Chronic kidney disease of uncertain etiology in Sri Lanka: Are leptospirosis and Hantaviral infection likely causes?

Gamage, Chandika D.; Sarathkumara, Yomani D.

doi:10.1016/j.mehy.2016.04.009

Cited by 42 publications

(43 citation statements)

References 25 publications

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“…Interestingly, Aristolochia spp were found in 66 ayuverdic prescriptions investigated by the WHO 55 . Moreover, as described in MeN, leptospirosis is endemic in Sri Lanka and has been linked to CKD u 86 . Hantavirus is another important zoonotic disease that is spread through the inhalation of aerosolized rodent excrement.…”

Section: Itai-itai Diseasementioning

confidence: 99%

Endemic Nephropathy Around the World

Gifford

Eddleston

et al. 2017

Kidney International Reports

135

125

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There have been several global epidemics of chronic kidney disease of unknown etiology (CKDu). Some, such as Itai-Itai disease in Japan and Balkan endemic nephropathy, have been explained, whereas the etiology of others remains unclear. In countries such as Sri Lanka, El Salvador, Nicaragua, and India, CKDu is a major public health problem and causes significant morbidity and mortality. Despite their geographical separation, however, there are striking similarities between these endemic nephropathies. Young male agricultural workers who perform strenuous labor in extreme conditions are the worst affected. Patients remain asymptomatic until end-stage renal failure. Biomarkers of tubular injury are raised, and kidney biopsy shows chronic interstitial nephritis with associated tubular atrophy. In many of these places access to dialysis and transplantation is limited, leaving few treatment options. In this review we briefly describe the major historic endemic nephropathies. We then summarize the epidemiology, clinical features, histology and clinical course of CKDu in Mesoamerica, Sri Lanka, India, Egypt, and Tunisia. We draw comparisons between the proposed etiologies and supporting research. Recognition of the similarities may reinforce the international drive to establish causality and to effect prevention.

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Section: Itai-itai Diseasementioning

confidence: 99%

Endemic Nephropathy Around the World

Gifford

Eddleston

et al. 2017

Kidney International Reports

135

125

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“…Several studies have reported presence of both infections in Sri Lanka. The proposed infectious hypothesis is under evaluation by means of observational study design to disclose the relationship between leptospirosis and CKDu in Sri Lanka [40].…”

Section: Sri Lankamentioning

confidence: 99%

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

Yang¹

2017

Nephron

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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.

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“…Mammalian pests in households may also be carriers of infectious disease that leads to increased susceptibility to CKDu. There is an emerging hypothesis that Hanta virus could be the possible causative agent for CKDu in Sri Lanka’s dry zone [26, 56]. Humans infected with Hanta virus show clinical signs similar to those of Leptospirosis, and Hanta virus infection in humans was first described in Sri Lanka in the mid-eighties [57].…”

Section: Discussionmentioning

confidence: 99%

“…A growing body of evidence suggests that CKDu is multi-factorial, making it difficult to identify individual risk factors and potential interactions involved in pathogenesis [7, 12, 17-20]. Recently, various heavy metal agents such as cadmium, arsenic agrochemicals, aluminum, and fluoride, as well as infectious diseases such as leptospirosis have been considered for association with CKDu [21-26].…”

Section: Introductionmentioning

confidence: 99%

A pilot study of behavioral, environmental, and occupational risk factors for chronic kidney disease of unknown etiology in Sri Lanka

Pry

Jackson

Rupasinghe

et al. 2019

Preprint

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23Mobile. +260 96 3088750 | +1 936-661-6885 24 ABSTRACT 25 Chronic kidney disease of unknown etiology (CKDu) was first recognized in Sri Lanka in the early 26 1990s, and since then it has reached epidemic levels in the North Central Province of the country.27 The prevalence of CKDu is reportedly highest among communities that engage in chena and paddy 28 farming, which is most often practiced in the dry zone including the North Central and East Central 29 Provinces of Sri Lanka. Previous studies have suggested varied hypotheses for the etiology of 30 CKDu; however, there is not yet a consensus on the primary risk factors, possibly due to disparate 31 study designs, sample populations, and methodologies. The goal of this pilot case-control study 32 was to evaluate the relationships between key demographic, cultural, and occupational variables 33 as risk factors for CKDu, with a primary interest in pesticide exposure both occupationally and 34 through its potential use as an ingredient in brewed kasippu alcohol. A total of 56 CKDu cases 35 and 54 control individuals were surveyed using a proctored, self-reported questionnaire. 36 Occupational pesticide exposure and alcohol consumption were not found to be significant risk 37 factors for CKDu. However, a statistically significant association with CKDu was observed with 38 chewing betel (OR: 6.11, 95% CI: 1.93, 19.35), age (OR: 1.07, 95% CI: 1.02, 1.13), owning a pet 39 dog (OR: 3.74, 95% CI: 1.38, 10.11), water treatment (OR: 3.68, 95% CI: 1.09, 12.43) and pests 40 in the house (OR: 5.81, 95% CI: 1.56, 21.60). The findings of this study suggest future research 41 should focus on practices associated with chewing betel, potential animal interactions including 42 pests in the home and pets, and risk factors associated with water.

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Chronic kidney disease of uncertain etiology in Sri Lanka: Are leptospirosis and Hantaviral infection likely causes?

Cited by 42 publications

References 25 publications

Endemic Nephropathy Around the World

Endemic Nephropathy Around the World

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

A pilot study of behavioral, environmental, and occupational risk factors for chronic kidney disease of unknown etiology in Sri Lanka

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