Kidney Disease Of Unknown Cause Research Articles

Heavy metal association with chronic kidney disease of unknown cause in central India-results from a case-control study

BackgroundChronic Kidney Disease of unknown cause (CKDu) a disease of exclusion, and remains unexplained in various parts of the world, including India. Previous studies have reported mixed findings about the role of heavy metals or agrochemicals in CKDu. These studies compared CKDu with healthy controls but lacked subjects with CKD as controls. The purpose of this study was to test the hypothesis whether heavy metals, i.e. Arsenic (As), Cadmium (Cd), Lead (Pb), and Chromium (Cr) are associated with CKDu, in central India.MethodsThe study was conducted in a case-control manner at a tertiary care hospital. CKDu cases (n = 60) were compared with CKD (n = 62) and healthy subjects (n = 54). Blood and urine levels of As, Cd, Pb, and Cr were measured by Inductively Coupled Plasma- Optical Emission Spectrometry. Pesticide use, painkillers, smoking, and alcohol addiction were also evaluated. The median blood and urine metal levels were compared among the groups by the Kruskal-Wallis rank sum test.ResultsCKDu had significantly higher pesticide and surface water usage as a source of drinking water. Blood As levels (median, IQR) were significantly higher in CKDu 91.97 (1.3–132.7) µg/L compared to CKD 4.5 (0.0–58.8) µg/L and healthy subjects 39.01 (4.8–67.4) µg/L (p < 0.001) On multinominal regression age and sex adjusted blood As was independently associated with CKDu[ OR 1.013 (95%CI 1.003–1.024) P < .05].Blood and urinary Cd, Pb, and Cr were higher in CKD compared to CKDu (p > .05). Urinary Cd, Pb and Cr were undetectable in healthy subjects and were significantly higher in CKDu and CKD compared to healthy subjects (P = < 0.001). There was a significant correlation of Cd, Pb and Cr in blood and urine with each other in CKDu and CKD subjects as compared to healthy subjects. Surface water use also associated with CKDu [OR 3.178 (95%CI 1.029–9.818) p < .05).ConclusionThe study showed an independent association of age and sex adjusted blood As with CKDu in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were found to have significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu subjects had significantly higher pesticide and surface water usage, which may be the source of differential As exposure in these subjects.

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.

#5940 CLINICAL UTILITY OF GENETIC TESTING IN A KIDNEY TRANSPLANT CLINIC

Abstract Background and Aims Inherited kidney disease (IKD) is one of the leading causes of end-stage of kidney disease. Genetic diagnosis plays an important role in the counseling and management of kidney transplant patients or those on the waiting list, as it makes it possible to identify the cause of CKD, help in the selection of living donors, carry out genetic counseling and find out the prognosis around the graft survival and the risk of recurrence of the primary disease. The objective of the following study is to analyze the prevalence of IKD in our kidney transplant population and those on the waiting list, the phenotypic characteristics, genetic findings, and the diagnostic reclassification performed after the genetic study. Method This retrospective study has incluyed all genetic test (by next-generation sequencing (NGS) until 529 genes associated with kidney disease) performance between January 2018 and January 2023 in kidney transplant patients or on the waiting list for kidney transplant at Doctor Peset Hospital, using a multidisciplinary team approach. The patients were considered for genomic evaluation if they met one of the inclusion criteria: CKD of unknown etiology, family history of CKD, glomerular disease or chronic tubulo–interstitial disease with no recognized cause, suspicion of aHUS, CKD and other extrarenal syndromic signs or with renal malformations or nephrocalcinosis. Demographic data, family burden and screening, CKD phenotype, urinary anormalities, hypertension, diabetes, results of genetic test, were analyzed. Results We performed genetic testing in 76 patients (43,4% women; 88% Caucasian). Median age at time of kidney failure was 37 years (range: 17–77), 62% of patients had a positive family history of CKD and 29% presented extrarenal manifestations. The majority were male patients (56.6%) and Caucasian patients (88.2%). Most patients presented with an original clinical diagnosis glomerular disease 52,6% (FSGS lesion on biopsy (8/27) and non-diagnostic histology (10/27)), followed by ciliopathy (13%), aHUS (10.5%), and chronic kidney disease of unknown cause (6.6%), tubulointerstitial nephritis (6.6%), and with congenital anomalies (6.6%). In 46 patients had a genetic diagnosis defined as finding a pathogenic or likely pathogenic gene variant that explained the patient's kidney disease. With majority being COL4 variants (26.3%), followed by autosomal dominant polycystic kidney disease (ADPKD) (10.5%), podocytopathy and autosomal dominant tubulointerstitial kidney diseases. There were confirmed within a clinical diagnostic in 28% (above all ADPKD) and resulted in reclassification of the clinical diagnosis in 33% (above all COL4-related nephropathy) and there are more frequently a negative result if clinical diagnosis was unknown etiology, congenital anomalies o aHUS until 60%. With this data, 78% of the patients could have avoided a biopsy and 50% a immunossuppresive treatment with the diagnosis by genetic test. A genetic cause was identified by family screening in 16 families comprising 19 patients. A genetic diagnosis were more likely to have a family history of kidney disease (47,4% versus 14,5%, P &amp;lt; 0.001). There was otherwise no statistically significant difference in any other clinical characteristic (age at onset of kidney disease, age at kidney failure, race, hypertension, diabetes, hematuria, renal cyst or stone). Conclusion Our study demonstrates the clinical utility of genetic study in kidney transplants with unknown etiology or glomerulonephritis or chronic tubule-interstitial disease with no recognized cause or with positive family history of kidney disease, getting a genetic diagnosis until 60%, with a reclassification of the clinical diagnosis in a one-third. A genetic diagnosis is necessary to evaluate to kidney transplant recipients, to identify the etiology of CKD, to perform a genetic counseling and to improve patient management and prognosis.

Safety of Stromal Vascular Fraction Cell Therapy for Chronic Kidney Disease of Unknown Cause (Mesoamerican Nephropathy)

Chronic kidney disease of unknown cause (CKDu), also known as Mesoamerican nephropathy, typically presents as an ischemic nephropathy with chronic tubulointerstitial fibrosis in normotensive patients, rapidly progressing to kidney failure. In this first-in-human, open-label, safety study, we followed 18 patients with CKDu (stages 3-5) for 36 months after receiving a single infusion of angiogenic/anti-fibrotic autologous adipose-derived stromal vascular fraction (SVF) cells into their kidneys bilaterally via renal artery catheterization. SVF therapy was safe and well tolerated. There were no SVF-related serious adverse events and no procedural complications. Color Doppler evaluation at 2 months demonstrated increased perfusion to the interlobar and/or arcuate artery levels in each kidney evaluated (36/36) with a reduction in resistance index at the hilar artery (35/36) kidneys. Beyond 12 months, patients with initial eGFR <30 mL/minute/1.73 m2 deteriorated, whereas those ≥30 mL/minute/1.73 m2 further sustained their renal function, suggesting a possible renal protective effect in that group.

"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.

Association of Pesticides and Kidney Function among Adults in the US Population 2001-2010.

Chronic kidney disease of unknown cause is prevalent in a range of communities; however, its etiology remains unclear. We examined the association between pesticide exposures and the risk of kidney function loss using four waves of the National Health and Nutrition Examination Survey (NHANES) to identify a pathological pathway. We pooled data from four cross-sectional waves of NHANES, with 41,847 participants in total. Exposure to malathion increased the risk of low kidney function (aOR = 1.26, 95% CI = 1.01–1.56) in the adjusted model. Increased risk of low kidney function was not found among those exposed to 2,4-D (aOR = 0.88, 95% CI = 0.72–1.09), 3,5,6-trichloropyridinol (aOR = 0.96, 95% CI = 0.83–1.12), and 3-PBA (aOR = 1.03, 95% CI = 0.94–1.13). Our findings provide evidence of altered kidney function in people exposed to malathion, highlighting the potential of organophosphate pesticides’ role in renal injury.

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.

Neglected Tropical Diseases and the Kidneys.

Clinical Background: Neglected tropical diseases (NTDs), a major public health problem, frequently affect the kidneys. In this chapter, we discuss the NTDs which have been most studied in terms of renal involvement and present a summary of current knowledge regarding kidney disease in all NTDs, through a literature review. Epidemiology: There are more than 1 billion people in the world affected by NTDs. These infections can also be one of the etiologies of chronic kidney disease of unknown cause, which is another great public health problem in Latin America, and these diseases are most prevalent in young people, males, in their productive years, which increases its burden on the society. Challenges: Early detection of renal involvement is crucial to decrease the magnitude of the manifestations and hence allow more favorable outcomes, and for this purpose novel kidney injury biomarkers are a promising solution. Unfortunately, specific treatments for NTDs have not changed in the last decades, as novel drugs have not been investigated. Prevention and Treatment: Prevention includes vector control, blood bank tests, periodic serologic surveys, and health surveillance in general in order to decrease oral transmission and to maintain good hygiene conditions. Recently, many potential therapeutic targets have been evidenced in both clinical and experimental studies.

The unresolved epidemic of chronic kidney disease of uncertain origin (CKDu) around theworld: A review and new insights.

An increasing number of inhabitants of Central America have developed a form of chronic kidney disease of unknown cause, named Mesoamerican nephropathy (MeN). Because similar epidemics have been reported in other parts of the world, such as Sri Lanka, India, Egypt, and Tunisia, this condition is currently called chronic kidney disease of uncertain origin (CKDu). This disease is characterized by minimal proteinuria, leukocyturia, hyperuricemia, hypokalemia reduced glomerular filtration rate, and renal tubular dysfunctions. Pathology: The kidneys manifest tubulo-interstitial nephritis and glomerulosclerosis. Electron microscopy shows large dimorphic lysosomes with dark electron-dense aggregates. Potential causes: The cause(s) of this disease remain largely unknown. Several hypotheses have been proposed including infections, dehydration, global warming, hyperuricemia, exposure to agro-chemicals or heavy metals, and genetic susceptibility. This review addresses a mounting body of evidence suggesting that the disease may be the result of exposure to a variety of water contaminants combined with volume depletion. Absent a clear understanding of the causes of the disease, no specific therapeutic interventions can be recommended. Preliminary studies suggest that reduction of working hours, frequent rest in shaded area, and administration of purified water may reduce the risk of CKDu.

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.

Delayed diagnoses of mitochondrial cytopathies in patients presenting with end stage kidney disease: two case reports

BackgroundUp to one third of patients on renal replacement programmes have an unknown cause of kidney disease, and the diagnosis may only be established following renal transplantation when the disease recurs or if new extra-renal symptoms develop.Case presentationWe present two patients who presented with progressive chronic kidney disease of unknown cause. Both patients underwent successful renal transplantation but subsequently developed multisystem abnormalities, and were ultimately diagnosed with mitochondrial cytopathy 10–15 years following transplantation.ConclusionsMitochondrial cytopathies are rare inborn errors of metabolism that should be considered in adults with renal impairment, especially in those with a family history of kidney or other multisystem disease. The widespread availability of genetic testing provides the potential for earlier diagnoses, thereby enhancing management decisions, anticipation of complications, avoidance of mitotoxic drugs, and informed prognosis prediction.

Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? Commentary.

The environmental nephrotoxin component as the etiology for CKD of unknown cause (CKDu) has been elegantly discussed in a debate by De Broe (pro) (1) and Wesseling (con) (2) in this issue of Kidney360 . The etiology of CKDu has been a topic of enormous controversy, and it seems that this same controversy has characterized this disease. Although it is currently unclear whether there is a unified underlying cause, these conditions have been collectively termed CKDu, but various names have emerged. They include the following: CKD of nontraditional cause, Mesoamerican nephropathy, chronic interstitial nephritis in agricultural communities, and kidney disease of unknown cause in agricultural laborers. I will refer to CKDu in my piece as it is a preferred and neutral term. It is evident that simple things, such as naming the disease or establishing a definition for CKDu, have generated enormous difficulties that create obstacles to the detection and optimal treatment. I would argue, however, that we do have consensus in some CKDu areas. First, we agree that those affected by CKDu do not have traditional risk factors or underlying conditions that lead to CKD, such as older age, diabetes mellitus, hypertension, GN, or structural kidney disease. …

Clinical and genetic variability of PAX2-related disorder in the Japanese population.

Pathogenic variants of paired box gene 2 (PAX2) cause autosomal-dominant PAX2-related disorder, which includes renal coloboma syndrome (RCS). Patients with PAX2-related disorder present with renal and ophthalmological pathologies, as well as with other abnormalities, including developmental problems and hearing loss. We sequenced PAX2 in 457 patients with congenital anomalies of the kidney and urinary tract or with renal dysfunction of unknown cause and identified 19 different pathogenic variants in 38 patients from 30 families (6.5%). Thirty-four patients had renal hypodysplasia or chronic kidney disease of unknown cause, and three had focal segmental glomerulosclerosis. Although no obvious genotype-phenotype correlation was observed, six of the seven patients who developed end-stage renal disease in childhood had truncating variants. Twenty-three patients had ocular disabilities, mostly optic disc coloboma. Non-renal and non-ophthalmological manifestations included developmental disorder, electrolyte abnormality, and gonadal abnormalities. Two unrelated patients had congenital cystic adenomatoid malformations in their lungs. Six of ten probands with PAX2 mutation identified by next-generation sequencing did not show typical RCS manifestations. We conclude that PAX2-related disorder has a variable clinical presentation and can be diagnosed by next-generation sequencing even in the absence of typical RCS manifestations.

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. .

Climate change and kidney disease

Journal of Kidney CareVol. 4, No. 6 Keeping Up with Kidney CareClimate change and kidney diseasePeter EllisPeter EllisEmail: E-mail Address: [email protected]Registered Manager, Whitepost Healthcare and Independent Nursing and Educational Consultant, KentSearch for more papers by this authorPeter EllisPublished Online:9 Dec 2019https://doi.org/10.12968/jokc.2019.4.6.344AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View articleReferencesGeraghty RM, Proietti S, Traxer O, Archer M, Somani BK. Incidence of renal colic and kidney stone disease: evidence from a systematic review of literature. J Endourol. 2017; 31(8): 729–735. https://doi.org/10.1089/end.2017.0123 Google ScholarJohnson RJ, Wesseling C, Newman LS. Chronic kidney disease of unknown cause in agricultural communities. N Engl J Med. 2019; 380(19):1843–1852. https://doi.org/10.1056/NEJMra1813869 Google ScholarSorenson C, Garcia-Trabanino R. A new era of climate medicine—addressing heat-triggered renal disease. N Engl J Med. 2019; 381(8):693–696. https://doi.org/10.1056/NEJMp1907859 Google ScholarWorld Health Organization. Climate change and health. 2018. https://www.who.int/news-room/fact-sheets/detail/climate-change-and-health (accessed 14 November 2019) Google Scholar FiguresReferencesRelatedDetails 2 November 2019Volume 4Issue 6ISSN (print): 2397-9534ISSN (online): 2397-9542 Metrics History Published online 9 December 2019 Published in print 2 November 2019 Information© MA Healthcare LimitedPDF download

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.