Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

Racial Disparities in Access to and Outcomes of Kidney Transplantation in Children, Adolescents, and Young Adults: Results From the ESPN/ERA-EDTA (European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association) Registry.

BACKGROUND Racial disparities in kidney transplantation in children have been found in the United States, but have not been studied before in Europe. STUDY DESIGN Cohort study. SETTING & PARTICIPANTS Data were derived from the ESPN/ERA-EDTA Registry, an international pediatric renal registry collecting data from 36 European countries. This analysis included 1,134 young patients (aged ≤19 years) from 8 medium- to high-income countries who initiated renal replacement therapy (RRT) in 2006 to 2012. FACTOR Racial background. OUTCOMES & MEASUREMENTS Differences between racial groups in access to kidney transplantation, transplant survival, and overall survival on RRT were examined using Cox regression analysis while adjusting for age at RRT initiation, sex, and country of residence. RESULTS 868 (76.5%) patients were white; 59 (5.2%), black; 116 (10.2%), Asian; and 91 (8.0%), from other racial groups. After a median follow-up of 2.8 (range, 0.1-3.0) years, we found that black (HR, 0.49; 95% CI, 0.34-0.72) and Asian (HR, 0.54; 95% CI, 0.41-0.71) patients were less likely to receive a kidney transplant than white patients. These disparities persisted after adjustment for primary renal disease. Transplant survival rates were similar across racial groups. Asian patients had higher overall mortality risk on RRT compared with white patients (HR, 2.50; 95% CI, 1.14-5.49). Adjustment for primary kidney disease reduced the effect of Asian background, suggesting that part of the association may be explained by differences in the underlying kidney disease between racial groups. LIMITATIONS No data for socioeconomic status, blood group, and HLA profile. CONCLUSIONS We believe this is the first study examining racial differences in access to and outcomes of kidney transplantation in a large European population. We found important differences with less favorable outcomes for black and Asian patients. Further research is required to address the barriers to optimal treatment among racial minority groups.

Examination of the influence of behavioral, normative and control beliefs on the adherence to a prescribed renal diet among elderly populations with chronic to end-stage renal disease

The 1999-2004 prevalence of chronic kidney disease in adults 20 year or older (15.5 million) is an estimated 7.69%. The risk of developing CKD is exacerbated by diabetes, hypertension and/or a family history of kidney disease. African Americans, Hispanics, Pacific Islanders, Native Americans, and the elderly are more susceptible to higher incidence of CKD. The challenges of aging coupled with co-morbidities such as kidney disease raises the potential for malnutrition among elderly (for the purpose of this study 55 years or older) populations. Lack of adherence to prescribed nutrition guidelines specific to renal failure jeopardizes body homeostasis and increases the likelihood of future morbidity and resultant mortality. The relationship and synergy that exists between diet and disease is evident. Clinical experience with renal patients has indicated the importance of adherence to diet therapy specific to kidney disease. Extension investigation of diet adherence among endstage renal disease patients revealed a sizeable dearth in the current literature. This thesis study was undertaken to help reduce that void. The study design is qualitative and descriptive. Support, cooperation, and collaboration were provided by the University of Texas Nephrology Department, University of Texas Physicians, and DaVita Dialysis Centers. Approximately 105 male and female chronic to end-stage kidney disease patients were approached to participate in elicitation interviews in dialysis treatment facilities regarding their present diet beliefs and practices. Eighty-five were recruited and agreed to participate. Inclusion criteria required individuals to be between 35-90 years of age; capable of completing a 5-10 minute interview; and English speaking. Each kidney patient was asked seven (7) non-leading questions developed from the constructs of the Theory of Planned Behavior. The study presents a descriptive comparison of behavioral, normative, and control beliefs that influence adherence to renal diets by age, race, and gender. The study successfully concluded that behavioral, normative, and control beliefs of chronic to end-stage renal patients promoted execution and adherence to prescribed nutrition. This study provides valuable information for dietitians, technicians, nurses, and physicians to assess patient compliance toward prescribed nutrition and the means to support or improve that performance. ^

Immunolocalization of ion transport proteins in human autosomal dominant polycystic kidney epithelial cells.

The kidneys of patients with autosomal dominant polycystic kidney disease become massively enlarged due to the progressive expansion of myriad fluid-filled cysts. The epithelial cells that line the cyst walls are responsible for secreting the cyst fluid, but the mechanism through which this secretion occurs is not well established. Recent studies suggest that renal cyst epithelial cells actively secrete Cl across their apical membranes, which in turn drives the transepithelial movement of Na and water. The characteristics of this secretory flux suggest that it is dependent upon the participation of an apical cystic fibrosis transmembrane conductance regulator (CFTR)-like Cl channel and basolateral Na,K-ATPase. To test this hypothesis, we have immunolocalized the CFTR and Na,K-ATPase proteins in intact cysts and in cyst epithelial cells cultured in vitro on permeable filter supports. In both settings, cyst epithelial cells were found to possess Na,K-ATPase exclusively at their basolateral surfaces; apical labeling was not detected. The CFTR protein was present at the apical surfaces of cyst epithelial cells that had been stimulated to secrete through incubation in forskolin. CFTR was detected in intracellular structures in cultured cyst epithelial cells that had not received the forskolin treatment. These results demonstrate that the renal epithelial cells that line cysts in autosomal dominant polycystic kidney disease express transport systems with the appropriate polarity to mediate active Cl and fluid secretion.

Urinary Biomarkers Indicative of Apoptosis and Acute Kidney Injury in the Critically Ill.

BACKGROUND Apoptosis is a key mechanism involved in ischemic acute kidney injury (AKI), but its role in septic AKI is controversial. Biomarkers indicative of apoptosis could potentially detect developing AKI prior to its clinical diagnosis. METHODS As a part of the multicenter, observational FINNAKI study, we performed a pilot study among critically ill patients who developed AKI (n = 30) matched to critically ill patients without AKI (n = 30). We explored the urine and plasma levels of cytokeratin-18 neoepitope M30 (CK-18 M30), cell-free DNA, and heat shock protein 70 (HSP70) at intensive care unit (ICU) admission and 24h thereafter, before the clinical diagnosis of AKI defined by the Kidney Disease: Improving Global Outcomes -creatinine and urine output criteria. Furthermore, we performed a validation study in 197 consecutive patients in the FINNAKI cohort and analyzed the urine sample at ICU admission for CK-18 M30 levels. RESULTS In the pilot study, the urine or plasma levels of measured biomarkers at ICU admission, at 24h, or their maximum value did not differ significantly between AKI and non-AKI patients. Among 20 AKI patients without severe sepsis, the urine CK-18 M30 levels were significantly higher at 24h (median 116.0, IQR [32.3-233.0] U/L) than among those 20 patients who did not develop AKI (46.0 [0.0-54.0] U/L), P = 0.020. Neither urine cell-free DNA nor HSP70 levels significantly differed between AKI and non-AKI patients regardless of the presence of severe sepsis. In the validation study, urine CK-18 M30 level at ICU admission was not significantly higher among patients developing AKI compared to non-AKI patients regardless of the presence of severe sepsis or CKD. CONCLUSIONS Our findings do not support that apoptosis detected with CK-18 M30 level would be useful in assessing the development of AKI in the critically ill. Urine HSP or cell-free DNA levels did not differ between AKI and non-AKI patients.

Nephron number, hypertension, renal disease, and renal failure

Essential hypertension is one of the most common diseases in the Western world, affecting about 26.4% of the adult population, and it is increasing (1). Its causes are heterogeneous and include genetic and environmental factors (2), but several observations point to an important role of the kidney in its genesis (3). In addition to variations in tubular transport mechanisms that could, for example, affect salt handling, structural characteristics of the kidney might also contribute to hypertension. The burden of chronic kidney disease is also increasing worldwide, due to population growth, increasing longevity, and changing risk factors. Although single-cause models of disease are still widely promoted, multideterminant or multihit models that can accommodate multiple risk factors in an individual or in a population are probably more applicable (4,5). In such a framework, nephron endowment is one potential determinant of disease susceptibility. Some time ago, Brenner and colleagues (6,7) proposed that lower nephron numbers predispose both to essential hypertension and to renal disease. They also proposed that hypertension and progressive renal insufficiency might be initiated and accelerated by glomerular hypertrophy and intraglomerular hypertension that develops as nephron number is reduced (8). In this review, we summarize data from recent studies that shed more light on these hypotheses. The data supply a new twist to possible mechanisms of the Barker hypothesis, which proposes that intrauterine growth retardation predisposes to chronic disease in later life (9). The review describes how nephron number is estimated and its range and some determinants and morphologic correlates. It then considers possible causes of low nephron numbers. Finally, associations of hypertension and renal disease with reduced nephron numbers are considered, and some potential clinical implications are discussed.

The relationship between high-sensitivity CRP and polyclonal Free Light Chains as markers of inflammation in chronic disease

Introduction: Serum concentrations of polyclonal free light chains (FLC) represent the activity of the adaptive immune system. This study assessed the relationship between polyclonal FLC and the established marker of innate immunity, C-reactive protein (CRP), in chronic and acute disease. Methods: We utilized four cross-sectional chronic disease patient cohorts: chronic kidney disease (CKD), diabetes, vasculitis and kidney transplantation; and a longitudinal intensive care case series to assess the kinetics of production in acute disease. Results: There was a weak association between polyclonal FLC and high-sensitivity CRP (hs-CRP) in the study cohorts. A longitudinal assessment in acute disease showed a gradual increase in FLC concentrations over time, often when CRP levels were falling, demonstrating clear differences in the response kinetics of CRP and FLC in this setting. Conclusion: Polyclonal FLC and hs-CRP provide independent information as to inflammatory status. Prospective studies are now required to assess the utility of hs-CRP and polyclonal FLC in combination for risk stratification in disease populations. © 2013 John Wiley & Sons Ltd.

Ankyrin is the major oxidised protein in erythrocyte membranes from end-stage renal disease patients on chronic haemodialysis and oxidation is decreased by dialysis and vitamin C supplementation

Chronically haemodialysed end-stage renal disease patients are at high risk of morbidity arising from complications of dialysis, the underlying pathology that has led to renal disease and the complex pathology of chronic kidney disease. Anaemia is commonplace and its origins are multifactorial, involving reduced renal erythropoietin production, accumulation of uremic toxins and an increase in erythrocyte fragility. Oxidative damage is a common risk factor in renal disease and its co-morbidities and is known to cause erythrocyte fragility. Therefore, we have investigated the hypothesis that specific erythrocyte membrane proteins are more oxidised in end-stage renal disease patients and that vitamin C supplementation can ameliorate membrane protein oxidation. Eleven patients and 15 control subjects were recruited to the study. Patients were supplemented with 2 × 500 mg vitamin C per day for 4 weeks. Erythrocyte membrane proteins were prepared pre- and post-vitamin C supplementation for determination of protein oxidation. Total protein carbonyls were reduced by vitamin C supplementation but not by dialysis when investigated by enzyme linked immunosorbent assay. Using a western blot to detect oxidised proteins, one protein band, later identified as containing ankyrin, was found to be oxidised in patients but not controls and was reduced significantly by 60% in all patients after dialysis and by 20% after vitamin C treatment pre-dialysis. Ankyrin oxidation analysis may be useful in a stratified medicines approach as a possible marker to identify requirements for intervention in dialysis patients.

Risk factors of coronary heart disease and correlates of type 2 diabetes among Cuban Americans

Cuban Americans, a minority Hispanic subgroup, have a high prevalence of type 2 diabetes. Persons with diabetes experience a higher rate of coronary heart disease (CHD) compared to those without diabetes. The objectives of the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) are to investigate the risk factors of CHD and the etiology of diabetes among diabetics of minority ethnic populations. No information is available on the etiology of CHD risks for Cuban Americans. ^ This cross-sectional study compared Cuban Americans with (N = 79) and without (N = 80) type 2 diabetes residing in South Florida. Data on risk factors of CHD and type 2 diabetes were collected using sociodemographics, smoking habit, Rose Angina, Modifiable Activity, and Willet's food frequency questionnaires. Anthropometrics and blood pressure (BP) were recorded. Glucose, glycated hemoglobin, lipid profile, homocysteine, and C-reactive protein were assessed in fasting blood. ^ Diabetics reported a significantly higher rate of angina symptoms than non-diabetics (P = 0.008). After adjusting for age and gender, diabetics had significantly (P < 0.001) larger waist circumference and higher systolic BP than non-diabetics. There was no significant difference in major nutrient intakes between the groups. One quarter of subjects, both diabetics and non-diabetics, exceeded the intake of percent calories from total fat and almost 60% had cholesterol intake >200 mg/d and more than 60% had fiber intake <20 gm/d. The pattern of physical activity did not differ between groups though, it was much below the recommended level. After adjusting for age and gender, diabetics had significantly (P < 0.001) higher levels of blood glucose, glycated hemoglobin, triglycerides, and homocysteine than non-diabetics. In contrast, diabetics had significantly (P < 0.01) lower levels of high-density lipoprotein cholesterol (HDL-C). ^ Multivariate logistic regression analyses showed that increasing age, male gender, large waist circumference, lack of acculturation, and high levels of triglycerides were independent risk factors of type 2 diabetes. In contrast, moderate alcohol consumption conferred protection against diabetes. ^ The study identified several risk factors of CHD and diabetes among Cuban Americans. Health care providers are encouraged to practice ethno-specific preventive measures to lower the burden of CHD and diabetes in Cuban Americans. ^

Long term effects of gestational hypertension and pre-eclampsia on kidney function : Record linkage study

This research was funded by the Chief Scientists Office, Scotland (CZH/4/659).

Trans-ethnic fine mapping highlights kidney-function genes linked to salt sensitivity

We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans.

Effect of Aging in the Perception of Health-Related Quality of Life in End-Stage Renal Disease Patients under Online-Hemodiafiltration

This work aimed to evaluate how aging could influence patients' perception of health quality of life (HRQOL), as well as, the effect of aging on dialysis adequacy and in hematological, iron status, inflammatory and nutritional markers. In this transversal study were enrolled 305 ESRD patients under online-hemodiafiltration (OL-HDF) (59.67% males; 64.9 ± 14.3 years old). Data about comorbidities, hematological data, iron status, dialysis adequacy, nutritional and inflammatory markers were collected from patient's records. Moreover, HRQOL score, by using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), was assessed. Analyzing the results according to quartiles of age, significant differences were found for some parameters evaluated by the KDQOL-SF instrument, namely for work status, physical functioning and role-physical, which decreased with increasing age. We also found a higher proportion of diabetic patients, a decrease in creatinine, iron, albumin serum levels, transferrin saturation and nPCR, with increasing age. Moreover, significant negative correlations were found between age and mean cell hemoglobin concentration, iron, transferrin saturation, albumin, nPCR, work status, physical functioning and role-physical. In conclusion, our results showed that aging is associated with a decreased work status, physical functioning and role-physical, with a decreased dialysis adequacy, iron availability and nutritional status, and with an increased proportion of diabetic patients and of patients using central venous catheter, as the vascular access. The knowledge of these changes associated with aging, which have impact in the quality of life of the patients, could be useful in their management.

Is renal medullary carcinoma the seventh nephropathy in sickle cell disease? A multi-center Nigerian survey.

Introduction: Previous studies had enlisted renal medullary carcinoma (RMC) as the seventh nephropathy in sickle cell disease (SCD). Clinical experience has contradicted this claim and this study is targeted at refuting or supporting this assumption. Objective: To estimate the prevalence of RMC and describe other renal complications in SCD. Materials and methods: 14 physicians (haematologists and urologists) in 11 tertiary institutions across the country were collated from patients’ case notes and hospital SCD registers. Results: Of the 3,596 registered sickle patients, 2 (0.056%) had been diagnosed with RMC over a ten year period, thereby giving an estimated prevalence rate of 5.6 per 100,000. The most common renal complication reported by the attending physicians was chronic kidney disease (CKD). The frequency of routine renal screening for SCD patients varied widely between centres – most were done at diagnosis, annually or bi-annually. Conclusion: The ten year prevalence of RMC in Nigerian SCD patients was determined to be 5.6 (estimated incidence of 0.56). RMC is not more common in SCD patients and therefore cannot be regarded as a “Seventh Sickle nephropathy”. Most of the managing physicians reported that the commonest nephropathy observed in their SCD patients was chronic kidney disease.

Deficiencies in education and experience in the management of acute kidney injury among Malawian healthcare workers

Background Acute kidney injury (AKI) is a common but under-recognised disease process, which carries a high risk of mortality or chronic complications, such as chronic kidney disease and other organ dysfunction. Management of AKI, however, is suboptimal, both in developed settings and in Malawi. This is partly because of deficiencies in AKI education and training. Aim To establish current levels of AKI education in a range of healthcare workers in Malawi. Methods An AKI symposium was held in Blantyre in March 2015. Delegates were asked to complete a survey at the start of the symposium to assess their clinical experience and education in the management of AKI. Results From 100 delegates, 89 nurses, clinical officers, and physicians, originating from 11 different districts, responded to the survey. Twenty-two percent of healthcare workers (including 28% of district workers of the various cadres and 31% of nurses) had never received teaching on any aspect of renal disease, and 50% (including 63% of district workers and 61% of nurses) had never received teaching specifically on AKI. Forty-four percent did not feel confident managing AKI, and 98% wanted more support managing patients with renal disease. Thirty-four percent (including 55% of district workers) were unaware that haemodialysis was available at Queen Elizabeth Central Hospital (QECH) for the treatment of AKI and 53% (74% of district workers) were unaware that peritoneal dialysis was available for the treatment of AKI in children. Only 33% had ever referred a patient with AKI to QECH. Conclusions There are deficiencies in education about, and clinical experience in, the management of AKI among Malawian healthcare workers, in addition to limited awareness of the renal service available at QECH. Urgent action is required to address these issues in order to prevent morbidity and mortality from AKI in Malawi.