Netherlands Cooperative Study Research Articles

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.

The effect of contraindications and patient preference on dialysis modality selection in ESRD patients in The Netherlands

Background: Patients with end-stage renal disease (ESRD) who are about to start long-term dialysis therapy are faced with the question of modality choice. The aim of the current study is to determine the influence of different factors on long-term dialysis modality choice. Methods: As part of a large Dutch prospective multicenter study, the Netherlands Cooperative Study on the Adequacy of Dialysis, we consecutively included all new patients with ESRD. Nephrologists indicated the most important reason for the modality selection. Results: Of 1,347 included patients, 36% (n = 483) had a contraindication to either peritoneal dialysis (PD) or hemodialysis (HD) therapy. Eighty percent (n = 386) of all contraindications were directed to PD therapy. The most frequently mentioned contraindication was a social one; ie, the expected incapability of patients to perform PD exchanges themselves. Patients with contraindications were older, had more comorbidity, and lived alone more often compared with patients without contraindications. In patients without contraindications (64%), modality choice was based on patient preference. Older age increased the odds of choosing HD, whereas receipt of predialysis care was associated with a lower preference for HD. Conclusion: Older age was associated with more contraindications to PD therapy and stronger patient preference for HD therapy. An elderly patient therefore was more likely to start with HD therapy. Results from the current study suggest that an increase in provision of predialysis care, in combination with a reduction in social contraindications to PD therapy, may be associated with an increase in likelihood of starting with PD therapy. In a time of an aging population, increasing demand on dialysis capacity, and limited amount of financial supplies, we may reconsider current strategies to provide future patients with ESRD the possibility to start with the dialysis modality they prefer.

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.

The nutritional status of chronic renal failure patients following the initiation of hemodialysis treatment

The nutritional status of chronic renal failure patients following the initiation of hemodialysis treatment

How to adjust for comorbidity in survival studies in ESRD patients: A comparison of different indices

Background: Many patients with end-stage renal disease (ESRD) have additional comorbid conditions. Differences in the presence and severity of these comorbid conditions can bias comparisons between treatment groups. Adjustment for prognostic factors can statistically counterbalance these differences. For this purpose, appropriate weighting of comorbid conditions is necessary. We evaluated three existing methods to score comorbidity in patients with ESRD and compared their ability to predict survival: the Khan, Davies, and Charlson indices. In addition, these three indices were compared with a new index that explicitly incorporates the severity grading of a number of comorbid diseases. Methods: In a large Dutch prospective multicenter study (Netherlands Co-operative Study on the Adequacy of Dialysis-2), new patients with ESRD were included. Comorbidity was assessed at the start of dialysis therapy. Patient data were randomly allocated to a modeling or testing set. The new index was developed in the modeling set. All indices were evaluated in the testing set. Results: We obtained data for 1,205 patients. Of the three existing indices, the Charlson index had the best discriminating features, with a concordance c statistic of 0.71. The addition of severity grading of several comorbid conditions did not improve discrimination. After combining the comorbidity indices with age, all c statistics improved. These final values ranged from 0.72 to 0.75. Conclusion: We conclude that the Khan, Davies, and Charlson scores are appropriate for expressing the prognostic impact of comorbidity on mortality risk in patients with ESRD provided sufficient adjustment for age is performed. Adding the severity grading of several comorbid conditions will not lead to improved prognostic power. © 2002 by the National Kidney Foundation, Inc.

Validation of the KDQOL-SF: a dialysis-targeted health measure.

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 KDQOL i.e. the KDQOL-SF, a dialysis-targeted instrument, and to assess its ability to detect changes over time. 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. The reliability of the KDQOL-SF was supported by test results that were above the recommended minimal values. Validity of KDQOL-SF 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-SF was able to detect clinical changes over time. The psychometric properties of the KDQOL-SF were good, and the different dialysis-targeted dimensions were informative with a high reliability and validity. These results support the application of the KDQOL-SF in studies evaluating dialysis therapy.

Evaluation of DOQI guidelines: early start of dialysis treatment is not associated with better health-related quality of life.

The National Kidney Foundation-Dialysis Outcomes Quality Initiative (DOQI) guideline, which is largely opinion based, promotes an earlier initiation of dialysis treatment than usual. Implementation of this guideline would require an expansion of dialysis capacity, leading to a considerable increase in costs. Such an expansion can only be justified by an improvement in patient outcome. We studied the effect of late versus timely initiation of dialysis treatment on the course of health-related quality of life (HRQOL) in new dialysis patients. As part of a large Dutch prospective multicenter study (Netherlands Cooperative Study on the Adequacy of Dialysis-2), we consecutively included all new patients with end-stage renal disease for whom residual renal function could be obtained 0 to 4 weeks before the start of dialysis therapy. HRQOL was assessed by means of the Kidney Disease and Quality of Life Short Form at regular intervals during the first year of chronic dialysis treatment. According to the DOQI guideline, 90 of the 237 included patients (38%) started dialysis treatment too late. All patients showed marked improvement in HRQOL during the first 6 months after the start of dialysis treatment. Compared with patients who started dialysis treatment too late, patients who started in time had significantly higher HRQOL for a number of dimensions immediately after the start of treatment. After 12 months of dialysis treatment, these differences had disappeared. An evidence-based recommendation on an early start of dialysis treatment is still difficult to give. In the short term, an earlier start resulted in better HRQOL. However, within 1 year, this advantage had disappeared. It is unclear whether this short-term benefit outweighs the extra restrictions associated with earlier initiation of dialysis therapy. Consequently, only the patient, in consultation with the nephrologist, is able to weigh both sides.

The Relationship between Kt/VUrea and Npna in Anuric Peritoneal Dialysis Patients: A Comparison with Predialysis Patients

It is unknown whether a given level of urea clearance by the native kidneys provides better or similar control of uremia than the same level of urea clearance by continuous peritoneal dialysis (PD). More insight into possible differences between renal and peritoneal urea clearances is warranted. Therefore, we investigated the relationship between Kt/V(urea) and protein equivalent of total nitrogen appearance normalized to body weight (nPNA), the relationship between urea clearance and creatinine appearance, and other nutritional parameters in PD patients without residual renal function, and in predialysis end-stage renal disease patients. All patients participated in the Netherlands Cooperative Study on the Adequacy of Dialysis. This is a prospective cohort study of incident dialysis patients, in whom regular assessments of renal function are done. A group of 75 PD patients was identified at the first follow-up assessment in which their urine production was less than 100 mL/day. These patients were considered the anuric group. This group was compared with a control group of 97 predialysis patients studied 0-4 weeks before the start of dialysis treatment. Linear relationships were present between Kt/V(urea) and nPNA, in both the predialysis patients and the anuric PD patients. A significant difference was present between the slopes of the two regression lines (0.40 vs 0.18, p = 0.007). When Kt/V(urea) exceeded 1.3/week, a given level of Kt/V(urea) was associated with a higher nPNA in predialysis than in anuric PD patients. Similar relationships were found between Kt(urea) and PNA. Kt(urea) was also significantly related to urine or dialysate creatinine appearance. A significant difference existed between the slopes of the regression lines in the two groups of patients (p < 0.001). A weekly Kt(urea) of 70 L was associated with a urine creatinine appearance of 11.0 mmol/day and a dialysate creatinine appearance of 8.4 mmol/day. Nutritional status measured with creatinine appearance and Subjective Global Assessment was better in the predialysis population, despite much lower values for Kt/V(urea) in these patients. The relationship between Kt/V(urea) and nPNA in anuric PD patients is different from that in a predialysis population. It follows from our results that, when Kt/V(urea) is above 1.3/week, a given level of Kt/V(urea) is associated with a higher nPNA in predialysis than in anuric PD patients. This challenges the concept of equivalency between renal and peritoneal Kt/V(urea) with respect to control of uremic morbidity.

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.

Predictors of poor outcome in chronic dialysis patients: The Netherlands Cooperative Study on the Adequacy of Dialysis. The NECOSAD Study Group.

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.

Quality of Life Over Time in Dialysis: The Netherlands Cooperative Study on the Adequacy of Dialysis, by Merkus MP, Jager KJ, Dekker FW, de Haan RJ, Boeschoten EW, Krediet RT, for the NECOSAD Study Group. Kidney Int 56:720–728, 1999

Quality of Life Over Time in Dialysis: The Netherlands Cooperative Study on the Adequacy of Dialysis, by Merkus MP, Jager KJ, Dekker FW, de Haan RJ, Boeschoten EW, Krediet RT, for the NECOSAD Study Group. <i>Kidney Int</i> 56:720–728, 1999

Dialysis in The Netherlands: the clinical condition of new patients put into a European perspective. NECOSAD Study Group. Netherlands Cooperative Study on the Adequacy of Dialysis phase 1.

The unadjusted annual mortality rate among prevalent Dutch dialysis patients increased from 1981 to 1992. Part of this increase may be attributed to the ageing of the dialysis population, but hardly any data were available on other important prognostic features of new Dutch dialysis patients, such as co-morbidity and other aspects of their clinical condition. The aim of the present study was to obtain these data and to put them into a European perspective. Two hundred and fifty consecutive new patients were included in this prospective multi-centre study. Data were collected 3 months after start of dialysis. Multivariate linear regression analysis was used to explain the variability of parameters of nutritional state and blood pressure. Mean age was 57 years, co-morbid conditions were present in 51%, diabetes mellitus in 18%, and cardiovascular disease in 28%. Decreased protein intake was related to diminished residual renal function. Our patients did not have more co-morbidity than Dutch patients participating in a European study some years earlier. Comparison with other studies was complicated by the use of different definitions of co-morbidity and of selected patient populations. Despite the fact that Dutch dialysis patients have become older and the incidence of diabetic nephropathy has increased, no conclusions could be drawn on a concomitant increase in co-morbidity. This patient group may serve as a reference population to study future changes in patient case-mix within the Netherlands. Furthermore, the use of common international definitions of co-morbidity is needed to be able to make comparisons of survival data.

Quality of life over time in dialysis: The Netherlands Cooperative Study on the Adequacy of Dialysis

Information on the longitudinal quality of life (QL) of patients treated by different dialysis modalities is lacking. Therefore, we performed a prospective cohort study on the QL over time in hemodialysis (HD) and peritoneal dialysis (PD) patients. New chronic dialysis patients from 13 Dutch dialysis centers were consecutively included. The patients' self-assessment of QL was measured with the SF-36 form at 3, 6, 12, and 18 months after the start of dialysis treatment. Out of 230 patients who completed the QL questionnaire at least once, 139 patients stayed on their initial dialysis modality, 26 patients switched dialysis modality, 35 patients were transplanted, 28 patients died, and two patients had a recovery of renal function. The QL of patients who died during the study period was considerably worse at baseline and worsened at a faster rate than in the other patient groups. In patients who stayed on their initial dialysis modality, the physical QL decreased over time, whereas the mental QL tended to remain stable. After an adjustment for the initial value of QL and comorbidity, a consistently favorable effect of HD on physical QL over time was found compared with PD, whereas mental QL values remained similar. Parameters of adequacy of dialysis were not associated with QL over time. This prospective cohort study shows that physical QL over time in HD patients is better than in PD patients.

Mortality and technique failure in patients starting chronic peritoneal dialysis: Results of the Netherlands Cooperative Study on the Adequacy of Dialysis

Recent studies have shown an association between small solute clearance and patient survival. Thus far, little attention has been paid to the potential effects of fluid overload. The aim of this study was to determine the relative importance of baseline patient and treatment characteristics to mortality and technique failure in patients starting peritoneal dialysis. One hundred and eighteen consecutive new patients were included in this prospective multicenter cohort study. Cox proportional hazards regression was used to predict mortality and technique failure. There were 33 deaths and 44 technique failures. The two-year patient survival was 77%, and the two-year technique survival was 64%. Age, systolic blood pressure, and the absolute quantity of small solutes removed at baseline were independent predictors of mortality. A one-year increase in age was associated with a relative risk (RR) of death of 1.05 (95% CI, 1.01 to 1.09) and a 10 mm Hg rise in systolic blood pressure, with a RR of 1.42 (95% CI, 1.17 to 1.73). The removal of 1 mmol/week/1.73 m2 of urinary and dialysate creatinine was associated with a RR of death of 0.95 (95% CI, 0.92 to 0.98) and 0.93 (95% CI, 0.89 to 0.98). The removal of urea had a similar association with the RR of death. Predictors for technique failure were urine volume, peritoneal ultrafiltration, and systolic blood pressure. Dialysate solute removal was an independent predictor of mortality. The association between systolic blood pressure and mortality shows that the maintenance of fluid balance and the removal of small solutes deserve equal attention.

Implantable cardioverter-defibrillators are preferable to drugs as primary therapy in sustained ventricular tachyarrhythmias

The choice of initial therapy for patients with malignant ventricular tachyarrhythmias is examined based on clinical efficacy, patient safety, and cost. Antiarrhythmic drug therapy can be administered using a guided or empiric approach. Guided type-1 antiarrhythmic drug therapy has been associated with high arrhythmia recurrence rates (>40% at 1 year) and moderate sudden death rates (10% at 1 year). Sotalol is associated with lower arrhythmia recurrence rates (20% at 1 year) that increase to 50% at 4 years. β-blocking agents have a limited role as stand-alone therapy in this condition. Empiric amiodarone therapy has sudden death-free survival rates of 82% at 2 years but has significantly poorer results in patients with ejection fractions ≤40%. In contrast, implantable cardioverter-defibrillator (ICD) therapy has reported sudden death recurrence rates of 1% to 2% per year, with a cumulative index of 10% at 5 years. Total survival rate of ICD recipients ranges from 85% to 92% at 2 years. In patients with good left ventricular function, it approaches 90% at 5 years, whereas it is between 50% to 60% in patients with severe left ventricular dysfunction. Data from device memory indicate an absolute reduction in mortality rates with ICD intervention. Comparison of drug and device therapy has been performed in retrospective and prospective studies. Improved survival with device therapy is noted, particularly in patients with ejection fractions ≤35% to 40% in retrospective studies. The results of two small prospective randomized trials also show significant survival advantage as compared with those for type-1C drugs and a mixed group of antiarrhythmic drugs. An initial strategy of ICD therapy was shown to be superior in the Netherlands Cooperative Study. The 30-day perioperative mortality rate of ICD therapy of 0.8% contrasts favorably with a 13% mortality rate in the ESVEM trial with antiarrhythmic drugs and a 3.5% mortality rate in the CASCADE study. Economic analyses show that drug therapy and device therapy are both within the range of other current cardiovascular therapies. An improving economic profile for device therapy has been observed with nonthoracotomy and pectoral implantation and direct use of ICD therapy because primary therapy shortens hospital stay and reduces costs. Based on available data, ICD therapy is preferable as initial therapy in patients with malignant ventricular tachyarrhythmias.