A look at the Diabetic Kidney
PKGhatak, MD
Diabetes mellitus type II is a chronic illness and about 30 % of the patients show abnormal kidney function and the incidence is increasing; whereas diabetes mellitus type I is an acute illness and still about 20 % in 10 years, will develop renal involvement. This secondary renal disease is known as Diabetic Nephropathy. Diabetic nephropathy is a progressive disease and advances in stages. Drs. Kimmelstiel and Wilson described the pathological features and clinical aspects in great detail. They described the final stage of diabetic nephropathy as glomerular sclerosis characterized by PSA positive module replacing the glomeruli. The patients present with massive urinary protein leaks, generalized edema, hypertension and renal failure. The illness is known as Kimmelstiel Wilson Syndrome (KW syndrome) and KW nodules are pathognomic of the disease.
A glomerulus is the filtering unit of the kidney, consisting of a tuft of capillary, encased in a thin walled capsule- Bowman's capsule. The capsule continues as a tubule and ends in the pelvis of the kidney. Each glomerulus is supplied by an afferent arteriole – a tiny branch of the renal artery, and the blood exits from the glomerulus via the efferent arteriole. Each kidney contains about 1 million of these units.
Filter:
Renal filters are made up of three layers - Capillary walls are lined with fenestrated endothelial cells, lying on a basement membrane. The capillary tuft sits on a cushion of mesangial cells, accounting for 30 % of all the cells of a capsule. Mesangial cells originate separately from the kidney, then migrate to the developing kidney, some mesangial cells enter the Bowman's capsule, and others remain outside the capsule and are located in the space between the afferent and efferent arterioles. Mesangial cells have contractile protein- actin and by selective contracting and relaxing can control blood flow and filtration pressure. In addition, these cells maintain the normal function of the basement membrane. They remove any tangled protein molecule in the basement membrane. The Mesangial cells can multiply when needed.
The capsular side of the endothelial cells is lined by Podocytes. The foot processes of the podocyte interdigitate with the foot process of the adjacent podocytes forming a fine network of filtering pores of about 50 nanometers in size overlying the fenestration of endothelial cells. Podocytes once damaged cannot repair or replace themselves.
Effect of high blood sugar on the filters.
High blood sugar induces metabolic stress in the renal cells. Glucose combines with amino acids forming glycosylate molecules and oxygen radicals. These molecules also add stress to the mesangial cells. Under stress, the mesangial cells multiply and secrete excess collagen, fibronectins and proteoglycans. These compounds change the filtering property of the basement membrane.
Effect on Macula densa.
Excess delivery of sugar to macula densa creates a relatively lower concentration of sodium chloride at this site. Macula densa cells signal renin secretion and activation of the renin-angiotensin-aldosterone pathway. This contributes to high BP.
Effect on Podocytes.
Higher afferent arterial pressure induces a shearing force damaging the delicate foot processes of podocytes and resulting in bigger filtration apertures. Serum albumin began to leak out of the blood in the filtrate. If this state is not reversed the protein loss will produce low blood albumin, low oncotic pressure and dependent edema.
In long standing diabetes, the above process gradually cuts off blood flow to individual small loops of glomerular capillaries. Initially, the closed capillaries appear as small isolated KW nodules. The small nodules coalesce together to form larger nodules.
Filtration:
In addition to the structural characteristic of the filter, the negative charges on the inner surface of the endothelial cells repel negatively charged protein molecules. Molecules of fat, cholesterol, hormones, and globulins are too large to pass through the filtering pores. The inorganic molecules dissolved in blood appear in the filtrate, however, 80 to 100 % are reabsorbed into the blood. Further modification of the filtrate continues along the tubule.
Cause of high BP.
Activation of renin-angiotensin-aldosterone is one main cause of hypertension. Constriction of the afferent arteriole and dilatation of efferent vessels increases filtration pressure and hyper-filtration takes place. This results in volume contraction and renin secretion, and intra-renal hypertension. Later, as the disease progress, produces systemic hypertension.
Cause of renal failure:
Disruption of renal arterial flow and changes in infiltration properties lead to the accumulation of creatinine and other waste products. In the very end, glomerulosclerosis ends in fibrosis of renal cortical tissue and the kidneys become atrophic.
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