Interactive exploration of adverse events and multimorbidity in CKD.

BACKGROUND AND HYPOTHESIS: Persons with chronic kidney disease (CKD) are at increased risk of adverse events, early mortality, and multimorbidity. A detailed overview of adverse event types and rates from a large CKD cohort under regular nephrological care is missing. We generated an interactive tool to enable exploration of adverse events and their combinations in the prospective, observational German CKD (GCKD) study. METHODS: The GCKD study enrolled 5217 participants under regular nephrological care with an estimated glomerular filtration rate of 30-60 or >60 mL/min/1.73m2 and an overt proteinuria. Cardio-, cerebro- and peripheral vascular, kidney, infection, and cancer events, as well as deaths were adjudicated following a standard operation procedure. We summarized these time-to-event data points for exploration in interactive graphs within an R shiny app. Multivariable adjusted Cox models for time to first event were fitted. Cumulative incidence functions, Kaplan-Meier curves and intersection plots were used to display main adverse events and their combinations by sex and CKD etiology. RESULTS: Over a median of 6.5 years, 10 271 events occurred in total and 680 participants (13.0%) died while 2947 participants (56.5%) experienced any event. The new publicly available interactive platform enables readers to scrutinize adverse events and their combinations as well as mortality trends as a gateway to better understand multimorbidity in CKD: incident rates per 1000 patient-years varied by event type, CKD etiology, and baseline characteristics. Incidence rates for the most frequent events and their recurrence were 113.6 (cardiovascular), 75.0 (kidney), and 66.0 (infection). Participants with diabetic kidney disease and men were more prone to experiencing events. CONCLUSION: This comprehensive explorative tool to visualize adverse events (https://gckd.diz.uk-erlangen.de/), their combination, mortality, and multimorbidity among persons with CKD may manifest as a valuable resource for patient care, identification of high-risk groups, health services, and public health policy planning.

Spot urinary sodium in CKD patients: correlation with 24h-excretion and evaluation of commonly used prediction equations.

BACKGROUND: Salt intake in CKD patients can affect cardiovascular risk and kidney disease progression. Twenty-four hour (24h) urine collections are often used to investigate salt metabolism but are cumbersome to perform. We assessed urinary sodium (U-Na) concentration in spot urine samples and investigated the correlation with 24h U-Na excretion and concentration in CKD patients under nephrological care. Further, we studied the role of CKD stage and diuretics and evaluated the performance of commonly used formulas for the prediction of 24h U-Na excretion from spot urine samples. METHODS: One hundred eight patients of the German Chronic Kidney Disease (GCKD) study were included. Each participant collected a 24h urine and two spot urine samples within the same period. The first spot urine sample (AM) was part of the second morning urine. The second urine sample was collected before dinner (PM). Patients were advised to take their medication as usual without changing dietary habits. U-Na concentrations in the two spot urine samples and their average ((AM + PM)/2) were correlated with U-Na concentration and total Na excretion in the 24h urine collections. Correlations were subsequently studied after stratification by CKD stage and diuretic intake. The usefulness of three commonly applied equations to estimate 24h U-Na excretion from spot urine samples (Kawasaki, Tanaka and Intersalt) was determined using Bland-Altman plots, analyses of sensitivity, specificity, as well as positive (PPV) and negative predictive values (NPV). RESULTS: Participants (42 women, 66 men) were on average (± SD) 62.2 (± 11.9) years old, with a mean serum creatinine of 1.6 (± 0.5) mg/dl. 95% had arterial hypertension, 37% diabetes mellitus and 55% were on diuretics. The best correlation with 24h U-Na total excretion was found for the PM spot U-Na sample. We also found strong correlations when comparing spot and 24h urine U-Na concentration. Correction of spot U-Na for U-creatinine did not improve strength of correlations. Neither CKD stage, nor intake of diuretics had significant impact on these correlations. All examined formulas revealed a significant mean bias. The lowest mean bias and the strongest correlation between estimated and measured U-Na excretion in 24h were obtained using the Tanaka-formula. Also, application of the Tanaka-formula with PM U-Na provided best sensitivity, specificity, PPV and NPV to estimate U-Na excretion > 4g/d corresponding to a salt consumption > 10g/d. CONCLUSION: U-Na concentration of spot urine samples correlated with 24h U-Na excretion especially when PM spot U-Na was used. However, correlation coefficients were relatively low. Neither CKD stage nor intake of diuretics appeared to have an influence on these correlations. There was a significant bias for all tested formulas with the Tanaka-formula providing the strongest correlation with measured 24h U-Na excretion. In summary, using spot urine samples together with the Tanaka-formula in epidemiological studies appears feasible to determine associations between approximate salt intake and outcomes in CKD patients. However, the usefulness of spot-urine samples to guide and monitor salt consumption in individual patients remains limited.

Drugs linked to plasma homoarginine in chronic kidney disease patients-a cross-sectional analysis of the German Chronic Kidney Disease cohort.

BACKGROUND: Elevated plasma concentrations of symmetric and asymmetric dimethylarginine (SDMA and ADMA, respectively) and a lower plasma concentration of the structurally related homoarginine are commonly observed in patients with chronic kidney disease (CKD) and independently predict total mortality as well as progression of renal disease. We aimed to identify drugs that may alter this adverse metabolite pattern in a favourable fashion. METHODS: Plasma ADMA, SDMA, homoarginine and l-arginine were determined by liquid chromatography-tandem mass spectrometry in 4756 CKD patients ages 18-74 years with an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 and overt proteinuria who were enrolled in the German Chronic Kidney Disease (GCKD) study. Associations between laboratory, clinical and medication data were assessed. RESULTS: Intake of several commonly used drugs was independently associated with plasma concentrations of homoarginine and/or related metabolites. Among these, the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist fenofibrate was associated with the most profound differences in ADMA, SDMA and homoarginine plasma concentrations: 66 patients taking fenofibrate had a multivariable adjusted odds ratio (OR) of 5.83 [95% confidence interval (CI) 2.82-12.03, P < 0.001] to have a plasma homoarginine concentration above the median. The median homoarginine plasma concentration in patients taking fenofibrate was 2.30 µmol/L versus 1.55 in patients not taking the drug (P < 0.001). In addition, fibrates were significantly associated with lower plasma SDMA and higher l-arginine concentrations. In contrast, glucocorticoids were associated with lower plasma homoarginine, with adjusted ORs of 0.52 (95% CI 0.40-0.67, P < 0.001) and 0.53 (95% CI 0.31-0.90, P = 0.018) for prednisolone and methylprednisolone, respectively. CONCLUSIONS: In a large cohort of CKD patients, intake of fenofibrate and glucocorticoids were independently associated with higher and lower plasma homoarginine concentrations, respectively. Effects on plasma homoarginine and methylarginines warrant further investigation as potential mechanisms mediating beneficial or adverse drug effects.

Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort.

BACKGROUND: Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. METHODS: The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) between 30-60 mL/min/1.73 m(2) or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. RESULTS: At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25(th)-75(th) percentile: 6.8-7.9 %), equalling 53 mmol/mol (51, 63); 24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m(2), 95 % CI 1.02-1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04-1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26-7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77-6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. CONCLUSIONS: Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels.

Multinational Assessment of Accuracy of Equations for Predicting Risk of Kidney Failure: A Meta-analysis.

IMPORTANCE: Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. OBJECTIVE: To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. DATA SOURCES: Thirty-one cohorts, including 721,357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. STUDY SELECTION: Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. DATA EXTRACTION AND SYNTHESIS: Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined using random-effects meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed. MAIN OUTCOMES AND MEASURES: Kidney failure (treatment by dialysis or kidney transplant). RESULTS: During a median follow-up of 4 years of 721,357 participants with CKD, 23,829 cases kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90; 95% CI, 0.89-0.92 at 2 years; C statistic at 5 years, 0.88; 95% CI, 0.86-0.90); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P = .04 and P = .02). CONCLUSIONS AND RELEVANCE: Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary.

Implementation of the KDIGO guideline on lipid management requires a substantial increase in statin prescription rates.

The KDIGO guideline on lipid management in adult patients with chronic kidney disease (CKD) reflects a paradigm shift as proposals for statin use are based on cardiovascular risk rather than cholesterol levels. Statin use is now universally recommended in CKD patients 50 years and older, assuming a 10-year risk of coronary heart disease (CHD) of over 10%. Specific comorbidities or formal risk calculation are required for younger patients. It is unknown to which extent these new guidelines differ from previous practice. Here we analyzed statin use in the German Chronic Kidney Disease study of 5217 adult patients with moderately severe CKD under nephrological care enrolled shortly before publication of the new guideline. Accordingly, 407 patients younger than 50 years would be eligible for statins compared with the 277 patients treated so far, and all 4224 patients 50 years and older would be eligible compared with the 2196 already treated. Overall, guideline implementation would almost double statin prescription from 47 to 88%. Among patients 50 years and older currently not on a statin, an estimated 10-year CHD and atherosclerotic event risks over 10% were present in 68% and 82%, respectively. Thus, implementation of the new lipid guideline requires a substantial change in prescription practice, even in CKD patients under nephrological care. Based on comorbidities and risk estimates, the universal recommendation for statin use in CKD patients 50 years and older appears justified.

Disease burden and risk profile in referred patients with moderate chronic kidney disease: composition of the German Chronic Kidney Disease (GCKD) cohort.

BACKGROUND: A main challenge for targeting chronic kidney disease (CKD) is the heterogeneity of its causes, co-morbidities and outcomes. Patients under nephrological care represent an important reference population, but knowledge about their characteristics is limited. METHODS: We enrolled 5217 carefully phenotyped patients with moderate CKD [estimated glomerular filtration rate (eGFR) 30-60 mL/min per 1.73 m(2) or overt proteinuria at higher eGFR] under routine care of nephrologists into the German Chronic Kidney Disease (GCKD) study, thereby establishing the currently worldwide largest CKD cohort. RESULTS: The cohort has 60% men, a mean age (±SD) of 60 ± 12 years, a mean eGFR of 47 ± 17 mL/min per 1.73 m(2) and a median (IQR) urinary albumin/creatinine ratio of 51 (9-392) mg/g. Assessment of causes of CKD revealed a high degree of uncertainty, with the leading cause unknown in 20% and frequent suspicion of multifactorial pathogenesis. Thirty-five per cent of patients had diabetes, but only 15% were considered to have diabetic nephropathy. Cardiovascular disease prevalence was high (32%, excluding hypertension); prevalent risk factors included smoking (59% current or former smokers) and obesity (43% with BMI >30). Despite widespread use of anti-hypertensive medication, only 52% of the cohort had an office blood pressure <140/90 mmHg. Family histories for cardiovascular events (39%) and renal disease (28%) suggest familial aggregation. CONCLUSIONS: Patients with moderate CKD under specialist care have a high disease burden. Improved diagnostic accuracy, rigorous management of risk factors and unravelling of the genetic predisposition may represent strategies for improving prognosis.

Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study.

BACKGROUND: Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. METHODS: Data from 5085 CKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of 30-<60 mL/min/1.73 m(2) or eGFR ≥60 and overt proteinuria at recruitment and non-missing values for self-reported gout, medications and urate measurements from a central laboratory were evaluated. RESULTS: The overall prevalence of gout was 24.3%, and increased from 16.0% in those with eGFR ≥60 mL/min/1.73 m(2) to 35.6% in those with eGFR <30. Of those with self-reported gout, 30.7% of individuals were not currently taking any gout medication and among gout patients on urate lowering therapy, 47.2% still showed hyperuricaemia. Factors associated with gout were serum urate, lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip ratio, higher triglyceride and C-reactive protein (CRP) concentrations, alcohol intake and diuretics use. While lower eGFR categories showed significant associations with gout in multivariable-adjusted models (prevalence ratio 1.46 for eGFR <30 compared with eGFR ≥60, 95% confidence interval 1.21-1.77), associations between gout and higher urinary albumin-to-creatinine ratio in this CKD population were not significant. CONCLUSIONS: Self-reported gout is common among patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study.

Circulating dendritic cell precursors in chronic kidney disease: a cross-sectional study.

BACKGROUND: Dendritic cells (DC) are professional antigen-presenting cells in the immune system. They patrol the blood as circulating dendritic cell precursors (DCP). Decreased blood DCP count has been shown to be related to atherosclerotic plaque burden. Since chronic kidney disease (CKD) is associated with chronic inflammation and increased cardiovascular risk, the aim of our study was to investigate a potential effect of CKD on circulating DCP numbers especially in patients with a history of cardiovascular disease. METHODS: The number of circulating myeloid (mDCP), plasmacytoid (pDCP), and total DCP (tDCP) was analysed by flow cytometry in 245 patients with CKD stage 3 (with and without known cardiovascular events) and 85 coronary healthy controls. In addition, data were compared with a historical group of 130 patients with known coronary artery disease (CAD). RESULTS: Compared to controls, patients with CKD 3 revealed a significant decrease in circulating mDCP (-29%), pDCP (-43%), and tDCP (-38%) (P < 0.001, respectively). Compared with CAD-patients, the decrease in circulating DCP in CKD was comparable or even more pronounced indicating a potential role for DCP in cardiovascular risk potentiation due to CKD. CONCLUSIONS: Based on previous findings in CAD, the marked decrease of DCP in CKD implicates a potential role for DCP as a mediator of cardiovascular disease. Whether DCP in CKD may act as new cardiovascular biomarkers needs to be established in future prospective trials.

The German Chronic Kidney Disease (GCKD) study: design and methods.

BACKGROUND: Chronic kidney disease (CKD) is increasingly recognized as a global health problem. The conditions leading to CKD, the health impact of CKD and the prognosis differ markedly between affected individuals. In particular, renal failure and cardiovascular mortality are competing risks for CKD patients. Opportunities for targeted intervention are very limited so far and require an improved understanding of the natural course of CKD, of the risk factors associated with various clinical end points and co-morbidities as well as of the underlying pathogenic mechanisms. METHODS: The German Chronic Kidney Disease (GCKD) study is a prospective observational national cohort study. It aims to enrol a total of 5000 patients with CKD of various aetiologies, who are under nephrological care, and to follow them for up to 10 years. At the time of enrolment, male and female patients have an estimated glomerular filtration rate (eGFR) of 30-60 mL/min×1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min×1.73 m2. Standardized collection of biomaterials, including DNA, serum, plasma and urine will allow identification and validation of biomarkers associated with CKD, CKD progression and related complications using hypothesis-driven and hypothesis-free approaches. Patient recruitment and follow-up is organized through a network of academic nephrology centres collaborating with practising nephrologists throughout the country. CONCLUSIONS: The GCKD study will establish one of the largest cohorts to date of CKD patients not requiring renal replacement therapy. Similarities in its design with other observational CKD studies, including cohorts that have already been established in the USA and Japan, will allow comparative and joint analyses to identify important ethnic and geographic differences and to enhance opportunities for identification of relevant risk factors and markers.

Designing and implementing a biobanking IT framework for multiple research scenarios.

This paper presents a biobanking IT framework, comprising a set of integrated biobanking information technology components. It provides adaptable and scalable IT support for varying biobanking scenarios, workflows and projects, while avoiding redundancy in data and technology. Feasibility of this approach is illustrated by implementations for four different biobanking projects at Erlangen University Hospital and with cooperating partners in Münster and Lübeck.

Deselection of base-learners for statistical boosting-with an application to distributional regression.

We present a new procedure for enhanced variable selection for component-wise gradient boosting. Statistical boosting is a computational approach that emerged from machine learning, which allows to fit regression models in the presence of high-dimensional data. Furthermore, the algorithm can lead to data-driven variable selection. In practice, however, the final models typically tend to include too many variables in some situations. This occurs particularly for low-dimensional data (p

Rosuvastatin does not affect intrarenal hemodynamics in patients with hypercholesterolemia.

BACKGROUND: It has been proposed that hyperlipidemia contributes to the progression of renal diseases, and conversely, that treatment with statins decreases the progressive decline of renal function. Increased glomerular pressure has been found to cause endothelial dysfunction of glomerular capillaries. However, the potential renoprotective effects of statin treatment have not been fully elucidated and so far no study has analyzed the effects of statin treatment on intrarenal hemodynamics. METHODS: Forty hypercholesterolemic patients were randomly assigned to receive rosuvastatin or placebo in a double-blind crossover study. Renal plasma flow(RPF) and glomerular filtration rate (GFR) were determined by constant input clearance technique with p-aminohippurate (PAH) and inulin. Glomerular hydrostatic pressure (Pglom) and resistances of the afferent(RA) and efferent arterioles (RE) were calculated according to the model originally established by Gomez. RESULTS: RPF and GFR were similar after treatment with rosuvastatin and placebo. Neither Pglom (66.2 +/- 3.9vs. 66.4 +/- 5.1 mm Hg, p=0.861) nor RA (3,200 +/- 1,780 vs.3,188 +/- 1,870 dyn-s-cm-5, p=0.957) or RE (3,620 +/- 1,174vs. 3,490 +/- 1,272 dyn-s-cm-5, p=0.378) were affected by treatment with rosuvastatin, compared with placebo. CONCLUSIONS: The beneficial effects on renal function by statin treatment seem not to be mediated by changes in intrarenal hemodynamics in patients with hypercholesterolemia.

Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study.

BACKGROUND: Patients with chronic kidney disease (CKD) bear a substantial burden of comorbidities leading to the prescription of multiple drugs and a risk of polypharmacy. However, data on medication use in this population are scarce. METHODS: A total of 5217 adults with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 or an eGFR ≥60 mL/min/1.73m2 and overt proteinuria (>500 mg/day) were studied. Self-reported data on current medication use were assessed at baseline (2010-12) and after 4 years of follow-up (FU). Prevalence and risk factors associated with polypharmacy (defined as the regular use of five or more drugs per day) as well as initiation or termination of polypharmacy were evaluated using multivariable logistic regression. RESULTS: The prevalence of polypharmacy at baseline and FU was almost 80%, ranging from 62% in patients with CKD Stage G1 to 86% in those with CKD Stage G3b. The median number of different medications taken per day was eight (range 0-27). ß-blockers, angiotensin-converting enzyme inhibitors and statins were most frequently used. Increasing CKD G stage, age and body mass index, diabetes mellitus, cardiovascular disease and a history of smoking were significantly associated with both the prevalence of polypharmacy and its maintenance during FU. Diabetes mellitus was also significantly associated with the initiation of polypharmacy [odds ratio (OR) 2.46, (95% confidence interval 1.36-4.45); P = 0.003]. CONCLUSION: Medication burden in CKD patients is high. Further research appears warranted to address the implications of polypharmacy, risks of drug interactions and strategies for risk reduction in this vulnerable patient population.

The betaboost package-a software tool for modelling bounded outcome variables in potentially high-dimensional epidemiological data.

Motivation: To provide an integrated software environment for model fitting and variable selection in regression models with a bounded outcome variable. Implementation: The proposed modelling framework is implemented in the add-on package betaboost of the statistical software environment R. General features: The betaboost methodology is based on beta-regression, which is a state-of-the-art method for modelling bounded outcome variables. By combining traditional model fitting techniques with recent advances in statistical learning and distributional regression, betaboost allows users to carry out data-driven variable and/or confounder selection in potentially high-dimensional epidemiological data. The software package implements a flexible routine to incorporate linear and non-linear predictor effects in both the mean and the precision parameter (relating inversely to the variance) of a beta-regression model. Availability: The software is hosted publicly at [http://github.com/boost-R/betaboost] and has been published under General Public License (GPL) version 3 or newer.

Correction: Blood pressure control in chronic kidney disease: A cross-sectional analysis from the German Chronic Kidney Disease (GCKD) study.

[This corrects the article DOI: 10.1371/journal.pone.0202604.].

Blood pressure control in chronic kidney disease: A cross-sectional analysis from the German Chronic Kidney Disease (GCKD) study.

We assessed the prevalence, awareness, treatment and control of hypertension in patients with moderate chronic kidney disease (CKD) under nephrological care in Germany. In the German Chronic Kidney Disease (GCKD) study, 5217 patients under nephrology specialist care were enrolled from 2010 to 2012 in a prospective observational cohort study. Inclusion criteria were an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min/1.73 m2. Office blood pressure was measured by trained study personnel in a standardized way and hypertension awareness and medication were assessed during standardized interviews. Blood pressure was considered as controlled if systolic < 140 and diastolic < 90 mmHg. In 5183 patients in whom measurements were available, mean blood pressure was 139.5 ± 20.4 / 79.3 ± 11.8 mmHg; 4985 (96.2%) of the patients were hypertensive. Awareness and treatment rates were > 90%. However, only 2456 (49.3%) of the hypertensive patients had controlled blood pressure. About half (51.0%) of the patients with uncontrolled blood pressure met criteria for resistant hypertension. Factors associated with better odds for controlled blood pressure in multivariate analyses included younger age, female sex, higher income, low or absent proteinuria, and use of certain classes of antihypertensive medication. We conclude that blood pressure control of CKD patients remains challenging even in the setting of nephrology specialist care, despite high rates of awareness and medication use.

High sodium intake modulates left ventricular mass in patients with G expression of +1675 G/A angiotensin II receptor type 2 gene.

OBJECTIVES: In patients with hypertension left ventricular hypertrophy (LVH) is associated with genetic variations of the angiotensin type 2 receptor (AT2R). Hypertension and LVH are often aggravated by salt intake. Our objective was to assess the relationship between AT2R gene variation and salt intake and their impact on left ventricular mass (LVM). METHODS AND RESULTS: In 205 subjects with normal or mildly elevated blood pressure, we assessed sodium intake and left ventricular structure and function by echocardiography. Intronic +1,675 G/A polymorphism of the AT2R gene was investigated. A-allele carriers had a greater LVM (P = 0.049) than G-allele carriers. Independent of diet, septal wall thickness was higher in A-allele carriers (P = 0.001). Fractional fibre shortening was greater in A-allele carriers (P = 0.034), and the velocity of circumferential fibre shortening tended to be greater in A-allele carriers (P = 0.057). When the two groups were stratified according to their salt intake, only G-allele carriers displayed a modulating effect of salt intake on LVM. Covariance analysis revealed that there was a trend towards a modulating effect of salt intake on LVM, even after taking blood pressure into account (P = 0.054). CONCLUSION: Our data clearly support the notion that LVM is influenced by AT2R polymorphisms. Furthermore, G-allele carriers in particular appear to be susceptible to a modifying effect of increased salt intake on LVM.

Depression, Anxiety, Resilience and Coping Pre and Post Kidney Transplantation - Initial Findings from the Psychiatric Impairments in Kidney Transplantation (PI-KT)-Study.

PURPOSE: Depression/anxiety, impaired Health-Related Quality of Life (HRQoL) and coping and resilience structures, are associated with increased mortality/poor outcome in chronic kidney disease (CKD) patients before (CKD/pre-KT) and after kidney (CKD-T) transplantation. Less is known about prevalence rates of psychiatric symptoms and impaired HRQoL of non-transplanted compared with transplanted patients. METHODS: In a cross-sectional study comparing 101 CKD/pre-KT patients with 151 cadaveric-transplanted (CKD-T) patients, we examined prevalence of depression/anxiety (HADS questionnaire) and coping, resilience and HRQoL (SF-12, Resilience-Scale and FKV-questionnaire). RESULTS: The prevalence of both depressive and anxiety symptoms was not significantly different between different pre-/and CKD-T patient groups. In CKD-T no significant relations of coping strategies with kidney function were identified. Furthermore, the Resilience Scales for acceptance and competence did not suggest any differences between the CKD/pre-KT and CKD-T subgroup. In the CKD/pre-KT patients, significant correlations were identified between the acceptance subscale and partnership, as well as between the competence subscale and older age/partnership. CONCLUSIONS: Both the CKD/pre-KT and CKD-T patients exhibited notable impairments in the HRQoL which which showed a comparable pattern of results. KT itself does not appear to be the main risk factor for the development of mental impairments.

Heart failure in a cohort of patients with chronic kidney disease: the GCKD study.

BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a risk factor for development and progression of heart failure (HF). CKD and HF share common risk factors, but few data exist on the prevalence, signs and symptoms as well as correlates of HF in populations with CKD of moderate severity. We therefore aimed to examine the prevalence and correlates of HF in the German Chronic Kidney Disease (GCKD) study, a large observational prospective study. METHODS AND RESULTS: We analyzed data from 5,015 GCKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73m² or with an eGFR ≥60 and overt proteinuria (>500 mg/d). We evaluated a definition of HF based on the Gothenburg score, a clinical HF score used in epidemiological studies (Gothenburg HF), and self-reported HF. Factors associated with HF were identified using multivariable adjusted logistic regression. The prevalence of Gothenburg HF was 43% (ranging from 24% in those with eGFR >90 to 59% in those with eGFR<30 ml/min/1.73m2). The corresponding estimate for self-reported HF was 18% (range 5%-24%). Lower eGFR was significantly and independently associated with the Gothenburg definition of HF (p-trend <0.001). Additional significantly associated correlates included older age, female gender, higher BMI, hypertension, diabetes mellitus, valvular heart disease, anemia, sleep apnea, and lower educational status. CONCLUSIONS: The burden of self-reported and Gothenburg HF among patients with CKD is high. The proportion of patients who meet the criteria for Gothenburg HF in a European cohort of patients with moderate CKD is more than twice as high as the prevalence of self-reported HF. However, because of the shared signs, symptoms and medications of HF and CKD, the Gothenburg score cannot be used to reliably define HF in CKD patients. Our results emphasize the need for early screening for HF in patients with CKD.