Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung.
Leptospirosis is a public health problem worldwide. Severe leptospirosis manifests as pulmonary edema leading to acute respiratory distress syndrome and polyuric acute renal failure (ARF). The etiology of leptospirosis-induced pulmonary edema is unclear. Lung edema clearance is largely affected by active sodium transport out of the alveoli rather than by reversal of the Starling forces. The objective of this study was to profile leptospirosis-induced ARF and pulmonary edema. We inoculated hamsters with leptospires and collected 24-h urine samples on postinoculation day 4. On day 5, the animals were killed, whole blood was collected, and the kidneys and lungs were removed. Immunoblotting was used to determine expression and abundance of water and sodium transporters. Leptospirosis-induced ARF resulted in natriuresis, lower creatinine clearance, and impaired urinary concentrating ability. Renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2 was lower in infected animals, whereas that of the Na-K-2Cl cotransporter NKCC2 was higher. Leptospirosis-induced lesions, predominantly in the proximal tubule, were responsible for the polyuria and natriuresis observed. The polyuria might also be attributed to reduced aquaporin 2 expression and the attendant urinary concentrating defect. In the lungs, expression of the epithelial sodium channel was lower, and NKCC1 expression was upregulated. We found that leptospirosis profoundly influences the sodium transport capacity of alveolar epithelial cells and that impaired pulmonary fluid handling can impair pulmonary function, increasing the chance of lung injury. Greater knowledge regarding sodium transporter dysregulation in the lungs and kidneys can provide new perspectives on leptospirosis treatment.
Andrade
Lúcia
L
Nephrology Department, University of São Paulo, Brazil.
Rodrigues
Adílson C
AC
Sanches
Talita R C
TR
Souza
Rodrigo B
RB
Seguro
Antonio Carlos
AC
D058186:Acute Kidney Injury / Q000503:physiopathology; D000818:Animals; D051399:Aquaporin 2 / Q000096:biosynthesis / Q000378:metabolism*; D015153:Blotting, Western; D006224:Cricetinae; D053503:Epithelial Sodium Channels / Q000096:biosynthesis*; D007668:Kidney / Q000503:physiopathology*; D007922:Leptospirosis / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology*; D011654:Pulmonary Edema / Q000503:physiopathology; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis*; D064466:Solute Carrier Family 12, Member 1; D064506:Solute Carrier Family 12, Member 2; D015854:Up-Regulation
D051399:Aquaporin 2; D053503:Epithelial Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D064506:Solute Carrier Family 12, Member 2; D000254:Sodium-Potassium-Exchanging ATPase