The nephrotic syndrome has diverse causes that share a common pathophysiology, a derangement in the capillary walls of the glomeruli that results in increased permeability to plasma proteins. Increased permeability of the glomerular basement membrane (GBM) may result from structural or physicochemical alterations in the GBM. With long-standing or heavy proteinuria, serum albumin is decreased, giving rise to hypoalbuminemia and a drop in plasma colloid osmotic pressure, which in turn leads to leakage of fluid from the blood into extravascular spaces. As discussed in Chapter 4, the resulting decrease in intravascular volume and renal blood flow triggers increased release of renin from renal juxtaglomerular cells. Renin in turn stimulates the angiotensin-aldosterone axis, which promotes the retention of salt and water by the kidney. This tendency is exacerbated by reductions in the cardiac secretion of natriuretic factors attributed to decreased intravascular volume. In the face of continuing proteinuria, salt and water retention further aggravates the edema and if unchecked may lead to the development of generalized edema (termed anasarca). At the onset, there is little or no azotemia, hematuria, or hypertension.
The genesis of the hyperlipidemia is more obscure. Presumably, hypoalbuminemia triggers increased synthesis of lipoproteins in the liver, or massive proteinuria causes loss of an inhibitor of their synthesis. There also is abnormal transport of circulating lipid particles and impairment of peripheral breakdown of lipoproteins. The associated lipiduria reflects the increased permeability of the GBM to lipoproteins.
The most important of the primary glomerular lesions that characteristically lead to the nephrotic syndrome are focal segmental glomerulosclerosis and minimal-change disease. The latter is more important in children; the former is more important in adults. The nephrotic syndrome is also commonly seen in two other primary kidney diseases, membranous nephropathy and membranoproliferative glomerulonephritis, and as a complication of the systemic disease diabetes mellitus.
By contrast, nephritic syndrome is characterized by the following:
Proteinuria (usually in the subnephrotic range) with or without edema
The nephritic syndrome usually has an acute onset and is caused by inflammatory lesions of glomeruli.
The lesions that cause the nephritic syndrome have in common proliferation of the cells within the glomeruli, often accompanied by an infiltrate of leukocytes. The inflammatory reaction injures the capillary walls, permitting blood to pass into the urine, and induces hemodynamic changes that lead to a reduction in the GFR. The reduced GFR is manifested clinically by oliguria, fluid retention, and azotemia. Hypertension probably is a result of both the fluid retention and augmented renin release from the ischemic kidneys. The acute nephritic syndrome may be caused by primary glomerular diseases, such as postinfectious glomerulonephritis (GN) and various forms of crescentic GN, or as a result of systemic disorders such as systemic lupus erythematosus.
Asymptomatic hematuria or nonnephrotic proteinuria or a combination of the two is the typical clinical presentation of IgA nephropathy, Alport syndrome, or mild forms or early presentations of other glomerular diseases.
Rapidly progressive glomerulonephritis (RPGN) results in rapid loss of renal function in a few days or weeks, typically in the setting of nephritic syndrome. The characteristic histologic finding associated with RPGN is the presence of crescents (crescentic GN). Rapidly progressive glomerulonephritis is a clinical syndrome and not a specific etiologic form of GN. If untreated, it leads to death from renal failure within a period of weeks to months.