A quantitative ultrastructural study of renal pathology in fatal Plasmodium falciparum malaria.

OBJECTIVE: To use electron microscopy to examine the role of parasitized red blood cell (PRBC) sequestration in the pathogenesis of acute renal failure in severe falciparum malaria. METHODS: Ultrastructural pathological examination of renal tissues from Southeast Asian adults (n = 63) who died from severe falciparum malaria. Qualitative and quantitative determination of the major pathological features of disease, including PRBC and leukocyte sequestration. Clinico-pathological correlation with the pre-mortem clinical picture and peripheral parasite count. RESULTS: There was a high incidence of malaria-associated renal failure in this population (> 40%) and a correlation between this incidence, severe malarial anaemia and shock. Pathological features included PRBC sequestration in glomerular and tubulo-interstitial vessels, acute tubular damage and mild glomerular hypercellularity resulting from the accumulation of host monocytes within glomerular capillaries. No evidence for an immune complex mediated glomerulonephritis was found. There was a correlation between parasite sequestration in the kidney and pre-mortem renal failure, although overall levels of sequestration were relatively low. Levels of sequestration (Knob+ PRBC) were significantly higher in malaria-associated renal failure than in fatal cases without renal failure (P = 0.005). CONCLUSION: Malaria-associated renal failure is a common and serious complication of severe Plasmodium falciparum malaria in this population, associated with acute tubular injury rather than glomerulonephritis, and linked to localization of host monocytes in the kidney as well as sequestration of PRBCs