Figure 1.

The mechanisms of proximal tubular defects caused by Leptospira spp. (A) Illustration of normal physiology and the important channels involved in the regulation of intraluminal bicarbonate, phosphate, sulfate, glucose, and amino acids via the aquaporin (AQP)-1 channel, sodium–hydrogen exchanger (NHE) 3 (or sodium–hydrogen antiporter 3), and sodium/phosphate cotransporter (Na/Pi). (B) Leptospira causes injury along proximal tubules, leading to altered regulation of these luminal gate channels in both apical and basolateral membranes, for instance, the reduction in NHE3, AQP1 channels, and the decreased expression of α-Na⁺/K⁺-ATPase along the apical and basolateral membranes, respectively. Hence, in the luminal part, there is an accumulation of free water (causing polyuria), sodium wasting, and characteristics of Fanconi’s tubular dysfunction, including bicarbonaturia, hyperphosphaturia, and glucosuria.