CHRONIC RENAL FAILURE:

CHRONIC RENAL FAILURE:

There is persistent renal impairment involving loss of both glomerular and tubular function. It gradually proceeds to ESRD. There is considerable decrease in number of functioning nephrons.  The GFR becomes less than 20 mL/min and there is uraemic syndrome. This condition is defined as either kidney damage or GFR<60 mL/min/1.73m² for at least 3 months. 

Classification of Chronic Kidney disease:

Stage	Description	eGFR (mL/min/1.73 m2)
1	Kidney damage with normal of increased GFR	=/>90
2	Kidney damage with mild decrease in GFR	60-89
3	Moderate decrease in GFR	30-59
4	Severe decrease in GFR	15-29
5	Kidney failure	<15 (or dialysis)

The common causes of CRF are glomerulonephritis, pyelonephritis, Diabetes mellitus, multisystem disease, etc.

In CRF most of nephrons are damaged, there is massive increase in renal blood flow due to decreased in afferent arteriolar resistance. This leads to increase in capillary hydrostatic pressure, increased permeability and passage of macromolecules, like proteins and lipoproteins through capillary wall. Some proteins are scavenged by mesangial cells, but overloading may cause functional derangement and cellular proliferation contributing glomerular sclerosis. Increased numbers of macrophages liberate growth factors that can damage endothelium and activate platelets and results in intraglomerular thrombosis with consequent fibrosis.

CRF causes hyperphosphataemia, and phosphate retention can contribute to renal damage through calcium phosphate precipitation. Dyslipidaemia is frequent finding and accumulation of lipids in glomeruli is thought to contribute to severity and progression of disease.

Developing kidney failure is most commonly monitored by changes in plasma creatinine concentration and calculated eGFR.

The Uraemic syndrome:

There is accumulation of uraemic toxins like urea (present in highest concentration), creatinine, hippuric acids, parathyroid hormone β₂-microglobulin, spermine, etc. in blood. It is more correctly called azotemia. Azotemia is the terminal manifestation of kidney failure. The biochemical characteristic of uremic syndrome includes:

·      

 Retained Nitrogenous metabolites like urea, creatinine, uric acids, Fluid, acid-base and electrolyte disturbances like metabolic acidosis, hyponatraemia, hypokalemia, hyperphosphatemia, hypocalcemia.

·         Abnormal lipid metabolism like hyper-TAG, decreased HDL, hyperlipoproteinemia, etc. 

Disturbances in CRF:

Retention of nitrogenous waste products: There is high plasma concentration of urea and creatinine. There is linear decrease in 1/Cr_p and thus GFR with time, in CRF. Hyperuricaemia is present but concentration does not often exceed 10 mg/dl and gout is rare.

Sodium and water metabolism: Sodium and water reabsorption is hampered causing sodium depletion and there is decreased ECF volume. Other solutes are also not reabsorbed nor secreted. Thus this lead to osmotic diuresis although due to reduced GFR there is no polyuria.

Potassium metabolism: Potassium balance can be maintained until the GFR falls below 5 mL/min. This is an adaptive response where distal tubular potassium secretion is increased; due to increased aldosterone secretion and increased sodium delivery to the distal tubule.

Kidneys excrete 40-80 mmol hydrogen ions per 24 h. In CRF this is impaired and there is acidosis as there is additional decrease in GFR. There is reduced phosphate excretion which diminishes the buffering capacity in urine, and reduced ammoniagenesis which also buffers hydrogen ions. There is defect in reclamation of filtered bicarbonate.

Calcium, phosphate and magnesium metabolism and renal osteodystrophy: CRF leads to decrease in calcitriol synthesis in kidney due to enzyme inhibition by retained phosphate and decrease amount of enzyme as renal mass decreases. Lack of calcitriol leads to decreased absorption of calcium from gut. This hypocalcaemia induce PTH production and mobilization of calcium from bone, in CRF PTH is very high in plasma but there is resistance to its action due to low calcitriol concentrations. So calcium levels are below normal.

Carbohydrate and lipid metabolism: There is impaired glucose tolerance may be due to insulin resistance. Dyslipoproteinaemia is present. There is increase in plasma Tg and VLDL, IDL. Total cholesterol and LDL are normal but HDL is reduced.