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Morphological and clinical findings in Sri Lankan patients with chronic kidney disease of unknown cause (CKDu): Similarities and differences with Mesoamerican Nephropathy.

ABSTRACT: In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies. Inclusion criteria were 20-65 years of age and plasma creatinine 100-220 ?mol/L. Exclusion criteria were diabetes mellitus, uncontrolled hypertension and albuminuria >1g/24h. Kidney biopsies, blood and urine samples were collected, and participants answered a questionnaire. Included participants were between 27-61 years of age and had a mean eGFR of 38±14 ml/min/1.73m2. Main findings in the biopsies were chronic glomerular and tubulointerstitial damage with glomerulosclerosis (8-75%), glomerular hypertrophy and mild to moderate tubulointerstitial changes. The morphology was more heterogeneous and interstitial inflammation and vascular changes were more common compared to our previous studies of MeN. In two patients the biopsies showed morphological signs of acute pyelonephritis but urine cultures were negative. Electrolyte disturbances with low levels of serum sodium, potassium, and/or magnesium were common. In the urine, only four patients displayed albuminuria, but many patients exhibited elevated ?-1-microglobulin and magnesium levels. This is the first study reporting detailed biochemical and clinical data together with renal morphology, including electron microscopy, from Sri Lankan patients with CKDu. Our data show that there are many similarities in the biochemical and morphological profile of the CKDu endemics in Central America and Sri Lanka, supporting a common etiology. However, there are differences, such as a more mixed morphology, more interstitial inflammation and vascular changes in Sri Lankan patients.

SUBMITTER: Wijkstrom J

PROVIDER: S-EPMC5841753 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Morphological and clinical findings in Sri Lankan patients with chronic kidney disease of unknown cause (CKDu): Similarities and differences with Mesoamerican Nephropathy.

Wijkström Julia J Jayasumana Channa C Dassanayake Rajeewa R Priyawardane Nalin N Godakanda Nimali N Siribaddana Sisira S Ring Anneli A Hultenby Kjell K Söderberg Magnus M Elinder Carl-Gustaf CG Wernerson Annika A

PloS one 20180307 3

In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and ex ...[more]

PMID: 29513702

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Project description:BackgroundIn Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). Identification of novel biomarkers that are customized to the specific causative factors would lead to early diagnosis and clearer prognosis of the diseases. This study aimed to find genetic biomarkers in blood to distinguish and identify CKDu from CKD as well as healthy populations from CKDu endemic and non-endemic areas of Sri Lanka.MethodsThe expression patterns of a selected panel of 12 potential genetic biomarkers were analyzed in blood using RT-qPCR. Fold changes of gene expressions in early and late stages of CKD and CKDu patients, and an apparently healthy population of a CKDu endemic area, Girandurukotte (GH) were calculated relative to apparently healthy volunteers from a CKDu non-endemic area, Kandy (KH) of Sri Lanka, using the comparative CT method.ResultsSignificant differences were observed between KH and early stage CKDu for both the insulin-like growth factor binding protein 1 (IGFBP1; p = 0.012) and kidney injury molecule-1 (KIM1; p = 0.003) genes, and KH and late stage CKD and CKDu for the glutathione-S-transferase mu 1 (GSTM1; p < 0.05) gene. IGFBP1 and KIM1 genes showed significant difference between the early and late stage CKDu (p < 0.01). The glutamate cysteine ligase catalytic subunit (GCLC) gene had significantly different expression between KH and all the other study groups (p < 0.01). The GH group was significantly different from the KH group for the oxidative stress related genes, G6PD, GCLC and GSTM1 (p < 0.01), and also the KIM1 gene (p = 0.003). IGFBP1, insulin-like growth factor binding protein 3 (IGFBP3), fibronectin 1 (FN1) and KIM1 showed significant correlations with serum creatinine, and IGFBP1, KIM1 and kallikrein 1 (KLK1) with eGFR (p < 0.05).ConclusionA panel consisting of IGFBP1, KIM1, GCLC and GSTM1 genes could be used in combination for early screening of CKDu, whereas these genes in addition with FN1, IGFBP3 and KLK1 could be used to monitor progression of CKDu. The regulation of these genes has to be studied on larger populations to validate their efficiency for further clinical use.

Project description:BackgroundIncrease in the number of cases in Chronic Kidney Disease of Unknown etiology (CKDu) in Sri Lanka has become a health issue of national concern. Even though, Northern Province is not identified as a high-risk province, there is an increasing trend of CKDu after the end of civil war in the Northern Province.MethodsThe present study was conducted in Thunukkai Division in Mullaitivu District to investigate the socio demographic and clinical pattern of CKDu patients and to evaluate the quality of their water sources. The samples were selected by using stratified purposive random sampling method which represented 29% of total CKDu patients in Thunukkai Division. Pretested structured questionnaire was administered to collect the data from the CKDu patients. The association between serum creatinine excreted by CKDu patients and the water quality parameters were determined by using linear regression model.ResultsAmong the patients, 80% were male with over 68% falling in the age range of 50-70. Majority (90%) were involved in agriculture related occupation. Smoking and alcohol consumption were detected as common habits among 40% of the patients. Secondarily developed, hypertension (60%) and diabetes (34%) were reported as common diseases in the area. Dug wells served as the commonest source of drinking water in the area (90% households) together with few tube wells. Physicochemistry of more than 50% of the water samples revealed higher electric conductivity, salinity, total dissolved solids, total hardness and Na levels compared to drinking water standards in Sri Lanka.ConclusionsSerum creatinine levels of the CKDu patients were significantly and negatively correlated with phosphate while positively correlated with total dissolved solids (TDS) and arsenic content of the drinking water. Geospatial mapping of TDS and arsenic in drinking water with the occurrence of higher serum creatinine levels confirmed the same trend. Thus, the total dissolved solids and arsenic in drinking water may have positive correlation with the occurrence of CKDu in Thunukkai region in the Mullaitivu District of Sri Lanka.

Dataset Information

Morphological and clinical findings in Sri Lankan patients with chronic kidney disease of unknown cause (CKDu): Similarities and differences with Mesoamerican Nephropathy.

Publications

Morphological and clinical findings in Sri Lankan patients with chronic kidney disease of unknown cause (CKDu): Similarities and differences with Mesoamerican Nephropathy.

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