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Background: Chronic kidney disease of unknown etiology (CKDu) is reported among male paddy farmers in the dry zone of Sri Lanka. The exact cause of this disease remains undetermined. Genetic susceptibility is identified as a major risk factor for CKDu. Background: Chronic kidney disease of unknown etiology (CKDu) is reported among male paddy farmers in the dry zone of Sri Lanka. The exact cause of this disease remains undetermined. Genetic susceptibility is identified as a major risk factor for CKDu. Objectives: In this study, small urinary RNAs were characterized in CKDu patients, healthy endemic and non-endemic controls. Differently expressed urinary miRNAs and their associated pathways were identified in the study population. Methods: Healthy and diseased male volunteers (n=9) were recruited from Girandurukotte (endemic) and Mawanella (non-endemic) districts. Urinary small RNAs were purified and sequenced using Illumina MiSeqTM. The sequence trace files were assembled and analyzed. Differentially expressed miRNAs among these three groups were identified and pathway analysis was conducted. Results: The urine samples contained 130,623 sequence reads identified as non-coding RNAs, PIWI-interacting RNAs (piRNA), and miRNAs. Approximately four percent of the total small RNA reads represented miRNA, and 29% represented piRNA. A total of 409 miRNA species were expressed in urine. Interestingly, both diseased and endemic controls population showed significantly low expression of miRNA and piRNA. Regardless of the health status, the endemic population expressed significantly low levels of miR-10a, miR-21, miR-148a, and miR-30a which have been linked with several environmental toxins. Conclusion: Significant downregulation of miRNA and piRNA expression in both diseased and healthy endemic samples indicates an epigenetic regulation of CKDu involving genetic and environmental interaction. Further studies of specific miRNA species are required to develop a miRNA panel to identify individuals susceptible to CKDu. other: None

Introduction: Malnutrition is very common and associated with adverse health outcomes among haemodialysis (HD) patients. In this study, we studied the nutritional intake and associated demographic, socio-economic characteristics among haemodialysis patients in Sri Lanka. Methodology: This is a descriptive cross-sectional study which was conducted in 305 HD patients at Nephrology and Transplant Unit, National Hospital, Kandy, Sri Lanka in 2018. Interviewer administered; semi-structured questionnaire was used to collect the data. Nutritional data was collected using 24-hour dietary recall method. Statistical analysis was performed via IBM SPSS version 20. Ethical approval was given from the Ethics Review Committee, Faculty of Allied Health Sciences, University of Peradeniya. Results: The mean age of the study participants was 50.45±13.063 years and majority were males (69.2%; n=211). Only 1.6% (n=5) of the patients fulfilled the recommended calorie intake per day (>30 Kcal/day). Majority of the patients had more than 60% of the calorie intake from carbohydrates (n=232; 76.1%). Overall, energy, protein and fat intakes in 98.4%, 96.1% and 91.8% of the participants were less than the recommended values. There were statistically significant differences found between age categories and blood urea (p=0.023), urine output (UOP) (p=0.000), inter-dialytic weight gain (IDWG) (p=0.000) and dry weight (p=0.015). The entire micronutrients intake was less than the recommended level and there were significant differences between micronutrients based on the monthly income. Such as, dietary PUFA (p=0.021), cholesterol (p=0.002), vitamin E (p=0.018), vitamin B2 (p=0.000), vitamin B6 (p=0.008), folic acid (p=0.004), sodium (p=0.000), potassium (p=0.010), calcium (p=0.001), magnesium (p=0.038), phosphorus (p=0.000), iron (p=0.042) and zinc (p=0.003). High median values of the micronutrients were reported with the 30,000–50,000 LKR and 50,000 LKR earned groups. Discussion and Conclusion: There is a wide gap between recommended nutrient intake and the actual nutrient intake of the participants of this study. Nutritional status and other clinical measures were influenced by age of the patients and monthly income. Regular optimal nutritional counseling and monitoring is very important to improve their outcome. Introduction of socio-economically and culturally sensitive dietary guidelines can be warranted.

Background. Chronic kidney disease of unknown aetiology (CKDu) is a major public health problem in Sri Lanka, especially among agrarian communities. Although the cause of CKDu is still unknown, hantavirus infection has been proposed as a risk factor. Methods. This study was performed using serological samples collected from two CKDu-endemic areas, Anuradhapura (2010) and Badulla districts (2010 and 2016), and a non-endemic area, Matale (2016) district. The presence of anti-Thailand orthohantavirus IgG antibodies was investigated in serum samples. Hantavirus seroprevalence and demographic data were epidemiologically analysed. Results. Seroprevalence was higher in CKDu patients (40.6–60.0 %) and healthy individuals in CKDu-endemic areas (17.6–25.5 %) than in healthy individuals in non-endemic areas (3.0 %). Statistically significant odds ratios (ORs) for hantavirus infection in CKDu patients were detected in CKDu-endemic areas [ORs: 3.2 and 3.1; 95 % confidence interval (CI): 1.8–5.5 and 1.8–5.2 in Anuradhapura and Badulla districts in 2010; and OR: 4.4, 95 % CI: 2.3–8.5 in 2016 in Badulla district). Furthermore, the OR for hantavirus infection in Badulla district has increased in the last decade from 3.1 (95 % CI: 1.8–5.3) to 4.4 (95 % CI: 2.3–8.5). Conclusion. Hantavirus infection has been prevalent in two distant CKDu-endemic areas since 2010. The observed significant association of hantavirus seropositivity with CKDu indicates a possible role of hantavirus infection in CKDu pathogenesis.

Ingestion of toxic trace elements in the human body has been considered one of the major reasons for renal dysfunction. Chronic kidney disease with uncertain etiological factors (CKDu) is a recently described clinical entity in which the disease is found in geographically isolated pockets in the dry zone of Sri Lanka. In CKDu regions, an increasing number of cases are reported with acute interstitial nephritis without any known reason (AINu). However, recent exposure to certain risk behaviors or nephrotoxins, or both, is suspected for the AINu. Consumption of foods that are contaminated with trace elements is one of the main pathways of human exposure to environmental toxins. The current study was carried out to assess the possibility of trace element-contaminated rice consumption on the etiopathogenesis of AINu. Samples of rice consumed by 32 clinically diagnosed AINu cases were collected and analyzed for possible nephrotoxic trace elements. Out of 32 patients, 26 were histologically confirmed with tubulointerstitial disease. The results revealed that the mean values of Cd, As, and Pb were 0.18, 0.055, and 0.135 mg/kg, with ranges of 0.020-1.06, 0.012-0.222, and 0.003-0.744 mg/kg (on dry weight basis), respectively. This study indicated that the investigated toxic trace element levels of rice consumed by AINu were reasonably below the recommended levels of the Codex Alimentarius Commission of FAO and WHO. Hence, it is less likely that rice consumption is to be a risk factor for the etiology of AINu.

BACKGROUND AND AIMS Chronic kidney disease of unknown etiology (CKDu) has been a critical health issue among the farming communities of Sri Lanka for decades [1]. However, the distribution of CKDu in Sri Lanka is geographically significant by representing endemicity on its own [2]. This study was conducted to identify the anthropological and geo-environmental characteristics of CKDu, in relation to the biochemical profile between known CKDu endemic and non-endemic communities. METHOD A total of 214 male individuals from Wilgamuwa (endemic) and 102 male individuals from Mathurata (non-endemic) of 30–60 years were recruited. For each participant, blood pressure (BP), random blood sugar (RBS), serum creatinine (μmol/L) and serum cholesterol (mg/dL) were tested using standard methods. Anthropological data including population structure, farming behaviour and poverty statistics were obtained from the respective government officials. Geo climatic data including elevation, monthly average (Avg.) temperature (°C), monthly Avg. rainfall (mm), monthly Avg. humidity (%) and monthly Avg. UV intensity, monthly Avg. Sun hours (hrs.) were obtained for the two study areas. RESULTS Most striking difference between two communities is significantly high serum creatinine (t = 3.5175, P = 0.0005) in male individuals between the age category of 40 to 65 years in CKDu endemic area (M = 109.00, SD = 66.41) in comparison to non-endemic participants in the same age category from non-endemic area for CKDu (M = 85.41, SD = 18.78). The non-endemic area for CKDu, Maturata was colonized since the 16th century due to natural population migrations while the colonization of Wilgamuwa was implemented in a more drastic manner, parallel to the green revolution after the 1960s. Mathurata is located at a high elevation level of 976 m, whereas Wilgamuwa is located at an elevation level of 528 m. In comparison with meteorological variables for the year of 2019, monthly Avg. rainfall (mm) (P = 0.005), monthly Avg. temperature (°C) (P = 0.001), monthly Avg. cloud cover (%) (P = 0.004), monthly Avg. Humidity (%) (P = 0.007), monthly Avg. Sun hours (hrs) (P = 0.001) were highly significant between the two geographical areas. CONCLUSION We report comparably adverse weather conditions, higher exposure to natural and artificial toxic exposure in genetically and behaviourally vulnerable group in the CKDu endemic area in comparison with non-endemic area for CKDu.

IntroductionA chronic interstitial disease, chronic kidney disease of uncertain etiology (CKDu) has emerged as a notable contributor to the CKD burden in rural Sri Lanka. Most therapeutic and diagnostic approaches of CKD are focusing towards glomerular diseases, thus not fully applicable to CKDu. Serum proteins, specifically profile of markers representing different facets of a disease are rewarding in a comprehensive evaluation of a disease, hence in CKD. Our aim is to identify the role of serum retinol binding protein 4 (RBP4), a marker of proximal tubular in the diagnosis of CKDu.MethodsDefinite CKDu cases were recruited from the renal clinic, Girandurukotte & Wilgamuwa (endemic regions). Healthy controls were recruited from Mandaramnuwara (non-endemic area). The levels of RBP4 and creatinine in serum were measured. An immunoassay (ELISA) on the serum samples were performed. The stages of CKD/ CKDu were classified according to eGFR. ResultsSerum RBP4 was significantly increased in CKDu compared to CKD and healthy controls. The results showed that normalized serum RBP4 to serum creatine (S.cr) acts as competitive marker for CKDu (AUC 0.762, sensitivity 0.733) than CKD (AUC 0.584, sensitivity 0.733) when compared against healthy controls. Furthermore, RBP4:S.cr ratio showed higher discriminating power (AUC 0.743) between CKDu and CKD, suggesting RBP4: S.cr ratio as potential serum marker to differentiate CKDu from CKDu.ConclusionRBP4: S.cr ratio was identified as a plausible indicator for differentiating CKDu from CKD with >70% sensitivity and specificity. Therefore, it could be used in the evaluation of tubular interstitial involvement of CKD.

People with end stage renal disease and undergoing hemodialysis experience a high symptom burden that impairs quality of life. This study aimed to assess the prevalence, dynamicity and determinants of symptom burden among middle-aged and older adult hemodialysis patients. A descriptive cross-sectional study together with a longitudinal assessment was used. A total of 118 and 102 hemodialysis patients were assessed at baseline and at a 6-month follow-up. Validated questionnaires were used to assess the symptom burden, stress, illness perception and social support. Multiple linear regression analysis was used to determine the factors associated with symptom burden. The median number of symptoms experienced was 21 (Interquartile Range (IQR); 18–23) and 19 (IQR; 13–22) at baseline and 6 months, respectively. Having elevated stress (β = 0.65, p ≤ 0.005) and illness perception (β = 0.21, p = 0.02) were significantly predicted symptom burden at baseline (F (4, 112) = 55.29, p < 0.005, R2 = 0.664). Stress (β = 0.28, p = 0.003), illness perception (β = 0.2, p = 0.03), poor social support (β = −0.22, p = 0.01) and low body weight (β = −0.19, p = 0.03) were the determinants for symptom burden at 6 months (F (5, 93) = 4.85, p ≤ 0.005, R2 = 0.24). Elevated stress, illness perception level, poor social support and low post-dialysis body weight were found to be determinants for symptom burden. Attention should be given to psychosocial factors of hemodialysis patients while conducting assessment and delivering care to patients.

Background Patients presenting with acute interstitial nephritis (AIN) of unknown aetiology, probably the earliest presentation of chronic kidney disease of unknown aetiology (CKDu), have been treated with oral prednisolone and doxycycline by physicians in Sri Lanka. This trial assessed the effectiveness of prednisolone and doxycycline based on eGFR changes at 6 months in patients with AIN of unknown aetiology. Method A randomized clinical trial with a 2 × 2 factorial design for patients presenting with AIN of unknown aetiology (n = 59) was enacted to compare treatments with; A-prednisolone, B-doxycycline, C-both treatments together, and D-neither. The primary outcome was a recovery of patients’ presenting renal function to eGFR categories: 61–90 ml/min/1.73m2 (complete remission– CR) to 31–60 ml/min/1.73m2 (partial remission– PR) and 0–30 ml/min/1.73m2 no remission (NR) by 6 months. A secondary outcome was progression-free survival (not reaching 2 eGFR), by 6–36 months. Analysis was by intention to treat. Results Seventy patients compatible with a clinical diagnosis of AIN were biopsied for eligibility; 59 AIN of unknown aetiology were enrolled, A = 15, B = 15, C = 14 and D = 15 randomly allocated to each group. Baseline characteristics were similar between groups. The number of patients with CR, PR and NR, respectively, by 6 months, in group A 3:8:2, group B 2:8:3 and group C 8:5:0 was compared with group D 8:6:1. There were no significant differences found between groups A vs. D (p = 0.2), B vs. D (p = 0.1) and C vs. D (p = 0.4). In an exploratory analysis, progression-free survival in prednisolone-treated (A + C) arms was 0/29 (100%) in comparison to 25/30 (83%) in those not so treated (B + D) arms, and the log-rank test was p = 0.02, whereas no such difference found (p = 0.60) between doxycycline-treated (B + C) arms 27/29 (93%) vs those not so treated (A + D) arms 27/30 (90%). Conclusion Prednisolone and doxycycline were not beneficial for the earliest presentation of CKDu at 6 months. However, there is a potential benefit of prednisolone on the long-term outcome of CKDu. An adequately powered steroid trial using patients reaching 2 eGFR by 3 years, as an outcome is warranted for AIN of unknown aetiology. Trial registration Sri Lanka Clinical Trial Registry SLCTR/2014/007, Registered on the 31st of March 2014.

Background Thrombotic microangiopathy is a pathological condition comprised of microvascular thrombosis involving any organ of the body leading to thrombocytopenia, Coombs-negative hemolytic anemia, and end-organ damage. The most common forms of thrombotic microangiopathies are Shiga toxin-producing Escherichia coli-mediated hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome. The atypical hemolytic uremic syndrome occurs due to genetic and acquired mutations in complement regulatory factors and to complement activation factors in the immune system, mainly the alternative pathway. Clinical manifestations and outcomes differ with the prevalent mutations of the patient. Currently, available treatment modalities are therapeutic plasma exchange and a monoclonal antibody against C5, eculizumab. We report a case of a Sri Lankan girl diagnosed with atypical hemolytic uremic syndrome complicated with septicemia, hemolytic anemia, acute kidney injury, pulmonary hemorrhage with respiratory failure, and hypertension who had a complete remission following long-term (30 months) therapeutic plasma exchange. Case presentation A 15-year-old Sri Lankan girl was transferred from a local hospital with the features of septicemia and acute kidney injury for specialized management. She had high blood pressure (180/100 mmHg) on admission. She underwent appendicectomy based on suspicion of acute appendicitis as the cause of sepsis. Following surgery, her condition deteriorated, and intensive care unit management was warranted because she developed pulmonary hemorrhages and respiratory failure requiring mechanical ventilation and renal replacement therapy in the form of hemodialysis. Her blood investigations showed microangiopathic hemolytic anemia, thrombocytopenia, elevated lactate dehydrogenase, and reduced human complement C3 levels, together with a normal coagulation profile. She was diagnosed with atypical hemolytic uremic syndrome and was initiated on therapeutic plasma exchange and other supportive therapy, including corticosteroids. Following a lengthy course of plasma exchange, complete recovery was achieved. Conclusion The atypical hemolytic uremic syndrome is a rare disease entity requiring a high index of suspicion to diagnose. It is a diagnosis of exclusion. Early diagnosis with prompt treatment will render a better outcome. The atypical hemolytic uremic syndrome needs to be considered in all patients with thrombotic microangiopathy.

Introduction: Chronic kidney disease of uncertain etiology (CKDu), an emerging chronic kidney disease (CKD) subtype, contributes to significant morbidity and mortality in certain tropical countries. Although several indicators of CKDu have been previously suggested, sensitive and specific tests to detect early disease or predict disease progression are currently unavailable. This study focused on evaluating 8 renal urinary markers, namely neutrophil gelatinase-associated lipocalin (NGAL), Kidney Injury Molecule-1 (KIM1), cystatin C (CST3), beta 2 microglobulin (B2M), osteopontin (OPN), alpha 1 microglobulin (A1M), tissue inhibitor of metalloproteinase 1 (TIMP1), and retinol binding protein 4 (RBP4), with the hypothesis that these have distinct expression patterns in patients with CKDu. Methods: A cross-sectional study was conducted with 5 study groups comprising subjects from CKDu, endemic CKD, nonendemic CKD, and endemic healthy and nonendemic healthy controls. The urinary levels of the 8 selected renal biomarkers were quantified using multiplex biomarker assay, and the data were subjected to systematic analysis using logistic regression algorithm aiming to extract the best marker combination that could distinctly identify the disease groups noninvasively from the healthy controls. Results: A 3-marker signature panel comprising A1M, KIM1, and RBP4 was identified to represent the best minimum marker combination for differentiating all CKD categories, including CKDu, from healthy controls with an overall sensitivity of ≥0.867 and specificity ≥0.765. The marker combination comprising OPN, KIM1, and RBP4 showed high predictive performance for distinguishing patients with CKDu from patients with CKD with both sensitivity and specificity ≥0.93, which was superior to any existing noninvasive indicator. Conclusion: In all, our systematic evaluation of urinary markers previously linked to CKD, in general, allowed identification of exclusive marker panel combination for early diagnosis and confirmation of CKDu. Keywords: chronic kidney disease of uncertain etiology, early diagnosis, urinary biomarkers

Background Brake oil is an automobile transmission fluid composed of a mixture of toxic alcohols such as ethylene glycols and glycol ethers. Both accidental and intentional ingestion cases have been reported and they can present with multisystem involvement. Life-threatening complications evolve from deleterious effects on cardiopulmonary and renal systems. Effects on neurological and gastrointestinal systems give rise to a multitude of complications although non-fatal in nature. The biochemical panel consists of a high concentration of ethylene glycol with severe metabolic acidosis, high anion gap, high osmolar gap, oxaluria, and hypocalcemia. The mainstay of treatment is enhanced elimination of ethylene glycol and its metabolites by hemodialysis, together with general supportive care, gastric decontamination, and vitamins such as thiamine and pyridoxine to minimize the adverse effects of intoxication. Case presentation A 26-year-old Sinhalese woman presented with reduced urine output, shortness of breath, reduced level of consciousness, abdominal pain, and vomiting with mild degree fever of 2 days’ duration. She had bilateral lower limb edema, crepitations over bilateral lower lung fields, and right-sided lower motor type facial nerve palsy. Investigations showed severe metabolic acidosis with high anion gap and high osmolar gap. With regular hemodialysis she made a complete recovery after 3 months. Conclusion Even without a clear history of poisoning, the presence of a high anion, high osmolar gap metabolic acidosis should prompt one to search for ethylene glycol ingestion. Uncommon manifestations like cranial neuropathies need to be examined and considered. Timely aggressive treatment leads to a better prognosis.

AIM Anaemia is a well-known complication of chronic kidney disease but there are no published studies on the pattern of anaemia in chronic kidney disease of uncertain aetiology (CKDu). This study aims to find out the prevalence, causes and associations of anaemia in CKDu to identify any unique features which are different from already described anaemia in chronic kidney disease. METHOD All (119) biopsy-confirmed CKDu patients in two endemic clinics (Girandurukotte and Wilgamuwa) were selected as cases. Blood samples (10 mL) were collected from the peripheral veins into Potassium-Ethylenediaminetetraacetic acid (K-EDTA) tubes, plain tubes and Na-citrated tubes. Serum was separated immediately by centrifugation at 3000 rpm for 10 min. Spot urine samples were collected into empty, sterile, polypropylene urine containers. All analyses were performed in IBM spss statistics version 23 (IBM Corp, Armonk, New York). RESULTS The overall prevalence of anaemia in 119 non-dialysis CKDu patients was 72.3% with the highest prevalence seen in females compared to males (P

Background: The assessment of body fat distribution is an important evaluation in patients with lupus nephritis (LN), which does not practice routinely. The objectives of this study were to determine the body composition by using bioelectrical impedance analysis and to identify the effects of age, body mass index, disease activity, and corticosteroid therapy on body composition.Methods: This was a single-centered, cross-sectional, and observational study conducted at the nephrology unit, National Hospital Kandy, Sri Lanka. Seventy-nine patients with biopsy-proven LN have participated in the study.Results: There were 79 lupus nephritis patients enrolled in this study. The duration of LN ranged from 8 months to 32 years. The main non-renal clinical manifestations included skin lesions (59%), arthritis (54%), and oral ulcers (48%). The disease activity was low with a mean SLEDAI score of 1.01 (SD=2.3). The body fat (BF) percentage (p=0.002) and subcutaneous fat (SF) percentage (p

Background and Aims Live donor kidney transplantation remains the mainstay of renal replacement therapy in Sri Lanka. The basic universal pre surgical investigations, human leucocyte antigen (HLA) matching and cross matching are routinely performed, however due to high rates chronic kidney disease (CKD) as well as increasing numbers of, chronic kidney disease unknown etiology (CKDu) in Sri Lanka, there is a possibility of subclinical kidney disease being present in donor kidneys which go undiagnosed. A study of pre-implantation biopsy along with follow-up outcomes of kidney transplant recipients is conducted to identify presence of subclinical kidney disease in a Sri Lankan cohort of patients. Method We collected thirty three (33) live donor pre-implantation biopsies during 4 consecutive months in 2020 as well as 1 month follow-up data. This is part of an ongoing follow-up study which is conducted at National Hospital, Kandy, Sri Lanka. Results Thirty three (33) live donor recipients and their pre-implantation renal biopsy samples were studied. The mean age of the study participants’ was 37.6 (SD 12.5, range 13 - 59) years. A predominant number of male patients were in the sample (n=21, 63.6%). Underlying aetiology of end stage renal disease (ESRD), was predominantly due to chronic hypertension (39.3%; n=13) and diabetic kidney disease (21.2%, n=7) accounting for nearly 60% of the study participants. Among the 33 live donors 1st degree, 2nd degree and non-relative donors were 54.4% (n=18), 18.2% (n=6) and 27.3% (n=9) respectively. Pre-implantation renal biopsy results reported 36.4% (n=12) with abnormal biopsy findings including chronic interstitial nephritis (n=4, 12.1%), interstitial fibrosis (n=6, 18.18%) and acute tubular necrosis (n=2, 6%). Follow-up revealed delayed graft function occurring in 18.2% (n=6) of recipients with 50% (n=3) of them showing abnormalities in the pre-operative donor biopsy sample. At one month follow-up, 48.5% (n=16) reported complications which included graft failure 3% (n=1), all-cause mortality 3% (n=1), acute rejection 39.4% (n=13) and infections 24.2% (n=8). Overall, 37.5% (n=6) of these recipients had abnormal donor biopsy findings, however no significant statistical association was identified. Conclusion Our study identified subclinical kidney disease in donor kidneys despite standard pre-transplant screening. Even though, statistically not significant, recipients with abnormal pre-implantation biopsy findings had adverse short term post-transplant complications.

Background and Aims Vitamin D deficiency (VDD) is a common, well known association in Chronic Kidney Disease (CKD). However, there are no published studies on the prevalence of VDD among CKDu (Chronic Kidney Disease of uncertain etiology) patients. This study aims to study on Vitamin D status of CKDu patients. Method This was a cross sectional survey conducted in Wilgamuwa area, in Mathale located in Central province of Sri Lanka. Among the 39 GN (Grama Niladahri) divisions at Wilgamuwa, GN divisions where the CKD prevalence was high areas were taken for the study. Data were collected by using clinical examination and interviewer administered questionnaire and analyzed using SPSS statistical software Results A total of 150 patients living in a CKDu endemic area in Sri Lanka was studied during the study period. Majority (n=118, 78.7%) of the CKDu patients were males. Mean age (years) was 56.75±7.89 and 54.34±7.87 for females and males respectively. More than half of the patients were middle aged outdoor workers. According to the BMI (Body mass index) results, majority (n= 87, 58%) of the CKDu patients were in the healthy weight category. More than one third of the patients were in the underweight category. VDD (30 ng/mL). As a summary the mean Vitamin D level was 24.85 ±7.93 ng/mL. There was a significant different in the prevalence of VDD between gender groups (p = 0.004). VDD is more common (82%) during the early stages of CKDu while less common during the late stage. However, there is no any significant association between the prevalence of VDD and CKDu stage (p=0.183). Conclusion VDD is more commonly encountered complication in during the early stages of CKDu and it was significantly high in male CKDu patients compared to females.

NAA

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with ‘traditional’ chronic kidney disease (CKD). However, chronic kidney disease of uncertain aetiology (CKDu), a tubular interstitial nephropathy is typically minimally proteinuric without high rates of associated hypertension or vascular disease and it is unknown if the rates of CVD are similar. This study aimed to identify the prevalence and the risk of CVD in patients with CKDu. This cross-sectional study included patients with confirmed CKDu who were attending two renal clinics in CKDu endemic-area. A detailed medical history, blood pressure, electrocardiogram (resting and six minutes vigorous walking), echocardiograms, appropriate laboratory parameters and medical record reviews were used to collect data at baseline. The WHO/Pan American Health Organization, cardiovascular risk calculator was employed to determine the future risk of CVD. The clinics had recorded 132 number of patients with CKDu, of these 119 consented to participation in the study. The mean age was 52 (± 9.5) years and mean eGFR was 51.1 (± 27.61); a majority (81.5% (n = 97)) were males. Thirty-four patients (28.6%) had evidence of ischaemic heart disease (IHD). Troponin-I (p = 0.02), Age >50 years (p = 0.01) and hyperuricemia (p = 0.01) were significantly associated with IHD in CKDu. Left ventricular hypertrophy was reported in 20.2% (n = 24). According to the risk calculator, 97% of the enrolled patients were at low risk (

Background and Aims An environmental nephropathy which is widely known as Chronic Kidney Disease of uncertain aetiology (CKDu) has been reported in dry zone of Sri Lanka and few other tropical countries. It is already become a major public health problem resulting immense social, economic and health impacts. In recent past, symptomatic presentation of CKDu with tubulitis (CKDuT)/ Acute Interstitial Nephritis indicating activity (AIN) has been reported from Sri Lanka and Central America. The AIN is a nonspecific response of kidney to an injurious agent. Usually the responsible aetiology is obvious in AIN, but not in CKDu cases, however, believed to be a sequel of interstitial nephritis. The aim of this study was to identify the occupational exposures or risk factors associated in AIN cases. Method In a two years of a comprehensive investigation, 60 individuals who reported with AIN were investigated. Once a case is reported, a home visit was carried out and behavioural pattern associated risk factors were assessed by a structured questionnaire in which working behaviours and conditions, spraying of agrochemical, usage of Personal Protective Equipment (PPE) and probable exposed environmental conditions were considered. Results Majority of AIN patients were male (90:10%) with the mean age of (44 ± 1.2) ranging from 26 - 62years. Among the study group, 53% were full time farmers while 77% of were doing farming either full time or part time. 55% of patients applied agrochemicals by themselves. 52% of individuals have used Personal Protective Equipment (PPE). 12% of individuals were sand miners while 7% and 5% were full time masons or labourers. 2% were engaged both farming and mason as full time employment. 15% were doing other employment except the above. Smoking, alcohol consumption and betel chewing were reported in the group as 50%, 57% and 72% respectively. Majority of patients were reported from Girandurukotte (17%), Wilgamuwa (32%) and Mahiyanganaya (35%) regions where CKDu are widely reported. Study indicated that there was no any significant pattern of AIN incidents over the study period. Conclusion Mean age of reported CKDuT were at least ten years younger than the mean age of CKDu. Comparatively higher number of sex ratio has been found in CKDuT indicating the male dominance. Some of the demographic features of AIN patients were similar with CKDu patients and both CKDu and AIN patients are engaged in farming either full time or part time.

Symptom burden and health-related quality of life (HRQOL) are important predictors of how a disease affects patients&rsquo, lives, especially for endemic health problems such as chronic kidney disease of uncertain etiology (CKDu). Our study describes symptom burden, HRQOL, and associated demographic and clinical variables in CKDu patients in the Girandurukotte area, Sri Lanka. A cross-sectional study included 120 CKDu patients attending the renal clinic in the endemic area. The instruments applied were the Kidney Disease Quality of Life&mdash, Short Form (KDQOL-SFTM) version 1.3 and CKD Symptom Index&mdash, Sri Lanka. Socio-demographic, disease-related, and anthropometric variables were also investigated. The mean age of patients was 61.87 (SD 11.31), while 69.2% were male. The mean glomerular filtration rate was 28.17 (SD 14.03) mL/min/1.73 min2, and 70.8% were anemic. Bone/joint pain was the most experienced symptom while the median number of symptoms reported by patients was 5 (IQR 3&ndash, 7). The mean symptom burden, physical component summary, mental component summary, and kidney-disease-specific component scores were 12.71 (SD 10.45), 68.63 (SD 19.58), 78.53 (SD 18.78), and 81.57 (SD 5.86), respectively. Age was found to be a significant predictor of HRQOL, while hemoglobin level and being a farmer were significant predictors of symptom burden. Our data indicate that CKDu patients in all stages experience at least one symptom affecting all aspects of HRQOL.

Fluoride is an element that is widely distributed in the environment. The involvement of fluoride in pathogenesis of Chronic Kidney Disease of uncertain aetiology (CKDu) in Sri Lanka is a much-debated topic. This study aimed to investigate the fluoride concentration in drinking water in CKDu affected areas in Sri Lanka and to evaluate the possible effect of renal impairment on serum fluoride levels in CKDu patients. Drinking water (n = 60) from the common water sources from two CKDu prevalent areas and serum samples of CKDu patients (n = 311) and healthy controls (n = 276) were collected. Both environmental and biological samples were analysed for the concentration of fluoride. The fluoride concentration in over 95% of drinking water samples was below the WHO guideline of 1.5 mg/L. Serum fluoride concentrations in majority of the unaffected and early-stage CKDu patients (stages 1 and 2, eGFR >60 ml/min/1.73m2) were below the normal upper concentration of 50 μg/l and significantly higher levels were observed in patients in late stages of CKDu compared to the healthy controls. The available guidelines for drinking water are solely based on healthy populations with normal renal function. But, it is evident that once the kidney function is impaired, patients enter a vicious cycle as fluoride gradually accumulates in the body, further damaging the kidney tissue. Thus, close monitoring of serum fluoride levels in CKDu patients and establishing health-based target guidelines for fluoride in drinking water for the CKDu patients are recommended to impede the progression to end stage renal disease.

Background Lupus Nephritis (LN) in males is poorly understood due to the low prevalence in men. Our aim was to identify the clinical and histological profile on initial presentation and to report the experience of disease course and management. Methods Seventeen biopsy proven LN males from nephrology clinic, Teaching Hospital Kandy were retrospectively analyzed. Results The median age at the time of renal biopsy was 25.7 years (range, 14–57 years). Commonest initial presentation was nephrotic syndrome in 10 of 17 patients followed by rapidly progressive glomerulonephritis (RPGN) in 4 and nephritic syndrome in 3. Anemia was noted in 11 patients. Thrombocytopenia was seen among 4 patients. ANA report was positive in 13 and negative in 4 patients. Diffuse LN was the commonest histological pattern accounting to 10 cases followed by Focal LN in 4, membranous LN in 2 and mesangial proliferative LN in 1 patient. After remission induction treatment, 10 patients achieved complete renal remission. Five patients achieved partial remission while two patients did not achieve remission. Induction was done with intravenous (IV) methyl prednisolone (0.5/1.0g) daily 3 doses and IV cyclophosphamide (750 mg/m2 body surface) 2 doses two weeks’ apart and 4 doses monthly. Maintenance treatment was with oral prednisolone and mycophenolate mofetil. Median follow-up of the cohort was 52 months (2–89 months). During the follow-up repeat biopsy was performed in 4 patients. The changes observed were, class shift from class III to IV in 2 patients and from class V to class IV in one patient. Only one patient required renal replacement therapy during the follow up period. Six patients developed chronic kidney disease (CKD) after a median of 33 months follow-up. Conclusion Commonest presentation of LN in males is nephrotic syndrome, and type IV LN is the most frequent histological form. Pattern of initial presentation is seemingly associated with the renal outcome. Better delineation needs further studies with larger cohorts.

Background: Haemodialysis (HD) patients are subjected to bio-psychosocial stress in many ways even after successful hemodialysis session. Therefore, this study was designed to survey on relationship between knowledge and treatment satisfaction with psychological well-being among haemodialysis patients.Methods: This cross-sectional study included 100 HD patients who were referred to emergency dialysis unit, nephrology and transplant unit, National Hospital, Kandy during the year 2019. Data were collected using a self-administered questionnaire.Results: Mean age of this study group was 45.17 (13.6) years; two dominant etiologies of chronic renal failure were diabetic nephropathy and hypertension accounting for nearly 61% of the study population. Only 19% of patients presented with emotional suffering and 40% of patients worried about their disease condition. However, majority of the patients satisfied with nursing care and nurses’ co-operation while they are on HD treatment. Moreover, they confirmed nurses’ co-operation helped to reduce their stress level. Further, knowledge on HD compliance (p=0.000), satisfaction on nursing staff attitudes (p=0.001), satisfaction on nursing staff concern about the health issues (p=0.001) and worrying about the kidney disease condition (p=0.000) had statistically significant association with mental stress in this study cohort.Conclusions: The topic of stressors is very important among patients receiving dialysis, as these affect their psycho-social and physiological wellbeing. Thus, health care team is playing an important role in providing patients with effective psycho-social and physiological support.

Over the last two decades, a global epidemic of chronic kidney disease of unknown etiology (CKDu) has emerged in rural, arid, agricultural, lowland areas. Endemic regions have reported 15 to 20% prevalence among residents aged 30–60 years. CKDu is a progressive and irreversible disease resulting in renal failure and death in the absence of dialysis or a kidney transplant. While much of the research has focused on identifying etiology, this project seeks to ascertain factors associated with the rapidity of kidney disease progression in one of Sri Lanka’s CKDu endemic areas. A sample of 296 male and female residents aged 21 to 65 with moderate CKD, as measured by their serum creatinine level, and a clinical diagnosis of CKDu are followed using quarterly serum testing to track the rate of progression. A baseline survey administered to the entire sample addresses potential risk factors, supplemented by a short survey focusing on changes through time. Concurrently water, soil and air are tested at the local and household levels. The study is the first to foster a multi-disciplinary approach that focuses on disease progression, identifying behavioural and exposure risk factors for rapid kidney function decline, in this progressively fatal disease.

Mortality in Chronic Kidney Disease of uncertain etiology (CKDu) is not well described despite being a major public health crisis in Sri Lanka. Data on CKDu have many gaps and published data on mortality are sparse. This retrospective descriptive study was designed to describe the mortality of CKDu in an endemic area. Deaths were identified by tracing clinic defaulters from 2005 to 2015 in renal clinic, Girandurukotte. The majority who passed away were male (83.70%) farmers (80.39%) in their productive age (mean age 58.0 ± 13.01). Immediate cause of death was end-stage renal disease (ESRD) in 94.12% of deaths, reflecting the unavailability of Renal Replacement Therapy (RRT). Therefore, strategies are urgently required to enhance early identification, to provide standard medical care and to expand RRT in CKDu affected areas.

[This corrects the article DOI: 10.1371/journal.pone.0232522.].

Chronic kidney disease of unknown etiology (CKDu) imposes a substantial burden on public health in Sri Lankan agricultural communities. High seroprevalences of hantavirus have been reported in CKDu patients in several locations of Sri Lanka. We carried out a cross-sectional study followed by an unmatched case-control comparison in two geographically distinct areas of Sri Lanka, Girandurukotte (CKDu endemic) and Kandy (CKDu non-endemic) to determine whether exposure to hantaviruses is a potential risk factor in patients with kidney disease. An indirect immunofluorescent antibody assay using two antigens, Thailand orthohantavirus-infected and recombinant N protein-expressing Vero E6 cells, were used for serodiagnosis. Participants' demographic and other socio-economic data were collected through a structured questionnaire. Fifty kidney disease patients and 270 controls from Kandy and 104 kidney disease patients and 242 controls from Girandurukotte were examined. Seropositivities were 50% and 17.4% in kidney patients and controls, respectively, in Girandurukotte, and they were 18% and 7% in Kandy. The odds of exposure to hantaviruses were higher for kidney disease patients than for controls in both Girandurukotte (OR:3.66, 95% CI:2.01 to 6.64) and Kandy (OR:2.64, 95% CI:1.07 to 6.54) in binary logistic regression models. According to statistical analysis, individuals exposed to hantaviruses had a higher risk of developing renal impairment. Therefore, hantavirus infection might be an important risk factor for development of kidney disease in Sri Lanka.

Chronic kidney disease of unknown etiology (CKDu) imposes a substantial burden on public health in Sri Lankan agricultural communities. High seroprevalences of hantavirus have been reported in CKDu patients in several locations of Sri Lanka. We carried out a cross-sectional study followed by an unmatched case-control comparison in two geographically distinct areas of Sri Lanka, Girandurukotte (CKDu endemic) and Kandy (CKDu non-endemic) to determine whether exposure to hantaviruses is a potential risk factor in patients with kidney disease. An indirect immunofluorescent antibody assay using two antigens, Thailand orthohantavirus-infected and recombinant N protein-expressing Vero E6 cells, were used for serodiagnosis. Participants&rsquo, demographic and other socio-economic data were collected through a structured questionnaire. Fifty kidney disease patients and 270 controls from Kandy and 104 kidney disease patients and 242 controls from Girandurukotte were examined. Seropositivities were 50% and 17.4% in kidney patients and controls, respectively, in Girandurukotte, and they were 18% and 7% in Kandy. The odds of exposure to hantaviruses were higher for kidney disease patients than for controls in both Girandurukotte (OR:3.66, 95% CI:2.01 to 6.64) and Kandy (OR:2.64, 95% CI:1.07 to 6.54) in binary logistic regression models. According to statistical analysis, individuals exposed to hantaviruses had a higher risk of developing renal impairment. Therefore, hantavirus infection might be an important risk factor for development of kidney disease in Sri Lanka.