Falciparum malaria and the kidney: a model of inflammation.

Renal and renal-related disorders commonly occur in infection with Plasmodium falciparum, which can cause fluid and electrolyte disorders, glomerulonephritis, and acute renal failure (ARF). It appears that ARF and other life-threatening complications in falciparum malaria are not directly caused by the parasite itself but are the result of interaction of mechanical, immunologic, and humoral components. P. falciparum-infected erythrocytes impair microcirculation and cause hemolysis. Glycosylphosphatidylinositol moieties covalently linked to the surface antigens of falciparum malarial parasites appear to act like endotoxin. Glycosylphosphatidylinositol, via CD14, which is a receptor on monocytes, stimulates monocytes to release tumor necrosis factor, which in turn enhances synthesis of various cytokine cascades and mediators. Besides contributing to ARF, these mediators also cause changes in blood volume status. The degree of vasodilatation caused by vasodilating mediators varies with the severity of infection. Increased vascular permeability by the mediators occurs in severe infection, which results in hypovolemia and contributes to ARF. Although the cornerstone of treatment of malaria still is antimalarial drugs, several new modalities of treatment targeting toxin, signal transduction, mediators, and cytokines have great potential.