Chronic Kidney Disease Of Uncertain Etiology Research Articles

The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project

Background and aimsGenetic testing presents a unique opportunity for diagnosis and management of genetic kidney diseases (GKD). Here, we describe the clinical utility and valuable impact of a specialized GKD clinic, which uses a variety of genomic sequencing strategies.MethodsIn this prospective cohort study, we undertook genetic testing in adults with suspected GKD according to prespecified criteria. Over 7 years, patients were referred from tertiary centres across Ireland to an academic medical centre as part of the Irish Kidney Gene Project.ResultsAmong 677 patients, the mean age was of 37.2 ± 13 years, and 73.9% of the patients had family history of chronic kidney disease (CKD). We achieved a molecular diagnostic rate of 50.9%. Four genes accounted for more than 70% of identified pathogenic variants: PKD1 and PKD2 (n = 186, 53.4%), MUC1 (8.9%), and COL4A5 (8.3%). In 162 patients with a genetic diagnosis, excluding PKD1/PKD2, the a priori diagnosis was confirmed in 58% and in 13% the diagnosis was reclassified. A genetic diagnosis was established in 22 (29.7%) patients with CKD of uncertain aetiology. Based on genetic testing, a diagnostic kidney biopsy was unnecessary in 13 (8%) patients. Presence of family history of CKD and the underlying a priori diagnosis were independent predictors (P < 0.001) of a positive genetic diagnosis.ConclusionsA dedicated GKD clinic is a valuable resource, and its implementation of various genomic strategies has resulted in a direct, demonstrable clinical and therapeutic benefits to affected patients.Graphical abstract

Heavy metal concentrations in the edible portions of Centella asiatica: Health risk toward chronic kidney disease of uncertain etiology

Centella asiatica is a commonly consumed green leafy vegetable in many developing countries due its high nutritious value and availability at low cost. The present study was conducted to assess the Cd, Cr and Pb uptake associated health risks of Centella asiatica harvested from organic and non-organic cultivations in a chronic kidney disease of uncertain etiology (CKDue) prevalent area in Sri Lanka. The health risk assessment was conducted in terms of the bioconcentration factor (BCF), soil-to-root and root-to-leaf translocation factors ({text{TF}},({text{soil-root}}) and {text{TF}},({text{root-leaf}})), Target hazard quotient for each heavy metal (THQ) and hazard index (HI). In addition, the spatial variation of physical and chemical parameters of the root zone soil were assessed using MINITAB 17 statistical software. Results indicated significant spatial variations in conductivity, organic matter content and Cr concentrations among organic and non-organic study sites. The Cr, Cd and Pb concentrations recorded from roots and leaves of Centella asiatica were higher than the safe limits for consumption established by the European Union. The health risk analysis indicated that there is a potential of hyper-accumulating Cd in the roots of Centella asiatica. Further, the THQ and HI of the heavy metals indicated possible adverse non-cancer health risks associated with long-term consumption of leaves of Centella asiatica. Therefore, necessary precautionary actions to prevent the excessive buildup of Cr, Cd and Pb in the edible portions of Centella asiatica are essential in order to ensure consumer safety.

Burden of Diabetes Mellitus in a Community Resident in an Area Designated as “High Risk” for Chronic Kidney Disease of Unknown Origin in Sri Lanka

Chronic kidney disease (CKD) where etiology cannot be attributed to any known etiology is named CKD of uncertain etiology (CKDu). The main aims of this study were to assess the prevalence of diabetes mellitus (DM), treatment coverage, and glycemic control and its effect on renal function of patients with DM in a rural community affected by CKDu in Sri Lanka. A cross-sectional representative household survey (n = 4803) was conducted in Anuradhapura district. A random blood sugar (RBS), blood pressure, bio-impedance measurements, and renal profile were measured using standard instruments and protocols. Prevalence of DM based on self-reports verified by records was 7.9% (95% confidence interval [CI]: 7.1–8.7). Among the 4425 who did not give a history of being diagnosed ever as having DM, 2.1% (95% CI: 1.7–2.5) were classified as “possible diabetes” (RBS of more than 200 mg/dl with no history of DM). Although 76.2% were on treatment, glycemic control was poor in 40.2% (95% CI: 34.9–45.0). The presence of DM was associated with poor renal function. One in ten individuals in the rural district of Anuradhapura has possible DM. DM poses a significant burden to CKD even in populations affected by CKDu. Hence, public health initiatives should be implemented to control both CKDu and DM in these rural communities.

Современные аспекты формирования и прогрессирования фтор-ассоциированной хронической болезни почек

Difficulties associated with the identification of a major risk factor for chronic kidney disease (CKD) (mainly in children without obvious anatomical causes), long-lasting asymptomatic phase, and irreversible kidney damage caused by chemical elements resulted in a particular interest to the problem of diagnosis and timely treatment of CKD. This review aims to summarize available information on the role of increased fluoride concentration in the development of CKD of uncertain etiology. We included more than 200 publications found in Scopus, Web of Science, Cochrane Library, and PubMed. We analyzed factors associated with an increased risk of fluoride-related CKD and identified possible mechanisms underlying disease progression. In addition to that, we proposed potential molecular markers to detect early stages of CKD. We described new promising therapeutic targets with the consideration of key elements of disease pathogenesis, poor prognosis, and age limits for existing nephroprotective drugs. Key words: fluoride, chronic kidney disease, risk factors, pathogenesis, molecular markers

SUN-258 ASSOCIATION BETWEEN AIR POLLUANTS AND GLOBAL BURDEN OF DISEASE IN CHRONIC KIDNEY DISEASE: A SYSTEMIC REVIEW AND META-ANALYSIS

Chronic kidney disease (CKD) is a prevalent disease conferring high burden worldwide, with a plethora of known risk factors. CKD of uncertain etiology (CKDu) denotes CKD which cannot be attributable to traditional risk factors. It is well recognized that the identification of modifiable risk factors for CKD is crucial for reducing its heavy global burden of disease (GBD), but our effort in uncovering non-traditional risk factors is still far from adequacy. To assess the association between air pollution and the risk of CKD, including incident case and renal function decline. Systematic review, random-effects meta-analysis, and population attributable fraction (PAF) was utilized to evaluate the proportion of disease burden that could be prevented. Electronic literature search of Cochrane Library, PubMed, Medline, and Embase for studies published up to March 2018 without language restriction. Studies investigating the association between the increases in gaseous (carbon monoxide, sulphur dioxide, nitrogen dioxide, ozone) or particulate [diameter < 2·5 μm (PM2·5) or <10 μm (PM10)] air pollutants and CKD, end-stage renal disease or renal dysfunction. We used a random-effects model to derive overall risk estimates per pollutant. Of 3,989 identified articles, 18 met inclusion criteria after screening and 10 were included in the meta-analysis. Pooled effect estimates showed that summary risk ratio (RR) for CKD per 10 μg/m3 increase in PM2.5 was 1.12 (95% confidence interval [CI] 0.97 - 1.29) and 1.16 (95% CI 1.05 - 1.29) for PM10; per 10 ppm increase in CO was 1.31 (95% CI 0.86 - 2.00); and per 10 ppb increase in NO2 was 1.11 (95% CI 1.09 - 1.14). For the pooled effect on estimated glomerular filtration rate (eGFR), an increase in PM10 (per 10 μg/m3) was significantly associated with lower eGFR by -0.83 (95% CI -1.54 - -0.12) mL/min/1.73 m2, while an increase in PM2.5 showed a trend toward faster eGFR decline. Also, an estimated 67.3 million excess prevalent CKD cases globally were attributable to PM2.5 exposure (population attributable fraction=24.6%; 95% uncertainty interval -1.9% - 43.2%). Air pollution is closely associated with CKD and renal function decline. Although more cross-national studies are required, air pollution can be pervasive for kidney health and should remain a prime focus among global health policy.

Prevalence and determinants of the metabolic syndrome among subjects with advanced nondiabetes-related chronic kidney disease in Gran Canaria, Spain

Background The relationship between the metabolic syndrome and mild chronic kidney disease (CKD) has been extensively studied. This study was aimed to estimate the prevalence and factors associated with the metabolic syndrome among subjects with advanced stages of nondiabetes-related CKD. Methods Study population was composed of incident patients with advanced CKD not related to diabetes in a tertiary hospital from Gran Canaria (Spain) since February 2011 to December 2014. Participants fulfilled a survey questionnaire and underwent physical examination and biochemical evaluation. Results The sample was composed of 167 subjects (mean age 63.9 ± 13.7 years; estimated glomerular filtration rate 21.9 ± 6.6 mL/min/1.73 m2). The prevalence of the metabolic syndrome was 68.9% (65.2% in men and 73.3% in women). Highest rates were observed in groups with chronic interstitial nephropathy (80%), CKD of uncertain etiology (76.7%) and CKD related to vascular causes (76.2%). Subjects with metabolic syndrome were older, had higher values of C-reactive protein and more often reported to have first-degree relatives with diabetes and to be physically inactive. In multivariate analyses, age (OR: 1.034 [CI 95%: 1.004–1.065]; p = 0.024) and family history of diabetes (OR: 2.550 [1.159–5.608]; p = 0.020) were independently associated with the metabolic syndrome. Conclusions The prevalence of the metabolic syndrome among subjects with advanced nondiabetes-related CKD is high, and greater than that observed in general Canarian population of similar age groups. Age and family history of diabetes are the two factors more strongly associated with the metabolic syndrome in this population.

Evidence of tubular damage in the very early stage of chronic kidney disease of uncertain etiology in the North Central Province of Sri Lanka: a cross-sectional study

In the North Central Province of Sri Lanka, chronic kidney disease of uncertain etiology (CKDue) has increased markedly over the past 15-20years. From around 4,700 patients who were followed up, 106 affected patients who visited two local clinics in the endemic area for CKDue on August 10, 2009 and 10 pedigrees of 10 of these cases with familial clustering of CKDue participated in this study. Urine samples, collected from affected patients (n=106), unaffected relative controls (n=81), and Japanese controls (n=50), were analyzed for two tubular markers: α1-microglobulin and N-acetyl-β-D: -glucosaminidase. Urine samples from patients with CKDue stages 1-4 (n=101) and all the samples from unaffected relatives and Japanese controls were analyzed for urinary cadmium concentration. Urinary excretion of α1-microglobulin was elevated even in the earliest stage of CKDue compared with its levels in unaffected relative controls. Urinary excretion of N-acetyl-β-D: -glucosaminidase was elevated only in stage 5. In contrast, urinary cadmium excretion was similar in CKDue patients and in the unaffected relative controls, and levels in both these groups were significantly lower than the level in the Japanese controls. All levels were below the threshold level for renal toxicity, indicating the absence of any evidence of cadmium toxicity. The present study indicates that renal tubular damage occurs in the very early stage of CKDue and demonstrates the existence of familial clustering, suggesting that CKDue is likely to be the outcome of exposure to an unknown nephrotoxin in susceptible subjects in the endemic region.