Renal Involvement in Leptospirosis: A Pathophysiologic Study

Abstract

The kidney involvement in leptospirosis appears to be a special form of acute renal failure due to a higher frequency of polyuric forms and the presence of hypokalemia with an elevated urinary fractional excretion of potassium. Using a clearance technique, we detected higher fractional urinary potassium excretion in leptospirotic guinea pigs (26.5 ± 4.7%) than in normal animals (14.1 ± 2,8%, p < 0.05). After blocking distal NaCl reabsorption with furosemide, it was observed that in leptospirotic animals both fractional sodium excretion (40.0 ± 7.4%) and fractional potassium excretion (136.3 ± 32.7%) were higher than in normal animals (20.4 ± 3.8%, p < 0.05, and 43.6 ± 9.0%, p < 0.05, respectively). Microperfusion studies showed that the normal and leptospirotic medullary thick ascending limb had both identical transepithelial potential difference (+ 3.7 ± 0.4 vs. 3.9 ± 0.2 mV) and relative sodium-to-chloride permeability. The same technique showed that the osmotic water permeability (P_osm; 0.9 ± 0.4 × 10^-5 cm/s · atm) and diffusional permeability (34.7 ± 6.6 × 10”5 cm/s) observed in the leptospirotic inner medullary collecting duct (IMCD) in the presence of vasopressin were unchanged, as was also the case for urea permeability (3.74 ± 0.7×10^-5 cm/s). These data show that acute renal failure in leptospirosis is characterized by tubular changes leading to potassium secretion probably due to a decrease in proximal sodium reabsorption. Furthermore, the inability to concentrate urine evidenced by the low P_osm present in leptospirotic animals is due, at least in part, to IMCD resistance to vasopressin.

Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin

“…That GLP inhibits Na,K-ATPase-mediated transport in rat thick ascending limb cells may appear at variance with the report of Magaldi et al (31) who showed that MTAL from normal and leptospirotic guinea pigs display similar transport capacity when microperfused in vitro. In fact, two explanations may account for this apparent discrepancy.…”

Peripheral Blood Mononuclear Cell Activation Induced byLeptospira interrogansGlycolipoprotein

“…In rabbit renal tubule epithelial cells, GLP inhibits sodium-potassium ATPase (Na,K-ATPase) pump activity in a dose-dependent manner (47). This may explain some electrolytic alterations observed in leptospirosis patients with acute renal failure (1,26,36). In experimental models with guinea pigs injected with pathogenic L. interrogans, GLP can be detected in the damaged tissues adhering to endothelial cells and to epithelial membranes, accompanying other antigen deposits resulting from bacterial destruction by the immune system (3,25).…”

Insuficiência renal aguda associada à leptospirose

“…The collecting tubules of those animals proved to be resistant to vasopressin action. 39 Recently, a clinical study with 20 patients infected with leptospirosis has shown the presence of proteinuria in all cases, hypermagnesuria in 75%, reduced tubular reabsorption in 50%, and reduced phosphate reabsorption in 45% of the patients. 43 …”

“…36,37,38 Experimental and clinical studies have shown that those findings result from injury to the proximal tubule and resistance of the medullary collecting tubule to vasopressin. 14,30,39 The injury of the proximal tubule leads to a reduction in the proximal reabsorption of sodium. The resistance of the medullary collecting tubule to vasopressin leads to a defect in the urinary concentration, causing polyuria.…”