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.