Jeannette G. van Manen

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.

Hemodialysis and Peritoneal Dialysis: Comparison of Adjusted Mortality Rates According to the Duration of Dialysis: Analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis 2

Various studies indicate that fair comparisons of mortality rates between hemodialysis (HD) patients and peritoneal dialysis (PD) patients are difficult because of differences in patient characteristics, because of nonconstant relative risks of death (RR), and because the survival times of patients who switch treatment modalities can be censored in different ways. The differences in mortality rates between HD and PD patients were investigated in an analysis in which these potential sources of bias were taken into account. The Netherlands Cooperative Study on the Adequacy of Dialysis is a multicenter, prospective, observational, cohort study in which new patients with ESRD are monitored until transplantation or death. A multivariate Cox regression analysis was used to analyze the mortality data according to treatment modality (HD, n = 742; PD, n = 480). No statistically significant differences in adjusted mortality rates between HD and PD patients were observed during the first 2 yr of dialysis. In the years thereafter, increases in mortality rates for PD patients and resulting decreases in RR in favor of HD were observed (e.g., months 24 to 36, adjusted RR, 0.53; 95% confidence interval, 0.31 to 0.91). This tendency was observed especially among patients >/=60 yr of age and was not influenced by the censoring strategy. These results suggest that long-term use of PD, especially among elderly patients, is associated with increases in mortality rates. Further analyses are required to determine the potential role of dialysis adequacy in the observed long-term differences in mortality rates between HD and PD patients and to establish the possible survival benefits for PD patients who switch to HD in time.

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.

Adjustment for Comorbidity in Studies on Health Status in ESRD Patients: Which Comorbidity Index to Use?

Health status can be an important outcome in studies on patients with end-stage renal disease (ESRD). In these studies, adjustment for prognostic factors, such as comorbidity, often has to be made. None of the comorbidity indices that are commonly used in research on ESRD patients has been validated for studies on health status. This study evaluated three existing indices (Khan, Davies, and Charlson) and four indices specifically developed for use in studies on health status. In a large prospective multi-center study (NECOSAD-2), new ESRD patients were included (n = 1041). Comorbidity was assessed at the start of dialysis. Health status was assessed with the physical and mental component summary score of the SF-36 (PCS and MCS), the symptoms dimension of the KDQOL-SF, and the Karnofsky Scale. Patient data were randomly allocated to a modeling or a testing set. The new indices were developed in the modeling set. The three existing indices explained about the same percentage of variance in the PCS (7 to 8%), MCS (1 to 3%), symptoms (2 to 4%), and Karnofsky (10 to 12%). The new indices performed better than the existing indices in the modeling population (13% PCS, 10% MCS, 10% symptoms, 18% Karnofsky), but not in the testing population (8% PCS, 1% MCS, 3% symptoms, 8% Karnofsky). Individual comorbidities explained more variance in PCS (10 to 15%), MCS (1 to 7%), symptoms (6 to 11%), and Karnofsky (11 to 18%) than comorbidity indices. The Khan, Davies, and the Charlson indices will adjust to the same extent for the potential confounding effect of comorbidity in studies with health status as an outcome. Separate comorbidity diagnoses will adjust best for comorbidity.

The influence of COPD on health-related quality of life independent of the influence of comorbidity.

BACKGROUND/OBJECTIVES The goal of this study was to determine the influence of chronic obstructive pulmonary disease (COPD) on health-related quality of life (HRQL) independent of comorbidity. METHODS Patients with COPD in general practice, >/=40 years, were selected. To recruit controls, a random sample of persons without COPD and >/=40 years, was taken. HRQL was assessed with the SF-36 and comorbidity was determined by questionnaire. RESULTS The influence of COPD on HRQL independent of comorbidity (represented by adjusted regression coefficients) was significant for physical functioning (-27.6), role functioning due to physical problems (-21.6), vitality (-14.4), and general health (-25.7), and was minor and not significant for social functioning (-5.6), mental health (-1.3), role functioning due to emotional problems (-2.7), and bodily pain (-2.5). Comorbidity contributed significantly to the HRQL of all domains (-7.6 to -27.1). CONCLUSIONS COPD patients can be impaired in all domains of HRQL. However, impairments in physical functioning, vitality, and general health are related to COPD and to some extent to comorbidity, while impairments in social and emotional functioning do not seem to be related to COPD, but only to comorbidity.

Effect of an Increase in C-Reactive Protein Level during a Hemodialysis Session on Mortality

The prevalence of chronic inflammation is high in dialysis patients. Moreover, it is associated with an increased mortality risk, yet the origin of chronic inflammation in dialysis patients remains unclear. The aim of this study was to determine the effect of a hemodialysis session (HD) on C-reactive protein (CRP) levels and to study the relation with survival. As part of a large, prospective, multicenter study in the Netherlands (Netherlands Cooperative Study on the Adequacy of Dialysis), patients who were started on dialysis treatment between September 1997 and May 1999 were included. Demographic data, clinical data, and serum samples were collected at regularly timed intervals. From this cohort, a random sample of patients was taken. CRP levels were determined before and after an HD session and before the next session. Date of death or censoring was recorded until September 2002. A total of 186 HD patients were included. Mean age was 65 yr (SD, 13); 56% were male. A total of 71 patients had a CRP level below the detection limit (3 mg/L), 68 patients showed no increase in CRP during an HD session (no-increase group), and 47 (25%) patients showed an increase in CRP level during an HD session (increase-group). No statistically difference in mean CRP levels before the dialysis session was found between the increase group (22.3 mg/L) and the no-increase group (19.4 mg/L). In the subsequent interdialytic period, CRP levels returned to the levels of the initial CRP value. Two-year survival was 44% in the increase group and 66% in the no-increase group (P = 0.09). Independent of CRP level before the session and adjusted for age, comorbidity, nutritional status, and primary kidney disease, a raise of 1 mg/L CRP during a session was associated with a 9% increased mortality risk (adjusted hazard ratio, 1.09; 95% CI, 1.02 to 1.16). The present study showed an increase in CRP level during a single dialysis session in 25% of the patients; during the succeeding interdialytic period, CRP level returned to its original value. More important, however, an increase in CRP level during an HD session was independently associated with a higher mortality risk.