Leptospirosis is recognized as a globally re-emerging zoonosis. Interstitial nephritis is the principal feature of the disease. Leptospirosis-induced acute kidney injury typically is nonoliguric and includes hypokalemia. Tubular function alterations precede a decrease in the glomerular filtration rate, which could explain the high frequency of hypokalemia. Studies in human beings and animals have shown increased urinary fractional excretion of potassium and sodium, as well as an increased potassium/sodium ratio, suggesting increased distal potassium secretion caused by increased distal sodium delivery consequent to functional impairment of proximal sodium reabsorption. Confirming these findings, Western blot studies have shown lower renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2, together with higher renal expression of the Na-K-2Cl cotransporter NKCC2, in infected animals. The severe form (Weil's disease) manifests as diffuse alveolar hemorrhage, pulmonary edema, acute respiratory distress syndrome, or a combination of these features, accompanied by acute kidney injury and can be highly lethal. Antibiotic treatment is efficient in the early and late/severe phases. For critically ill leptospirosis patients, the following are recommended: daily hemodialysis, low daily net fluid intake (because of the risk for pulmonary hemorrhage), and lung-protective strategies (low tidal volumes and high positive end-expiratory pressures after recruitment maneuvers).