Chronic Kidney Disease Of Unknown Cause Research Articles

Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology

Kidney disease of unknown etiology accounts for 1 in 10 adult end-stage renal disease (ESRD) cases worldwide. The aim of this study is to clarify the genetic background of patients with chronic kidney disease (CKD) of unknown etiology who initiated renal replacement therapy (RRT) in adulthood. This is a multicenter cross-sectional cohort study. Of the 1164 patients who attended 4 dialysis clinics in Japan, we first selected patients who started RRT between the ages of 20 and 49 years. After excluding patients with apparent causes of CKD (e.g., diabetic nephropathy, polycystic kidney disease (PKD) with family history, patients who underwent renal biopsy), 90 patients with CKD of unknown cause were included. The 298 genes associated with CKD were analyzed using capture-based targeted next-generation sequencing. Of the 90 patients, 10 (11.1%) had pathogenic variants in CKD-causing genes and 17 (18.9%) had variant of unknown significance (VUS). Three patients had PKD1 pathogenic variants, and 1 patient had PKD1 and COL4A4 pathogenic variants. In addition, 2 patients were diagnosed with atypical hemolytic uremic syndrome (aHUS) due to C3 or CFHR5. One patient each was diagnosed with Alport syndrome due to COL4A4 and COL4A3 variants, nephronophthisis due to NPHP1 variants, Fabry disease due to GLA variants, and autosomal-dominant tubulointerstitial kidney disease due to UMOD variants. Genetic diagnoses were not concordant with clinical diagnoses, except for patients with PKD1 variant. This largest study on genetic analysis in hemodialysis-dependent adults revealed the presence of undiagnosed inherited kidney diseases.

Clinical findings and kidney morphology in chronic kidney disease of unknown cause in India.

Chronic kidney disease of unknown cause (CKDu) is an emerging health problem in India and other countries worldwide. However, clinical descriptions, including kidney pathology, are scarce. This is a descriptive case series of patients with CKDu from an endemic region in India, with a focus on clinical and biochemical characteristics, kidney biopsy findings, and environmental exposure. Patients with suspected CKDu, aged 20-65, and eGFR 30-80mL/min/1.73m2 from rural areas with endemic prevalence of CKDu were included. The exclusion criteria were diabetes mellitus, uncontrolled hypertension, proteinuria >1g/24h, or other known kidney diseases. The participants underwent kidney biopsies, and blood and urine samples were collected. Fourteen participants (3 females, 11 males) with a mean eGFR of 53 (range 29-78) mL/min/1.73m2 were included. Kidney biopsies showed a combination of chronic tubulointerstitial damage, glomerulosclerosis, and glomerular hypertrophy, with varying degrees of interstitial inflammation. Eight participants had polyuria (diuresis≥3L/day). The urinary sediments were bland, with no haematuria. Serum potassium and sodium levels were, in most cases, normal but within the lower reference interval. The kidney morphology and clinical characteristics in patients with CKDu in India were similar to those described for CKDu in Central America and Sri Lanka.

Advances in Chronic Kidney Disease in Africa

Africa, particularly sub-Sharan Africa (SSA), faces major challenges in respect to chronic kidney disease (CKD). There is a rising prevalence due to the combined effects of hypertension, diabetes, and human immunodeficiency virus (HIV) (and the interaction between them) and the effect of apolipoprotein L1 (APOL1) variants on the susceptibility to CKD. Epidemiological data on the prevalence of CKD are of low-to-medium quality, and reliable data are urgently needed for health planning. Furthermore, there are important deficiencies in creatinine-based equations in underestimating the prevalence of CKD in Africa, and evidence suggests that cystatin C based equations are more reliable. There is a changing spectrum of HIV related CKD with the greater availability of antiretroviral treatment. Major clinical trials using SGLT2 inhibitors have signalled a major advance in the treatment of CKD, especially in relation to type 2 diabetes, but the affordability, availability, and relevance to the African population is not established. The importance of the effects of hypertension in pregnancy and pregnancy related acute kidney injury on CKD and the newer concept of CKD of unknown cause (CKDu) are highlighted. Hypertension remains a dominant cause of CKD in Africa, and newer information suggests that the most appropriate treatment to control blood pressure and thus prevent CKD is the combination of either amlodipine plus a thiazide diuretic or angiotensin converting enzyme (ACE) inhibitor.

Prevalence of anemia and its predictors among patients with chronic kidney disease admitted to a teaching hospital in Ethiopia: A hospital-based cross-sectional study.

Anemia is a common complication of chronic kidney disease (CKD) and is associated with adverse patient outcomes. However, data on the prevalence of anemia in CKD patients is sparse, particularly in resource-limited settings. Therefore, this study aimed to assess the prevalence of anemia and its predictors among patients with CKD admitted to the Jimma medical center, southwest Ethiopia. A hospital-based prospective cross-sectional study was conducted from September 1 to November 30, 2020. All adult patients with CKD aged ≥18 years who fulfilled the inclusion criteria were consecutively recruited into the study. Data were entered into the Epi data manager version 4.4.1 and then exported to SPSS version 22 (IBM Corp., Armonk, NY) for analysis. The predictors of anemia were determined using multivariable logistic regression analysis. Statistical significance was set at P < .05. A total of 150 patients were included in this study. Of these, 64.67% were male, 56.67% had stage 5 CKD, 78% had a CKD duration of less than 1 year, and 74% had proteinuria. Hypertension (40.7%) and diabetes (14.7%) were the common causes of CKD. The prevalence of anemia was 85.33%. Of the patients, 28.67%, 40.67%, and 16% had mild, moderate, and severe anemia, respectively. On multivariate logistic regression, stage 4 CKD (adjusted odds ratio [AOR] 3.2, confidence interval [CI]: 1.78-12.91, P = .025), stage 5 CKD (AOR 4.03, CI: 1.17-13.73, P = .016), and CKD duration of less than 1 year (AOR 3, CI: 1.19-9.11, P = .007) were significantly associated with anemia. The prevalence of anemia among stage 3 to 5 CKD patients was very high. Anemia was significantly associated with the severity and duration of CKD. Therefore, serial follow-up of patients with a long duration and advanced stages of CKD may help prevent anemia and its adverse consequences.

"Failing kidneys in a failing planet; CKD of unknown origin".

The 'alarm clock' for human beings in the era of climate medicine has rung. Original diseases have appeared, that could not be explained and attributed to common causes, which are suggested to be linked to global warming and environmental factors. Such an indolent disease is the chronic kidney disease of unknown cause (CKDu), introduced also as Mesoamerican or Uddanam nephropathy. Scientists equate the climate impact on kidneys with the canary in the coal mine; coal miners used to carry caged canaries with them, so that if poisonous gases, such as methane or carbon monoxide leaked into the mine-shaft, the gases would kill the canary before killing the miners; similarly, kidneys are injured before devastating and lethal complications occur in humans. In some regions of Central America, the deaths due to chronic kidney disease increased by 177% with a death toll being as high as over 20,000. It was first documented in animals that periodic heat and dehydration have a major role in causing chronic kidney disease. Based on that observation, it is advocated that young male agricultural workers in Central America and South Asia, develop renal disease by getting exposed to extreme heat repeatedly. The clinico-pathological characteristics of this type of kidney injury, do not belong to an existing classification, even though a form of tubulo-interstitial renal disease has been proposed. In this review, we will discuss about CKDu, its epidemiology and pathophysiological mechanisms, clinical presentation and diagnostic biomarkers and examine potential therapeutic options.

Body Composition, Anemia, and Kidney Function among Guatemalan Sugarcane Workers

Rates of anemia among agricultural workers, who are also at risk for kidney injury and chronic kidney disease of unknown cause (CKDu), are unknown. We evaluated body composition through the sum of three skinfolds among 203 male sugarcane cutters and assessed the relationship of variables related to nutrition, anemia (hemoglobin < 13 g/dL), and elevated hemoglobin A1c (HbA1c ≥ 5.7%) with estimated glomerular filtration rate (eGFR) using linear regression. Eleven percent of workers were at the level of essential body fat (2–5%). Anemia was present among 13% of workers, 70% of which were normochromic normocytic, a type of anemia suggesting potential underlying chronic disease. Anemia was more common among those with lower BMI and fat free mass. The prevalence of elevated HbA1c was 21%. A moderate negative correlation was found between hemoglobin and HbA1c (Pearson’s r = −0.32, p < 0.01) which suggests that HbA1c values should be interpreted with caution in populations that have high rates of anemia. Twelve percent of workers had reduced kidney function with an eGFR < 90 mL/min/1.73 m2. On average, the eGFR was 18 mL/min per 1.73 m2 lower [(95% CI:−24, −12), p < 0.01)] for those with anemia than those without, and 8 mL/min per 1.73 m2 lower among those with elevated HbA1c [(95% CI: −13, −2), p < 0.01]. Results will inform future studies examining the role of anemia in the evaluation of CKDu and interventions to improve nutrition for workers in low-resource settings.

Metal concentrations in cereals are not related to the Chronic Kidney Disease of unknown cause (CKDu) in Sri Lanka

BACKGROUND AND AIM: Exposure to nephrotoxic metals (As, Pb, and Cd), as well as Se deficiency has been hypothesized as a possible cause of Chronic Kidney Disease of unknown cause (CKDu) in Sri Lanka; however, evidence is inconclusive. Here, we determined the concentrations of these elements in rice and other grains consumed in endemic and non-endemic regions of CKDu. METHODS: Dried and fine ground cereals were digested completely with trace metal grade nitric and hydrochloric acids and hydrogen peroxide. The clear completely digested solutions were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS:Our results showed comparable mean concentrations (in µg/kg) of 23±17, 7.4±6.7, and 15.1±15.2 for As, Pb, and Cd, respectively, in rice from endemic regions, and 26±14, 10.5±6.3, and 12.3±15 in rice from non-endemic regions. Selenium concentrations (in mg/kg) were 0.05±0.02 and 0.04±0.02 in rice cultivated in endemic and non-endemic regions, respectively. Arsenic and Cd concentrations were significantly higher in rice compared to other grains, which themselves had higher Se than rice. All samples were below the Codex standards established for Cd (400 µg/kg for rice; 100 µg/kg for cereal grains), Pb (200 µg/kg), and total As (300 µg/kg). Our findings show that dietary exposure to low levels of As, Pb, Cd, and inadequate Se in staple grains cannot be linked to CKDu, suggesting that the disease could be multifactorial. Our previous water quality evaluation in the study area similarly does not appear to be implicated, which further highlights the lack of strong evidence on nephrotoxic metals exposure from food and water in the study area. CONCLUSIONS:More research is needed to understand the contribution of additional food materials among other risk factors to identify preventive strategies and minimize CKDu health cases in Sri Lanka and affected regions globally. KEYWORDS: CKDu, Nephrotoxic metals, Selenium deficiency, CKDu endemic and non-endemic regions, Sri Lanka.

Environmental metal exposures and kidney function of Guatemalan sugarcane workers.

Background:Exposure to environmental metals can cause nephrotoxicity. There is an international epidemic of chronic kidney disease of unknown cause (CKDu). Whether metal exposures contribute to kidney dysfunction in populations at-risk for CKDu remains unresolved.Objective:Urinary metals (arsenic, cadmium, nickel, and uranium) were examined in 222 sugarcane cutters in Guatemala at three time points over one year.Methods:We explored the relationships between metal concentrations and markers of kidney function using multivariable linear mixed-effect models.Results:Arsenic, cadmium, and nickel were detected in the majority of the 340 urine samples and were generally within limits previously considered to be non-nephrotoxic. Nevertheless, higher urine cadmium was inversely associated with estimated glomerular filtration rate (eGFR) (β: −4.23, 95% confidence interval [CI]: −6.92, −1.54) and positively associated with neutrophil gelatinase-associated lipocalin (NGAL) (β: 2.92, 95% CI: 1.20, 4.64). Higher urine arsenic was also inversely associated with eGFR (β: −4.36, 95% CI: −7.07, −1.64).Significance:Our findings suggest that exposures to metals, including cadmium and arsenic, might contribute to kidney toxicity seen in workers at risk for CKDu. These findings are consistent with the potential for metal nephrotoxicity at lower than expected levels in the setting of manual work in a very hot environment.

CKD and CKDu in northern Peru: a cross-sectional analysis under the DEGREE protocol

BackgroundThis study estimated the prevalence and risk factors for decreased estimated glomerular filtration rate (eGFR) in those without known hypertension, type 2 diabetes mellitus, or heavy proteinuria as a surrogate marker for chronic kidney disease of unknown cause (CKDu) among adults in the North of Peru.MethodsA cross-sectional study was conducted following the Disadvantaged Populations eGFR Epidemiology (DEGREE) Study protocol. Low eGFR was defined based on a single eGFR ≤60 mL/min/1.7m2 estimated using the CKD-EPI equation. Environmental conditions related to CKDu (i.e., work in agriculture or sugarcane, water source, heat intolerance, and pesticide exposure) were evaluated, in addition to traditional risk factors for CKD (i.e., smoking, heavy drinking, physical activity, hypertension, type 2 diabetes mellitus, urolithiasis, among others).ResultsA total of 1514 subjects were included in the study, mean age 45.1 (SD: 16.4), and 55.2% were females. Overall, only 26 cases (1.7%; 95%CI: 1.1–2.5%) had an eGFR < 60 mL/min/1.7m2 compatible with CKD definition; when those with hypertension and type-2 diabetes or heavy proteinuria were excluded, according to the DEGREE protocol, the estimate fell to 0.9% (95%CI: 0.4–1.5%). Low physical activity levels (OR = 1.99; 95%CI: 1.18–3.34), hypertension (OR = 2.07; 1.26–3.41), and urolithiasis (OR = 1.97; 95%CI: 1.18–3.27) were factors associated with low eGFR.ConclusionsA low population-based prevalence of low eGFR (as a surrogate for CKDu), both in rural and urban settings areas, in the Northern Peru, was found. Low physical activity levels, hypertension and urolithiasis were factors associated with low eGFR. Interventions to prevent CKD cases may be focused on well-known CV risk factors and urolithiasis.

Environmental metal exposures and kidney function of Guatemalan sugarcane workers

Background: Exposure to environmental metals can cause nephrotoxicity. There is an international epidemic of chronic kidney disease of unknown cause (CKDu), referred to in Latin America as Mesoamerican Nephropathy (MeN). Whether metal exposures contribute to kidney dysfunction in populations at-risk for CKDu remains unresolved.Methods: We examined the presence and concentrations of urinary heavy metals (arsenic, cadmium, and nickel) in 201 sugarcane cutters in Guatemala at three time points over one year. We explored relationships between urine metal concentrations and markers of kidney function by calculating β estimates and 95% confidence intervals of kidney function markers using multivariable linear mixed-effect models.Results: Urine arsenic, cadmium, and nickel were detected in the majority of the 332 urine samples. After adjusting for age, systolic blood pressure, Hemoglobin A1c, body mass index, time of collection, and urine creatinine, higher urine cadmium was inversely associated with estimated glomerular filtration rate (eGFR) (β: -6.11, 95% Confidence Interval [CI]: -8.83, -3.39) and positively associated with neutrophil gelatinase-associated lipocalin (NGAL) (β: 2.73, 95% CI: 1.03, 4.43). Higher urine arsenic was inversely associated with eGFR (β: -4.55, 95% CI: -7.08, -2.01).Conclusions: Our findings are suggestive of kidney toxicity due to metal exposure, as measured by urinary cadmium and arsenic.

Prevalence and risk factors for chronic kidney disease of unknown cause in Malawi: a cross-sectional analysis in a rural and urban population

BackgroundAn epidemic of chronic kidney disease of unknown cause (CKDu) is occurring in rural communities in tropical regions of low-and middle-income countries in South America and India. Little information is available from Southern African countries which have similar climatic and occupational characteristics to CKDu-endemic countries. We investigated whether CKDu is prevalent in Malawi and identified its potential risk factors in this setting.MethodsWe conducted a cross-sectional study from January–August 2018 collecting bio samples and anthropometric data in two Malawian populations. The sample comprised adults > 18 years (n = 821) without diabetes, hypertension, and proteinuria. Estimates of glomerular filtration rate (eGFR) were calculated using the CKD-EPI equation. Linear and logistic regression models were applied with potential risk factors, to estimate risk of reduced eGFR.ResultsThe mean eGFR was 117.1 ± 16.0 ml/min per 1.73m2 and the mean participant age was 33.5 ± 12.7 years. The prevalence of eGFR< 60 was 0.2% (95% confidence interval (95% CI) 0.1, 0.9); the prevalence of eGFR< 90 was 5% (95% CI =3.2, 6.3). We observed a higher prevalence in the rural population (5% (3.6, 7.8)), versus urban (3% (1.4, 6.7)). Age and BMI were associated with reduced eGFR< 90 [Odds ratio (OR) (95%CI) =3.59 (2.58, 5.21) per ten-year increment]; [OR (95%CI) =2.01 (1.27, 3.43) per 5 kg/m2 increment] respectively. No increased risk of eGFR < 90 was observed for rural participants [OR (95%CI) =1.75 (0.50, 6.30)].ConclusionsReduced kidney function consistent with the definition of CKDu is not common in the areas of Malawi sampled, compared to that observed in other tropical or sub-tropical countries in Central America and South Asia. Reduced eGFR< 90 was related to age, BMI, and was more common in rural areas. These findings are important as they contradict some current hypothesis that CKDu is endemic across tropical and sub-tropical countries. This study has enabled standardized comparisons of impaired kidney function between and within tropical/subtropical regions of the world and will help form the basis for further etiological research, surveillance strategies, and the implementation and evaluation of interventions.

Chronic kidney disease of unknown cause in Mexico: The case of Poncitlan, Jalisco.

Chronic kidney disease of unknown cause (CKDu) is relatively common in low- and middle-income countries. A high prevalence of CKDu has been reported among the inhabitants of Poncitlan, Mexico. We did a cross-sectional study to compare the characteristics of residents in Poncitlan, a very poor municipality, with those from other municipalities in Jalisco state. We also estimated the prevalence of renal replacement therapy (RRT) in this region. We assessed 51,789 individuals in Jalisco: 16,351 (32.1%) were men, mean age 51.8±15.3 years; 650 (1.3%) were aged &lt;18 years. Overall the prevalence of CKD (10.5%) and proteinuria (11.5%), were similar to the overall Mexican population. There were 283 adult and 144 child participants who resided in Poncitlan: adults were more likely to be female (78.0 vs. 67.9%, p=0.000) but were of similar age as compared to those from other municipalities; children were younger (8.78±3.97 vs. 15.03±2.57 years, p=0.000) but had a similar proportion of females compared to children from other municipalities. In Poncitlan, the prevalence of CKD and proteinuria were both higher in adults compared to those from other municipalities (CKD: 20.1 vs. 10.4%, p=0.002; proteinuria: 36.1 vs. 11.0%, p=0.000), and the prevalence of proteinuria in children was also higher (44.4 vs. 4.8%, p=0.000). However, the prevalence of diabetes mellitus and obesity were lower in Poncitlan than elsewhere. The prevalence of RRT in Poncitlan was 2,228 pmp, twice as high as the prevalence for Jalisco state as a whole. In conclusion, CKD and proteinuria were detected frequently in residents of the Poncitlan community. Future studies should consider the possibility that CKDu is due to multifactorial causes, especially in poor communities. .

SAT-187 EPIDEMIOLOGY 0F CHRONIC TUBULO-INTERSTITIAL NEPHRITIS IN A NEPHROLOGY SERVICE IN SRI LANKA- ARE THESE CKDu ALL?

Epidemic chronic kidney disease (CKD) from agricultural communities in many regions of the world has been termed CKD of unknown cause (CKDu) and has been widely recognized as an idiopathic chronic tubulo-interstitial nephritis (iCTIN). This unique CKD which affects people of a similar social stratum and environment, appeared from agricultural communities in these regions around the same period of time, and has very similar clinical and biochemical features. Attempted case definitions of CKDu from Sri Lanka and Central America only narrow it down to a non-proteinuric CKD. CTIN from any cause would fit into these case definitions. In all renal biopsy registries in the world there have been iCTIN, ranging from 11-30%, even before the emergent epidemic of CKDu. In one case series from Texas in 1990, 25% of CTIN were idiopathic and in another series published in 2001, the incidence of iCTIN among Indo-Asians in a London hospital was seven times that of white Caucasians. Obviously, all these cannot be termed CKDu. A retrospective study was conducted in those who underwent renal biopsies at Sri Jayewardenepura General Hospital, Sri Lanka, situated in the non-endemic region for CKDu, but gets many referrals from the endemic area. All case records of patients who underwent renal biopsies during the period March 2016-March 2018 were analyzed. 1218 patients with CKD were treated during this period. 297 underwent a renal biopsy. 77/297 (26%) had primary CTIN. 13/77 (17%) had identifiable causes of CTIN, while the rest-64/77(83%) - were idiopathic. 24/64 (38%) were from known endemic agricultural areas. 14 of 40 from non-endemic areas (35%) were from areas with high agricultural activity. Hence, 26 of the cohort of 64 iCTIN (40%) were from urban or semi-urban areas with neither significant agricultural activity nor occupational exposure to heat stress. Idiopathic CTIN of unknown cause was a recognized biopsy diagnosis even before the CKDu epidemic. The epidemic CKDu which appeared from agricultural communities in Sri Lanka, Central America and India are likely to have similar, if not the same etiology due to the simultaneity of their emergence, and the similar demographic, clinical, biochemical and pathological features. The name CKDu confusingly mixes up all patients with undiagnosed CTIN hence the name CINAC (chronic interstitial nephritis of agricultural communities) is more appropriate to identify the global epidemic CKD identified since the 1990s.

Prevalence and risk factors for impaired kidney function in the district of Anuradhapura, Sri Lanka: a cross-sectional population-representative survey in those at risk of chronic kidney disease of unknown aetiology

BackgroundOver the last 20 years there have been reports of a form of chronic kidney disease of unknown cause (CKDu) affecting rural communities in the North Central Province of Sri Lanka. Valid prevalence estimates, using a standardised methodology, are needed to assess the burden of disease, assess secular trends, and perform international comparisons.MethodsWe conducted a cross-sectional representative population survey in five study areas with different expected prevalences of CKDu. We used a proxy definition of CKDu involving a single measure of impaired kidney function (eGFR< 60 mL/min/1.7m2, using the CKD-Epi formula) in the absence of hypertension, diabetes or heavy proteinuria.ResultsA total of 4803 participants (88.7%) took part in the study and 202 (6.0%; 95% CI 5.2–6.8) had a low eGFR in the absence of hypertension, diabetes and heavy proteinuria and hence met the criteria for proxy CKDu. The proportion of males (11.2%; 95% CI 9.2–13.1) were triple than the females (3.7%; 95% CI 2.9–4.5). Advancing age and history of CKD among parents or siblings were risk factors for low GFR among both males and females while smoking was found to be a risk factor among males.ConclusionsThese data, collected using a standardised methodology demonstrate a high prevalence of impaired kidney function, not due to known causes of kidney disease, in the selected study areas of the Anuradhapura district of Sri Lanka. The aetiology of CKDu in Sri Lanka remains unclear and there is a need for longitudinal studies to describe the natural history and to better characterise risk factors for the decline in kidney function.

Heavy metal imaging in fibrotic human kidney tissue using the synchrotron X-ray fluorescence microprobe.

Abnormally high exposure to heavy metals and their accumulation in some tissues are recognized as causes of many acute and chronic human diseases. Because of the roles many metals have in normal human physiology, proving cause and effect between exposure to heavy metals and pathogenesis of disease is problematic. Therefore, many illnesses that develop through occupational and environmental exposure are not considered directly related to heavy metal toxicity. The high sensitivity and spatial resolution of elements using the synchrotron X-ray fluorescence microprobe (XFM) may give a robust means to investigate spatial distribution of heavy metals in correlation with specific pathologies. For example, proven presence of different heavy metals may correlate spatially with kidney fibrosis, suggesting a mechanistic link between heavy metal-induced fibrosis and chronic kidney disease. One specific example that may benefit from such an analysis relates to a cluster of people with chronic kidney disease of unknown cause (CKDu), in a significant proportion of the population of the North Central Province of Sri Lanka. Here, it was postulated that heavy metal exposure, in particular of cadmium, in foods and agriculture may be one cause of end-stage kidney disease and premature death of patients with CKDu. Synchrotron methods had not been applied previously to this particular problem. This manuscript provides a brief review of the literature and reports some pilot data from an investigation of localization of kidney fibrosis in CKDu with selected heavy metals including cadmium.

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

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 μmol/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 α-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.

Whole-Exome Sequencing in Adults With Chronic Kidney Disease

The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown. To study the diagnostic utility of WES in a selected referral population of adults with CKD. Observational cohort. A major academic medical center. 92 adults with CKD of unknown cause or familial nephropathy or hypertension. The diagnostic yield of WES and its potential effect on clinical management. Whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of unknown cause and encompassing 13 distinct genetic disorders. Among these, loss-of-function mutations were identified in PARN in 2 probands with tubulointerstitial fibrosis. PARN mutations have been implicated in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these findings extend the phenotype of PARN mutations to renal fibrosis. In addition, review of the American College of Medical Genetics actionable genes identified a pathogenic BRCA2 mutation in a proband who was diagnosed with breast cancer on follow-up. The results affected clinical management in most identified cases, including initiation of targeted surveillance, familial screening to guide donor selection for transplantation, and changes in therapy. The small sample size and recruitment at a tertiary care academic center limit generalizability of findings among the broader CKD population. Whole-exome sequencing identified diagnostic mutations in a substantial number of adults with CKD of many causes. Further study of the utility of WES in the evaluation and care of patients with CKD in additional settings is warranted. New York State Empire Clinical Research Investigator Program, Renal Research Institute, and National Human Genome Research Institute of the National Institutes of Health.

Star fruit toxicity: a cause of both acute kidney injury and chronic kidney disease: a report of two cases.

BackgroundStar fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit as a remedy for diabetes mellitus—the first, in a patient with normal renal function and the second case which we believe is the first reported case of chronic kidney disease (CKD) due to prolonged and excessive consumption of star fruits.Case presentationThe first patient is a 56-year-old female diabetic patient who had normal renal function prior to developing acute kidney injury (AKI) after consuming large amount of star fruit juice at once. The second patient, a 60-year-old male, also diabetic presented with acute on chronic renal failure following ingestion of a significant number of star fruits in a short duration with a background history of regular star fruit consumption over the past 2–3 years. Both had histologically confirmed oxalate induced renal injury. The former had histological features of acute tubulo-interstitial disease whilst the latter had acute-on-chronic interstitial disease; neither had histological evidence of diabetic nephropathy. Both recovered over 2 weeks without the need for haemodialysis.ConclusionThese cases illustrate the importance of obtaining the patient’s detailed history with respect to ingestion of herbs, traditional medication and health foods such as star fruits especially in AKI or CKD of unknown cause.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1640-8) contains supplementary material, which is available to authorized users.

Clinical and Pathological Characterization of Mesoamerican Nephropathy: A New Kidney Disease in Central America

An endemic of chronic kidney disease (CKD) of unknown cause among rural inhabitants in Central America has been identified. Young and otherwise healthy men working in plantations are frequently affected. The name Mesoamerican nephropathy (MeN) has been suggested. Clinically, MeN presents with low-grade proteinuria and progressive kidney failure. The renal pathology of this disease has not yet been described. Case series. 8 male patients with CKD of unknown cause and clinically suspected MeN were recruited from a nephrology unit in El Salvador. All recruited patients had been working on plantations. Kidney biopsies, blood, and urine samples were collected. Renal morphology examined with light microscopy, immunofluorescence, and electron microscopy; clinical and biochemical characteristics. A similar pattern was seen in all 8 biopsy specimens, with extensive glomerulosclerosis (29%-78%) and signs of chronic glomerular ischemia in combination with tubular atrophy and interstitial fibrosis, but only mild vascular lesions. Electron microscopy indicates podocytic injury. Biochemical workup showed reduced estimated glomerular filtration rate (27-79 mL/min/1.73 m(2) with the CKD Epidemiology Collaboration [CKD-EPI] creatinine equation), low-grade albuminuria, and increased levels of tubular injury biomarkers. Hypokalemia was found in 6 of 8 patients. Small number of patients from one country. This study is the first report of the biochemical and morphologic findings in patients with MeN. Our findings indicate that MeN constitutes a previously unrecognized kidney disease with damage to both glomerular and tubulointerstitial compartments.