Pathophysiology of Leptospirosis Kidney Disease

Leptospirosis is the most widespread zoonosis globally and is caused by Leptospira interrogans. Its major animal hosts include rodents, dogs, cattle, sheep, pigs, and rabbits. Leptospirosis is a global public health issue, characterized by a sudden onset of fever, myalgia, conjunctival injection, and renal dysfunction. Renal dysfunction ranges from mild-to-severe acute kidney injury to chronic kidney disease (CKD) requiring dialysis. Chronic infection with leptospirosis may progress to renal fibrosis and subsequent renal failure. The pathogenesis of leptospirosis-related CKD has been linked to chronic tubulointerstitial nephritis. Leptospirosis causes sodium transport dysregulation in the kidneys and decreased aquaporin 2 expression in the renal medulla, resulting in polyuria and natriuresis. Nonoliguria renal failure and hypokalemia are common because of tubular damage with transport defects in tubular epithelial cells. The clinical presentation of Leptospira infection is influenced by both the bacterial serotype and host immune system. A broad spectrum of renal pathological changes is possible, including direct bacterial invasion and interstitial nephritis and fibrosis caused by pro-inflammatory cytokines and chemokines. Moreover, Leptospira outer membrane proteins may induce tubular injury and inflammation through activation of nuclear transcription factor kappa B, mitogen-activated protein kinases, and induction of cytokines and chemokines by the toll-like receptor-dependent pathways. This chapter describes current knowledge of Leptospira-host interactions in the kidney.