. Drugs
-NSAIDS, ACEI, ARB
Intrinsic 1. Acute tubular necrosis
-well defined ischemic
event/ toxic exposure
2. Allergic interstitial
nephritis
-antibiotics, NSAIDS
3. Radiographic contrast
dye
4. Vascular procedure
-coronary angiography,
thrombolysis,
anticoagulant therapy
Clinical feature Diagnostic workup Management
1. Volume depletion 1. Uraemia 1. Volume depletion-IV fluid
-orthostatic hypotension, -d/t ↑PCT absorption administration
tachycardia, ↓ JVP, dry 2. Urine chemistry 2. CCF-vasodilator &
mucous membrane -hypoNa, hyperK inotrophic agent
2. ARF in CCF 3. Urinalysis 3. Monitor BP or central
-S3 gallop, distended -hyaline and granular venous pressure monitoring
JVP, Pulmonary edema cast+/- cellular casts -fluid administration may
4. Renal ultrasound- lead to volume overload with
normal pulmonary edema
**to differentiate btw pre-
renal and intrinsic
5. Urine specific
gravity>1.020
6. Urine
osmolarity>500mOsm/kg
7. Urine sodium
<20mmol/l
8. Fractional excretion of
Na (ratio of Na clearance
to Creatinine clearance)
<1%
1. AKI in AGN 1. Urine chemistry 1. AKI in AGN, SLE,
-hypertension, edema, -undistinguishable from vasculitis
proteinuria, hematuria prerenal causes -↑ dose glucocorticoids,
2. Other extrarenal 2. Urinalysis cytotoxic agents,
symptom -RBC, WBC, cellular casts plamapheresis, plasma
-hemoptysis, pulmonary allergic interstitial exchange
haemorrhage, arthralgia, nephritis (↑ eosinophils) 2. AKI in pyelonephritis and
arthritis, serositis, pyelonephritis (↑WBC) endocarditis
sinusitis ATN (muddy brown -antibiotics
granular casts + tubular
epithelial cells)
3.Ultrasonography-↑ renal
 5. AGN, thrombotic
microangiopathies
6. Drugs-calcineurin
inhibitor, quinine, antiplt
agents, chemotherapeutics
Postrenal Urinary tract obstruction
-stones, sloughed renal
papillae, malignancy
-symptom of urinary
tract obstruction
echogenicity
**to differentiate btw pre-
renal and intrinsic
4. Urine specific gravity
<1.010
5. Urine
osmolariy<350mOsm/kg
6. Urine sodium
>40mmol/l
7. Fractional excretion of
Na>1%
1.Ultrasound-obstruction -foley catheter placement
of urinary collection -multiple urethral stents
system -nephrostomy tubes
***urine chemistry& -surgery
urinalysis were not helped

NOTE ON ACUTE TUBULAR NECROSIS

Cause -renal ischemia
-direct renal toxin, eg. aminoglycosides, lithium, platinum derivatives
-hemorrhage, burns
-diarrhoea, vomiting, fluid loss from fistulae
-pancreatitis
-diuretics
-MI, CCF
-endotoxic shock
-snake bite
-myoglobinaemia
-haemoglobinemia (d/t hemolysis, eg. in falciparum malaria, blackwater fever)
-hepatorenal syndrome
-radiological contrast agent
-drugs, eg. aminoglycosides, NSAIDS, ACEI, platinum derivatives
-abruptio placentae
-pre-eclampsia, eclampsia

Pathogenesi 1. Intrarenal microvascular vasoconstriction

s -↑ vasoconstriction in response to endothelin, adenosine, thromboxane A2, leukotriene, SNS
-↓ vasodilation d/t ↓ response to NO, PGE2, Ach, bradykinin
-↑ leukocyte endothelial adhesion, vascular congestion and obstruction, leucocyte activation and inflammation
2. Tubular cell injury
-ischemic injury resulting in rapid depletion of intracellular ATP store resulting in cell death either by necrosis and
apoptosis
-mechanism:
(a) entry of Ca into the cell
(b) hypoxia induce NO synthase lead to ↑ NO
(c) ↑ intracellular protease lead to proteolysis of cytoskeletal protein and cell wall collapse
(d)Activation of phospholipase A2 which act on lipid bilayer of cell membrane to ↑ production of free fatty acids
(e) Cell injury resulting from reperfusion of the blood after initial ischemia l/t excessive free radical generation
(f) Tubular obctruction by desquamated necrotic or viable cell
(g) loss of cell polarity
3. Tubular cellular recovery
-tubular cell have capacity to regenerate rapidly and to reform the disrupted basement membrane, which explained
the reversibility of ATN

Ischemic tubular damage contribute to ↓GFR by a number of intercalated mechanism

1. Glomerular contraction: ↓ surface area available for filtration
: d/t reflex afferent arteriolar spasm mediated by increase solute delivery to the macula
densa
: impaired Na absorption in the PCT because loss of polarity with mislocalization of
Na/K ATPase
2. Back leak of filtrate: loss of function in tubular cell
3. Obstruction of the tubule: by debris shed from ischemic tubular cell
Clinical -early stage: oliguria
course -recovery stage: GFR remain low while urine output increase
: d/t defective tubular reabsorption of filtrate
: renal function usually returns to normal, exp in renal cortical necrosis
 Biochemical -azotemia: d/t ↑ tissue breakdown
-hyperkalemia: d/t trauma to muscle and in haemolytic states
-hyponatremia
-metabolic acidosis
-pulmonary edema: d/t salt and water retention
-hypocalcemia: d/t ↓ production od 1, 25-DHCC
-hyperphosphatemia: d/t phosphate retention

Management
General -good nursing and physiotherapy
-regular oral toilet, chest physiotherapy, consistent documentation of fluid intake and output
-consistent documentation of the fluid intake and output
Emergency 1. HyperK (cardiac arrhythmia, ventricular fibrillation
-IV sodium bicarbonate

2. Pulmonary edema
-diuresis (by IV furosemide)
-dialysis
-haemofiltration

3. Sepsis
-bear in mind to avoid nephrotoxic drugs
-prophylactic antibiotics or barrier nursing is not recommended in all cases

4. Fluid and electrolyte balance

-once pt is euvolaemic, daily fluid intake should equal urine output plus losses from fistulae and from vomiting
and 500ml daily for insensible loss
-Na and K intake should be minimised
-additional fluid and electrolyte if there is abnormal loss of fluid

5. Diet
-Na, K, protein restriction
-route of intake: enteral by mouthenteral by nasogastric tubeparenteral
-vitamin supplement

6. Dialysis and hemofltration

-indication: symptom of uraemia, complication of uraemia, severe biochemical derangement in the absence of
symptom, hyperkalemia not controlled by conservative measures, pulmonary edema, acidosis, for removal of
drugs
-main option: intermittent haemodialysisintermittent haemofiltrationcontinuous arteriovenous or
venovenous haemofiltrationhaemofiafiltrationperitoneal dialysis

7. Continuous renal replacement treatment

-blood flow is achieved by using the pt’s own blood pressure to generate arterial blood flow through a filter or
by the use of a blood pump to draw blood from the lumen or dual lumen catheter placed in the jugular,
subclavian or femoral vein

Recovery phase -when increase urine volume and improve serum biochemistry

1. A careful watch on clinical state, salt and water balance and serum chemistry
2. IV fluid replacement with supplement of NaCl and K
2.0 CHRONIC KIDNEY DISEASE
CKD implies longstanding (more than 3 months) and usually progressive, impairment in renal function where no effective means
are available to reverse the primary disease process.

Classification
Stage GFR ( ml/min/ Description
1.73m3)
1 ≥90 Normal or increased GFR with other evidence of kidney damage
2 60-89 Slight decrease in GFR with other evidence of kidney damage
3A 45-59 Moderate decrease in GFR with/ without other evidence of kidney damage
3B 30-44
4 15-29 Severe decrease in GFR with/ without other evidence of kidney damage
5 <15 Estalblish renal failure

Causes
Congenital and inherited disease
Glomerular disease
Vascular disease
Tubulointerstitial disease
Urinary tract obstruction
-polycystic kidney disease
-medullary cystic disease
-tuberous sclerosis
-oxalosis
-cystinosis
-congenital obstructive uropathy
-primary glomerulonephritides (including focal glomerulosclerosis)
-secondary glomerular disease (SLE, Wegener granulomatosis, amyloidosis, diabetic
glomerulosclerosis, accelerated HPT, HUS, thrombotic thrombocytopenic purpura, systemic
sclerosis, sickle cell disease
-hypertensive nephrosclerosis
-renovascular disease
-small and medium size vessel vasculitis
Tubulointerstitial nephritis-idiopathic, d/t drug (nephrotoxic analgesics), immunologically
mediated
-reflux nephropathy
-TB
-schistosomiasis
-nephrocalcinosis
-multiple myeloma
-Balkan nephropathy
-Renal papillary necrosis (DM, SCA, analgesics nephropathy)
-chinese herb nephropathy
-Calculus disease
-prostatic disease
-pelvic tumor
-retroperitoneal fibrosis
-schitosomiasis

Clinical feature
Symptom Sign
asymptomatic despite accumulation of numerous 1. General inspection
metabolites -sallow (dirty brown appearance), Kussmaul’s breathing, cushingnoid,
symptomatic when serum urea concentration > myoclonic jerks (sudden involuntary jerking of a muscular or group of
40mmol/l muscle), hiccups
-malaise, loss of energy
-loss of apetite 2. Hands
-insomnia -pallor, leukonychia, asterixis,tinel’s sign
-nocturia and polyuria
-itching 3. Forearm
-nausea, vomiting, diarrhoea -scratch marks, bruishing (platelet dysfunction), hyperthricosis (side
-paraesthesia d/t polyneuropathy effect of long term cyclosporine therapy for renal transplant, vasculitis,
-“restlessness leg” syndrome: overwhelming need to arteriovenous fistula
frequently alter the position of the lower limb
-bone pain d/t metabolic bonedisease 4. Face
-paraesthesia and tetany d/t hypocalcemia -anaemia, band keratopathy (appearance of an opaque white band of
-symptom d/t salt and water retention: peripheral or variable density across central cornea, formed by precipitation of Ca salt
pulmonary edema on cornea surface), gum hypertrophy (S/E of long term cyclosporine)
-symptom d/t anaemia
-amenorrhoea in women, erectile dysfunction in men 5. Neck
 in CKD stage 5: -Raised JVP
-mental slowing, clouding of consciousness and 6. Chest
seizure -pericardial rub, gallop rhythm, basal lung crackles, vertebral tenderness
-myoclonic twitching
7. Abdomen
-look for tenchkoff catheter, transplant scar, ballotable kidney, loin
tenderness, prostatomegaly

8. Legs: ankle edema, areflexia periphera neuropathy

Complication
Anaemia d/t:
-erythropoietin deficiency
-BM toxin retained in CKD
-BM fibrosis secondary to hyperparathyroidism
-hematinic deficiency: iron, vitamin B12, folate
-increased red cell destruction
-abnormal red cell membrane causing increasing osmotic fragility
-increased blood loss: occult gastrointestinal bleeding, blood loss during hemodialysis or plt
dysfunction
-ACEI: interfere with the control of endogenous erythropoietin release
Renal osteodystrophy -phosphate retention d/t reduced excretion by the kidney in early stage of CKD result in release of
FGF 23and other phosphaturic agent by osteoblast as a compensatory mechanism
phosphaturia
downregulate 1α hydroxylase to reduce intensity of absorption of phosphate
-however, consistently elevated level of FGF 23 after a while cannot control phosphate level and are
overwhelm by development of secondary hyperparathyroidism
↓ production of 1α hydroxylase↓ conversion of 25-(OH2)D3 to 1,25-(OH)2D3
↓ activation of Vitamin D receptor in parathyroid gland lead to ↑release of PTH (2 nd
hyperthyroidism)
Ca sensing receptor react rapidly to low calcium lead to ↑ release of PTH
1, 25-Dihydroxycholecalciferol deficiencygut calcium malabsorption
phosphate retention result in ↑ PTH which promote reabsorption of calcium from bone and
increase proximal renal tubular reabsorption of Ca
secondary hyper PTH: ↑ osteoclastic activity, cyst formation, BM fibrosis

Skin disease -pruritus: d/t

retention of nitrogenous waste products of protein catabolism
hypercalcemia, hyperphosphatemia, elevated calcium x phosphate products, hyperparathyroidism
-dry skin
-eczematous lesions in AV fistula
-porphyria cutanea tarda (PCT) : blistering photosensitivity skin rash
: d/t ↓ uroporphyrinogen decarboxylase + ↓ clearance of porphyrin
Neurogenic systemic -systemic fibrosing disorder with predominant skin
fibrosis -d/t gadolinium containing contrast
GIT complication -↓gastric emptying and ↑ risk of GERD, peptic ulcer, acute pancreatitis and constipation
-↑ of serum amylase with no evidence of pancreatic disease: d/t retention of HMCWform of amylase
normally excreted in the urine
Metabolic complication 1. Gout: urate retention
2. Insulin: as insulin is catabolised by and to some extent excreted via the kidney, hence in CKD,
insulin requirement is reduced
3. Lipid metabolism abnormalities:
-impaired clearance of TG rich particles
-hypercholesterolemia
4. Metabolic acidosis: ↓ renal production of ammonia and bicarbonate reabsorption
Endocrine abnormalties -hyperprolactenemia (present with galactorrhoea)
-↑ LH
-↓ testosterone level: erectile dysfunction and spermatogenesis
-absence of normal cyclical changes in female sex hormone: oligomenorrhea or amenorrhoea
-complex abnormalities of GH: impaired growth for children
-abnormal TH level: d/t protein binding
Muscular dysfunction -uraemia interfere with muscle energy metabolism
Nervous system 1. Central nervous system
-severe uraemia result in depressed cerebral function and decreased seizure threshold
-rapid correction of uraemia by hemodialysis lead to dialysis disequilibrium owing to osmotic
cerebral swelling
 -dialysis dementia: progressive intellectual deterioration, speech disturbances, myoclonus and fits d/t
aluminium intoxification
: tx-desferrioxamine (chelating agent)
-psychiatric problem: anxiety, depression, phobias and psychoses

2. Autonomic nervous system

-increasing circulating catecholamine level associated with downregulation of α receptor, impaired
baroreceptor sensitivity and impaired efferent vagal function

3. Peripheral nervous system

-median nerve compression: d/t β2 macroglobulin related amyloidosis
-“ restlessness leg” syndrome: d/t uraemia

4. Polyneuropathy: in inadequate dialysis pt

Calciphylaxis -calcific uraemic arteriolopathy

-present with non- healing eschars with pannicullitis and dermal necrosis
-histology: vascular calcification and superimposed small vessel thrombosis
Cardiovascular disease -hypertension: lead to LVH (LVF), stroke and malignant hypertension
-coronary artery stenosis
↑ calcium X phosphate products
hyperPTH: ↑ intracellular calcium
vascular calcification: vascular SMC acquire osteoblast like characteristics in response to elevated
phosphate
inflammation: potent mediator of vascular calcification by inhibition of fetuin
-pericarditis
uraemic pericarditis: feature of pre-terminal uraemia or of underdialysis
: haemorrhagic pericardial effusion, atrial arrhythmia, pericardial temponade
dialysis pericarditis: d/t intercurrent illness or surgery
Malignancy -can occur in CKD with dialysis and multicystic kidney disease

Investigation
Urinalysis -hematuria: indicate glomerulonephritis
-proteinuria: suggest glomerular disease and urinary infection
-urine culture: early morning urine sample for TB
Urine microscopy -pyuria: active bacterial infection (if sterile pyuria:papillary necrosis and renal TB)
-eosinophilia: allergic tubulointerstitial nephritis or cholesterol embolization
-casts: granular casts-active renal disease; red- cell casts- glomerulonephritis
-hematuria: can be from anywhere between glomerulus and urethral meatus
Urine biochemistry -urine osmolarity: measure of concentrating ability
: low urine osmolarity is normal in the presence of a high fluid intake but indicate
renal disease when kidney should be concentrating urine, such as in
hypovolaemia and hypotension
-urine electrophoresis and immunofixation- necessary for detection of light chain

Serum biochemistry -urea and creatinine

-calculation of eGFR
-electrophoresis and immunofixation for myeloma
-elevation of CK and disproportionate elevation in serum creatinine and potassium
Hematology -eosinophilia: vasculitis, allergic tubulointerstitial nephritis, cholesterol embolism
-raised ESR: myeloma and vasculitis
-fragmented red cell and thrombocytopenia: intravascular hemoysis d/t acceerated hypertension,
HUS, TTP
-test for sickle cell disease
Immunology -complement component: low in SLE, mesangiocapillary glomerulonephritis, post streptococcal
glomerulonephritis and cryoglobulinemia
-antibody screening: detect SLE, scleroderma, Wegener’s granulomatosis, microscopic polyangitis,
Goodpasture syndrome
-Cryoglobulins: mesangiocapillary glomerulonephritis
-antibodies to streptococcal antigen (ASO & anti- DNAse B): post- streptococcal glomerulonephritis
-antibodies to hepatitis B and C: polyarterits, membranous nephropathy, cryoglobulinemic renal
disease
-antibodies to HIV: HIV associated renal disease

Radiological -ultrasound: for renal size, and to exclude hydronephrosis, low density renal stone and
abnormalities nephrocalcinosis
 -CT: diagnosis of retroperitoneal fibrosis and other cause of urinary obstruction and demonstrate
cortical scarring
-MRI: renovascular disease
Renal disease -performed in person with unexplained CKD and normal size kidneys

Management
HyperK 1. Shift ECF K into ICF
-K > 5.5mmol/l -administer dextrose/ insulin: 40-50ml D50W IV over 5-10 min and 10 units
Mild <6.0mmol/l Normal or regular insulin as separate bolus
peak T -administer sodium bicarbonate 1 mEq/ kg body weight as bolus 5min in pt with
waves moderate to severe metabolic acidosis, repeat 30 min in severe acidosis
Moderate 6.0-7.0 Peak T
mmol/l waves 2. Stabilisation of membrane potential
Severe 7.0-8.0 Flattening P -administer calcium chloride or gluconate 10%: 10-20ml IV over 3-10min, to
mmol/l waves and maximum 20ml
QRS -used only when there is ECG evidence of severe hyperkalemia, significant
widening neuromuscular weakness, serum K > 7.0

3. Remove K from the body

-hemodialysis

4. Prevent further K increase

-review all medication
-dietary review and advise
Fluid overload -manage in ICU
-place pt in upright position
-administer supplemental high flow oxygen
-monitoring: ECG, vital sign, pulse oximetry
-precerve one UL for future AV access
-draw blood for FBC, urea, electrolytes, creatinine, ABG, cardiac enzyme
-drrug therapy:
1. Morphine 2.5-5mg IV
2. GTN 0.5mg SL
3. Felodipine 2.5 mg PO if BP is high
4. Frusemide 120-240mg
Metabolic acidosis -sodium bicarbonate supplement
-suspected in pt @ hyperventilation, altered -calcium carbonate supplement
mental state, haemodynamic instability
Anaemia -synthetic (recombinant) human EPO (epoietin-α and epoietin-β) IV
-blood pressure, haemoglobin concentration and reticulocyte count measured
every 2 weeks
-advantage: improve quality of lives, exercise tolerance, secuala nd cognitive
function in dialysis pt, and lead to regression of LVH
-disadvantage: expensive
: cause rise in BP
: peripheral resistance d/t loss of hypoxic vasodilation, increased
Blood viscosity, encephalopathy with fits, transient cortical
blindness, hypertension
Dialysis Indication
-severe pulmonary edema
-severe fluid overload
-hyperkalemia
-severe metabolic acidosis
-some poisoning, eg methanol, ethylene gycol, salicyclates
-uraemia, including pericarditis and encephalopathy

Problem associated with dialysis:

(a) Vascular: bleeding, loss of thrill in shunt, infection
(b) Non vascular
-hypotension (posthaemodialysis hypotension d/t reduction in circulating
intravascular volume)
-dyspnoea (volume overload, sudden heart failure, pericardial temponade, pleura
effusion, severe acidosis, severe anaemia and sepsis
-chest pain (ischemic in origin with underlying IHD exacerbated by transient
hypotension and hypoxaemia a/w dialysis process
-neurological dysfunction (d/t electrolyte imbalance, infection, major intracranial
 catastrophies)

3.0 DRUG AND KIDNEY

3.1 DRUG INDUCED IMPAIRMENT OF RENAL FUNCTION
Pre renal Drug that cause:
(a) Hypovolaemia-loop diuretics, eg furosemide
-renal salt and water loss, eg hypercalcemia induced by vitamin D deficiency
that affect renal tubular salt and water conservation

(b) ↓CO that impair renal perfusion-B blocker

(c) ↓ renal blood flow-ACEI
Renal -Acute tubular necrosis: from direct nephrotoxicity (eg. aminoglycosides, amphotericin B, heavy
metal, carbon tetrachloride)
-Acute tubulointerstitial nephritis: CMI hypersensitivity nephritis with interstitial edema and
inflammatory cell infiltration
-Chronic interstitial nephritis d/t all drug that cause ATN and ciclosporin
-membranous glomerulonephritis, penicillamine, gold, anti-TNF
Post renal -retroperitoneal fibrosis with urinary tract obstruction (refer subtitle UTO)

3.2 USE OF DRUGS IN PATIENTS WITH IMPAIRED RENAL FAILURE

Absorption -may be unpredictable in uraemia, as nausea and vomitingare frequently present
Metabolism -oxidative metabolism of drugs by the liver is altered in uraemia, although is rarely of clinical
significance
(a) Reduced drug catabolism: eg. insulin is catabolised by normal kidney. In renal disease, insulin
catabolism is reduced and hence insulin requirement is reduced
(b) Reduced conversion of precursor to a more metabolically active form, eg 1α hydroxylase is
located in the kidney. In renal disease, production of the enzyme declines and deficiency of 1,25-
(OH)2D3
Protein binding -reduced protein binding of a drug potentiates its activities and increases the potential for toxic side
effects
Other cause:
retained hydrogen ion which are retained in CKD, bind to receptor for acidic drugs such as
sulphonamides, penicillin, salicylates
Volume distribution -salt and water overload or depletion affect the concentration of the drugs given
End organ sensitivity -renal response to drug treatment may be reduced
Renal elimination -reduced elimination of many drugs normally excreted by the kidney
Drugs causing uraemia Eg.
-tetracycline, except doxycycline
-tetracycline
Problem patient -patient in whom renal function is altering rapidly

4.0 NEPHROLITHIASIS (RENAL CALCULI)

Factors predisposing to stone formation is:
(a) Chemical composition of the urine that favour stone crystallization
(b) Production of concentrated urine as a consequences of dehydration a.w life or work in hot climate
(c) Impairment of inhibitor that prevent crystalisation in normal urine, eg inorganic magnesium, phosphate and citrate,
glycosaminoglycan and nephrocalcin

Hypercalcemia -if GFR is normal, hyperCaemiahyperCauria

-Cause:
(a) Primary hyperparathyroidism (most common)
(b) Vitamin D ingestion
(c) Sarcoidosis
Hypercalciuria -definition: 24 hr calcium excretion of >7.5mmol in male stone former and >6.25mmol in female
stone former
-causes:
(a) hyperCaemia
(b) ↑ dietary Ca intake
(c) excessive reabsorption of Calcium from the skeleton, eg prolonged immobilisation and
weightlessness
(d) idiopathic hypercalciuria
Hyperoxaluria Mild:
-excessive ingestion of foodstuff high in oxalate, eg spinach, rhubarb and tea
-dietary calcium restriction, with compensatory increased absorption of oxalate
-GIT disease (eg. Crohn’s) with intestinal resection

Hyperuricemia and
hyperuricosuria
Severe (poor prognosis):
-inborn error of glycoxalate metabolism that cause increase endogenous oxalate biosynthesis
Type 1: alanine- glycoxylate aminotransferase deficiency
Type 2: glycoxylate reductase hydroxypyruvate reductase deficiency
-cause: as a primary defect in idiopathic gout and secondary consequence of increased cell
turnover,eg myeloproliferative disorder
-some uric acid stone former have hyperuricosuria (>4mmol/ 24 hrs on low purine diet), without
hyperuricemia
-patient with ileostomies are at particular risk both from dehydration and loss of bicarbonate from
gastrointestinal secretion result in the production of an acid urine (uric acid is more soluble in an
alkaline than in an acid medium)

UTI -mixed infective stones are composed of magnesium ammonium phosphate together with variable
amount of calcium
-such struvite stones are usually large, forming a cast of the collecting system (staghorn calculus)
-the most common etiological agent is Proteus mirabilis that hydrolyse urea with the formation of
strong base ammonium hydroxide which lead to alkaline urine that favour stone formation
Cystinuria -result in the formation of cystine stones
Primary renal disease 1. Polycystic renal disease
2. Medullary sponge kidney- dilatation of the collecting duct with associated stasis and
calcification
3. Renal tubular acidoses- production of persistently alkaline urine and reduced urinary citrate
excretion
Drugs -promote calcium stone: loop diuretics, antacids, glucocorticoids, theophylline, vitamin D and C,
acetazolamide
-promote uric acid stones: thiazide, sallicylate
-precipitate into stones: indinavir, triamterene, sulphadiezine
Aetiology of bladder stone -bladder outflow obstruction, eg. urethral stricture, neuropathic bladder, prostatic obstruction
-presence of foreign body (eg. catheter, non absorbable suture)

Clinical feature Investigation

-asymptomatic
-pain (sharp, dull, constant, intermittent, colicky)
measure that increase urine volume make pain worse (eg.
copious fluid intake, diuretics, alcohol, physical exertion)
radiation from the flank to the iliac fossa and testis or labium
in the distribution of first lumbar nerve root are common
pallor, sweating and restlessness often occur
pt is restlessness, trying to obtain relief from the pain
pain subsides after a few hours
-hematuria
-UTI: acute pyelonephritis or of gram –ve septicaemia
frequency, disuria, hematuria
-calculus at the bladder neck or an obstruction in the urethra:
bladder outflow obstruction resulting in anuria and painful
bladder distention
1. Midstream specimen of urine
2. Serum urea, electrolyte, creatinine and calcium levels
3. Plain abdominal X ray
4. CT- KUB (kidney, ureter, bladder)
**to find out the cause
5. Renal imaging: to define presence primary renal disease
predisposing to stone formation
6. Significant bacteriuria: indicate mixed infective stone
formation
7. Chemical analysis: in diagnosis of cystinuria or uric acid
stone formation
8. Serum calcium concentration: to detect hypercalcemia
9. Serum urate concentration: elevated in uric acid acid stone
former
10. Screening test for cystinuria: carried out by adding sodium
nitroprussideto a random unacidified urine sample, a
purple colour indicates cystinuriamay be present
11. Urine calcium, oxalate and uric acid output
12. Plasma carbonate: low in renal tubular acidosis

Management
Treatment -adequate analgesia, eg NSAIDS and diclofenac 75mg by IV infusion
-stone
(a) <0.5cm diameter: usually pass spontaneously
(b) <0.6 cm: alpha blocker (eg. tamsulosin) facilitate spontaneous expulsion
(c) >1.0cm: urological or radiological intervention (eg. extracorporeal shock wave lithotripsy, uteroscopy
with a YAG laser, percutaneous nephrolithotomy
Prophylaxis 1. Idiopathic stone formers
-maintenance of high intake of fluid throughout the day and night
-ensure daily urine volume of 2- 2.5 L

2. Idiopathic hypercalciuria
-severe dietary calcium restriction is inappropriate
-high fluid intake
 -thiazide is used to reduce urinary calcium excretion by an indirect effect d/t mild volume contraction result
in increased calcium absorption in PCT (used if hypercalciuria persist)
-reduction of animal protein to 50g/ day and sodium to 50mmol/day is advisable

3. Mixed infective stone

-high fluid intake and meticulous control of bacteriuria
-long term low dose prophylactic antibacterial agents

4. Uric acid stone

-long term allopurinol
-high fluid intake
-long term sodium bicarbonate supplement (uric acid is more soluble at alkaline pH
**S/E: favour calcium oxalate and phosphate

5. Cystine stones
-can be prevented and indeed will dissolve slowly with high fluid intake (5L in 24 hrs)
-chelating agent penicillamine: convert cysteine to penicillamine- cysteine complex
S/E: drug rashes, blood dyscrasias, immune complex mediated glomerulonephritis
-cysteine binding drug tiotroponin

6. Mild hyperoxaluria with calcium oxalate stones

-Type 1: respond to oral high dose pyridoxine
-Type 2: not respond to oral high dose pyridoxine

Note:
Nephrocalcinosis (not nephrolithiasis). It is diffuse renal parenchymal calcification
Causes:
Cortical (rare) Renal cortical necrosis
Medullary Hypercalcemia (primary hyperparathyroidism, hypervitaminosis D, sarcoidosis)
Renal tubular acidosis
Primary hyperoxaluria
Medullary sponge kidney
TB
5.0 URINARY TRACT OBSTUCTION
Causes, pathophysiology, clinical feature
Pathophysiology
-progressive rise in intraluminal pressure
-dilatation proximal to the site of obstruction
-compression and thinning of the renal parenchymal↓
size of the kidney

Clinical feature
1. Symptom
UT pbstruction
loin pain: dull or sharp/ constant or intermittent
: provoked by measure that ↑ urine volume
anuria: complete bilateral obstruction
polyuria: partial obstruction owing to impairment of
renal tubular concentrating capacity

Bladder obstruction
hesitancy, diminished flow of urinary stream, terminal
dribbling and sense of terminal bladder emptying
infection: ↑ frequency, urgency, dysuria, cloudy
smelly urine

Sign
-loin tenderness
-enlarged hydronephrotic kidney palpable
-examination of the genitalia, rectum and vaginal is
essential (prostatic obstruction and pelvic malignancy)

Prognosis
Depend on
-obstruction: partial or complete
-duration of obstruction
-presence of infection
-site of obstruction

Clinical management
Investigation Treatment
1. Routine blood and chemical investigation -relieving the obstruction
-raised serum urea and creatinine, hyperkalemia, anaemia -treating the underlying cause
-preveting and treating infection
2. Plain abdominal X ray
-detect radiolucent stones/ calcification temporary external drainage of urine by nephrostomy
complete upper urinary tract obstruction: urgent relieve to
3. CT scan preserve kidney function
-high sensitivity and can visualise uric acid stones as small as partial urinary tract obstruction: no immediate obstruction
1mm surgical management with dialysis prior to surgery
treatment of diuresis follow relieve of obstruction at any site
4. Ultrasonography in the urinary tract
-can rule out upper urinary tract dilatation Note:
-d/t previous salt and water overload and the osmotic effect of
5. Excretion urography retained solutes combined with a defective renal tubular
-nephrogram is delayed on the obstructed site, d/t ↓ GFR reabsorptive capacity
-with time, the nephrogram is denser than normal, owing to the -a/w ↑ blood volume and ANP
prolonged nephron transit time -sodium and potassium replacement
severe: IV
6. Radionucleic studies mild: oral with high fluid intake
 -used in possible long standing obstruction to differentiate true
obstructive nephropathy from retention of tracer in a baggy,
low pressure, unobstructed pelvicalyceal system

7. Antegrade pyelography and ureterography

-define the site and cause of obstruction

8. Retrograde ureterography
-if antegrade examination cannot be carried out or if there is the
possibility of dealing with ureteric obstruction from below at
the time of examination

9. Cystoscopy, urethroscopy, urethrography

-visualise obstructing lesion within the bladder and urethra
directly

6.0 POLYCYSTIC KIDNEY DISEASE

An inherited disorder usually presenting in adult life with development of multi renal cysts associated with extrarenal (mainly
hepatic and cardiovascular abnormalities)

Pathophysiology
-mutation of PDK1 gene in chromosome 16 that encode for polycystin 1, an integral membrane glycoprotein involved in cell- to-
cell or cell- to- matrix interaction
(Autosomal recessive: PKD2 gene in chromosome 4)
-polycystine 1 act as a regulator of PKD2 channel activity by its colocalisation on cilia of collecting tubular cell
-disruption of the polycystin pathway result in reduced cytoplasmic calcium in the principal cell of collecting duct, stimulate
calcium inhibitable adenyl cyclise and inhibition of CAMP phosphodiesterase
-defective ciliary signalling result in disoriented division of the cell by upregulation of mammalian target of rapamune and its
downstream cell cycline kinases along the nephron, resulting in the cyst formation
-patient experience declining renal function at a variable rate which is d/t discrepancy in the growth and size of the cysts

Clinical feature
-acute loin pain +/-hematuria: d/t haemorrhage into a cysts, cyst infection, urinary stone formation, increasing size of the kidney
-subarachnoid haemorrhage with berry aneurysm rupture
-complication of hypertension
-complication of associated renal cysts
-symptom of uraemia and anaemia a/w CKD

Complication
Pain -occur in minority of patient
-resistant to analgesics owing to pressure of large cysts
-treatment: surgical decompressionand laparoscopic cyst decortications
Cysts infection -poor response to antibiotic therapy d/t poor penetration of conventional antibiotics across the
cysts wall
-treatment: use lipophilic antibiotics (eg. co- trimozaxole and fluoroquinolone) that penetrate
the cysts wall better
Hypertension -very common feature of ADPKD
-may result in LVH
-treatment: ACEI
Progressive CKD -rate of decline of GFR is more rapid than in other primary renal disorder
Hepatic cysts -massive enlargement of polycystic liver is seen
pain
infection
compression of the bile duct, portal vein or hepatic venous outflow occur
Intracranial aneurysm formation -asymptomatic intracranial aneurysm
-clinical feature:headache of sudden onset and unusual character
Mitral valve prolapse -20% pt with ADPKD

Diagnosis
-PE reveals large, irregular kidneys and hepatomegaly
-definitive diagnosis: ultrasound
(a) ADPKD is estalblished if
15-39 years: ≥3 cysts (unilateral or bilateral)
40-59 years: ≥ 2 cysts in each kidney
≥60 years: ≥ 4 cysts in each kidney
Therapy
-no therapy is yet available but potential agent eg,
(a) vasoactive receptor antagonist
(b)adenylyl cyclise agonist
(c) CAMP phosphodiesterase inhibitor
(d)long acting somatostatin analogue
 (b) ADPKD is excluded if
≥ 40 years: < 2 cysts
30-39 years: 0 cysts

Differential diagnosis
-tuberous sclerosis
-von Hippel Lindau syndrome
-multicystic dysplastic kidney
-juvenile nephronopthisis
-glomerulocystic kidney disease
-acquired cystic disease
-renal cell carcinoma

7.0 ACID BASE DISTURBANCES

Change in ABG
pH PCO2 HCO3-
Respiratory acidosis ↓ ↑↑ ↑ (compensatory)
Respiratory alkalosis ↑ ↓↓ ↓
Metabolic acidosis ↓ ↓ ↓↓
Metabolic alkalosis ↑ ↑ ↑↑

Respiratory acidosis and alkalosis

Respiratory acidosis
Respiratpry alkalosis
-this is caused by retention of CO2PCO2↑pH↓  renal retention of bicarbonate (partial
compensation)
-Causes
(a) Pulmonary
chronic: COPD, chronic bronchitis, emphysema
acute: pneumonia, pulmonary edema, pulmonary embolism, acute asthmatic attack
(c) Non pulmonary
depression of central respiratory centrehypoventilation
**drug (eg. barbiturates, benxodiazepine), neurological disorders (eg. infection, brainstem
disease, trauma)
chest wall disorder, eg. kyphoscoliosis
obesity
laryngeal and tracheal
-compensatory mechanism
1. Chemical buffer to take up additional H+
2. Respiratory mechanism: nil (as impaired respiration is the problem in first place)
3. Renal: conserve all filtteres HC03- and produce new HCO3- while secreting more H+
-HCO3↑
-pH αHCO3-(↑)/ CO2(↑)
-restore pH to normal
-increase removal of CO2 is caused by hyperventilation↓PCO2↑ pH
-cause:
hypoxia (high altitude, severe anaemia, pneumonia)
direct stimulation of respiratory centre (salicylate overdose, liver failure, septicaemia, fever,
trauma)
cerebral trauma, infection of tumour
mechanical overventilation
psychological (anxiety, stress, fear, pain)
-compensatory mechanism
1. Chemical buffer: liberate+ to ↓ severity of alkalosis
2. Respiratory: as CO2 and H+ ↓, two of the poent stimuli for hyperventilation are removed and
hyperventilation does not continue completely unabated
3. Renal: conserve H+ and excrete more HCO3-

Metabolic acidosis and alkalosis

Metabolic acidosis
-d/t accumulation of acid other than carbonic acid and primary decrease in plasma HCO3-
(a) acid administration
(b) acid generation (eg. lactic acidosis during shock and cardiac arrest)
(c) impaired acid secretion by the kidney
(d) bicarbonate loss from GIT and kidney

-need to calculate anion gap to identify whether the acidosis is d/t retention of HCl or to other acid
(a) Cation: Na, K, Ca, Mg
(b) Anion: Cl, HCO3, -ve charges from (albumin, phosphate, sulphate, lactate, other organic acids)
(c) Sum of +ve and –ve charges should be equal (normal anion gap= 10-18mmol/l)

Normal anion gap MA -HCl is retained or NaHCO3 is loss

High anion gap MA -unmeasured anion present in increased quantities

Note:
Renal tubular acidosis
-impairment of the ability of the renal tubules to maintain acid- base balance
-4 type:
(a) Type 1 (distal) renal tubular acidosis
-d/t failure of H+ excretion in the distal tubule
-feature: acidosis, hypoK, inability to lower urine pH <5.3 despite systemic acidosis, ↓ urinary ammonium production
-complication: osteomalacia (buffering of H+ by Ca2+ in bone, resulting in depletion of calcium from the bone
: renal stone formation, d/t: hypercalciuria
: hypocitraturia (citrate inhibit calcium phosphate precipitation)
: alkaline urine (favour precipitation of calcium phosphate)
: recurrent UTI (caused by renal stone)
: sensorineural deafness
-treatment: sodium bicarbonate, potassium supplement, citrate

(b) Type 2 (proximal) renal tubular acidosis

-d/t failure of sodium bicarbonate reabsorption in the proximal tubule
-features: acidosis, hypokalemia, inability to lower urine pH <5.5 despite systemic acidosis, appearance of HCO3 in the urine
despite subnormal plasma HCO3
-treatment: sodium bicarbonate

(c) Type 3 renal tubular acidosis

-combination of type 1 and type 2
-caused by mutation resulting in carbonic anhydrase type II deficiency
-feature: osteopetrosis, RTA of mixed type, cerebral calcification, mental retardation

(d) Type 4 renal tubular acidosis

-hyporeninaemic hypoaldosteronism
-feature: hyperkalemia, low plasma bicarbonate and hyperchloraemia, normal ACTH stimulation test, low basal 24 hrs urinary
aldosterone, subnormal response of plasma renin and plasma aldosterone to stimulation, correction of hyperkalemia by
fludrocortisone 0.1mg daily
-cause: CKD (tubulointerstitial disease or diabetes), Gordon’s syndrome, NSAIDS
-treatment: fludrocortisone, sodium bicarbonate, diuretics, ion exchange resin to remove potassium

Clinical feature Diagnosis Treatment

-stimulation of respirationair hunger Plasma HCO3- <21mmol/l, urine pH -correct the primary cause
(Kussmaul respiration) >5.3 -↑ oxygen delivery (protect airway,
-↑ delivery of oxygen to the tissue by -to differentiate btw proximal and distal improve breathing and circulation)
shifting the oxyhaemoglobin dissociation require bicarbonate infusion test inotrophic agent, mechanical
curve to the right but also lead to -suspection of partial RTA if Plasma ventilation, invasive monitoring
inhibition of 2, 3-BPG which returns the HCO3- >21mmol/l -administration of sodium bicarbonate
curve towards the normal -correction of hyperkalemia a/w acidosis
-cardiovascular dysfunction (acidosis is –
ve inotropic and cause venoconstriction)
-worsen pulmonary edema
-hypotension d/t arteriolar vasodilation
-cerebral dysfunction (acidosis a/w
cerebral dysfunction and fits)
Metabolic alkalosis
-normally seen in hospitalised pt

Clinical feature Treatment

-difficult to separate from those from chloride, volume or 1. Chloride responsive metabolic alkalosis
potassium depletion -chloride replacement
-tetany, apathy, confusion, drowsiness, cardiac arrhythmia, selection of accompanying cation- Na, K or proton is
neuromuscular instability dependent to extracellular fluid volume, associated K depletion,
-depressed respiration reversibility of any depression of GFR
2. Chloride resistant metabolic alkalosis
-eg. metabolic alkalosis d/t hypoK
-mild to moderate alkalosis: oral KCl
-pt with cardiac arrhythmia or generalised weakness: IV KCl

8.0 FLUID AND ELECTROLYTE IMBALANCE

8.1 FLUID IMBALANCE
Increased intracellular volume
Cause 1. Heart failure
-↓ CO
-↑ RAAS and ↑ renal sympathetic nerves via volume receptor and baroreceptor
-↑ peripheral and renal arteriolar resistance and sodium and water retention

2. Hepatic cirrhosis
-peripheral vasodilation d/t ↑NO
-reduced effective arterial blood volume and arterial filling
-lead to activation of chain of event common to cardiac failure (↑ peripheral and renal resistance, salt and water
retention, edema)

3. Nephrotic syndrome
-@ cortical CD where Na/ K ATPase are increased threefold alang basolateral surface
in normal, should be counterbalanced by increasing secretion of sodium in the inner medullary CD BUT altered in
pt with nephrotic syndrome by enhancing kidney specific catabolismof cGMP (secondary messenger for ANP)
following phosphodiesterase activation
-edema d/t
↑ TNF α level activate protein kinase C, which change phosphorylation of occludin and capillary permeability
 which made up the tigth junction and adherent protein
↑ ANP can alter the permeability of intracellular junctional complex
↓ effective circulating volume↓ CO and arterial fillingchain of event similar to HF and cirrhosis

4. Sodium retention
-↓ GFR ↓ renal capacity to excrete sodium
-eg. estrogen (weightgain in premenstrual state), mineralocorticoids and liquorice, NSAIDS (activation oof RAAS),
thiazolidinediones (activation of PPARγ that is essential to the control of energy metabolism-lead to salt and water
retention)

5. Other cause of edema

-initiation of insulin treatment and refeeding after malnutrition lead to development of transient edema
d/t upregulation of ENaC in the principal cell of collecting duct
-↑capillary pressure owing to relaxation of precapillary arterioles, eg dihydropyridine Ca channel blocker
-complement deficient syndrome↑ capillary permeability to protein↑ interstitial oncotic pressure
-local increase in edema
ankle edema d/t venous damage following thrombosis and surgery
ankle or leg edema d/t immobility
arm edema d/t subclavian thrombosis
facial edema d/t SVC obstruction
Clinical -peripheral edema(eg. ankle, face, sacral area)
feature -expansion in interstitial volume: pulmonary edema, pleural effusion, pericardial effusion and ascites
-expansion of blood volume: ↑ JVP, cardiomegaly, added heart sound, basal crepts
Treatment

Decreased extracellular volume

Cause
Clinical 1. Symptom
feature -thirst, muscle cramps, nausea, vomiting, postural dizziness
-hypotension, impaired cerebral perfusion, confusion and coma (severe)

2. Sign
-divided into:
(a) loss of interstitial fluid: loss of skin elasticity (turgor: the rapidity in which the skin recoil to normal after being
pinched
(b) loss of circulating volume: ↓ pressure in the venous and (if severe) arterial compartment
postural hypotension: normally the BP rises if subject stand up, as a result of increased venous return d/t
venoconstriction (this maintain cerebral perfusion) BUT loss of extracellular fluid prevent this and cause a fall in
BP
↓ JVP: can be seen only when pt is lying flat or even head down
peripheral venoconstriction: cold skin with empty peripheral vein, which are difficult to cannulate just when the
patient need IV
tachycardia: not a reliable sign (eg. in B blocker, antiarrhythmia, hypovolaemia)
Investigatio -blood test is not helpful as it can cause misleading
n ↑ plasma urea
↓ urine sodium
↑ urine osmolarity
Treatment -depending on the underlying cause
1. Haemorrhage
-infusion of combination of red cell and plasma substitude
2. Loss of plasma
-treated with human plasma and plasma substitude
3. Loss of water and electrolyte
-oral water and sodium salt
-mild: sodium bicarbonate 500mg 6mmol each of Na and HCO3-
-IV fluids: if there is hypotension and evidence of impaired organ perfusion (eg. oliguria)
: plasma expanders (colloids) are prefered
-regularly monitoring of fluid balance charts, bodyweight and plasma expanders
4. Loss of water (eg. in diabetes mellitus and pt after surgery unable to drink water)
-give water
-IV water with 5% glucose with K+, because pure water lead to osmotic lysis of blood cell

8.2 SALT IMBALANCE (SODIUM AND POTASSIUM- REFER EMERGENCY)

9.0 TUBULOINTERSTITIAL NEPHRITIS
9.1 ACUTE TUBULOINTERSTITIAL NEPHRITIS
Classification (based on etiology)
Drug induced acute TIN

Clinical feature: fever, arthralgia, skin rashes, acute oliguric or non-oliguric kidney injury,
oliguria, eosinophiluria, renal histology show intense interstitial cellular infiltrate

Treatment: withdrawal of offending drug

Infection induced TIN
: high dose steroid therapy (prednisolone 60mg daily)
Etiological agent:
-virus: Hantavirus, EBV, HIV, measles, adenovirus
-bacteria: Legionella, Leptospira, streptococci, mycoplasma, brucella, chlamydia)
-others: Leishmania, Toxoplasma

Acute TIN as a part of
multisystem inflammatory
disease
Tubulointerstitial nephritis
with uveitis (TINU) syndrome
Idiopathic
Treatment
-eradication of infection by appropiate antibiotics or antiviral agentts and in renal transplant
modifying immunosuppressive regimen
-eg. Sjogren syndrome, SLE, Wegener’s granulomatosis
-in this syndrome, uveitis generally coincide with acute TIN
-it is common in childhood, but had been reported in adulthood (more common in women)
-a/w autoantibodies directed against CRP

Clinical onset
-benign abrupt with AKI
-occurs within days of exposure to offending drug/ several month to NSAIDS
-rash, fever, eosinophilia, ↑ IgE, tubular function abnormalities +/-Fanconi syndrome
-proteinuria usually absent
-mild +/-microscopic hematuria
- +/- sterile pyuria
-renal biopsy may be required to make a definitive diagnosis
-NSAIDS induced may a/w nephritic range proteinuria

Treatment
-supportive treatment
-discontinuation of the offending agents/ treatment
-not responding (serum creatinine not reduced)
-methylrednisolone followed by oral prednisolone
-tapered over 4-8 weeks

9.2 CHRONIC TUBULOINTERSTITIAL NEPHRITIS

-characterised by chronic inflammatory cellular infiltration of the interstitium with tubular atrophy and generalised interstitial
oedema or fibrosis
-clinical feature: polyuria, nocturia, proteinuria, uraemia
: papillary necrosis with ischemic damage to the papillae which separate and pass in the urine
: hematuria and sterile pyuria, and sloughed papillacausing ureteric colic and acute ureteric obstruction
: tubular damage to the medullary area of the kidney- defects in the urine concentration and sodium conservation
with polyuria and salt wasting
-type:
Analgesics nephropathy -chronic consumption of large amount of analgesics (especially those containing phenacetin) and
papillary necrosis
-more common in women
-patient often depressed and neurotic
-clinical feature: anaemia, CKD, UTI, hematuria, urinary tract obstruction
: salt and water wasting
: uroepithelial tumours
-treatment: consumption of the above analgesics should be discouraged
: dihydrocodeine or paracetamol as altermative

Chinese herb nephropathy
Balkan nephropathy
Other cause
-chinese herbal medicines have been increasingly used in the West eg for slimming and cause
nephropathy
-renal histology is similar to Balkan nephropathy but the clinical course is very aggressive which is
charaterised by relentless prograssion to ESKD
-the causative agent is aristolochic acid which is a result of fungal contamination of the herbal
medicine
-endemics in areas along the tributaries of the River Danube where inhabitants are subjected to
frequent flooding and where the water supply come from shallow well
-new research suggest that chronic dietary poisoning by aristolochic acid is responsible for Balkan
nephropathy and is associated with urothelial cancer

Clinical feature
-insidious onset
-often diagnosed incidentally on routine screening/ evaluation of HPT
-usually asymptomatic
-HPT is common
-elevation in serum creatinine
-tubular dysfunction
-Fanconi syndrome
-mild proteinuria (< 1g/ day)
-renal biopsy (interstitial fibrosis, tubular atrophy, arteriolar sclerosis, mononuclear cell infitrate)
-papillary necrosis with analgesics nephropathy causes gross hematuria, flank pain +/-obstrucction

Treatment
-treat the underlying cause
-adequate BP control and management of anaemia
-no role for corticosteroid therapy

10.0 RENAL ARTERY STENOSIS (REFER SST)

11.0 URINARY TRACT INFECTION (REFER SST)

12.0 INTERPRETATION OF RENAL PROFILE

The usual blood test which checks that the kidneys are working properly measures the level of urea, creatinine and certain
dissolved salts.

Creatinine Plasma creatinine concentration is the most reliable

biochemical test for glomerular function
-reference range for plasma craetinine in the adult population is
60-120umol/l
-plasma creatinine concentration is inversely proportional to
GFR
-normal plasma creatinine does not necessary indicate impaired
renal function
-change in creatinine concentration, provided it is outside the
limit of biological and analytical variation, does sugget change
in GFR
-changes in plasma creatinine can occur independently of renal
function, owing to changes in renal mass
↓: starvation, wasting disease, surgery, corticosteroids
↑: pregnancy
Urea -urea is synthesised in the liver, as by product of deamination
of amino acid and its elimination in the urine represent the
major route for nitrogen excretion
-less reliable indicator of renal glomerular function than
creatinine
↑: high protein intake, catabolic state, absorption of amino
acid and peptide after GIT haemorrhage
↓: low protein intake, in pt with liver disease
GFR Amount of plasma filtered through the glomerulus per unit time
-average: 125ml/min=180L/day
GFR=Kf X (PGC –PBC) –(∏GC-∏BC)
Kf= coefficient filtration
=surface area X permeability of capillries
-factors affecting GFR:
(a) Permeability of membrane
(b) Size of capillary bed
(c) Change in arteriolar hydrostatic pressure
constriction of afferent arterioles ↓GFR (d/t epinephrine and
norepinephrine)
constriction of efferent arterioles ↑ GFR (d/t Ag II)

Dissolved salts that are routinely measured are sodium, potassium, chloride and
bicarbonate. They are sometimes referred to as 'electrolytes'.
Abnormal blood levels of any of these may be due to a kidney
problem. (Some other conditions may also alter the salt balance
in the blood.)
13.0 GLOMERULOPATHIES
A group of disorder where:
-There is primarily an immunological mediated injury to glomeruli, although renal interstitial damage is a regular accompainiment
-The kidney are involved symmetrical
-Secondary mechanism of glomerular injury come into play following an initial immune insult eg. fibrin deposition, plt
aggregation, neutrophil infiltration, free radical induced damage
-renal lesions may be part of generalisedd disease

General term:
-Focal: some, but not all glomeruli show the lesion
-Diffuse: most of the glomeruli (>75%) have the lesion
-Segmental: only part of glomeruli is affected
-Proliferative: an increase in cell numbers d/t hyperplasia or one or more of the resident glomerular cell +/- inflammation
-Membrane alteration: capillary wall thickening d/t deposition of immune deposits, alteration in basement membrane

Pathogenesis
-immunologically mediated disorder with involvement of cellular immunity (T lymphocyte, macrophages, dendritic cell), humoral
immunity (antibodies, immune complexes, complement), and other inflammatory mediator (including cytokine, chemokine and
coagulation cascade)
-immune response directed against known target antigen, particular when GN complicates infection, neoplasia and drug
-primary glomeurlonephritis occur in genetically susceptible individual (determine by HLA) following an environmental insult
(drug, chemicals, infectious agent)

Classification
Nephrotic syndrome -massive proteinuria (>3.5g/day), hypoalbuminaeemia, edema, lipiduria, hyperlipidemia
Acute nephritic syndrome -haematuria, non nephrotic range of proteinuria, edema, HPT, transient renal impairment
Rapidly progressive -acute nephritis, focal necrosis +/- crescent, rapidly progressive renal failure
glomerulonephritis
Asymptomatic haematuriaa,
proteinuria
13.1 NEPHROTIC SYNDROME
Pathophysiology
Hypoalbuminaemia -urinary protein loss of the order 3.5g daily or more in an adult is required to cause hypoalbuminaemia
-increased catabolism of reabsorbed albumin in the proximal tubule during the nephrotic syndrome even
though actual albumin synthesis rate is increased
hence to maximise serum albbumin concentration in nephrotic patients, a reduction in urinary albumin
excretion with ACEI is always necessary
Proteinuria Mechamism:
-structural damage to the glomerular BM lead to increase in size and no. of pores, allowing passage of more
or larger molecule
-fixed negatively charged components are present in glomerular capillary wall, which repel negatively
charged protein molecule
Hyperlipidemia -increase synthesis of lipoprotein as a consequences of low plasma albumin
-reduced clearance of principal trigycerides being lipoprotein in direct response to albuminuria
Edema d/t hypoalbuminaemia

Management
Initial treatment -dietary sodium restriction and thiazide diuretics
-unresponsive patient: furosemide with addition of amiloride with K concentration
monitored regularly
-some pt malabsorb diuretics (d/t gut mucosa edema): parenteral administration
Normal protein intake -too high protein diet (80-90g daily) increase proteinuria and harmful in the long term
Albumin infusion -transient, only given to pt who is diuretics resistant and those with oliguria and uraemia
in the absence of severe glomerular damage
Long term prophylactic anticoagulant -d/t hypercoagulable state d/t loss of clotting factor and increase hepatic production of
fibrinogen which predispose to venous thrombosis
Early detection of treatment of -in sepsis as there is loss of immunoglobulin I the urine lead to increase susceptibility to
infection infection
HMG-CoA reductase -lipid abnormalities
ACEI, ARB Antiproteinuric properties

13.1(A) NEPHROTIC SYNDROME WITH BLAND URINE SEDIMENTS

Minimal change -Triggering factor: drugs (NSAIDS, lithium, antibiotics, biphospphobates, sulfasalazine), atopy, allergic
disease reaction, infection
-Histology: normal on light microscope
: on EM show fusion of foot process of epithelial cell
: Immunofluorescent-immune complex and anti-GBM antibody can be demostrated
-clinical feature: case of nephrotic syndrome (proteinuria, edema), does not lead to CKD
-management: high dose corticosteroids therapy with prednisolone 60mg/m2 daily (up to maximum
80mg/day) for 4-6 weeks followed by 40mg/m2 every other day
: +cyclophosphamide
alternative: ciclosporin 3-5mg/kg per day (effective but must be continued long term to
prevent relapse on stopping treatment)immunosuppressive effect, stabilise
the actin cytoskeleton in kidney podocyte

Congenital nephrotic -Pathogenesis: mutation in the gene coding for transmembrane protein, nephrin
syndrome -Histology: diffuse mesangial hypercellularity
: some tubules develop microcysts and are dilated
: EM- complete effacement of the foot process of eithelial cell
Focal segmental -Pathogenesis: a circulating permeability factor(eg. cardiotrophin like cytokine 1, soluble urokinase
glomeruloscelrosis receptor) cause ↑ protein leak as plasma from patient increases membrane permeability inisolated
glomeruli
-5 histologic variant:
(a) classic FXGS- sclerotic segments in any location of the glomerulus
(b) Glomerular tip lesion: segmental lesion at the tubular pole of all the affected glomeruli at very early
Stage
: capillaries forming foam cell and overlying visceral epithelial cell are enlarged
(d) Collapsing FSGS: visceral cell are usually enlarged and coarsely vacoulated with wrinkled and
collapsed capillary walls
(e) Prehilar variant: prehilar sclerosis and hyalinosis in >50% segmenta sclerotic glomeruli
(f) Cellular variant: at least 1 glomerulus with segmental endocapillary hypercellularity that occlude
capillaries lumen
-clinical feature: massive proteinuria, hematuria, hypertension and renal impairment, often resistant to
Treatment
-Treatment: Prednisolone 0.5-2 mg/kg per day and continue for 6 mth before patient is considered to
 resistant to therapy
: Ciclosporin at doses to maintain serum trough level at 150-300ng/ml
: Ciclophosphamide used for second line therapy in adults

Membranous -Cause: primary (idiopathic- 75%)

glomerulopathy : secondary (drug, autoimmune disease, infection, neoplasia, sarcoidosis, kidney transplant, SCA)
-Pathogenesis: IgG4 type autoantibodies against phospholipase receptor A2 (linked to HLA-DQA1)
-Histology: immunofluorescent- presence of uniform granular capillary wall deposit of IgG and
complement C3
: EM-small electron dense deposits in the subepithelial aspect of the capillary wall (early stage)
-deposits are encircling by basement membrane which give appearance of spikes on silver
staining (intermediate stage)
-deposits are completely surrounded by basement membrane which appear as uniform
thickening of capillaries basement membrane (late stage)
-Clinical features: asymptomatic proteinuria and frank nephrotic syndrome
: microscopic hematuria, hypertension, renal impairment
: almost half remit spontaneously or therapy related with 40% develop CKD
-Treatment: cyclophosphamide and chloramburacil (reserve for severe and prolonged nephrosis, renal
insufficiency, hypertension)
: anti-CD20 antibodies (rituximab) improves renal function, reduce proteinuria, increase
serum serum albumin
Amyloidosis -acquired or inherited disorder of protein, normally soluble proteins or fragments are deposited
extracellularly as abnormal insoluble fibrils causing progressive organ dysfunction and death
-Cause: amylodosis also referred to as secondary amyloidosis, rare but serious complication of chronic
inflammatory disease and chronic infection
-Histology: light microscope-eosinophilic deposits are seen in the mesangium, capillary loops and
arteriolar wall
: congo red-pink deposits which show green birefringent under polarised light
: EM- characteristic fibrils of amyloids can be seen
-Treatment: can be decreased by treatment of the underlying inflammatory condition but cannot be
completely suppressed
: renoprotective measures( dialysis and kidney transplant)
Diabetic nephropathy -diabetic renal disease is the leading cause of ESKD
-people with type 1 and 2 diabetes have equal rates of proteinuria, azotemia and ESKD
-histology: early-glomerular basement membrane thickening and mesangial expansion
: progressive depletion of podocyte from from the filtration barrier d/t apoptosis or detachment
lead to podocyturia appears to be very early ultrastructural change
: late-glomerulosclerosis develop with nodules and hyaline deposits in the glomerular arterioles
-treatment: lifestyle changes (cessation of smoking and increase in exercise), hypertension, poor
metabolic regulation and hyperlipidemia
: ACEI and ARB
: paracalcitol (a selective activator of the Vitamin D receptor)

13.1 (B) NEPHROTIC SYNDROME WITH ACTIVE URINE SEDIMENTS(MIXED NEPHROTIC/ NEPHRITIC)
Membranoproliferative -have 3 subtype:
disease (a) Type 1 MCGN: d/t activation of complement cascade by the classical pathway
(b) Type 2 MCGN: d/t activation of complement cascade by the alternative pathway
(c) Type 3 MCGN: d/t activation of complement cascade by the common pathway
-histology: mesangial cell proliferation with mainly subendothelial immune deposition and apparent
splitting of the capllary basement membrane, giving “ tram-line” effect
-management: idiopathic-no specific therapy
-follow up every 4 month with specific attention to BP
: children-steroids (alternate day prednisolone 40mg/m2 for a period of 6-12 month if no
benefit discond, regular follow up with control of BP)
: adults-aspirin (325 mg) or dipyridamole (75-100mg) daily or combination of two,
should be given for 6-12 month

Mesangial proliferative IgM nephropathy

GN -↑ mesangial cellularity in most of the glomeruli, a/w granular immune deposits (IgM and complement)
in the mesangial region
-poor prognosis as steroid response only 5%

C1q nephropathy
-C1q deposits in the mesangium
-seronegative lupus (similar to SLE just there is intense C1q staining and absence of tubuloreticular
inclusion of EM
Lupus
glomerulonephritis

Pathogenesis
-autoantigen driven, T cell dependent and B cell mediated autoimmune disorder
-LN has circulating autoantibodies to cellular antigen (anti-dsDNA, anti-Ro) and complement activation
which lead to ↓ serum level of C3, C4, C1q
there nephrogenic antibodies have specific pysiochemical characteristic and collerate well with the
pattern of renal injury
-Nucelosome (structure comprising DNA and histone, generated during apoptosis) are the most likely
autoantigen
>+ve charge histone component of the nucleosome bind to the negatice charged heparan sulfate
inciting an inflammatory reaction and resulting in mesanglial cell proliferation, mesanglial matrix
expansion, inflammatory leukocyte

Management
-Type I: no treatment
-Type II: benign course but some patient treated with steroids
-Type III, IV, V: steroid and high dose IV cyclophosphamide
-remission maintained by mycophenolate mofetil
Cryoglobulinaemic Classification
renal disease -Type I: the crypercipitate Ig is a single monoclonal type, as is found in multiple myeloma and
lymphoproliferative disease
-Type II and III: mixed type (with Type II monoclonal, Type III polyclonal)
: no underlying associated disease is found (viral infection, fungal and spirochoetal
infection, malaria, IE, autoimmune rheumatic disease

Clinical feature: 4th and 5th decades of life

:women more commonly affected than men
: systemic features: purpura, arthralgia, leg ulcers
: Raynaud phenomenon, evidence of systemic vasculitis, polyneuropathy, hepatic
Involvement
: asymptomatic proteinuria, microscopic hematuria

Treatment: corticosteroids or immunosuppressive therapy with cyclophosphamide

: intensive plasma exchange or cryofiltration
: interferon with ribavarin reduce viraemia in hepatitis C
Henoch Scholein Clinical feature: skin rash, abdominal colic, joint pain and glomerulonephritis
 syndrome Histology: focal segmental proliferative glomerulonephritis, if severe epithelial cresent is present
: Immunoglobulin-IgA in glomerular mesangium distribution
Treatment: usually supportive
Idiopathic fibrillary Clinical feature: nephrotic range proteinuria, microscopic hematuria, hypertension, CKD, 40-50%
glomerulopathy develop ESKD 2-6 yrs

Histology: EM-microfibrillary structure are seen in the mesangium and glomerular capillary wall that do
not stain in Congo Red
Immunotactoid -microtubules are much larger than the fibril in fibrillary glomerulopathies
glomerulopathy -majority of patients have circulating paraproteins, monoclonal immunoglobulin deposition seen in
glomeruli on immunofluorescence microscopy
Fibronectin -d/t fibrillar deposits
glomerulopathy -a/w massive deposition of fibronectin, a large dimeric glycoprotein consisting of two similar subunit
-rare
-the disease is followed by hypertension, microscopic hematuria, slow progression to ESKD in most
patient
-Diagnosis: renal biopsies which demonstrate enlarged glomeruli with minimal proliferation and
massive Congo red –ve fibrillary deposits in the capillary wall
-Treatment: adequate BP control by ACEI
: dialysis
: renal transplant

13.2 ACUTE NEPHRITIC SYNDROME

Clinical feature: hematuria, proteinuria, hypertension, edema (periorbital, leg or sacral), temporary oliguria and uraemia
Histology: cellular proliferation (mesangial and endothelial) and inflammatory cell infiltration (neutrophils, macrophages)

Note:
Post streptococcal -usually in children which suffer strep infection 1-3 week before onset of acute nephritic syndrome (throat
glomerulonephritis infection, otitis media or cellulitis)
-the time interval between the infection and development of symptom and sign or renal involvement reflect
the time aken for immune complex formation and deposition and glomerular injury to occur
-renal biopsy show diffuse, florid, acute inflammation in the glomerulus with neutrophil and deposition of
immunoglobulin and complement

Management
-acute phase: antihypertensive, diuretics, salt restrictionn, dialysis
-if recovery is slow: corticosteroids
-old patient: annual BP check and measurement of serum creatinine are required
Glomerulonephritis -occur rarely and often manifest itself as acute nephritic syndrome
-microscopic feature: resemble post- infectious GN, but usually focal and segmental
: crescentic (in staph aureus)
-treatment: anttibiotics therapy or surgical eradication
Glomerulonephritis -indistinguishable from post- infectious GN both clinical feature and microscopic, but complement level are
associated with normal and immune deposits are absent on biopsy
visceral abscessess -treatment: antibiotic and surgical drainage
13.3 ASYMPTOMATIC URINARY ABNORMALITY
Feature: isolated proteinuria without haematuria
subnephrotic range without an active urine sediment and there is normal renal function
outcome: excellent (but occasionally have serious glomerular disease)
: haematuria with or without sub- nephrotic range proteinuria
early discovery of potentially serious glomerular disease, eg SLE, Henoch Scolein Purpura, post- infectious
glomerulonephritis

IgA nephropathy -commonest form of glomerulonephritis worldwide

-pathogenesis:
exaggerated bone marrow IgA1 immune response to viral or other antigens and is associated with
an abnormality in O- linked galactosylation in the hinge of IgA1 moleccule
strong a/w on chromosome 6p in the region of MCH/ DQ and HLA- B loci
IgA nephropathy is d/t circuating immune complex composed of glycan specific IgG and a
galactose deficient IgA1 antibody which deposits in the glomerular mesangium and induce the
mesangioproliferative gloerulonephritis
disease a/w IgA deposits: Henoch Schonlein purpura, chronic liver disease, malignancies,
seronegative spondyloarthritis, coeliac disease, mycosis fungoides and psoriasis
-histology: focal and segmental proliferative glomerulonephritis with mesangial deposits of
polymeric IgA1
-clinical feature: asymptomatic microscopy haematuria or recurrent macroscopic haematuria
: proteinuria may occur
: good prognosis (especially in those with normal BP, renal function and absence
of proteinuria)
ESKD: 25% in those with proteinuriaof more than 1g per day, ↑ serum
creatinine, hypertension, ACE gene polymorphism
-treatment: steroids (for pt with proteinuria, mild glomerular changes)
: fish oil or oral prednisolone with cyclophosphamide for 3 month, followed by
maintenance with prednisolone and azathioprine
: tonsillectomy (for pt with recurrent tonsillitis)
Alport’s syndrome -hereditary nephritis with haematuria, proteinuria (<1-2g/ day), progressive kidney disease, high
frequency nerve deafness with 15% have ocular abnormalities eg. bilateral anterior lenticonus and
macular and perimacular retinal flecks
-pathogenesis: mutation in the COL4α5 gene encoding the COL4α5 collagen chain (X linked)
: mutation in COL4α3 and COL4α4 gene (autosomal recessive or dominant)
: pt are more sensitive to selective basement membrane proteolysis which may explain
why their glomerular membrane thickened unevenly, split and ultimate deteriorate
-treatment: mild CKD-ACEI to attenuate proteinuria
: exciting experimental evidence suggest that mesenchymal stem cell can
transdifferentiate into podocyte and repair basement abnormalities and slow the rate of
progression
Thin glomerular BM -autosomal dominant inherited condition in which pt present with persistent microscopic glomerular
disease hematuria
-cause: d/t secondary FSGN or concominant IgA nephropathy
-diagnosis: renal biopsy (thinning of the glomerular basement membrane on electron microscope)
Complement factor H -persistent microscopic haematuria, synpharyngitic mcroscopic haematuria, progressive CKD
related protein 5 culmitating in ESKD
nephropathy

14.4 RAPIDLY PROGRESSIVE GLOMERULONEPRITIS

-asymptomatic glomerular hematuria, rapid progressive AKI over weeks to months and focal glomerular necrosis with or without
glomerular crescent development or renal biopsies (which is an aggregate of macrophages or epithelial cell in Bowman’s space)
and can develop with or without immune deposits)

Anti-GBM -linear capillary loop staining with IgG and C3 and extensive crescent formation
glomerulo -abt two thirds have Goodpasture’s syndrome with associated lung haemorrhage
nephritis -pathogenesis: anti GBM antibodies are present in serum and are directed against the non collagenous component
of α3 collagen of basement membrane
: anti-GBM is restricted by the major histocompatibility complex
HLA-DRB1*1501 and HLA-DRB*1502: ↑ susceptibility
HLA-DR7 and HLA-DR1: ↓ susceptibility
-management:
plasma exchange: remove circulating antibodies
steroids: suppress inflammation from antibodies already deposited in the tissue
 cyclophosphamide: to suppress further antibody synthesis
-prognosis: related to the extent of glomerular damage (determine by % of crescent) at the initiation of treatment
ANCA -inflammation and necrosis of blood vessel wall
positive -eg. microscopic polyangitis and Churg Strauss syndrome
vasculitides -diagnosis: renal histology (gold standard)
focal
cresentic
mixed
sclerotic
-there are 2 form of ANCA:
(a) PR3-ANCA positivity: found in Wegener’s granulomatosis and microscopic polyangitis
(b) Anti-MPO positivity: idiopathic crescentic glomerulonephritis
: drug induced ANCA (eg. propylthiouracil, hydralazine, minocycline,
penicillamide)
present with constitutional syndrome, arthralgia/ arthritis, cutaneous
Vasculitis
-PR3 and MPO are aberrantly expressed in mature neutrophils of patients with ANCA vasculitis d/t upsilencing of
both antigens because of epigenetic mdifications
(a) Autoimmunity-can be initiated through an immune response against a peptide, that is antisense or
complementary to the autoantigen
(b) Infection-by fimbricated bacteria (gram –ve pathogens eg. E.coli, Klebsiella pneumoniae,
Proteus mirabilis)
-can trigger by molecular mimicry, a cross reactive autoimmunity to lysosomal
membrane protein 2
-Treatment:
(a) corticosteroids (prednisolone 80mh/ day reducing over time to 15mg/ day by 3 month) and cyclophosphamide
(2mg/kg per day, adjusted for age, renal function, and prevailing WBC count)
(b) for pt with fulminant disease need intensification of immunosuppresion with adjuvant plasma exchange or IV
pulse methyl prednisolone (1g/ day for 3 consecutive days)
(c) once remission, azathioprine should be substitude for cyclophosphamide
(d) treat colonization of Staph Aureus increases the risk of relapse and treatment with sulfamethoxazole/
trimetroprim
(e) IV Ig, lymphocyte depleting anti- CD52 antibodies and anti-TNF therapy-treat severe and drug resistant
therapy