Influence of renal impairment on plasma concentrations of conjugated bilirubin in cases of Plasmodium falciparum malaria

Abstract

In a study of the influence of malaria-associated renal impairment on plasma concentrations of bilirubin, 111 Indian cases of Plasmodium falciparum malaria who had >34.2 μmol total bilirubin/litre plasma were investigated. As the aim was to exclude those cases who had concomitant hepatic or (non-malarial) renal dysfunction, 19 cases who had serum concentrations of alanine aminotransferase (ALT) or alkaline phosphatase (AP) that were at least double the normal mean values were withdrawn. Of the remaining 92 patients, 47 showed evidence of renal impairment, the other 45 having plasma concentrations of creatinine that were <177 μmol/litre. Plasma concentrations of the liver enzymes ALT and AP were similar for those with and without renal impairment. The plasma concentration of conjugated bilirubin (P<0.02), that of total bilirubin (P<0.05) and the ratio between the two (P<0.01) were, however, all significantly higher in the 47 patients with renal impairment than in the 45 with apparently normal renal function. The plasma concentration of creatinine was found to be not only positively correlated with the plasma concentrations of total (r=0.34; P<0.01) and conjugated (r=0.41; P<0.001) bilirubin but also negatively correlated with the urinary excretion rate for conjugated bilirubin (r=-0.34; P<0.001). The malaria-associated mortality was significantly higher among the patients with renal impairment than among those with apparently normal renal function, with 12 and three deaths, respectively (P<0.001). With increasing renal impairment there therefore appears to be a fall in the renal excretion of conjugated bilirubin. This leads to a disproportionate rise in the plasma concentration of conjugated bilirubin and this, since bilirubin can be toxic to renal tissue, may further worsen the renal impairment.