Friedo W. Dekker

Cardiovascular and noncardiovascular mortality among patients starting dialysis

CONTEXT Cardiovascular mortality is considered the main cause of death in patients receiving dialysis and is 10 to 20 times higher in such patients than in the general population. OBJECTIVE To evaluate if high overall mortality in patients starting dialysis is a consequence of increased cardiovascular mortality risk only or whether noncardiovascular mortality is equally increased. DESIGN, SETTING, AND PATIENTS Using data from between January 1, 1994, and January 1, 2007, age-stratified mortality in a European cohort of adults starting dialysis and receiving follow-up for a mean of 1.8 (SD, 1.1) years (European Renal Association-European Dialysis and Transplant Association [ERA-EDTA] Registry [N = 123,407]) was compared with the European general population (Eurostat). MAIN OUTCOME MEASURES Cause of death was recorded by ERA-EDTA codes in patients and matching International Statistical Classification of Diseases, 10th Revision codes in the general population. Standardized cardiovascular and noncardiovascular mortality rates, their ratio, difference, and relative excess of cardiovascular over noncardiovascular mortality were calculated. RESULTS Overall all-cause mortality rates in patients and the general population were 192 per 1000 person-years (95% confidence interval [CI], 190-193) and 12.055 per 1000 person-years (95% CI, 12.05-12.06), respectively. Cause of death was known for 90% of the patients and 99% of the general population. In patients, 16,654 deaths (39%) were cardiovascular and 21,654 (51%) were noncardiovascular. In the general population, 7,041,747 deaths (40%) were cardiovascular and 10,183,322 (58%) were noncardiovascular. Cardiovascular and noncardiovascular mortality rates in patients were respectively 38.1 per 1000 person-years (95% CI, 37.2-39.0) and 50.1 per 1000 person-years (95% CI, 48.9-51.2) higher than in the general population. On a relative scale, standardized cardiovascular and noncardiovascular mortality were respectively 8.8 (95% CI, 8.6-9.0) and 8.1 (95% CI, 7.9-8.3) times higher than in the general population. The ratio of these rates, ie, relative excess of cardiovascular over noncardiovascular mortality in patients starting dialysis compared with the general population, was 1.09 (95% CI, 1.06-1.12). Relative excess in a sensitivity analysis in which unknown/missing causes of death were regarded either as noncardiovascular or cardiovascular varied between 0.90 (95% CI, 0.88-0.93) and 1.39 (95% CI, 1.35-1.43). CONCLUSION Patients starting dialysis have a generally increased risk of death that is not specifically caused by excess cardiovascular mortality.

Risk of depression in patients with chronic obstructive pulmonary disease and its determinants

Background: Although it has been repeatedly suggested that chronic obstructive pulmonary disease (COPD) is associated with depression, no conclusion has so far been reached. A study was undertaken to investigate whether depression occurs more often in patients with COPD than in controls. The demographic and clinical variables associated with depression were also determined. Methods: Patients with a registered diagnosis of obstructive airway disease in general practice, aged ≥40 years, forced expiratory volume in 1 second (FEV1) <80% predicted, FEV1 reversibility ≤12%, FEV1/VC ≤ predicted – 1.64 × SD, and a history of smoking were selected. A random sample of subjects without a registered diagnosis of asthma or COPD aged 40 years or older acted as controls. Depression was assessed using the Centers for Epidemiologic Studies Depression (CES-D) scale. Results: In patients with severe COPD (FEV1 <50% predicted), the prevalence of depression was 25.0% compared with 17.5% in controls and 19.6% in patients with mild to moderate COPD. When the results were adjusted for demographic variables and comorbidity, the risk for depression was 2.5 times greater for patients with severe COPD than for controls (OR 2.5, 95% CI 1.2 to 5.4). In patients with mild to moderate COPD this increased risk of depression was not seen. Living alone, reversibility of FEV1 % predicted, respiratory symptoms and physical impairment were significantly associated with the scores on the CES-D scale. Conclusion: Patients with severe COPD are at increased risk of developing depression. The results of this study underscore the importance of reducing symptoms and improving physical functioning in patients with COPD.

Long-term risks for kidney donors

Previous studies have suggested that living kidney donors maintain long-term renal function and experience no increase in cardiovascular or all-cause mortality. However, most analyses have included control groups less healthy than the living donor population and have had relatively short follow-up periods. Here we compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation. All-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years. Hazard ratio for all-cause death was significantly increased to 1.30 (95% confidence interval 1.11-1.52) for donors compared with controls. There was a significant corresponding increase in cardiovascular death to 1.40 (1.03-1.91), while the risk of ESRD was greatly and significantly increased to 11.38 (4.37-29.6). The overall incidence of ESRD among donors was 302 cases per million and might have been influenced by hereditary factors. Immunological renal disease was the cause of ESRD in the donors. Thus, kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.

Screening strategies for chronic kidney disease in the general population: follow-up of cross sectional health survey

Objective To find an effective screening strategy for detecting patients with chronic kidney disease and to describe the natural course of the disease. Design Eight year follow-up of a cross sectional health survey (the HUNT II study). Setting Nord-Tr�ndelag County, Norway Participants 65�604 people (70.6 % of all adults aged ≥20 in the county). Main outcome measures Incident end stage renal disease (ESRD) and cardiovascular mortality monitored by individual linkage to central registries. Results 3069/65 604 (4.7%) people had chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m2), so we would need to screen 20.6 people (95% confidence interval 20.0 to 21.2) to identify one case. Restriction of screening to those with hypertension, diabetes, or age >55 would identify 93.2% (92.4% to 94.0%) of patients with chronic kidney disease, with a number needed to screen of 8.7 (8.5 to 9.0). Restriction of screening according to guidelines of the United States kidney disease outcomes quality initiative (US KDOQI) gave similar results, but restriction according to the United Kingdoms chronic kidney disease guidelines detected only 60.9% (59.1% to 62.8%) of cases. Screening only people with previously known diabetes or hypertension detected 44.2% (42.7% to 45.7%) of all cases, with a number needed to screen of six. During the eight year follow-up only 38 of the 3069 people with chronic kidney disease progressed to end stage renal disease, and the risk was especially low in people without diabetes or hypertension, women, and those aged ≥70 or with a glomerular filtration rate 45-59 ml/min/1.73 m2 at screening. In contrast, there was a high cardiovascular mortality: 3.5, 7.4, and 10.1 deaths per 100 person years among people with a glomerular filtration rate 45-59, 30-44, and <30 ml/min/1.73 m2, respectively. Conclusion Screening people with hypertension, diabetes mellitus, or age >55 was the most effective strategy to detect patients with chronic kidney disease, but the risk of end stage renal disease among those detected was low.

Performance of the Cockcroft-Gault, MDRD, and New CKD-EPI Formulas in Relation to GFR, Age, and Body Size

BACKGROUND AND OBJECTIVES We compared the estimations of Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to a gold standard GFR measurement using (125)I-iothalamate, within strata of GFR, gender, age, body weight, and body mass index (BMI). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS For people who previously underwent a GFR measurement, bias, precision, and accuracies between measured and estimated kidney functions were calculated within strata of the variables. The relation between the absolute bias and the variables was tested with linear regression analysis. RESULTS Overall (n = 271, 44% male, mean measured GFR 72.6 ml/min per 1.73 m(2) [SD 30.4 ml/min per 1.73 m(2)]), mean bias was smallest for MDRD (P < 0.01). CKD-EPI had highest accuracy (P < 0.01 compared with Cockcroft-Gault), which did not differ from MDRD (P = 0.14). The absolute bias of all formulas was related to age. For MDRD and CKD-EPI, absolute bias was also related to the GFR; for Cockcroft-Gault, it was related to body weight and BMI as well. In all extreme subgroups, MDRD and CKD-EPI provided highest accuracies. CONCLUSIONS The absolute bias of all formulas is influenced by age; CKD-EPI and MDRD are also influenced by GFR. Cockcroft-Gault is additionally influenced by body weight and BMI. In general, CKD-EPI gives the best estimation of GFR, although its accuracy is close to that of the MDRD.

Relative Contribution of Residual Renal Function and Different Measures of Adequacy to Survival in Hemodialysis Patients: An analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2

A high delivered Kt/V(urea) (dKt/V(urea)) is advocated in the U.S. National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines on hemodialysis (HD) adequacy, irrespective of the presence of residual renal function. The contribution of treatment adequacy and residual renal function to patient survival was investigated. The Netherlands Cooperative Study on the Adequacy of Dialysis is a prospective multicenter study that includes incident ESRD patients older than 18 yr. The longitudinal data on residual renal function and dialysis adequacy of patients who were treated with HD 3 mo after the initiation of dialysis (n = 740) were analyzed. The mean renal Kt/V(urea) (rKt/V(urea)) at 3 mo was 0.7/wk (SD 0.6) and the dKt/V(urea) at 3 mo was 2.7/wk (SD 0.8). Both components of urea clearance were associated with a better survival (for each increase of 1/wk in rKt/V(urea), relative risk of death = 0.44 [P < 0.0001]; dKt/V(urea), relative risk of death = 0.76 [P < 0.01]). However, the effect of dKt/V(urea) on mortality was strongly dependent on the presence of rKt/V(urea), low values for dKt/V(urea) of <2.9/wk being associated with a significantly higher mortality in anuric patients only. Furthermore, an excess of ultrafiltration in relation to interdialytic weight gain was associated with an increase in mortality independent of dKt/V(urea). In conclusion, residual renal clearance seems to be an important predictor of survival in HD patients, and the dKt/V(urea) should be tuned appropriately to the presence of renal function. Further studies are required to substantiate the important role of fluid balance in HD adequacy.

The relative importance of residual renal function compared with peritoneal clearance for patient survival and quality of life: an analysis of the netherlands cooperative study on the adequacy of dialysis (Necosad)-2

BACKGROUND The guidelines from the US National Kidney Foundation Dialysis Outcomes Quality Initiative on peritoneal dialysis (PD) assume equivalence between the peritoneal and the renal solute clearance. The authors examined in a prospective cohort study of incident dialysis patients the relative contribution of residual renal function and peritoneal clearance to patient survival and quality of life (QoL). METHODS The authors analyzed the longitudinal data on residual renal function, clearance by dialysis, and QoL of those patients who were treated with PD 3 months after the start of dialysis and participated in a prospective multicenter study in the Netherlands (n = 413). RESULTS The mean age was 52 years, the mean residual glomerular filtration rate (rGFR) at 3 months was 4.1 mL/min/1.73 m2 (SD: 2.7), and the mean peritoneal creatinine clearance (pCrCl) at 3 months was 4.1 mL/min/1.73 m2 (SD: 1.1). The 2-year survival was 84%. For each mL/min/1.73 m2 increase in rGFR, a 12% reduction in mortality rate was found (relative risk of death [RR] = 0.88, P = 0.039). In contrast, no significant effect of pCrCl on patient survival was established (RR = 0.91, P = 0.47). The differential impact of rGFR and pCrCl was confirmed in an analysis on combined patient and technique survival and in an analysis on a number of generic and disease-specific dimensions of QoL. CONCLUSION The beneficial effect of renal clearance and the absence of an effect of peritoneal clearance in the range of values common in current practice on patient outcome indicate that the 2 components of total solute clearance should not be regarded as equivalent. Higher peritoneal clearance targets do not necessarily improve patient outcome.

Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients

Aims Dialysis patients experience an excess mortality, predominantly of sudden cardiac death (SCD). Accumulating evidence suggests a role of vitamin D for myocardial and overall health. This study investigated the impact of vitamin D status on cardiovascular outcomes and fatal infections in haemodialysis patients. Methods and results 25-hydroxyvitamin D [25(OH)D] was measured in 1108 diabetic haemodialysis patients who participated in the German Diabetes and Dialysis Study and were followed up for a median of 4 years. By Cox regression analyses, we determined hazard ratios (HR) for pre-specified, adjudicated endpoints according to baseline 25(OH)D levels: SCD (n = 146), myocardial infarction (MI, n = 174), stroke (n = 89), cardiovascular events (CVE, n = 414), death due to heart failure (n = 37), fatal infection (n = 111), and all-cause mortality (n = 545). Patients had a mean age of 66 ± 8 years (54% male) and median 25(OH)D of 39 nmol/L (interquartile range: 28–55). Patients with severe vitamin D deficiency [25(OH)D of≤ 25 nmol/L] had a 3-fold higher risk of SCD compared with those with sufficient 25(OH)D levels >75 nmol/L [HR: 2.99, 95% confidence interval (CI): 1.39–6.40]. Furthermore, CVE and all-cause mortality were strongly increased (HR: 1.78, 95% CI: 1.18–2.69, and HR: 1.74, 95% CI: 1.22–2.47, respectively), all persisting in multivariate models. There were borderline non-significant associations with stroke and fatal infection while MI and deaths due to heart failure were not meaningfully affected. Conclusion Severe vitamin D deficiency was strongly associated with SCD, CVE, and mortality, and there were borderline associations with stroke and fatal infection. Whether vitamin D supplementation decreases adverse outcomes requires further evaluation.

Effect of Helicobacter pylori eradication on gastritis in relation to cagA: A prospective 1-year follow-up study

BACKGROUND & AIMS Whether Helicobacter pylori eradication resolves intestinal metaplasia and atrophy and whether infection with cagA+ H. pylori is related to a specific clinical outcome are not known. The aim of this study was to investigate the role of H. pylori eradication on the course of intestinal metaplasia (IM) and atrophy in relation to cagA. METHODS In a large prospective study, the cagA status of H. pylori isolated from consecutive dyspeptic patients was related to clinical outcome before and 1 year after successful eradication of H. pylori. At pretreatment and 4-6 weeks and on average 1 year after eradication therapy, the degree of gastritis and the status of H. pylori were assessed by culture and histopathology. RESULTS Specimens of cagA+ H. pylori were recovered from 122 of 155 (79%) patients infected with H. pylori. Pretreatment degrees of gastritis activity, superficial epithelial damage, IM, and atrophy were significantly greater in patients infected with cagA+ H. pylori (P < 0.001). After successful eradication of H. pylori, a significant improvement of activity of gastritis and superficial epithelial damage occurred (P < 0.001), but the degree of IM and atrophy did not change, irrespective of the cagA status. CONCLUSIONS The usefulness of H. pylori eradication to revert precancerous lesions such as IM and atrophy after 1-year follow-up is questionable.

Risk prediction models

Prognostic research focuses on the prediction of the future course of a given disease in probability terms. Prognostication is performed by clinical decision makers by using risk prediction models that allow us to estimate the probability that a specific event occurs in a given patient over a predefined time period conditional on prognostic factors (predictors). Before application in clinical practice, risk prediction models should be properly validated by assessing their discrimination and calibration, or explained variation. Reclassification analyses allow us to evaluate the gain in risk prediction by using a new model compared with an established one. We discuss the concepts of developing and validating risk prediction models by means of two examples, the Framingham risk calculator for prediction of coronary heart disease (CHD), and the recently published Renal Risk Score to predict progression of chronic kidney disease (CKD).