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

Abstract

Leptospirosis is the most prevalent zoonosis affecting more than 1 million populations worldwide. Interestingly, leptospirosis endemic regions coincide with chronic kidney disease (CKD) hotspots largely due to flooding and agricultural overlaps. Acute leptospirosis induces multiple organ dysfunction including acute kidney injury and may predispose to CKD and end-stage renal disease, if not treated timely. Asymptomatic infection may carry the bacteria in the kidney and CKD progresses insidiously. Histologic finding of leptospirosis renal disease includes tubulointerstitial nephritis, interstitial fibrosis, and tubular atrophy. Proximal tubule dysfunction and hypokalemia are observed in adult male workers with leptospirosis, a characteristic similarity to CKD unknown etiology (CKDu). CKDu is a form of CKD that is not attributable to traditional risk factors clustering in agricultural communities affecting young male farmers. Kidney pathology shows a chronic tubulointerstitial disease. CKDu is being reported as an endemic nephropathy across the globe. Recent surveys suggest that asymptomatic leptospira renal colonization is an overlooked risk for renal fibrosis and CKDu. Population with anti-leptospira seropositivity is associated with lower estimated glomerular filtration rate in endemic regions and carrier may progress to CKD. Leptospirosis has been considered as a risk factor for CKDu in Sri Lanka and in Mesoamerican area. Sugarcane workers in Nicaragua showed increased anti-leptospira seropositivity and higher urinary biomarkers for kidney injury. Emerging evidence with signs of infection were reported in these endemic population, indicating that leptospira exposure could play a role in CKDu as a cause of primary kidney disease or a susceptible factor when secondary injury such as heat stress or dehydration aggravates kidney disease. Therefore, leptospirosis as an emerging culprit of CKDu deserves further in-depth investigation.

Leptospiral LPS escapes mouse TLR4 internalization and TRIF-associated antimicrobial responses through O antigen and associated lipoproteins

“…Infection by pathogenic species such as L. interrogans in humans may often cause asymptomatic or “flu-like” infections, but can also cause severe disease with a fatality rate of up to 10%. Notably, it may also be an overlooked cause of chronic kidney disease [3]. All other vertebrates can be infected, with symptoms varying from one species to another.…”

Taiwan renal care system: A learning health‐care system

“…Uncontrolled diabetes mellitus, hypertension and glomerulonephritis patients would rapidly progress to ESRD. History of several clinical insults, such as acute kidney injury (AKI), cardiovascular events and infections has been identified as risk factors of CKD progression, too . Environmental contamination, such as heavy metals and air pollution, occupational exposure and Mesoamerican nephropathy were considered as overlooked risk factors of CKD .…”

“…History of several clinical insults, such as acute kidney injury (AKI), cardiovascular events and infections has been identified as risk factors of CKD progression, too. 8 Environmental contamination, such as heavy metals and air pollution, occupational exposure and Mesoamerican nephropathy were considered as overlooked risk factors of CKD. [9][10][11] The rapid increase of ageing population of Taiwan casts a new domain in renal care, such as palliative care.…”

Murine Models for Leptospirosis Kidney Disease

“…However, recent studies showed that human populations living in endemic area of leptospirosis could also asymptomatically excrete leptospires in their urine for a long time [2] . As a consequence, it was recently proposed that leptospirosis, in most cases asymptomatic, may be an overlooked cause of chronic kidney disease [3,4] .…”