Els W. Boeschoten

Predictors of poor outcome in chronic dialysis patients: The Netherlands cooperative study on the adequacy of dialysis

In a prospective cohort study, we constructed a composite index of poor outcome that incorporates survival, morbidity, and quality of life (QL). We identified baseline patient and treatment characteristics that predicted poor outcome 1 year after the start of chronic dialysis. Outcome was classified as poor if a patient had died or if at least two of the following criteria were present: (1) 30 days or greater of hospitalization per year, (2) serum albumin level of 30 g/L or less or a malnutrition index score of 11 or greater, (3) a 36-item Medical Outcomes Study (MOS)-Short Form Health Survey Questionnaire (SF-36) physical summary QL score of 2 or more SDs less than the general population mean score, and (4) an SF-36 mental summary QL score of 2 or more SDs less than the general population mean score. Multivariate logistic regression analysis was used to identify independent predictors of poor outcome. Of 250 included patients, 189 were assessable with respect to poor outcome. Of these patients, 47 (25%) were classified as poor. A baseline presence of comorbidity, serum albumin level of 30 g/L or less, physical or mental QL score 2 or more SDs less than the general population mean score, and, to a lesser extent, residual glomerular filtration rate of 2.5 mL/min/1.73 m(2) or less were independently associated with a greater risk for poor outcome. A post hoc analysis indicated a mean arterial blood pressure greater than 107 mm Hg was predictive of poor outcome in patients undergoing peritoneal dialysis. In conclusion, our prognostic model provides a useful tool to identify chronic dialysis patients at risk for poor health status. Strategies aimed at preserving residual renal function, controlling blood pressure, monitoring QL, and consequently giving psychosocial support may reduce the risk for poor outcome.

Validation of the KDQOL-SFTM: A dialysis-targeted health measure

Background: In evaluations of dialysis therapy, an assessment of health-related quality of life (HRQOL) is often important. The aim of this study was to determine the basic psychometric properties, reliability and validity of the short form of the KDQOLTM i.e. the KDQOL-SFTM, a dialysis-targeted instrument, and to assess its ability to detect changes over time. Methods: In a prospective cohort study (Netherlands Cooperative Study on the Adequacy of Dialysis, NECOSAD), all new adult ESRD patients in 32 different Dutch centers were consecutively enrolled. Demographic, clinical and HRQOL data were obtained 3 and 12 months after the start of chronic dialysis therapy. Results: The reliability of the KDQOL-SFTM was supported by test results that were above the recommended minimal values. Validity of KDQOL-SFTM was confirmed by the hypothesized positive correlations of the overall health rating and renal function, and by the negative correlations between the number of comorbidities and dialysis dose. Moreover, dialysis-targeted dimensions were more sensitive in detecting relevant differences pertaining to kidney diseases than generic dimensions. The KDQOL-SFTM was able to detect clinical changes over time. Conclusions: The psychometric properties of the KDQOL-SFTM were good, and the different dialysis-targeted dimensions were informative with a high reliability and validity. These results support the application of the KDQOL-SFTM in studies evaluating dialysis therapy.

Trimestral variations of C-reactive protein, interleukin-6 and tumour necrosis factor-α are similarly associated with survival in haemodialysis patients.

BACKGROUND The impact of intra-individual changes of inflammatory markers [other than C-reactive protein (CRP)] on mortality in haemodialysis (HD) patients is unknown. We therefore studied survival in relation to trimestral variations of CRP, interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). METHODS In 201 prevalent HD patients from the Mapping of Inflammatory Markers in Chronic Kidney Disease cohort, serum CRP, IL-6 and TNF-α were measured 3 months apart and survival was assessed during follow-up. Based on fluctuations along tertiles of distribution, four patterns were defined for each inflammatory marker: stable low, decrease, increase and stable high. Hazard ratios were calculated by the Cox proportional hazard model, and Pearsons test was used to correlate changes. CRP analyses were replicated in 472 incident HD patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. RESULTS Patients with persistently elevated CRP values had the worst mortality in crude [HR 2.98 (95% CI 1.71-5.20)] and adjusted [2.79 (1.58-4.94)] Cox models, together with those who increased in their CRP levels [crude 3.27 (1.91-5.60); adjusted 3.13 (1.79-5.45)]. Similar survival patterns were observed for IL-6 and TNF-α variation categories. Correlations among these changes were, however, not strong. In the replication cohort, individuals with persistently elevated CRP values also showed the highest mortality risk [crude 3.38 (2.31-4.94); adjusted 2.33 (1.58-3.45)]. CONCLUSIONS Trimestral variations of TNF-α, IL-6, and CRP are similarly associated with survival in HD patients. The agreement between changes of these biomarkers was low, suggesting that different pathways may trigger each of these markers.

Antifungal Treatment of Candida Peritonitis in Continuous Ambulatory Peritoneal Dialysis Patients

Nine peritonitis episodes caused by Candida sp were diagnosed in eight continuous ambulatory peritoneal dialysis (CAPD) patients. Treatment with intraperitoneal administration of amphotericin B and 5-fluorocytosine while the peritoneal catheter was left in situ was effective in six episodes in five patients. Of the three other patients, two started again with CAPD after peritonitis had been cured, but one patient preferred to stay on hemodialysis. In four episodes, peritoneal white cell counts remained high during treatment despite negative cultures. This was probably the result of irritation of the peritoneal membrane caused by the antifungal treatment, possibly by amphotericin B. Persistently-elevated leukocyte counts during antifungal therapy, with or without signs and symptoms of peritonitis, are not necessarily an indication of treatment failure.

New primary renal diagnosis codes for the ERA-EDTA

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry has produced a new set of primary renal diagnosis (PRD) codes that are intended for use by affiliated registries. It is designed specifically for use in renal centres and registries but is aligned with international coding standards supported by the WHO (International Classification of Diseases) and the International Health Terminology Standards Development Organization (SNOMED Clinical Terms). It is available as supplementary material to this paper and free on the internet for non-commercial, clinical, quality improvement and research use, and by agreement with the ERA-EDTA Registry for use by commercial organizations. Conversion between the old and the new PRD codes is possible. The new codes are very flexible and will be actively managed to keep them up-to-date and to ensure that renal medicine can remain at the forefront of the electronic revolution in medicine, epidemiology research and the use of decision support systems to improve the care of patients.

CYP3A5 genotype is associated with longer patient survival after kidney transplantation and long-term treatment with cyclosporine

The CYP3A5*1 allele has been linked to high expression of CYP3A5 and metabolism of cyclosporine. We evaluated the role of CYP3A5*1 for long-term survival in renal transplant patients in a cohort of 399 patients who underwent cadaveric or living donor kidney allograft transplantation. All patients were treated with a similar cyclosporine-based immunosuppressive maintenance therapy protocol. The mean duration of follow-up was 8.6±3.7 years. In univariate survival analysis, the presence of the CYP3A5*1 allele in recipients significantly increased patient survival P=0.028 (log-rank), resulting in a hazard ratio (HR) of 0.52 (95% CI=0.29–0.94). When the presence of the CYP3A5*1 allele was included in multivariate Cox regression analyses accounting for major risk factors for patient death, CYP3A5*1 still conferred a protective effect. Further, haplotype analysis at the CYP3A5 locus confirmed that CYP3A5*1 might indeed be responsible for this survival benefit.

Venous and arterial thrombosis in dialysis patients

Whether the risk of both venous and arterial thrombosis is increased in dialysis patients as compared to the general population is unknown. In addition, it is unknown which subgroups are at highest risk. Furthermore, it is unknown whether having a history of venous thrombosis or arterial thrombosis prior to dialysis treatment increases mortality risk. A total of 455 dialysis patients were followed for objectively verified symptomatic thrombotic events between January 1997 and June 2009. The incidence rates in dialysis patients as compared to the general population was 5.6-fold (95% CI 3.1-8.9) increased for venous thrombosis, 11.9-fold (95% CI 9.3-14.9) increased for myocardial infarction, and 8.4-fold (95% CI 5.7-11.5) increased for ischaemic stroke. The combination of haemodialysis, lowest tertile of albumin, history of venous thrombosis, and malignancy was associated with subsequent venous thrombosis. Increased age, renal vascular disease, diabetes, high cholesterol levels, history of venous thrombosis, and history of arterial thrombosis were associated with subsequent arterial thrombosis. The all-cause mortality risk was 1.9-fold (95% CI 1.1-3.3) increased for patients with a history of venous thrombosis and 1.9-fold (95% CI 1.4-2.6) increased for patients with a history of arterial thrombosis. A potential limitation of this study was that in some risk categories associations with venous thrombosis did not reach statistical significance due to small numbers. In conclusion, dialysis patients have clearly elevated risks of venous thrombosis and arterial thrombosis and occurrence of venous thrombosis or arterial thrombosis prior to the start of dialysis is associated with an increased mortality risk.

Variations in C-reactive protein during a single haemodialysis session do not associate with mortality

BACKGROUND An increase in C-reactive protein (CRP) levels during a single haemodialysis (HD) session has been associated with mortality. These associations, however, are difficult to understand from the current understanding of CRP metabolism. METHODS In 190 Swedish haemodialysis (HD) patients from the Mapping of Inflammatory Markers in Chronic Kidney Disease (MIMICK) cohort, CRP was measured before and after a HD session. During follow-up, events of death and censoring were recorded, and hazard ratios were calculated and analysed as a function of CRP variation. Results were replicated in 94 Dutch HD patients from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD). In this cohort, also correlation and kappa statistics were calculated to assess concordance in CRP changes amid multiple dialysis sessions from the same individuals. RESULTS In both cohorts, mean CRP values did not increase during a single HD session. In the MIMICK, median (interquartile range) dialysis vintage was 29.0 (14.8-57.0) months. In both crude [hazard ratio (95% confidence interval): 1.008 (0.971-1.047)] and multivariate Cox models [0.996 (0.949-1.046)], no association was observed with mortality. In the NECOSAD, individuals endured 6.0 (6.0-12.0) months on dialysis. No association was found with mortality neither in a crude [0.961 (0.908-1.018)] nor in an adjusted analysis [0.978 (0.923-1.037)]. Finally, the concordance between changes in different sessions was poor. CONCLUSIONS CRP changes during a single HD session do not associate with mortality, thereby adding to the biological uncertainty concerning the ability of CRP to rise in such a short period.

What happens to patients starting dialysis in the Netherlands

BACKGROUND despite improvements in dialysis technology, publications around 1990 showed increasing mortality rates in dialysis patients. The Dialysis Group of the Netherlands initiated the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) to investigate the association of patient and therapy characteristics with outcome. METHODS 250 patients were included in this prospective multicentre study 3 months after the start of dialysis. We used Cox regression to predict mortality and technique failure and repeated measures analysis of variance to study the time course of continuous parameters. RESULTS there were considerable differences in patient populations among dialysis centres. Patient survival was 76% at 2 years. Technique survival was higher in haemodialysis. Hospitalisation decreased from 25 days between 3 and 12 months to 19 days per patient year in the third year. Residual renal function decreased at a similar rate in both modalities, but blood pressure tended to increase in females receiving peritoneal dialysis. Outcome was predominantly dependent on patient characteristics. CONCLUSIONS In the light of the increasing age of patients starting dialysis, increasing mortality can be expected. Furthermore, if outcome is to play a role in the quality assessment of dialysis centres, it is essential to know the characteristics of their patient populations.

The −174G/C variant of IL6 as risk factor for mortality and technique failure in a large cohort of peritoneal dialysis patients

BACKGROUND Functional variants in the IL6 gene, in particular the -174G/C polymorphism (rs1800795), affect the mortality risk in dialysis patients. Peritoneal dialysis (PD) patients harbouring the C allele of the -174G/C polymorphism of IL6 showed faster peritoneal transport. The aim of this study was to investigate this IL6 variant as risk factor for mortality and technique failure in a large cohort of Caucasian PD patients. METHODS A Dutch multicentre cohort of 398 incident PD patients (NECOSAD) was analysed. Survival analysis was performed for death and technique failure with a maximum follow-up of 5 years. A combined PD cohort from Amsterdam (Academic Medical Center, N = 71) and Brussels (Université catholique de Louvain Medical School, N = 102) was used for independent replication. RESULTS In NECOSAD, 105 patients died on dialysis [incidence rate 10.3/100 person-years (py)], and 138 patients experienced technique failure (16.2/100 py), with peritonitis as important cause. Patients with the C/C genotype had a 71% increased mortality risk compared to patients with the G/G genotype (95% confidence interval 0.98-2.98); this effect was mainly a long-term effect: a 2.7-fold increased mortality risk was found in patients having survived 2 years since the start on dialysis, and a 1.7-fold increased risk for the combined end point (mortality or technique failure). In the combined replication cohort, no increased risks were found in patients with the C/C genotype. CONCLUSIONS The C/C genotype of the -174G/C polymorphism was associated with an increased mortality risk in 398 Dutch incident PD patients. The existence of substantial differences between the two academic replication cohorts and the discovery cohort from NECOSAD and the limited power of these cohorts prevented an independent replication of the NECOSAD findings.