Correlation Between Renal Distribution Of Leptospires During The Acute Phase And Chronic Renal Dysfunction In A Hamster Model Of Infection With Leptospira Interrogans

BackgroundLeptospirosis has been described as a biphasic disease consisting of hematogenous dissemination to major organs in the acute phase and asymptomatic renal colonization in the chronic phase. Several observational studies have suggested an association between leptospirosis and chronic kidney disease (CKD). We investigated the dynamics of leptospires and histopathological changes in the kidney to understand the relationship between them, and also investigated the extent of renal dysfunction in the acute and chronic phases of leptospirosis using a hamster model.FindingsHamsters (n = 68) were subcutaneously infected with 1 x 10(4) cells of the Leptospira interrogans serovar Manilae strain UP-MMC-SM. A total of 53 infected hamsters developed fatal acute leptospirosis, and the remaining 15 hamsters recovered from the acute phase, 13 of which showed Leptospira colonization in the kidneys in the chronic phase. Five asymptomatic hamsters also had renal colonization in the chronic phase. Immunofluorescence staining showed that leptospires were locally distributed in the renal interstitium in the early acute phase and then spread continuously into the surrounding interstitium. The kidneys of the surviving hamsters in the chronic phase showed patchy lesions of atrophic tubules, a finding of chronic tubulointerstitial nephritis, which were substantially consistent with the distribution of leptospires in the renal interstitium. The degree of atrophic tubules in kidney sections correlated statistically with the serum creatinine level in the chronic phase (rs = 0.78, p = 0.01).ConclusionSubcutaneous infection with pathogenic leptospires could cause acute death or chronic leptospirosis in hamsters after surviving the acute phase. We suggest that the renal distribution of leptospires during the acute phase probably affected the extent of tubular atrophy, leading to CKD.Author summaryLeptospirosis is the most widespread zoonotic disease, particularly in tropical and subtropical regions. Leptospires are transmitted to humans via contaminated urine, soil and water from carrier animals such as rodents. Human leptospirosis is mostly asymptomatic or a mild acute febrile illness, but some patients progress to Weil's disease, characterized by kidney failure, jaundice, and pulmonary hemorrhage, and some of them die. To understand pathogen-host interactions in the kidney, a major target of leptospirosis, the authors collected kidneys and blood samples from the acute to chronic phase using a subcutaneously infected hamster model to compare the renal distribution of Leptospira with histopathological findings and renal function. The results demonstrated that the increase in antibody titers in the acute phase affected the outcome in the natural course of acute leptospirosis, and that the distribution of leptospires in the kidney during the acute phase may affect the decline of renal function during the chronic phase. It is possible that leptospirosis is one of the causes of unexplained renal dysfunction in tropical and subtropical regions.