Important types of glomerulonephritis

Acute diffuse proliferative glomerulonephritis

usually presents as the nephritic syndrome. Acute proliferative glomerulonephritis is a diffuse global disease of glomeruli caused by deposition of immune complexes in glomeruli, which is stimulated by a preceding infection. Although infection is most

commonly streptococcal, a range of bacterial, viral and protozoal infections can also stimulate this pattern of disease.

Macroscopically, the kidneys are symmetrically enlarged, weighing one and a half to twice the normal weight. The cortical layer as well as sectioned surface show petechial hemorrhages giving the characteristic appearance of fleabitten kidney.

Microscopically, there is increased cellularity of the glomerulus, with four main features:

1. Proliferation of endothelial cells produces occlusion of capillary lumina, leading to reduced glomerular filtration, with rising blood pressure and blood levels of nitrogenous components (urea and creatinine).

2. Presence of immune complexes in lumps on the epithelial side.

3. Presence of neutrophil polymorphs in capillaries.

4. Mild mesangial cell proliferation. In diffuse acute proliferative glomerulonephritis there is endothelial proliferation with neutrophils, subepithelial lumpy immune-complex deposits, and mesangial cell increase. The glomerulus is hypercel-lular due to proliferation of endothelial and mesangial cells. Glomerular capillary lumina cannot be identified because they are obliterated by the proliferating endothelial cells. The immune-complex deposits can only be seen by electron microscopy.

Membranous nephropathy presents with proteinuria and the nephrotic syndrome.

The disease passes through three pathological stages:

1) Immune-complex deposited on epithelial side of basement membrane.

2) New basement membrane deposited around immune-complex deposits.

3) Immune-complex deposits disappear, leaving thickened basement membrane.

The abnormality of the basement membrane renders it unusually permeable; it no longer selectively retains proteins, leading to heavy proteinuria and the nephrotic syndrome. With time, the abnormal glomeruli develop increase in mesangial matrix produced by the mesangial cells. This, together with membrane thickening, causes gradual hyalinization of the glomeruli and death of individual nephrons. This process takes place over many years and, from a nephrotic syndrome, the patient may develop chronic renal failure with uremia.

Complications: rapidly progressive and chronic glomerulonephritis, uremia, chronic renal failure.

Diffuse membranoproliferative glomerulonephritis often presents as a nephrotic or a mixed nephritic and nephrotic syndrome. Membranoproliferative glomerulonephritis (MPGN), also called mesangiocapillary glomerulonephritis, is a pattern of

glomerular reaction to complement abnormalities. Some are secondary to systemic disorders.

Macroscopically, the kidneys are pale in appearance and firm in consistency.

Microscopically, as the name implies, the common factors in this process are mesangial proliferation and basement membrane thickening as the main structural abnormalities. The basement membrane abnormality is responsible for the clinical symptoms of proteinuria or a full nephrotic syndrome. Because there is cellular proliferation, patients may also develop hematuria or a nephritic syndrome. A mixed nephrotic and nephritic syndrome is seen in some cases.

Focal segmental proliferative glomerulonephritis can be either primary or secondary.

In almost every case, focal glomerulonephritis is also «segmental», only occasional lobules of the glomerular tuft being involved in disease. In this type of reaction, there is cellular proliferation affecting only one segment of the glomerular tuft and occurring in only a proportion of all glomeruli. As there is cellular proliferation, patients tend to present with hematuria or the nephritic syndrome with proteinuria. In some cases the focal glomerulonephritis can be a stimulus for crescent formation.

Chronic glomerulonephritis. The term «chronic glomerulonephritis)) is used when a patient has chronic

renal failure with small contracted kidneys in which all the glomeruli are hyalinised. Because renal glomeruli are destroyed, it is often not possible to ascertain the cause.

The conditions which may progress to chronic glomerulonephritis, in descending order of frequency, are rapidly progressive glomerulonephritis, membranous glomerulonephritis, membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis, IgA nephropathy, acute post-streptococcal glomerulonephritis.

Morphology. Macroscopically, the kidneys are usually small and contracted weighing as low as 50 gm each. The capsule is adherent to the cortex. The cortical surface is generally diffusely granular. On cut section, the cortex is narrow and atrophic, while the medulla is unremarkable. Microscopically, the changes vary greatly depending upon the underlying glomerular disease. In general, the following changes are seen: glomeruli are reduced in number and most of those present show completely hyalinised tufts, giving the appearance of acellular, eosinophilic masses which are PAS-positive. Many tubules completely disappear and there may be atrophy of tubules close to scarred glomeruli. Tubular cells show hyalin-droplet degeneration and tubular lumina frequently contain eosinophilic, homogeneous casts. There is fine and delicate fibrosis of the interstitial tissue and varying number of chronic inflammatory cells are often seen.

Advanced cases which are frequently associated with hypertension show conspicuous arterial and arteriolar sclerosis.

Diseases of pre-glomerular vessels,or central pump failure, have a major impact on the function of the kidney.

In general, slowly progressive disease of the vessels leads to slowly progressive destruction of nephrons, ischemic glomerular filtration failure and ischemic tubular atrophy, culminating in chronic renal failure and a small, shrunken end-stage kidney.

1. In accelerated hypertensionthe rise in blood pressure is very rapid, causing a pattern of renal damage different from that seen in benign hypertension. Larger muscular vessels respond with a loose fibroelastic proliferation of the intima, but the afferent arterioles exposed to the sudden high pressures frequently undergo necrosis, often with fibrin in their damaged walls (fibrinoid necrosis). Similarly, the glomerular capillary network may also undergo segmental tuft necrosis. When sufficient nephrons are rendered non-functional because of damage to glomerular tufts and afferent arterioles, the patient may develop acute renal failure.

2. In most cases the atherosclerotic occlusionof the renal artery is most severe at its origin from the aorta; this renal artery stenosis can lead to chronic

ischemia of the affected kidney, with reduction in function of all nephrons on that side, producing an end-stage shrunken kidney. The unaffected kidney undergoes compensatory hypertrophy, so renal function is largely unaffected in most cases Renal artery stenosis is also caused by arterial fibromuscular dysplasia.

3. The kidney is frequently affected in diabetes mcllitus.

Diabetes causes increased severity of atherosclerosis in large, medium and small arteries, predisposing to renal ischaemia. In addition, diabetes causes hyaline arteriolosclerosis in afferent arterioles, resulting in ischemic glomerular damage.

Diabetic glomerular damage involves diffuse thickening of the glomerular capillary basement membrane, leading to an increase in permeability, proteinuria and, occasionally, the nephrotic syndrome.