:Chronic kidney diseases

Chronic kidney disease (CKD) refers to an irreversible deterioration in renal function

.that classically develops over a period of years

in another definition , it is an abnormality in kidney function or structure , last more

than 3 months and impact health

:The kidneys perform many important functions, including

• maintaining overall fluid balance

• regulating and filtering minerals from blood

• filtering waste materials from food, medications, and toxic substances

• help in producing red blood cells( erythropoietin ), promote bone health

( through vitamin D ,PTH calcium , phosphorus cycle) , and regulate blood
pressure( renin angiotensin aldosterone system).

So in case of chronic kidney damage some of these functions or all of them

will be lost or at least affected.

So if the fluid balance function is inadequate , we expect to have a volume

overload , this can be manifested as peripheral odema( leg , back periorbital) ,
accumulation of fluids in any potential space like pleura causing shortness of breath
or peritoneum ( abdomen ) causing ascites ( fluid in abdominal cavity ) ,pericardium
( pericardial effusion ) or even in body tissues causing symptoms accordingly( for
example accumulation in lungs causing pulmonary odema .

Disturbance in fluid balance is associated with a defect in [H] ion excretion and
leads to metabolic acidosis , this is usually manifested as deep rapid breathing and
disturbance in conscious level.

Defect in mineral regulation function leads to abnormal levels of essential minerals in

the body ( most importantly Calcium , Phosphorus and potassium) and this can be
manifested by a wide range of symptoms ranging from bone ach or muscle ache to
arrhythmia and sudden death.

Defect in filtering waste products leads to accumulation of these waste product in

the body , this is referred to as uremic syndrome , it is usually manifested as loss of
appetite , nausea , vomiting and according to the level of uremia it may cause
pericarditis or cross to brain and cause CNS symptoms ( ranging from confusion to
coma ).
Lastly loss of erythropoietin leads to anemia , disturbance in the cycle maintaining
bone health leads to metabolic bone diseases and alteration in renin angiotensin
aldosterone system leads to hypertension ( note that hypertension is a cause of
CKD and a complication of CKD ).

Now let's talks about kidney , remember the the nephron ? it is the smallest
functional unit in the kidney , it composed of glomerulus , which is the main site
where the blood is filtered , then the net product which contain water and minerals
pass to tubules and collecting duct where a reabsorption of certain minerals and water
takes place as needed , then the rest excreted as urine , so from clinical point of view ,
kidneys can be divided into nephrons (glomeruli , tubules and their surrounding
vessels ) and interstitial tissues connecting them .

So diseases affecting glomeruli ( glomerulonephritis), tubules and \ or interstitial

tissues (tubulointerstitial or interstitial nephritis ) or blood vessels entering the
kidneys ( renovascular diseases ) are some of the main causes of chronic kidney
disease .

But of course the most common cause of CKD is diabetes mellitus ( diabetic
nephropathy ) and hypertension remains one of the important causes , table below
show in order the most common causes of CKD
Glomerular filtration rate :

As we learned , the glomeruli are the main site of blood filtration and" urine making ",

how much the glomeruli filtrate? And how can we assess this ?

there are many equations used to measure this , the most commonly used are : the
Cockcroft-Gault equation, the Modification of Diet in Renal Disease (MDRD) study
equation, and the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration
equation.

GFR is estimated through the use of equations that account for age in years, race, sex,
and serum creatinine( what is this ?)

Creatinine is a by-product of muscle metabolism in which creatine in the muscle is

converted nonenzymatically to creatinine. Because the total body content of creatine
is fairly constant, there is a continual production of creatinine and a continual
excretion of it in the urine it has been chosen to assess kidney function .

How much albumin is secreted in urine ( albuminuria ) is directly associated with

renal damage so combining this to GFR can leads to more accurate assessment of
CKD .
When death is likely without renal replacement therapy, the condition is called end-stage
renal disease (ESRD).

Clinical features :

Patients may remain asymptomatic until GFR falls < 30 mL/min (stage 4 or 5). Thereafter,
symptoms and signs may develop that are related to almost every body system. You can
figure out some of the symptoms from the previous introduction.

Generally patient may look ill and pale with increasing tiredness and breathlessness.
,deep respiration , uremic symptoms ( anorexia and nausea. Later, hiccoughs, pruritus,
vomiting, muscular twitching, fits, drowsiness and coma)

Note that the insulin and prolactin are secreted by the kidneys so if there secretion is
suppressed there level is increased so patient may develop decreased libido (prolactin) or
hypoglycemia ( insulin ).
 Cardiovascular disease: The risk of cardiovascular disease is substantially increased in CKD
stage 3 or worse. Left ventricular hypertrophy due to hypertension increases the risk of
sudden death with arrhythmia.

Vascular calcification, associated with increased phosphate levels, may be sufficient to cause
limb ischaemia.

Pericarditis is common in untreated or inadequately treated end-stage renal disease (ESRD)

and can cause pericardial tamponade and, later, constrictive pericarditis.

Metabolic bone disease: Disturbances of calcium and phosphate metabolism occur in CKD,
leading to metabolic bone diseases such as osteomalacia, hyperparathyroid bone disease
(osteitis fibrosa) and osteoporosis

Immune dysfunction: Cellular and humoral immunity are impaired in CKD, leading to
infections – the second most common cause of death in dialysis patients, after cardiovascular
disease.

The infection range from infected access devices to pneumonias.

Haematological: CKD leads to a bleeding tendency through impaired platelet function, and
this risk is increased if anticoagulants are used.

Anaemia is common and, in part, related to the relative deficiency of erythropoietin; it

usually correlates with the severity of renal failure and contributes to many of the non-
specific symptoms of CKD.

Investigations :

When we face a patient with suspected CKD , we have to

1. assess renal function

a. blood urea and serum creatinine

b. measure GFR and urine albumin ( 24 hour urine collection or protein creatinine ratio).

2. looking for the cause of CKD AND Address reversible factors that are making renal
function worse ( HT , UTI , nephrotoxin)

a.( history of diabetes mellitus or hypertension ) measure RBS

b.General urine examination (GUE) looking for Red blood cell cast ( glomerulonephritis )

,leukocyte casts( tubulointerstitial disease ) , hematuria ( vascular disease or stones or

malignancies ) .

c. Ultrasound looking for kidney size ( in CKD when the kidneys are small less than 9 cm this
indicates irreversibility and possible need of renal replacement therapy ) , also structural
kidney diseases ( polycystic kidney ) or obstruction .

4. Screen for complications such as osteodystrophy ( serum electrolutes ) or anaemia. (CBC)

5. Screen for cardiovascular risk factors.( echocardiography ).

Management

This is aimed at preventing further renal damage, managing and limiting metabolic and
cardiovascular complications, and preparing for renal replacement therapy if required.

Antihypertensive therapy and antidiabetic therapy:

Suggested target BP is 130/80 mmHg for uncomplicated CKD and 125/75 mmHg for CKD
with proteinuria > 1 g/day. And intensifying blood sugar control aiming at HbA1c of <7% for
most patients

Reduction of proteinuria:

The degree of proteinuria is clearly related to the rate of progression of renal disease, and
reducing proteinuria slows progression. ACE inhibitors and angiotensin II receptor blockers
(ARBs) reduce proteinuria and retard progression of CKD,

Dietary and lifestyle modifications:

Evidence that restricting dietary protein is beneficial in humans is not clear-cut.

Patients with stage 4 or 5 CKD should be advised to avoid excessive protein, but to take
sufficient calories

and to avoid excessive dietary potassium and phosphate. Severe protein restriction is not
recommended.

Smoking cessation slows disease progression and reduces cardiovascular risk.

Exercise and weight loss may also be beneficial.

Lipid-lowering therapy:

Hypercholesterolaemia is almost universal in patients with significant proteinuria, and

increased triglycerides are common in CKD. Control of dyslipidaemia with statins may slow
disease progression.

Treatment of anaemia:

Recombinant human erythropoietin is effective in correcting the anaemia of CKD. The target
haemoglobin is between 10 and 12 mg/dL.

Maintenance of fluid and electrolyte balance:

Patients with fluid retention should have dietary sodium intake limited to 100 mmol/ day, but
in addition loop diuretics are often needed to treat fluid overload.

Renal bone disease: treated by optimizing levels of calcium , phosphorus , VIT D and
parathyroid hormone .

.
RENAL REPLACEMENT THERAPY

Renal replacement therapy (RRT) may be required temporarily for AKI or permanently for
CKD.

The aim of RRT is to replace the excretory functions of the kidney, and to maintain normal
water and electrolyte balance. Options include haemodialysis, peritoneal dialysis and
transplantation.

all patients with end-stage kidney disease are considered candidates for kidney transplantation
unless they have systemic malignancy, chronic infection, severe cardiovascular disease, or
neuropsychiatric disorders.