Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka

Nanayakkara, Shanika; Senevirathna, Lalantha; Parahitiyawa, Nipuna; Abeysekera, Tilak; Chandrajith, Rohana; Ratnatunga, Neelakanthi; Hitomi, Toshiaki; Kobayashi, Hatasu; Harada, Kouji H.; Koizumi, Akio

doi:10.1007/s12199-015-0475-1

Cited by 38 publications

(24 citation statements)

References 44 publications

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“…Additional exome studies by the same investigators have provided some preliminary evidence for risk variants in a gene called KCNA10, a voltage-gated potassium channel, though the potential role for this gene in CKDu is not immediately clear. 44…”

Section: Ckdu In Sri Lankamentioning

confidence: 99%

Genes and environment in chronic kidney disease hotspots

Friedman

2019

Current Opinion in Nephrology and Hypertension

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Purpose of Review: Chronic Kidney Disease (CKD) can cluster in geographic locations or in people of particular genetic ancestries. We explore APOL1 nephropathy and Balkan Nephropathy as examples of CKD clustering that illustrate genetics and environment conspiring to cause high rates of kidney disease. Unexplained hotspots of kidney disease in Asia and Central America are then considered from the perspective of potential gene x environment interactions. Recent Findings: We report on evidence supporting both genes and environment in these CKD hotspots. Differing genetic susceptibility between populations and within populations may explain why causal environmental risk factors have been so hard to identify conclusively. Similarly, one cannot explain why these epidemics of kidney disease are happening now without invoking environmental changes. Summary: Approaches to these CKD hotspots are of necessity becoming more holistic. Genetic studies may help us identify the environmental triggers by teaching us about disease biology and may empower environmental risk factor studies by allowing for stratification of study participants by genetic susceptibility.

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Section: Ckdu In Sri Lankamentioning

confidence: 99%

Genes and environment in chronic kidney disease hotspots

Friedman

2019

Current Opinion in Nephrology and Hypertension

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“…Hypertension, diabetes, glomerulonephritis and other traditional causes are not associated with CKDu. However, multiple causes have been suggested such as chronic low dose exposure to multiple heavy metals and agrochemicals [ 6 , 7 ], heat stress and recurrent dehydration [ 8 – 11 ], heat driven pathophysiologic mechanisms [ 12 ], nephrotoxic drugs [ 13 ], hyperuricemia and hyperuricosuria [ 14 – 17 ], leptospirosis [ 18 , 19 ] and genetic susceptibility [ 20 , 21 ]. Based on clinical and pathological studies, CKDu cases in Sri Lanka show glomerular and tubulointerstitial injury in kidneys [ 1 , 22 , 23 ] and similar glomerular and tubulointerstitial injury have also been reported in Mesoamerican nephropathy [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka

et al. 2016

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Chronic Kidney Disease of uncertain etiology (CKDu) is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are widely recognised for their sensitivity, specificity and accuracy in determining CKDu and early renal injury. However, these biomarkers have never been used in diagnosing CKDu in Sri Lanka. Male farmers (n = 1734) were recruited from 4 regions in Sri Lanka i.e. Matara and Nuwara Eliya (farming locations with no CKDu prevalence) and two CKDu emerging locations from Hambantota District in Southern Sri Lanka; Angunakolapelessa (EL1) and Bandagiriya (EL2). Albuminuria (ACR ≥ 30mg/g); serum creatinine based estimation of glomerular filtration rate (eGFR); creatinine normalized urinary kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured. Fourteen new CKDu cases (18%) from EL1 and nine CKDu cases (9%) from EL2 were recognized for the first time from EL1, EL2 locations, which were previously considered as non-endemic of the disease and associated with persistent albuminuria (ACR ≥ 30mg/g Cr). No CKDu cases were identified in non-endemic study locations in Matara (CM) and Nuwara Eliya (CN). Analysis of urinary biomarkers showed urinary KIM-1 and NGAL were significantly higher in new CKDu cases in EL1 and EL2. However, we also reported significantly higher KIM-1 and NGAL in apparently healthy farmers in EL 1 and EL 2 with comparison to both control groups. These observations may indicate possible early renal damage in absence of persistent albuminuria and potential capabilities of urinary KIM-1 and NGAL in early detection of renal injury among farming communities in Southern Sri Lanka.

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“…8,9 Although certain occupations are clearly at risk (Table 1), genetic susceptibility may also be contributory, given an association of cases with family history of CKD and disease linkage with single-nucleotide polymorphisms in the SLC13A3 and KCNA10 genes, as in Sri Lankan nephropathy. 8,9,19,20 The cause of these regional nephropathies remains elusive to date. Data emanating from Sri Lanka indicate a significant association of CKD cases with "chena" (slash and burn) cultivation, whereas elevated urinary pesticide levels in cases and higher urinary cadmium (although not toxic) levels in both cases and controls raise the issue of environmental pollution.…”

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confidence: 99%

Uddanam Nephropathy/Regional Nephropathy in India: Preliminary Findings and a Plea for Further Research

Ganguli

2016

American Journal of Kidney Diseases

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Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka

Cited by 38 publications

References 44 publications

Genes and environment in chronic kidney disease hotspots

Genes and environment in chronic kidney disease hotspots

Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka

Uddanam Nephropathy/Regional Nephropathy in India: Preliminary Findings and a Plea for Further Research

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