Argument for the Classical Concept:

Acute and Chronic Serum Sickness

(If the index is not shown on your left hand side: click here)

Numerous experimental models have demonstrated that glomerulonephritis can be produced in animals by immunological methods. In one of the first models, acute or one-shot serum sickness, rabbits were injected with bovine serum albumin. A few days´ later, when the rabbit´s immune system has started to produce antibodies against the injected antigen, typical acute glomerulonephritis with proteinuria and haematuria develops, a strong argument that an acute infection may induce glomerulonephritis (Germuth 1953). The injected antigen, the bovine serum albumin molecules, are caught in the glomerular filters and when the antigens are attacked by the rabbit´s anti-bovine-albumin antibodies the resulting formation of immune complexes injures the glomeruli. If several injections of bovine albumin are given (chronic serum sickness), the rabbit eventually may develop serious glomerulonephritis with impaired renal function (Dixon et al 1961).

Counter-Argument

No doubt, the acute serum sickness model is a good simulation of human, acute glomerulonephritis. However, no serious or persistent renal damage is produced after a single injection of foreign serum albumin. Just as in most human types of acute glomerulonephritis, the only symptoms are transient proteinuria and haematuria at most and the renal function remains normal. In numerous similar animal models the researchers have claimed that they have produced glomerulonephritis. The only thing that has been produced however, is a formation or deposition of immune complexes in the glomeruli followed by mild and transient urinary abnormalities, or less than that. 

Let me stress again: a deposition of immune complexes in the kidneys (or elsewhere) without any other symptoms is not a disease. In all mammals, including human beings, there is normally a steady production of immune complexes in the body. This is part of the normal defense against foreign molecules and microorganisms. Immune complexes are disposed by various ways as garbage and may be found in many parts of the body, including the glomeruli, in all healthy individuals. Glomerulonephritis is a clinical problem, or a serious disease, only if it is followed by kidney failure or the nephrotic syndrome. (You may add also: a high blood pressure, but a high blood pressure rarely appears in the absence of renal failure or the nephrotic syndrome).

The chronic serum sickness model seems to be a good argument for the classical hypothesis. However, to induce serious glomerulonephritis it is necessary to inject large amounts of the antigen several times during several weeks. In most human infections bacterial or viral antigen rarely appear during longer periods in the blood circulation because it is quickly eliminated by our immune system. But there are exceptions. Serious glomerulonephritis may be seen associated with chronic infections, such as hepatitis, malaria, schistosomiasis, and an infected atrioventricular shunt. In these diseases the steady discharge of microbial antigens into the blood may be a contributing and perhaps even the main cause of glomerulonephritis. In accordance, glomerulonephritis secondary to chronic bacterial infections are most often cured by antibiotics directed against the infectious agent, whereas antibiotics have no effect on other types of glomerulonephritis, not even on glomerulonephritis secondary to an acute infection.

Next section: Active Heymann Nephritis