Overlooked Risk for Chronic Kidney Disease after Leptospiral Infection: A Population-Based Survey and Epidemiological Cohort Evidence

Abstract

BackgroundLeptospirosis is the most widespread zoonosis. Chronic human infection and asymptomatic colonization have been reported. However, renal involvement in those with leptospira chronic exposure remains undetermined.Methods and FindingsIn 2007, a multistage sampling survey for chronic kidney disease (CKD) was conducted in a southern county of Taiwan, an area with a high prevalence of dialysis. Additionally, an independent cohort of 88 participants from a leptospira-endemic town was followed for two years after a flooding in 2009. Risks of CKD, stages of CKD, associated risk factors as well as kidney injury markers were compared among adults with anti-leptospira antibody as defined by titers of microscopic agglutination test (MAT). Of 3045 survey participants, the individuals with previous leptospira exposure disclosed a lower level of eGFR (98.3±0.4 vs 100.8±0.6 ml/min per 1.73 m2, P<0.001) and a higher percentage of CKD, particularly at stage 3a-5 (14.4% vs 8.5%), than those without leptospira exposure. Multivariable linear regression analyses indicated the association of leptospiral infection and lower eGFR (95% CI -4.15 to -1.93, P < 0.001). In a leptospiral endemic town, subjects with a MAT titer ≥400 showed a decreased eGFR and higher urinary kidney injury molecule–1 creatinine ratio (KIM1/Cr) level as compared with those having lower titers of MAT (P<0.05). Furthermore, two participants with persistently high MAT titers had positive urine leptospira DNA and deteriorating renal function.Conclusions and SignificanceOur data are the first to show that chronic human exposure of leptospirosis is associated significantly with prevalence and severity of CKD and may lead to deterioration of renal function. This study also shed light on the search of underlying factors in areas experiencing CKD of unknown aetiology (CKDu) such as Mesoamerican Nephropathy.

Leptospirosis Renal Disease: Emerging Culprit of Chronic Kidney Disease Unknown Etiology

“…However, leptospira seropositivity was associated with eGFR decline in sugarcane applicants, who was excluded by initial employee physical check due to elevated creatinine at the time of testing [4]. These data indicate that leptospira infection is associated with kidney dysfunction, a consistent finding to previous population study where leptospira seropositivity is associated with declined eGFR [22]. On the other hand, urine albumin/creatinine ratio is not associated with leptospira exposure consistent to the nonproteinuric renal disease of CKDu.…”

“…Timely treatment with penicillin and tetracycline are effective and may dramatically rescue patients from multiple organ failure. On the other hand, chronic leptospirosis may develop if leptospira persists in the tubular lumen and interstitium as a continuum of acute kidney injury or asymptomatic renal colonization with insidious clinical symptoms that occur in 2.3-52.7% of population at risk [4,22]. Chronic leptospira kidney infection may present with characteristic chronic tubulointerstitial nephritis and interstitial fibrosis, a wellknown characteristic in animals.…”

“…Of 3,045 survey participants, 33.2% of the individuals have had previous leptospira exposure harboring positive anti-leptospiral antibody. These seropositive populations disclosed a 2.5% lower level of estimated glomerular filtration rate (eGFR) and a higher percentage of CKD at stage 3a-5 (14.4 vs. 8.5%), than those without leptospira exposure [22]. In a leptospiral endemic town, subjects with a higher anti-leptospiral antibody by MAT titer of more than 400 showed a decreased eGFR and higher urinary kidney injury molecule-1 creatinine ratio level as compared with those having lower titers of MAT in a 2-year cohort.…”

“…In a leptospiral endemic town, subjects with a higher anti-leptospiral antibody by MAT titer of more than 400 showed a decreased eGFR and higher urinary kidney injury molecule-1 creatinine ratio level as compared with those having lower titers of MAT in a 2-year cohort. Furthermore, 2 residents with persistently high MAT titers had detectable urine leptospira DNA and deteriorating renal function in a 2-year cohort indicating that asymptomatic kidney infection may lead to CKD [22].…”

Experimental heat stress nephropathy and liver injury are improved by allopurinol

“…The primary histologic finding is chronic tubulointerstitial disease, often associated with some degree of global glomerulosclerosis (41). The etiology remains unknown, although some believe it may relate to exposure of toxins, heavy metals, or subacute infections (18,42). Our group has postulated that it may be the consequence of recurrent heat stress, resulting in renal injury driven by effects of hyperosmolarity (via activation of the polyol pathway), heat, vasopressin, and/or hyperuricemia (9,15,30), and we have established experimental models in which some of these pathways can be shown to induce chronic tubulointerstitial damage (11,12,31,33).…”