[Individualising antihypertensive therapy in patients with diabetes. A guideline by the Austrian Diabetes Association (update 2023)]. / Individualisierung der antihypertensiven Therapie bei Patient:innen mit Diabetes mellitus. Leitlinie der Österreichischen Diabetes Gesellschaft (Update 2023).

Hypertension is one of the most important comorbidities of diabetes, contributing significantly to death and leading to macrovascular and microvascular complications. When assessing the medical priorities for patients with diabetes, treating hypertension should be a primary consideration. In the present review practical approaches to hypertension in diabetes, including individualized targets for preventing specific complications are discussed according to current evidence and guidelines. Blood pressure values of about 130/80 mm Hg are associated with the best outcome; most importantly, at least blood pressure values < 140/90 mm Hg should be achieved in most patients. Angiotensin converting enzyme inhibitors or angiotensin receptor blockers should be preferred in patients with diabetes, especially in those who also have albuminuria or coronary artery disease. Most patients with diabetes require combination therapy to achieve blood pressure goals; agents with proven cardiovascular benefit should be used (including, besides angiotensin converting enzyme inhibitors and alternatively angiotensin receptor blockers, dihydropyridin-calcium antagonists and thiazide diuretics), preferable in single-pill combinations. Once the target is achieved, antihypertensive drugs should be continued. Newer antidiabetic medications such as SGLT-2-inhibitors or GLP1-receptor agonists have also antihypertensive effects.

Growth differentiation factor-15 predicts major bleeding, major adverse cardiac events and mortality in patients with end-stage kidney disease on haemodialysis: findings from the VIVALDI study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular events and bleeding. Optimizing risk assessment of ESKD patients regarding the risk of thromboembolism and bleeding complications in comorbid conditions, including atrial fibrillation and coronary heart disease, is challenging. To improve risk prediction we investigated growth differentiation factor-15 (GDF-15), a promising cardiovascular biomarker, and its relation to adverse outcomes. METHODS: In this prospective, multicentre, population-based cohort study, GDF-15 was measured in 594 ESKD patients on haemodialysis (median age 66 years, 38% female), who were followed up for a median of 3.5 years. The association of GDF-15 with major bleeding, arterial thromboembolism, major adverse cardiac events (MACE) and death was analysed within a competing risk framework. Further, we evaluated the additive predictive value of GDF-15 to cardiovascular and death risk assessment. RESULTS: GDF-15 levels were in median 5475 ng/l (25th-75th percentile 3964-7533) and independently associated with major bleeding {subdistribution hazard ratio [SHR] 1.31 per double increase [95% confidence interval (CI) 1.00-1.71]}, MACE [SHR 1.47 (95% CI 1.11-1.94)] and all-cause mortality [SHR 1.58 (95% CI 1.28-1.95)] but not arterial thromboembolism [SHR 0.91 (95% CI 0.61-1.36)]. The addition of GDF-15 to the HAS-BLED score significantly improved discrimination and calibration for predicting major bleeding [C-statistics increased from 0.61 (95% CI 0.52-0.70) to 0.68 (95% CI 0.61-0.78)]. Furthermore, we established an additive predictive value of GDF-15 beyond current risk models for predicting MACE and death. CONCLUSION: GDF-15 predicts the risk of major bleeding, cardiovascular events and death in ESKD patients on haemodialysis and might be a valuable marker to guide treatment decisions in this challenging patient population.

Atrial fibrillation and anticoagulation are associated with hospitalisations in patients with end-stage kidney disease on haemodialysis: a prospective population-based cohort study.

BACKGROUND: Patients with end-stage kidney disease on haemodialysis suffer from frequent complications requiring hospitalisation. Atrial fibrillation is a burdensome comorbidity amongst patients on haemodialysis. We aimed to assess frequency, reasons, and duration of hospitalisations in haemodialysis patients and their association with atrial fibrillation and anticoagulation. METHODS: Prevalent patients with end-stage kidney disease on haemodialysis were recruited into a prospective cohort study and observed for a median observation time of 3.4 years. Hospitalisations were recorded from discharge letters, medical records, and patient interviews. The association of atrial fibrillation, anticoagulation, and time-in-therapeutic range of vitamin K antagonist treatment with hospitalisations was analysed using negative binomial regression. RESULTS: Out of 625 patients, 238 (38.1%) had atrial fibrillation. Median number of hospitalisations per patient was 3.0 (1.0-5.0). Incidence rate of hospitalisation was 1.7 per patient-year in all and 1.9 in atrial fibrillation patients, median duration per hospitalisation was 7.9 (4.8-12.9) and 8.8 (5.7-13.3) days, respectively. Most frequent reasons for hospitalisation were vascular access complication/intervention (11.7%) and infection/fever (11.4%), while bleeding events comprised 6.0% of all hospitalisations. Atrial fibrillation patients had 27% higher risk of hospitalisation than patients without atrial fibrillation (incidence rate ratio [IRR] 1.27, 95% confidence interval [CI] 1.10-1.47). In atrial fibrillation patients, anticoagulation (enoxaparin or phenprocoumon, 41.6% of AF patients) was associated with increased risk of all-cause (IRR 1.38, 95%CI 1.14-1.69) and bleeding-related hospitalisation (IRR 1.96, 95%CI 1.06-3.63). There was no association between anticoagulation and stroke-related hospitalisation. In atrial fibrillation patients on phenprocoumon, increasing time-in-therapeutic range was associated with decreased risk of all-cause (IRR 0.35, 95%CI 0.14-0.87), but not bleeding-related hospitalisation (IRR 0.13, 95%CI 0.01-1.38). CONCLUSION: In haemodialysis patients, presence of atrial fibrillation and, among those with atrial fibrillation, anticoagulation were associated with higher risk of all-cause hospitalisation, including bleeding-related hospitalisation in the latter. Increasing time-in-therapeutic range in patients on vitamin K antagonist treatment was associated with decreased risk of all-cause, but not bleeding-related hospitalisation.

Bleeding Risk Assessment in End-Stage Kidney Disease: Validation of Existing Risk Scores and Evaluation of a Machine Learning-Based Approach.

BACKGROUND: Patients with end-stage kidney disease (ESKD) on hemodialysis (HD) are at increased risk for bleeding. However, despite relevant clinical implications regarding dialysis modalities or anticoagulation, no bleeding risk assessment strategy has been established in this challenging population. METHODS: Analyses on bleeding risk assessment models were performed in the population-based Vienna InVestigation of Atrial fibrillation and thromboemboLism in patients on hemoDialysIs (VIVALDI) study including 625 patients. In this cohort study, patients were prospectively followed for a median observation period of 3.5 years for the occurrence of major bleeding. First, performances of existing bleeding risk scores (i.e., HAS-BLED, HEMORR2HAGES, ATRIA, and four others) were evaluated in terms of discrimination and calibration. Second, four machine learning-based prediction models that included clinical, dialysis-specific, and laboratory parameters were developed and tested using Monte Carlo cross-validation. RESULTS: Of 625 patients (median age: 66 years, 37% women), 89 (14.2%) developed major bleeding, with a 1-year, 2-year, and 3-year cumulative incidence of 6.1% (95% confidence interval [CI]: 4.2-8.0), 10.3% (95% CI: 8.0-12.8), and 13.5% (95% CI: 10.8-16.2), respectively. C-statistics of the seven contemporary bleeding risk scores ranged between 0.54 and 0.59 indicating poor discriminatory performance. The HAS-BLED score showed the highest C-statistic of 0.59 (95% CI: 0.53-0.66). Similarly, all four machine learning-based predictions models performed poorly in internal validation (C-statistics ranging from 0.49 to 0.55). CONCLUSION: Existing bleeding risk scores and a machine learning approach including common clinical parameters fail to assist in bleeding risk prediction of patients on HD. Therefore, new approaches, including novel biomarkers, to improve bleeding risk prediction in patients on HD are needed.

Anticoagulation use and the risk of stroke and major bleeding in patients on hemodialysis: From the VIVALDI, a population-based prospective cohort study.

BACKGROUND: Evidence supporting the use of anticoagulation for the prevention of stroke and thromboembolism in patients with kidney failure on hemodialysis (HD) and atrial fibrillation (AF) is limited. We prospectively assessed the incidences of stroke and major bleeding, as well as anticoagulation strategies in patients on HD with AF. METHODS: We recruited 625 prevalent HD patients into a population-based observational cohort study. The primary prospective outcomes were thromboembolic events (stroke, transient ischemic attack, systemic embolism) and major bleeding. Secondary outcomes included a composite of thromboembolic events, major bleeding, and cardiovascular death to determine net clinical harm. RESULTS: A total of 238 patients (38.1%) had AF, 165 (26.4%) already at baseline and 73 (15.9%) developed AF during a median follow up of 870 days. Forty (6.4%) thromboembolic events and 89 (14.2%) major bleedings occurred. Overall, 256 patients died (41.0%). In AF patients, use of vitamin K antagonists (VKAs) in 61 patients (25.6%) was not significantly associated with reduced risk of the primary thromboembolic outcome (subdistribution hazard ratio [SHR] 1.41 adjusted for age, sex, congestive heart failure, hypertension, stroke/transient ischemic attack/thromboembolism, vascular disease, and diabetes history score and antiplatelet co-medication (95% CI, 0.49-4.07), but with increased risk of major bleeding (SHR: 2.28; 95% CI, 1.09-4.79) compared with AF patients without anticoagulation (N = 139, 58.4%). Use of VKAs was associated with net clinical harm (adjusted SHR: 2.07; 95% CI, 1.25-3.42). CONCLUSIONS: Although the nonrandomized nature of the study is prone to bias, anticoagulation with VKAs was not associated with decreased thromboembolic risk, but rather with increased risk of major bleeding and may be net harmful to patients with AF on HD.

Antithrombotic agents for primary and secondary prevention of cardiovascular events in patients with end-stage renal disease on chronic hemodialysis.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is common in patients with end-stage renal disease (ESRD) on hemodialysis (HD). However, antithrombotic therapy to prevent CVD increases the risk of bleeding. We aimed to investigate the prevalence of CVD and the practice patterns of antithrombotic agents in patients with ESRD on HD. METHODS: In a cross-sectional population based cohort of chronic HD patients (n = 626) from Vienna, Austria, the medical histories of patients and use of antithrombotic treatment were recorded, and the distribution of antithrombotic therapies for primary (n = 260, 41.5%) or secondary (n = 366, 58.5%) prevention of CVD was analyzed. RESULTS: Single antiplatelet therapy (SAPT) was used in 234 patients (37.4%), dual antiplatelet (DAPT) in 50 (8.0%), combination of anticoagulation and antiplatelet in 59 (9.4%), anticoagulation monotherapy in 78 (12.5%), and no antithrombotics in 205 patients (32.7%). The prevalence of CVD was 58.5%. In primary CVD prevention, 23.5% (n = 61) of patients were treated with SAPT. For secondary prevention, SAPT was used in 173 (47.3%), DAPT in 49 (13.4%), and dual antithrombotic therapies in 50 patients (13.7%), while 55 (15.0%) patients received no antithrombotics. Age (odds ratio [OR] per 1 year increase 0.96, 95%CI 0.94-0.99, p = 0.004) and hereditary nephropathy (OR 4.13, 95%CI 1.08-15.78, p = 0.038) were independently associated with the absence of antithrombotic therapy in secondary CVD prevention. CONCLUSION: The majority of patients did not receive antithrombotic therapy for primary prevention. Only 15% did not receive antithrombotic agents in the secondary prevention setting. The net-clinical benefit of antithrombotic therapy in ESRD needs to be determined.

Venous thromboembolism and vascular access thrombosis in patients with end-stage renal disease on maintenance hemodialysis: Cross-sectional results of the Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemoDIalysis (VIVALDI).

BACKGROUND: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) are at risk for occurrence of vascular access thrombosis and venous thromboembolism (VTE). Understanding the extent of these complications and identifying risk factors can help improve management strategies. METHODS: Adult HD patients were cross-sectionally recruited into the Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemoDIalysis (VIVALDI). In this investigation, retrospective data on the incidence and risk of VTE and vascular access thrombosis was analyzed using logistic regression and negative binomial regression for counts of vascular access thrombosis episodes. RESULTS: The analysis includes 626 patients on HD, which constitutes 73% of the total HD population in Vienna, Austria. One-hundred-seventy-eight patients (28.4%) had 275 vascular access thrombosis events during 2463.1 patient-years on HD, corresponding to an incidence rate (IR) of 111.6 events per 1000 patient-years on HD. In the multivariable negative binomial regression model, we found that patients suffered from vascular access thrombosis 2.5 times more often (IR ratio 2.63, 95% confidence interval [CI] 1.48-4.68, p=0.001) if toxic nephropathy was their cause of ESRD (n=28, 4.5%) compared to patients with other causes of ESRD. Sixty-one patients (9.7%) had a history of VTE and the IR of VTE events during the time on HD was 10.9 per 1000 patient-years on HD (women: IR 15.1, men IR 8.6). Female sex (odds ratio [OR] 1.90, 95%CI 1.07-3.36, p=0.029) and atrial fibrillation (OR 2.00, 95%CI 1.10-3.64, p=0.023) were independently associated with VTE. CONCLUSIONS: Thromboembolic events including vascular access thrombosis and VTE are frequent complications in patients on HD. Risk evaluation for thromboembolism, including sex and clinical parameters, may identify high-risk patients and improve their clinical management.

Blood volume-monitored regulation of ultrafiltration to decrease the dry weight in fluid-overloaded hemodialysis patients: a randomized controlled trial.

BACKGROUND: Because chronic fluid volume overload is associated with higher mortality, we tested whether blood-volume monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) would facilitate dry weight reduction, in comparison to conventional dialysis (CONV). METHODS: We carried out a multicenter, 4-week, randomized controlled trial in hemodialysis patients ≥15% above normal extracellular fluid volume (ECV), per bioimpedance spectroscopy, who were randomized 1:1:1. Applying UCR (Nikkiso), UTR (Fresenius) and CONV, initial dry weight was reduced rapidly to target. Dry weight reduction was attenuated and eventually stopped at the occurrence of dialysis complications. The primary outcome was defined as intra- and postdialytic complications. Secondary outcomes were magnitudes of dry weight and blood pressure reduction. RESULTS: Of 244 patients assessed, N = 95 had volume overload ≥15% above normal ECV. Fifty patients received the allocated interventions (N = 16 UCR, N = 18 UTR, N = 16 CONV) and completed the trial. The rate of complications was significantly lower in UTR compared to CONV (21 ± 21% vs 34 ± 20%, p = 0.022), and also compared to UCR (vs 39 ± 27%, p = 0.028), but not statistically different between UCR and CONV (p = 0.93). Dry weight reduction was significantly higher in UTR compared to UCR (5.0 ± 3.4% vs 2.0 ± 2.7% body weight, p = 0.013), but not compared to CONV (vs 3.9 ± 2.1% body weight, p = 0.31). Systolic blood pressure reduction throughout the intervention phase was 17 ± 22 mmHg overall, but not significantly different between the three groups. Average maximum ultrafiltration rates were significantly higher in UTR than in UCR and CONV, at statistically similar dialysis times. Retrospective examination of randomly selected hemodialysis sessions in the UCR group identified technical mistakes in 36% of the dialysis sessions, despite considerable training efforts. CONCLUSIONS: Even in patients with volume overload, fluid removal was challenging. Despite the relative advantage of UTR, which must be interpreted with caution in view of the poor technical execution of UCR, this study renders clear that fluid removal must not be reinforced rapidly. Apprehension of this obstacle is imperative for future clinical and academic endeavors aimed at improving dialysis outcomes by correcting volume status. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01416753 ), trial registration date: August 12, 2011.

Prevalence of Atrial Fibrillation and Antithrombotic Therapy in Hemodialysis Patients: Cross-Sectional Results of the Vienna InVestigation of AtriaL Fibrillation and Thromboembolism in Patients on HemoDIalysis (VIVALDI).

BACKGROUND: Atrial fibrillation (AF) adds significant risk of stroke and thromboembolism in patients on hemodialysis (HD). The aim of this study was to investigate the prevalence of AF in a population-based cohort of HD patients and practice patterns of antithrombotic therapy for stroke prevention in AF. METHODS: The Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemodialysis (VIVALDI), an ongoing prospective observational cohort study, investigates the prevalence of AF and the risk of thromboembolic events in HD patients in Vienna, Austria. We analyzed cross-sectional data of 626 patients (63.4% men, median age 66 years, approx. 73% of HD patients in Vienna), who provided informed consent. A structured interview with each patient was performed, recent and archived ECGs were viewed and medical histories were verified with electronic records. RESULTS: The overall prevalence of AF was 26.5% (166 patients, 71.1% men, median age 72 years) of which 57.8% had paroxysmal AF, 3.0% persistent AF, 32.5% permanent AF, and 6.6% of patients had newly diagnosed AF. The median CHA2DS2-VASc Score was 4 [25th-75th percentile 3-5]. In multivariable analysis, AF was independently associated with age (odds ratio: 1.05 per year increase, 95% confidence interval: 1.03-1.07), male sex (1.7, 1.1-2.6), history of venous thromboembolism (2.0, 1.1-3.6), congestive heart failure (1.7, 1.1-2.5), history of or active cancer (1.5, 1.0-2.4) and time on HD (1.08 per year on HD, 1.03-1.13). Antithrombotic treatment was applied in 84.4% of AF patients (anticoagulant agents in 29.5%, antiplatelet agents in 33.7%, and both in 21.1%). In AF patients, vitamin-K-antagonists were used more often than low-molecular-weight heparins (30.1% and 19.9%). CONCLUSIONS: The prevalence of AF is high amongst HD patients and is associated with age, sex, and distinct comorbidities. Practice patterns of antithrombotic treatment indicate a lack of consensus for stroke prevention in HD patients with AF.

Management of secondary hyperparathyroidism: practice patterns and outcomes of cinacalcet treatment with or without active vitamin D in Austria and Switzerland - the observational TRANSIT Study.

Secondary hyperparathyroidism is a complex disorder requiring an individualized multicomponent treatment approach. This study was conducted to identify treatment combinations used in clinical practice in Austria and Switzerland and the potential to control this disorder. A total of 333 adult hemodialysis and peritoneal dialysis patients were analyzed. All patients received conventional care prior to initiation of a cinacalcet-based regimen. During the study, treatment components, e.g. cinacalcet, active vitamin D analogues and phosphate binders, were adapted to individual patient requirements and treatment dynamics were documented. Overall, the mean intact parathyroid hormone (iPTH) increased from 64.2 pmol/l to 79.6 pmol/l under conventional therapy and decreased after cinacalcet initiation to 44.0 pmol/l after 12 months (mean decrease between baseline and 12 months -45%). Calcium remained within the normal range throughout the study and phosphorus ranged around the upper limit of normal. The Kidney Disease: Improving Global Outcomes (KDIGO) target achievement for iPTH increased from 44.5% of patients at baseline to 65.7% at 12 months, corrected calcium from 58.9% to 51.9% and phosphorus from 18.4% to 24.4%. On average, approximately 30% of patients adapted their regimen from one observation period to the next. The reasons for changing a given regimen were to attain or maintain any of the bone mineral markers within recommended targets and to avoid developments to extreme values. Some regional differences in practice patterns were identified. No new safety signals emerged. In conclusion, cinacalcet appears to be a necessary treatment component to achieve recommended targets. The detailed composition of the treatment mix should be adapted to patient requirements and reassessed on a regular basis.

Paricalcitol treatment of secondary hyperparathyroidism in hemodialysis patients: a German-Austrian, single-arm, open-label, prospective, noninterventional, observational study.

BACKGROUND: Safety and efficacy of paricalcitol in hemodialysis patients with secondary hyperparathyroidism (sHPT) was investigated under routine clinical practice in German and Austrian dialysis centers. METHODS: Hemodialysis patients with sHPT initiating intravenous paricalcitol were enrolled in this noninterventional study regardless of concomitant sHPT treatment. Prior active vitamin D therapy was discontinued. Clinical laboratory values, including intact parathyroid hormone (iPTH), total serum calcium (Ca), phosphorus (P), Ca × P product, and alkaline phosphatase (AP), were recorded for 6 months following initiation of paricalcitol treatment. RESULTS: 1,313 patients (Austria, n = 280; Germany, n = 1,033) from 169 dialysis centers were enrolled. Most patients (n = 932; 79.1%) had received dialysis for ≥1 year. Median iPTH fell from 518.9 pg/ml [55.0 pmol/l] at baseline to 264.0 pg/ml [28.0 pmol/l] after 6 months (p < 0.0001). After 6 months of treatment, ≥30 and ≥60% reductions in iPTH were observed in 63.0 and 35.9% of patients, respectively. At 6 months, 27.2% of patients achieved iPTH levels between 150 and <300 pg/ml [15.9 and <31.8 pmol/l] compared with 9.7% at baseline. Ca, P, and Ca × P levels remained stable in the majority of patients. AP levels declined from a median of 98 U/l at baseline to 83 U/l (p < 0.0001) at 6 months. Monitoring of adverse events and clinical laboratory assessments identified no unexpected safety signals for paricalcitol. CONCLUSIONS: Paricalcitol is an effective and well-tolerated treatment option for the control of iPTH levels in hemodialysis patients with sHPT. The results of this study support the results of previous trials under real-time clinical practice conditions in Austria and Germany.

Blood volume-monitored regulation of ultrafiltration in fluid-overloaded hemodialysis patients: study protocol for a randomized controlled trial.

BACKGROUND: Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients. METHODS/DESIGN: BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, 'final' dry weight is set to normohydration weight -7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters). DISCUSSION: Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01416753.

Acute infection with a single hepatitis C virus strain in dialysis patients: Analysis of adaptive immune response and viral variability.

BACKGROUND/AIMS: While the adaptive immune response is crucial for spontaneous resolution of acute hepatitis C virus (HCV) infection, it also constitutes the driving force for viral escape. For acutely HCV-infected dialysis patients, little is known about the host response and its impact on viral evolution. METHODS: Four haemodialysis patients accidentally infected with the same HCV strain were prospectively investigated with respect to the clinical course, CD4+ and CD8+ T-cell responses, neutralizing antibodies, viral kinetics and sequence variability. RESULTS: In one patient, a robust CD4+ T-cell response was associated with transient control of infection, while in the other patients, weak responses correlated with persistently high viremia. Despite the presence of CD8+ T-cell effectors in the first patient, no sequence differences were detected in targeted regions of the viral genome in any of the patients when viral persistence was established. Genetic stability in the envelope genes, including the hypervariable regions, correlated with low-level or absent neutralizing antibodies in all of the patients. CONCLUSIONS: The establishment of viral persistence in the special patient group of dialysis patients is due to a failure of the adaptive immune system, as shown by the absence of significant T-cell and antibody responses, as well as viral variability.

Body mass index modifies the risk of cardiovascular death in proteinuric chronic kidney disease.

BACKGROUND: In subjects with end-stage renal disease, a high body mass index (BMI) is inversely related to overall mortality, which has been coined reverse epidemiology phenomenon. This study sought to investigate this paradox as well as a possible risk modification by proteinuria on the relationship of BMI with earlier stages of chronic kidney disease (CKD) concerning cardiovascular mortality. METHODS: We used the Vienna Health Screening Initiative, a longitudinal cohort study from 1990 to 2006, including 49 398 volunteers (49.9% women, age 20-89 years): n = 2487 showed mild CKD (proteinuria and GFR >60 ml/min/1.73 m(2)) and n = 392 showed moderate CKD (GFR = 30-59 ml/min/1.73 m(2)). The follow-up period was 5.5 +/- 4.2 years; n = 148 cardiovascular deaths occurred. Exposure variables were BMI, glomerular filtration rate (GFR) and proteinuria. Cox regression models on cardiovascular mortality with adjustment for age, sex, log(cholesterol/HDL), uric acid, smoking, glucose, diabetes, mean blood pressure, hypertension and antihypertensive drug use were fitted. RESULTS: The risk factor paradox is shown in moderate CKD (GFR = 45 ml/min/1.73 m(2)): hazard ratios (HR) of BMI contrasts decreased consistently from 1.28 (95% CI 0.33-5.82) at BMI 20 kg/m(2) versus 25 kg/m(2) to 0.76 (95% CI 0.38-1.50) at BMI 30 kg/m(2) versus 25 kg/m(2) and to 0.58 (95% CI 0.13-2.64) at BMI 35 kg/m(2) versus 25 kg/m(2), thus showing an inverse relationship compared to mild CKD/healthy participants. Examining proteinuria as an effect modifier in this context showed that in moderate CKD (contrast: proteinuria versus no proteinuria) HR decreased more profoundly from 9.43 (95% CI 2.66-27.40) at BMI 25 kg/m(2) to 3.74 (95% CI 0.93-15.70) at BMI 30 kg/m(2) and to 1.95 (95% CI 0.37-22.30) at BMI 35 kg/m(2), and conversely in non-proteinuric subjects, hazards for cardiovascular mortality increased in underweight as well as in overweight/obese subjects in a U-shaped manner. CONCLUSIONS: Our results suggest that obese subjects with proteinuric CKD may not be counselled for weight reduction since a higher BMI was associated with a remarkably reduced risk of death.

Elevated uric acid increases the risk for kidney disease.

Recent epidemiologic studies suggest that uric acid predicts the development of new-onset kidney disease, but it is unclear whether uric acid is an independent risk factor. In this study, data from 21,475 healthy volunteers who were followed prospectively for a median of 7 yr were analyzed to examine the association between uric acid level and incident kidney disease (estimated GFR [eGFR] <60 ml/min per 1.73 m(2)). After adjustment for baseline eGFR, a slightly elevated uric acid level (7.0 to 8.9 mg/dl) was associated with a nearly doubled risk for incident kidney disease (odds ratio 1.74; 95% confidence interval 1.45 to 2.09), and an elevated uric acid (> or =9.0 mg/dl) was associated with a tripled risk (odds ratio 3.12; 95% confidence interval 2.29 to 4.25). These increases in risk remained significant even after adjustment for baseline eGFR, gender, age, antihypertensive drugs, and components of the metabolic syndrome (waist circumference, HDL cholesterol, blood glucose, triglycerides, and BP). In a fully adjusted spline model, the risk for incident kidney disease increased roughly linearly with uric acid level to a level of approximately 6 to 7 mg/dl in women and 7 to 8 mg/dl in men; above these levels, the associated risk increased rapidly. In conclusion, elevated levels of uric acid independently increase the risk for new-onset kidney disease.

Predictors of new-onset decline in kidney function in a general middle-european population.

BACKGROUND: Limited epidemiological data are available on predictors of new-onset kidney disease. METHODS: In this longitudinal cohort study, 17 375 apparently healthy volunteers of the general Viennese population (46.4% women, age range 20-84 years, men 20-89 years) performed a baseline examination at some time within the study period (1990-2005) and completed a median of two follow-up examinations [interquartile range (IQR) 1 to 4]; the median follow-up period was 7 years (IQR 4 to 11). The outcome of interest was the development of kidney disease, defined as a decrease of the glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) at the follow-up examinations [calculated by the abbreviated modification of diet in renal disease (MDRD) equation]. Logistic generalized estimating equations were used to analyse the relationship between the covariates and the outcome variable. RESULTS: The following parameters [odds ratios (OR) with 95% confidence intervals] predicted new-onset kidney disease: Age (increase by 5 years), OR = 1.36 (1.34-1.40); National Kidney Foundation-chronic kidney disease (NKF-CKD) stage 1 with proteinuria (+), OR = 1.39 (1.10-1.75); NKF-CKD stage 1 with proteinuria (>/=++), OR = 2.07 (1.11-3.87); NKF-CKD stage 2 with proteinuria (+), OR = 2.71 (2.10-3.51); NKF-CKD stage 2 with proteinuria (>/=++), OR = 3.80 (2.29-6.31); body mass index, OR = 1.04 (1.02-1.06); current-smoker, OR = 1.20 (1.01-1.43); performing no sports, OR = 1.57 (1.27-1.95); uric acid (increase by 2 mg/dl), OR = 1.69 (1.59-1.80); HDL-cholesterol (decrease by 10 mg/dl), OR = 1.12 (1.07-1.17); hypertension stage 1, OR = 1.35 (1.08-1.67); hypertension stage 2, OR = 2.01 (1.62-2.51); diabetes mellitus, OR = 1.44 (1.07-1.93). CONCLUSIONS: Cardiovascular risk factors as well as NKF-CKD stages 1 and 2 and proteinuria, the more the higher and an entirely novel finding, performing no sports, predicted new-onset kidney disease.