The Association of Effluent Ca125 with Peritoneal Dialysis Technique Failure.

UNLABELLED: ♦ BACKGROUND AND OBJECTIVES: Cancer antigen 125 (CA125) reflects the mesothelial cell mass lining the peritoneal membrane in individual patients. A decline or absence of mesothelial cells can be observed with duration of peritoneal dialysis (PD) therapy. Technique failure due to peritoneal membrane malfunction becomes of greater importance after 2 years of PD therapy in comparison to the initial period. In this study, we aimed to investigate the association between effluent CA125 and technique survival in incident PD patients with a PD therapy period of at least 2 years. ♦ METHODS: Within the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a Dutch multicenter cohort including 2,000 incident dialysis patients, we identified all PD patients who developed technique failure after 2 years of PD therapy and randomly selected a number of them as cases in a nested case-control study. Controls were PD patients matched on follow-up time without technique failure. Cases and controls were included if they had a dialysate specimen available within 24 ± 6 months of PD therapy for retrospective CA125 determinations. Odds ratios for technique failure related to CA125 were estimated. We used a prospective cohort with incident PD patients from the Academic Medical Center-University of Amsterdam (AMC) for replication of effect estimates. In these patients, absolute risk of technique failure was estimated and related to effluent CA125 levels. ♦ RESULTS: A total of 38 PD patients were selected from the NECOSAD cohort. From the AMC cohort as replication cohort, 91 PD patients were included. Incidence rates of PD technique failure per 100 patient-years were 16.3 in the NECOSAD cohort and 12.9 in the AMC cohort. In both study populations CA125 levels below 12 - 14 kU/L were associated with an increased risk for technique failure. Technique survival rates in the AMC were 87% in patients with levels of CA125 above 12.1 kU/L and 65% for those with CA125 levels below this threshold after a maximum 5-year follow-up. ♦ CONCLUSIONS: Patients with high CA125 levels after at least 2 years of PD therapy tend to have better technique survival than patients with low CA125 levels. These results support the importance of effluent CA125 as a risk factor for dropout in long-term PD therapy.

The role of social support in dialysis patients' feelings of autonomy and self-esteem: is support more beneficial for patients with specific illness perceptions?

The purpose of this study was to investigate whether effects of various types of support on dialysis patients' perceived autonomy and self-esteem depend on patients' perceived concerns and personal control regarding their illness. One hundred sixty-six patients completed written questionnaires. Main and interaction effects of support, concern, and personal control on autonomy and self-esteem were examined using linear regression analyses. General emotional support was positively related to autonomy in highly concerned patients (p < .05). Overprotection was negatively associated with autonomy (p < .05), and this association was stronger in patients with high perceived personal control (p < .01). A positive main effect of general emotional support (p < .05) and a negative main effect of overprotection (p < .01) on self-esteem were observed. The role of support in dialysis patients' autonomy appears to depend on patients' illness perceptions, whereas the role of support in patients' self-esteem does not. These findings suggest that dialysis patients' personal views about their illness can provide insight into whether patients could benefit from support, and that the provision of support should be tailored to patients' individual needs.

Single nucleotide variants in the protein C pathway and mortality in dialysis patients.

BACKGROUND: The protein C pathway plays an important role in the maintenance of endothelial barrier function and in the inflammatory and coagulant processes that are characteristic of patients on dialysis. We investigated whether common single nucleotide variants (SNV) in genes encoding protein C pathway components were associated with all-cause 5 years mortality risk in dialysis patients. METHODS: Single nucleotides variants in the factor V gene (F5 rs6025; factor V Leiden), the thrombomodulin gene (THBD rs1042580), the protein C gene (PROC rs1799808 and 1799809) and the endothelial protein C receptor gene (PROCR rs867186, rs2069951, and rs2069952) were genotyped in 1070 dialysis patients from the NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort) and in 1243 dialysis patients from the German 4D cohort. RESULTS: Factor V Leiden was associated with a 1.5-fold (95% CI 1.1-1.9) increased 5-year all-cause mortality risk and carriers of the AG/GG genotypes of the PROC rs1799809 had a 1.2-fold (95% CI 1.0-1.4) increased 5-year all-cause mortality risk. The other SNVs in THBD, PROC, and PROCR were not associated with 5-years mortality. CONCLUSION: Our study suggests that factor V Leiden and PROC rs1799809 contributes to an increased mortality risk in dialysis patients.

Predicting mortality in patients with diabetes starting dialysis.

BACKGROUND: While some prediction models have been developed for diabetic populations, prediction rules for mortality in diabetic dialysis patients are still lacking. Therefore, the objective of this study was to identify predictors for 1-year mortality in diabetic dialysis patients and use these results to develop a prediction model. METHODS: Data were used from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a multicenter, prospective cohort study in which incident patients with end stage renal disease (ESRD) were monitored until transplantation or death. For the present analysis, patients with DM at baseline were included. A prediction algorithm for 1-year all-cause mortality was developed through multivariate logistic regression. Candidate predictors were selected based on literature and clinical expertise. The final model was constructed through backward selection. The model's predictive performance, measured by calibration and discrimination, was assessed and internally validated through bootstrapping. RESULTS: A total of 394 patients were available for statistical analysis; 82 (21%) patients died within one year after baseline (3 months after starting dialysis therapy). The final prediction model contained seven predictors; age, smoking, history of macrovascular complications, duration of diabetes mellitus, Karnofsky scale, serum albumin and hemoglobin level. Predictive performance was good, as shown by the c-statistic of 0.810. Internal validation showed a slightly lower, but still adequate performance. Sensitivity analyses showed stability of results. CONCLUSIONS: A prediction model containing seven predictors has been identified in order to predict 1-year mortality for diabetic incident dialysis patients. Predictive performance of the model was good. Before implementing the model in clinical practice, for example for counseling patients regarding their prognosis, external validation is necessary.

Type of arteriovenous vascular access and association with patency and mortality.

BACKGROUND: There are only a few risk factors known for primary patency loss in patients with an arteriovenous graft or fistula. Furthermore, a limited number of studies have investigated the association between arteriovenous access modality and primary patency loss and mortality. The aim of this study was to investigate risk factors for patency loss and to investigate the association between graft versus fistula use and outcomes (patency loss and mortality). METHODS: We prospectively followed 919 incident hemodialysis patients and calculated hazard ratios (HRs) for putative risk factors of primary patency loss using Cox regression. Furthermore, HRs were calculated to study the association between graft versus fistula use and two-year primary patency loss and two-year mortality. RESULTS: Cardiovascular disease, prior catheter use, lowest tertile of albumin, highest tertile of hsCRP, and lowest tertile of fetuin-A were associated with primary patency loss in both patients with grafts and fistulas. Increased age, female sex, and diabetes mellitus were only associated with primary patency loss in patients with a fistula. We did not observe an association between primary patency loss and BMI, residual GFR, levels of calcium, phosphorus, and total cholesterol. Furthermore, graft use as compared with fistula use was associated with an 1.4-fold (95% CI 1.0-1.9) increased risk of primary patency loss and with an 1.5-fold(95% CI 1.0-2.2) increased mortality risk. CONCLUSION: Cardiovascular disease, prior catheter use, albumin, hsCRP, and fetuin-A are risk factors for patency loss. Graft use as compared with fistula use was associated with an increased risk of patency loss and mortality.

Is the decline of renal function different before and after the start of dialysis?

BACKGROUND: The presence of glomerular filtration in dialysis patients is associated with improved survival and quality of life. This study explores the time course of the glomerular filtration rate (GFR) between 1 year before and 1 year after the start of haemodialysis (HD) and peritoneal dialysis (PD). METHODS: This study included 1861 incident dialysis patients (NECOSAD cohort; 62% male, 60 ± 15 years, 61% HD, GFR 5.2 ± 3.6 mL/min/1.73 m(2)). A decline of the GFR was estimated using linear mixed-effects models adjusted for age, sex, primary kidney disease, cardiovascular disease and diabetes. The rate of decline was allowed to change at a certain point in time. RESULTS: The decline of the GFR attenuated from -0.53 mL/min/1.73 m(2)/month (95% CI: -0.58, -0.48) in the period before the start of dialysis to -0.12 (95% CI: -0.20, -0.04) at 2-4 months of dialysis in all patients. In HD, decline attenuated from -0.51 (95% CI: -0.57, -0.44) to -0.14 (95% CI: -0.26, -0.02); in PD from -0.55 (95% CI: -0.62, -0.48) to -0.11 (95% CI: -0.23, 0.01). In patients who started dialysis with a GFR equal/above median GFR at dialysis start, the decline attenuated (at 3 months) from -0.70 (95% CI: -0.78; -0.62) to -0.21 (95% CI: -0.36; -0.05). In patients who started dialysis with a GFR below median GFR at dialysis start, the decline attenuated (at 1 month) from -0.73 (95% CI: -0.88; -0.58) to -0.04 (95% CI: -0.27 , 0.19). CONCLUSIONS: The apparent decline of the GFR slows down after 2-4 months of dialysis. This decline was similar in HD and PD patients, although at a different level of GFR. Further studies are needed to examine explanations for this phenomenon.

Illness perceptions and treatment perceptions of patients with chronic kidney disease: different phases, different perceptions?

OBJECTIVES: To examine the variability of illness and treatment perceptions - that have been found to be associated with chronic kidney disease (CKD) patients' outcomes (e.g., quality of life) - across the CKD trajectory, by investigating whether there are differences in perceptions in patients: (1) on varying treatments (pre-dialysis, haemodialysis, peritoneal dialysis), (2) with varying lengths of time on (dialysis) treatment, and (3) over time on dialysis, with an 8-month interval. DESIGN AND METHODS: Mixed cross-sectional and longitudinal design, using self-report questionnaires on illness and treatment perceptions; the study sample consisted of 105 pre-dialysis and 161 dialysis patients; of the 161 dialysis patients, 87 patients filled in the questionnaires again after an 8-month interval. Data were examined using multilevel (multivariate) repeated measurements regression analyses, controlled for background characteristics and repeated measures. RESULTS: Patients on haemodialysis and peritoneal dialysis believed more strongly that their treatment controls their illness (p < .05, p < .01, respectively) and perceived more illness consequences (p < .001, p < .05, respectively) than pre-dialysis patients. Haemodialysis patients perceived more treatment consequences than pre-dialysis (p < .001) and peritoneal dialysis patients (p < .01). The perception of illness understanding fluctuated between patients with varying lengths of time on dialysis (p < .05). Perceived treatment consequences were more negative in patients who were on dialysis for longer lengths of time (p < .01). Lastly, perceptions of illness and treatment varied within dialysis patients over an 8-month interval, with treatment control and personal control showing the lowest correlations. CONCLUSIONS: Findings suggest that illness and treatment perceptions vary across the CKD trajectory. This indicates that perceptions are amenable to influences and that interventions might potentially be helpful in influencing them in order to improve outcomes. STATEMENT OF CONTRIBUTION: What is already known on this subject? Dialysis patients' perceptions of illness understanding and illness symptoms vary over the first year on dialysis. Established haemodialysis patients' perceptions of illness understanding, emotional response and treatment control vary over a 2-year period. Certain illness perceptions as well as treatment perceptions vary as a function of treatment type in patients with CKD stage 5 (dialysis patients, patients with a kidney transplant). What does this study add? Patients' perceptions of illness understanding and treatment consequences vary between patients as a function of length of time on (haemo-, peritoneal-) dialysis, taking into account a wide range of time (0-10 years). Illness perceptions and treatment perceptions of patients on haemodialysis and peritoneal dialysis vary within patients over an 8-month interval, with perceptions of treatment control and personal control showing the highest variations. Perceptions of illness consequences, treatment consequences and treatment control vary as a function of type of treatment, taking into account pre-dialysis treatment (CKD stage 4) and dialysis (haemodialysis, peritoneal dialysis) treatment (CKD stage 5).

Proteinuria as a risk marker for the progression of chronic kidney disease in patients on predialysis care and the role of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment.

BACKGROUND/AIMS: Proteinuria is a risk marker for progression of chronic kidney disease (CKD) and treatment with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) is beneficial in these patients. However, little is known about proteinuria and ACEi/ARB treatment in patients on specialized predialysis care. Therefore, we investigated the association of urinary protein excretion (UPE) and ACEi/ARB treatment with renal function decline (RFD) and/or the start of renal replacement therapy (RRT) in patients on predialysis care. METHODS: In the PREPARE-1 cohort, 547 incident predialysis patients (CKD stages IV-V), referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included (1999-2001) and followed until the start of RRT, mortality, or January 1, 2008. The main outcomes were rate of RFD, estimated as the slope of available eGFR measurements, and the start of RRT. RESULTS: Patients with mild proteinuria (>0.3 to ≤1.0 g/24 h) had an adjusted additional RFD of 0.35 ml/min/1.73 m(2)/month (95% CI: 0.01; 0.68) and a higher rate of starting RRT [adjusted HR: 1.70 (1.05; 2.77)] compared with patients without proteinuria (≤0.3 g/24 h). With every consecutive UPE category (>1.0 to ≤3.0, >3.0 to ≤6.0, and >6.0 g/24 h), RFD accelerated and the start of RRT was earlier. Furthermore, patients starting (n = 16) or continuing (n = 133) treatment with ACEi/ARBs during predialysis care had a lower rate of starting RRT compared with patients not using treatment [n = 152, adjusted HR: 0.56 (0.29; 1.08) and 0.90 (0.68; 1.20), respectively]. CONCLUSION: In patients on predialysis care, we confirmed that proteinuria is a risk marker for the progression of CKD. Furthermore, no evidence was present that the use of ACEi/ARBs is deleterious.

Short-term versus long-term effects of depressive symptoms on mortality in patients on dialysis.

OBJECTIVE: Depressive symptoms seem to pose a risk factor for mortality among patients on dialysis. It is currently unknown whether the association is only short-lived and whether associations over time depend on specific causes of mortality. METHODS: In a prospective nationwide cohort study, 1528 patients with end-stage renal disease starting on dialysis completed the Mental Health Inventory. Patients were observed up to 5 years or until the end of follow-up in April 2011. Cox regression analyses were used to calculate associations between depressive symptoms and short-term (0-6 months), medium-term (6-24 months), or long-term (24-60 months) cardiovascular and noncardiovascular mortality. RESULTS: The adjusted hazard ratio (HR) was 1.43 (95% confidence interval [CI] = 1.08-1.88) for cardiovascular mortality and 2.07 (95% CI = 1.62-2.64) for noncardiovascular mortality. Depressive symptoms posed a strong risk factor for noncardiovascular mortality at the short term (HR = 2.82, 95% CI = 1.58-5.05), medium term (HR = 2.08, 95% CI = 1.40-3.09), and long term (HR = 1.84, 95% CI = 1.26-2.69), whereas the association between depressive symptoms and cardiovascular mortality was not observed during the first 6 months of follow-up (HR = 1.03, 95% CI = 0.49-2.15). CONCLUSIONS: Depressive symptoms at the start of dialysis therapy are associated with short-, medium-, and long-term mortality. The cause-specific mortality risk over time may help clinicians to understand multifactorial causes of the association between depressive symptoms and survival.

Association of blood pressure with the start of renal replacement therapy in elderly compared with young patients receiving predialysis care.

BACKGROUND: In the growing elderly predialysis population, little is known about the effect of identified risk factors on the progression to end-stage renal disease. Therefore, we investigated the association of systolic (SBP) and diastolic blood pressure (DBP) with the start of renal replacement therapy (RRT), in elderly (≥65 years) compared with young (<65 years) predialysis patients. METHODS: In the PREPARE-1 cohort, 547 incident predialysis patients, referred as part of the usual care to eight Dutch predialysis care outpatient clinics, were included (1999-2001) and followed until the start of dialysis, transplantation, death, or until 1 January 2008. The outcome was the start of RRT. All analyses were stratified for age; <65 years (young) and ≥65 years (elderly). RESULTS: In young predialysis patients (n = 268) higher SBP (every 20 mm Hg increase) and high DBP (DBP ≥100 mm Hg compared with 80-89 mm Hg) were associated with a higher rate of starting RRT (adjusted hazard ratio (HR) (95% confidence interval) 1.21 (1.09;1.34) and 1.74 (1.16;2.62), respectively). However, in elderly predialysis patients (n = 240) only patients with SBP ≥180 mm Hg had an increased rate compared with patients with 140-159 mm Hg (adjusted HR 2.33 (1.41;3.87)). Furthermore, patients with DBP <70 or ≥100 mm Hg had an increased rate of starting RRT, independent of SBP, compared with patients with 80-89 mm Hg (fully adjusted HR 1.72 (1.01;2.94) and 2.05 (1.13;3.73), respectively). CONCLUSIONS: The association of SBP and DBP with the start of RRT is different between elderly and young predialysis patients.

Time course of peritoneal function in automated and continuous peritoneal dialysis.

BACKGROUND AND OBJECTIVES: In automated peritoneal dialysis (APD), a patient's peritoneal membrane is more intensively exposed to fresh dialysate than it is in continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in incident peritoneal dialysis (PD) patients, the influence of APD-compared with that of CAPD-on peritoneal transport over 4 years. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Patients were included if at least 2 annual standard permeability analyses (SPAs) performed with 3.86% glucose were available while the patient was using the same modality with which they had started PD (APD or CAPD). Patients were followed until their first modality switch. Differences in the pattern of SPA outcomes over time were tested using repeated-measures models adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start. RESULTS: The 59 CAPD patients enrolled were older than the 47 APD patients enrolled (mean age: 58 ± 14 years vs 49 ± 14 years; p < 0.01), and they had started PD earlier (mean start year: 2000 vs 2002). Over time, no differences in solute (p > 0.19) or fluid transport (p > 0.13) were observed. Similarly, free water transport (p = 0.43) and small-pore transport (p = 0.31) were not different between the modalities. Over time, patients on APD showed a faster decline in effective lymphatic absorption rate (ELAR: p = 0.02) and in transcapillary ultrafiltration (TCUF: p = 0.07, adjusted p = 0.05). Further adjustment did not change the results. CONCLUSIONS: Compared with patients starting on CAPD, those starting on APD experienced a faster decline in ELAR and TCUF. Other transport parameters were not different over time between the groups.

Obesity and mortality risk among younger dialysis patients.

BACKGROUND AND OBJECTIVES: Many studies show that obesity in dialysis patients is not strongly associated with mortality but not whether this modest association is constant over age. This study investigated the extent to which the relation of body mass index (BMI) and mortality differs between younger and older dialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Adult dialysis patients were prospectively followed from their first dialysis treatment for 7 years or until death or transplantation. Patients were stratified by age (<65 or ≥65 years) and baseline BMI (<20, 20-24 [reference], 25-29, and ≥30 kg/m(2)). RESULTS: The study sample included 984 patients younger than 65 years and 765 patients 65 years or older; cumulative survival proportions at end of follow-up were 50% and 16%. Age-standardized mortality rate was 1.7 times higher in obese younger patients than those with normal BMI, corresponding to an excess rate of 5.2 deaths/100 patient-years. Mortality rates were almost equal between obese older patients and those with normal BMI. Excess rates of younger and older patients with low compared with normal BMI were 8.7 and 1.1 deaths/100 patient-years. After adjustment for age, sex, smoking, comorbidity, and treatment modality, hazard ratios by increasing BMI were 2.00, 1, 0.95, and 1.57 for younger patients and 1.07, 1, 0.88, and 0.91 for older patients, implying that obesity is a 1.7-fold (95% confidence interval, 1.1- to 2.9-fold) stronger risk factor in younger than older patients. CONCLUSIONS: In contrast to older dialysis patients, younger patients with low or very high BMI had a substantially elevated risk for death.

Plasma concentration of von Willebrand factor predicts mortality in patients on chronic renal replacement therapy.

BACKGROUND: Traditional cardiovascular risk factors do not explain the high incidence of cardiovascular mortality and morbidity in patients with end-stage renal disease. A prothrombotic state could accelerate the process of vascular disease in these patients. METHODS: In this study, four platelet activation markers (NAP-2, P-selectin, GP1b and RANTES) and two endothelial cell activation markers (von Willebrand factor and its propeptide) were measured in 671 haemodialysis patients and 275 patients on continuous ambulatory peritoneal dialysis (PD). All were long-term dialysis patients. The risk of all-cause and cardiovascular mortality was assessed in relation to these markers after a mean follow-up time of 2.5 years. RESULTS: The von Willebrand factor showed a positive correlation with total mortality in the haemodialysis patients. In an unadjusted model, the hazard rate (HR) of total mortality was 2.4 [95% confidence interval (95% CI) 1.7-3.4] in the upper quartile of von Willebrand factor compared with the lowest quartile. It remained statistically significant (HR 1.8; 95% CI 1.2-2.6) after adjustment for traditional risk factors. In contrast, no significant correlation was found between von Willebrand factor levels and total mortality in PD patients. Finally, no relationship between platelet activation markers and total mortality was found in either the haemodialysis or the PD patients. CONCLUSION: It can be concluded that chronic endothelial cell activation, but not platelet activation, is related to all-cause mortality in end-stage renal disease patients on long-term dialysis.

The role of psychosocial factors in ethnic differences in survival on dialysis in the Netherlands.

INTRODUCTION: Ethnic minority patients on dialysis are reported to have better survival rates relative to Caucasians. The reasons for this finding are not fully understood and European studies are scarce. This study examined whether ethnic differences in survival could be explained by patient characteristics, including psychosocial factors. METHODS: We analysed data of the Netherlands Cooperative Study on the Adequacy of Dialysis study, an observational prospective cohort study of patients who started dialysis between 1997 and 2007 in the Netherlands. Ethnicity was classified as Caucasian, Black or Asian, assessed by local nurses. Data collected at the start of dialysis treatment included demographic, clinical and psychosocial characteristics. Psychosocial characteristics included data on health-related quality of life (HRQoL), mental health status and general health perception. Cox proportional hazards analysis was used to explore ethnic survival differences. RESULTS: One thousand seven hundred and ninety-one patients were Caucasian, 45 Black and 108 Asian. The ethnic groups differed significantly in age, residual glomerular filtration rate, diabetes mellitus, erythropoietin use, plasma calcium, parathormone and creatinine, marital status and general health perception. No ethnic differences were found in HRQoL and mental health status. Crude hazard ratios (HRs) for mortality for Caucasians compared to Blacks and Asians were 3.1 [95% confidence interval (CI) 1.6-5.9] and 1.1 (95% CI 0.9-1.5), respectively. After adjustment for a range of potential explanatory variables, including psychosocial factors, the HRs were 2.5 (95% CI 1.2-4.9) compared with Blacks and 1.2 (95% CI 0.9-1.6) compared with Asians. CONCLUSIONS: Although patient numbers were rather small, this study demonstrates, with 95% confidence, better survival for Black compared to Caucasian dialysis patients and equal survival for Asian compared to Caucasian dialysis patients in the Netherlands. This could not be explained by patient characteristics, including psychosocial factors.

Survival in dialysis patients is not different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

BACKGROUND: On dialysis, survival among patients with diabetes mellitus is inferior to survival of non-diabetic patients. We hypothesized that patients with diabetes as primary renal disease have worse survival compared to patients with diabetes as a co-morbid condition and aimed to compare all-cause mortality between these patient groups. METHODS: Data were collected from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a multicenter, prospective cohort study in which new patients with end stage renal disease (ESRD) were monitored until transplantation or death. Patients with diabetes as primary cause of ESRD were compared with patients with diabetes as co-morbid condition and both of these patient groups were compared to patients without diabetes. Analysis was performed using Kaplan-Meier and Cox regression. RESULTS: Fifteen % of the patients had diabetic nephropathy as primary renal disease (N = 281); 6% had diabetes as co-morbid condition (N = 107) and 79% had no diabetes (N = 1465). During follow-up 42% of patients (N = 787) died. Compared to non-diabetic patients, mortality risk was increased for both patients with diabetes as primary renal disease HR: 1.9 (95% CI 1.6, 2.3) and for patients with diabetes as co-morbid condition HR: 1.7 (95% CI 1.3, 2.2). Mortality was not significantly higher in patients with diabetes as primary renal disease compared to patients with diabetes as co-morbid condition (HR 1.06; 95% CI 0.79, 1.43). CONCLUSIONS: This study in patients with ESRD showed no survival difference between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition. Both conditions were associated with increased mortality risk compared to non-diabetic patients.

Association of blood pressure with decline in renal function and time until the start of renal replacement therapy in pre-dialysis patients: a cohort study.

BACKGROUND: To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and diastolic blood pressure (DBP) with decline in renal function and time until the start of renal replacement therapy (RRT) in patients with CKD stages IV-V on pre-dialysis care. METHODS: In the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1st 2008). Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT. RESULTS: A total of 508 patients, 57% men and median (IQR) age of 63 (50-73) years, were available for analyses. Mean (SD) decline in renal function was 0.35 (0.75) ml/min/1.73 m2/month. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function (adjusted additional decline 0.04 (0.02;0.07) and 0.05 (0.00;0.11) ml/min/1.73 m2/month respectively) and an earlier start of RRT (adjusted HR 1.09 (1.04;1.14) and 1.16 (1.05;1.28) respectively). Furthermore, patients with SBP and DBP above the BP target goal of < 130/80 mmHg experienced a faster decline in renal function (adjusted additional decline 0.31 (0.08;0.53) ml/min/1.73 m2/month) and an earlier start of RRT (adjusted HR 2.08 (1.25;3.44)), compared to patients who achieved the target goal (11%). Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg) and patients with both SBP and DBP below the target (< 130/80 mmHg), showed that the results were almost similar as compared to patients with both SBP and DBP above the target (adjusted additional decline 0.31 (0.04;0.58) ml/min/1.73 m2/month and adjusted HR 2.24 (1.26;3.97)). Therefore, it seems that especially having SBP above the target is harmful. CONCLUSIONS: In pre-dialysis patients with CKD stages IV-V, having blood pressure (especially SBP) above the target goal for CKD patients (< 130/80 mmHg) was associated with a faster decline in renal function and a later start of RRT.

Using a genetic, observational study as a strategy to estimate the potential cost-effectiveness of pharmacological CCR5 blockade in dialysis patients.

BACKGROUND AND OBJECTIVE: Randomized clinical trials are expensive and time consuming. Therefore, strategies are needed to prioritise tracks for drug development. Genetic association studies may provide such a strategy by considering the differences between genotypes as a proxy for a natural, lifelong, randomized at conception, clinical trial. Previously an association with better survival was found in dialysis patients with systemic inflammation carrying a deletion variant of the CC-chemokine receptor 5 (CCR5). We hypothesized that in an analogous manner, pharmacological CCR5 blockade could protect against inflammation-driven mortality and estimated if such a treatment would be cost-effective. METHODS: A genetic screen and treat strategy was modelled using a decision-analytic Markov model, in which patients were screened for the CCR5 deletion 32 polymorphism and those with the wild type and systemic inflammation were treated with pharmacological CCR5 blockers. Kidney transplantation and mortality rates were calculated using patient level data. Extensive sensitivity analyses were performed. RESULTS: The cost-effectiveness of the genetic screen and treat strategy was &OV0556;18 557 per life year gained and &OV0556;21 896 per quality-adjusted life years gained. Concordance between the genetic association and pharmacological effectiveness was a main driver of cost-effectiveness. Sensitivity analyses showed that even a modest effectiveness of pharmacological CCR5 blockade would result in a treatment strategy that is good value for money. CONCLUSION: Pharmacological blockade of the CCR5 receptor in inflamed dialysis patients can be incorporated in a potentially cost-effective screen and treat programme. These findings provide formal rationale for clinical studies. This study illustrates the potential of genetic association studies for drug development, as a source of Mendelian randomized evidence from an observational setting.

Bone alkaline phosphatase and mortality in dialysis patients.

BACKGROUND AND OBJECTIVES: Serum alkaline phosphatase (AP) is associated with vascular calcification and mortality in hemodialysis patients, but AP derives from various tissues of origin. The aim of this study was to assess the effect of bone-specific AP (BAP) on morbidity and mortality in dialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From a prospective cohort study of incident dialysis patients in The Netherlands, all patients with measured BAP at 12 months after the start of dialysis (baseline) were included in the analysis (n = 800; mean age, 59 ± 15 years; mean BAP = 18 ± 13 U/L). By Cox regression analyses, we assessed the impact of BAP levels on short-term mortality (6 months) and longer-term mortality (4-year follow-up). RESULTS: High levels of BAP strongly affected short-term mortality. After adjustment for confounders, patients in the highest BAP tertile had a 5.7-fold increased risk of death within 6 months compared with patients in the lowest tertile. The effect applied to both cardiovascular and noncardiovascular mortality. Furthermore, high levels of BAP were associated with increased cardiovascular mortality in the longer term. In comparison with total AP, the effect sizes related to clinical outcomes were much higher for BAP. CONCLUSIONS: High levels of BAP were strongly associated with short-term mortality in dialysis patients, pointing out the important impact of bone turnover. Longitudinal assessments of BAP may be useful for the treatment monitoring in clinical practice in dialysis patients.