Nonrenal clearance and tubular load in renal failure

Twelve studies on the pharmacokinetics of various antibiotics (11 beta-lactams, 1 quinolone) in renal failure were re-examined on a meta-level. It was found that besides the expected (and obvious) decrease of renal clearance in impaired renal function, the nonrenal clearance (CLNR) also decreased: in terminal renal insufficiency, CLNR was approximately only half the value found in healthy subjects. A possible explanation for this could be the uremic intoxication and the resulting disturbance of the metabolic processes. Though the absolute value decreases, nonrenal clearance in renal failure is a relevant part of the total elimination: the ratio nonrenal to total elimination doubled and was even more. Furthermore, the amount of substances eliminated per nephron was found to increase. The ratio "renal clearance/glomerular filtration rate", the tubular load, increased as well. This might have positive effects (exceptionally high concentrations of antibiotics at important sites in kidney infections) but also negative consequences (higher tubular toxicity depending on the concentration).