Roger Greenwood

Survival of elderly patients with stage 5 CKD: comparison of conservative management and renal replacement therapy

Background. Elderly patients with end-stage renal disease and severe extra-renal comorbidity have a poor prognosis on renal replacement therapy (RRT) and may opt to be managed conservatively (CM). Information on the survival of patients on this mode of therapy is limited. Methods. We studied survival in a large cohort of CM patients in comparison to patients who received RRT. Results. Over an 18-year period, we studied 844 patients, 689 (82%) of whom had been treated by RRT and 155 (18%) were CM. CM patients were older and a greater proportion had high comorbidity. Median survival from entry into stage 5 chronic kidney disease was less in CM than in RRT (21.2 vs 67.1 months: P < 0.001). However, in patients aged > 75 years when corrected for age, high comorbidity and diabetes, the survival advantage from RRT was ~ 4 months, which was not statistically significant. Increasing age, the presence of high comorbidity and the presence of diabetes were independent determinants of poorer survival in RRT patients. In CM patients, however, age > 75 years and female gender independently predicted better survival. Conclusions. In patients aged > 75 years with high extra-renal comorbidity, the survival advantage conferred by RRT over CM is likely to be small. Age > 75 years and female gender predicted better survival in CM patients. The reasons for this are unclear.

Choosing not to dialyse: evaluation of planned non-dialytic management in a cohort of patients with end-stage renal failure.

Objectives: To study factors influencing the recommendation for palliative (non-dialytic) treatment in patients approaching end-stage renal failure and to study the subsequent outcome in patients choosing not to dialyse. Design: Cohort study of patients approaching end-stage renal failure who underwent multidisciplinary assessment and counselling about treatment options. Recruitment was over 54 months, and follow-up ranged from 3 to 57 months. Groups were defined on the basis of the therapy option recommended (palliative or renal replacement therapy). Setting: Renal unit in a district general hospital serving a population of about 1.15 million people. Subjects: 321 patients, mean age ± SD 61.5 ± 15.4 years (range: 16–92), 57% male, 30% diabetic. Main Outcome Measures: Survival, place of death (hospital or community). Results: Renal replacement therapy was recommended in 258 patients and palliative therapy in 63 (19.6%). By logistic regression analysis, patients recommended for palliative therapy were more functionally impaired (modified Karnofsky scale), older and more likely to have diabetes. The comorbidity severity score was not an independent predictor. Thirty-four patients eventually died during palliative treatment, 26 of whom died of renal failure. Ten patients recommended for palliative treatment opted for and were treated by dialysis. Median survival after dialysis initiation in these patients (8.3 months) was not significantly longer than survival beyond the putative date of dialysis initiation in palliatively treated patients (6.3 months). 65% of deaths occurring in dialysed patients took place in hospital compared with 27% in palliatively treated patients (p = 0.001). Conclusions: In high-risk, highly dependent patients with renal failure, the decision to dialyse or not has little impact on survival. Dialysis in such patients risks unnecessary medicalisation of death.

Is there a rationale for rationing chronic dialysis? A hospital based cohort study of factors affecting survival and morbidity

Abstract Objectives: To determine factors influencing survival and need for hospitalisation in patients needing dialysis, and to define the potential basis for rationing access to renal replacement therapy. Design: Hospital based cohort study of all patients starting dialysis over a 4year recruitment period (follow up 15-63months). Groups were defined on the basis of age, comorbidity, functional status, and whether dialysis initiation was planned or unplanned. Setting: Renal unit in a district general hospital, which acts as the main renal referral centre for four other such hospitals and serves a population of about 1.15million people. Subjects: 292 patients, mean age 61.3years (18-92years, SD 15.8), of whom 193(66%) were male, and 59(20%) were patients with diabetes. Dialysis initiation was planned in 163(56%) patients and unplanned in 129(44%). Main outcome measures: Overall survival, 1year survival, and hospitalisation rate. Results: Factors affecting survival in the Coxs proportional hazard model were Karnofsky performance score at presentation (hazard ratio 0.979,95% confidence interval 0.972to 0.986), comorbidity severity score (1.240,1.131to 1.340), age (1.036,1.018to 1.054), and myeloma (2.15,1.140to 4.042). The Karnofsky performance score used 3months before presentation was significant (0.970,0.956to 0.981), as was unplanned presentation in this model (1.796,1.233to 2.617). Using these factors, a high risk group of 26patients was defined, with 19.2% 1year survival. Denying dialysis to this group would save 3.2% of the total cost of the chronic programme but would sacrifice five long term survivors. Less rigorous definition of the high risk group would save more money but lose more long term survivors. Conclusions: Severity of comorbid conditions and functional capacity are more important than age in predicting survival and morbidity of patients on dialysis. Late referral for dialysis affects survival adversely. Denial of dialysis to patients in an extremely high risk group, defined by a new stratification based on logistic regression, would be of debatable benefit.

Urea kinetics and when to commence dialysis.

Blood urea and serum creatinine levels are important factors in deciding when to start dialysis. Recently, in the assessment of dialysis adequacy, emphasis has shifted from reliance on these parameters to use of kinetic methods. We therefore applied urea kinetic modelling (UKM) to 63 consecutive chronic renal failure (CRF) patients at the time dialysis commenced and compared the results to those obtained after 6 months of dialysis treatment. Mean normalised urea clearance (daily KT/V) at the commencement of dialysis (KTi/V) was 0.15 +/- 0.05, a level indicative of underdialysis in regularly dialysed patients. After 6 months, mean daily KT/V was 0.35 +/- 0.12 in patients subsequently established on CAPD, and 0.49 +/- 0.08 in those subsequently haemodialysed (both p < 0.001 compared to mean KTi/V). Serum creatinine levels on commencing dialysis were similar to those after 6 months treatment by either mode. Mean age (p < 0.01) and co-morbidity index (p < 0.05) were higher, and mean KTi/V lower (p < 0.05) in the 6 patients who died during a mean follow-up period of 10 +/- 4.5 months than in survivors. Hospitalisation rates during follow-up (excluding admissions for access surgery and training) correlated with age (r = 0.332, p < 0.01), co-morbidity index (r = 0.351, p < 0.01) and KTi/V (r = -0.302, p < 0.05). Blood urea and serum creatinine levels on commencing dialysis were the same in those who died and in survivors and did not correlate with hospitalisation rates. Diabetics started dialysis with a similar mean KTi/V to non-diabetics but with a lower mean serum creatinine (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

The survival advantage for haemodialysis patients taking vitamin D is questioned: findings from the Dialysis Outcomes and Practice Patterns Study

BACKGROUND Retrospective studies of haemodialysis patients from large dialysis organizations in the United States have indicated that intravenous vitamin D may be associated with a survival benefit. However, patients prescribed vitamin D are generally healthier than those who are not, suggesting that treatment by indication may have biased previous findings. Additionally, no survival benefit associated with vitamin D has been shown in a recent meta-analysis in CKD patients. Because treatment-by-indication bias due to both measured and unmeasured confounders cannot be completely accounted for in standard regression or marginal structural models (MSMs), this study evaluates the association between vitamin D and mortality among participants in the Dialysis Outcomes and Practice Patterns Study (DOPPS) using standard regression and MSMs with an expanded set of covariates, as well as by instrumental variable models to minimize potential bias due to unmeasured confounders. METHODS Data from 38 066 DOPPS participants from 12 countries between 1996 and 2007 were analysed. Mortality risk was assessed using standard baseline and time-varying Cox regression models, adjusted for demographics and detailed comorbidities, and MSMs. In models similar to instrumental variable analysis, the facility percentage of patients prescribed vitamin D, adjusted for the patient case mix, was used to predict patient-level mortality. RESULTS Vitamin D prescription was significantly higher in the USA compared to other countries. On average, patients prescribed vitamin D had fewer comorbidities compared to those who were not. Vitamin D therapy was associated with lower mortality in adjusted time-varying standard regression models [relative ratio (RR) = 0.92 (95% confidence interval: 0.87-0.96)] and baseline MSMs [RR = 0.84 (0.78-0.98)] and time-varying MSMs [RR = 0.78 (0.73-0.84)]. No significant differences in mortality were observed in adjusted baseline standard regression models for patients with or without vitamin D prescription [RR = 0.98 (0.93-1.02)] or for patients in facility practices where vitamin D prescription was more frequent [RR for facilities in 75th versus 25th percentile of vitamin D prescription = 0.99 (0.94-1.04)]. CONCLUSIONS Vitamin D was associated with a survival benefit in models prone to bias due to unmeasured confounding. In agreement with a meta-analysis of randomized controlled studies, no difference in mortality was observed in instrumental variable models that tend to be more independent of unmeasured confounding. These findings indicate that a randomized controlled trial of vitamin D and clinical outcomes in haemodialysis patients are needed and can be ethically conducted.

Factors associated with health-related quality of life among hemodialysis patients in the DOPPS

ObjectiveTo identify modifiable factors associated with health-related quality of life (HRQOL) among chronic hemodialysis patients.MethodsAnalysis of baseline data of 9,526 hemodialysis patients from seven countries enrolled in phase I of the Dialysis Outcomes and Practice Patterns Study (DOPPS). Using the Kidney Disease Quality of Life Short Form (KDQOL-SFTM), we determined scores for 8 generic scale summaries derived from these scales, i.e., the physical component summary [PCS] and mental component summary [MCS], and 11 kidney disease-targeted scales. Regression models were used to adjust for differences in comorbidities and sociodemographic and treatment factors. The Benjamin-Hochberg procedure was used to correct P-values for multiple comparisons.ResultsUnemployment and psychiatric disease were independently and significantly associated with lower scores for all generic and several kidney disease-targeted HRQOL measures. Several other comorbidities, lower educational level, lower income, and hypoalbuminemia were also independently and significantly associated with lower scores of PCS and/or MCS and several generic and kidney disease-targeted scales. Hemodialysis by catheter was associated with significantly lower PCS scores, partially explained by the correlation with covariates.ConclusionAssociations of poorer HRQOL with preventable or controllable factors support a greater focus on psychosocial and medical interventions to improve the well-being of hemodialysis patients.

Long-Term Outcomes in Online Hemodiafiltration and High-Flux Hemodialysis : A Comparative Analysis

BACKGROUND AND OBJECTIVES Theoretical advantages exist of online hemodiafiltration (HDF) over high-flux hemodialysis (HD), but outcome data are scarce. Our objective was to compare outcomes between these modalities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied 858 incident patients in our incremental high-flux HD and online HDF program during an 18-yr period. We compared outcomes, including survival, in those who were treated predominantly with HDF (>50% sessions) and those with high-flux HD. Survival comparisons used a Cox model taking into account the time-varying proportion of time spent on HDF. All data were prospectively collected. RESULTS A total of 152,043 sessions were delivered as HDF and 291,222 as high-flux HD. A total of 232 (27%) patients were treated predominantly with HDF and 626 (73%) with high-flux HD. Total Kt/V, serum albumin, erythropoietin resistance index, and BP were similar in both groups up to 5 yr after HD initiation. Intradialytic hypotension was less frequent in the predominant HDF group. Predominant HDF treatment was associated with a reduced risk for death after correction for confounding variables. In a second Cox model, proportion of time spent on HDF predicted survival, such that patients who were treated solely by HDF would have a hazard for death of 0.66 compared with those who solely used high-flux HD. CONCLUSIONS We found no benefits of HDF over high-flux HD with respect to anemia management, nutrition, mineral metabolism, and BP control. The mortality benefit associated with HDF requires confirmation in large randomized, controlled trials. These data may contribute to their design.

International Differences in Dialysis Mortality Reflect Background General Population Atherosclerotic Cardiovascular Mortality

Existing national, racial, and ethnic differences in dialysis patient mortality rates largely are unexplained. This study aimed to test the hypothesis that mortality rates related to atherosclerotic cardiovascular disease (ASCVD) in dialysis populations (DP) and in the background general populations (GP) are correlated. In a cross-sectional, multinational study, all-cause and ASCVD mortality rates were compared between GP and DP using the most recent data from the World Health Organization mortality database (67 countries; 1,571,852,000 population) and from national renal registries (26 countries; 623,900 population). Across GP of 67 countries (14,082,146 deaths), all-cause mortality rates (median 8.88 per 1000 population; range 1.93 to 15.40) were strongly related to ASCVD mortality rates (median 3.21; range 0.53 to 8.69), with Eastern European countries clustering in the upper and Southeast and East Asian countries in the lower rate ranges. Across DP (103,432 deaths), mortality rates from all causes (median 166.20; range 54.47 to 268.80) and from ASCVD (median 63.39 per 1000 population; range 21.52 to 162.40) were higher and strongly correlated. ASCVD mortality rates in DP and in the GP were significantly correlated; the relationship became even stronger after adjustment for age (R(2) = 0.56, P < 0.0001). A substantial portion of the variability in mortality rates that were observed across DP worldwide is attributable to the variability in background ASCVD mortality rates in the respective GP. Genetic and environmental factors may underlie these differences.

Residual renal function improves outcome in incremental haemodialysis despite reduced dialysis dose

BACKGROUND AND METHODS The importance of residual renal function is well recognized in peritoneal dialysis but its role in haemodialysis (HD) has received much less attention. We studied 650 incident patients in our incremental high-flux HD programme over a 15-year period. Target total Kt/V urea (dialysis plus residual renal) was 1.2 per session and monitored monthly. Renal urea clearance (KRU) was estimated 1-3 monthly. RESULTS KRU declined during the first 5 years of HD from 3.1 +/- 1.9 at 3 months to 0.9 +/- 1.2 ml/min/1.73 m(2) at 5 years. The percentage of patients with KRU >or= 1 ml/min at these time points was 85% and 31%, respectively. Patients with KRU >or= 1 ml/min had a significantly lower mean creatinine (all time points), ultrafiltration requirement (all time points) and serum potassium (6, 12, 36 and 48 months). Nutritional parameters were also significantly better in respect to nPCR and serum albumin (6, 12, 24 and 36 months). Patients with KRU >or= 1 ml/min had significantly lower erythropoietin requirements and erythropoietin resistance indices (12, 24, 36 and 48 months). Mortality was significantly lower in patients with a KRU >or= 1 at 6, 12 and 24 months after HD initiation, this benefit being maintained after correcting for albumin, age, comorbidities, HDF use and renal diagnosis. Our unique finding was that these benefits occurred despite those with KRU >or= 1 ml/min having a significantly lower dialysis Kt/V at all time points. CONCLUSION The associations demonstrated suggest that residual renal function contributes significantly to outcome in HD patients and that efforts to preserve it are warranted. Comparative outcome studies should be controlled for residual renal function.

Blood pressure levels and mortality risk among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.

KDOQI practice guidelines recommend predialysis blood pressure <140/90 mm Hg; however, most prior studies had found elevated mortality with low, not high, systolic blood pressure. This is possibly due to unmeasured confounders affecting systolic blood pressure and mortality. To lessen this bias, we analyzed 24,525 patients by Cox regression models adjusted for patient and facility characteristics. Compared with predialysis systolic blood pressure of 130-159 mm Hg, mortality was 13% higher in facilities with 20% more patients at systolic blood pressure of 110-129 mm Hg and 16% higher in facilities with 20% more patients at systolic blood pressure of ≥160 mm Hg. For patient-level systolic blood pressure, mortality was elevated at low (<130 mm Hg), not high (≥180 mm Hg), systolic blood pressure. For predialysis diastolic blood pressure, mortality was lowest at 60-99 mm Hg, a wide range implying less chance to improve outcomes. Higher mortality at systolic blood pressure of <130 mm Hg is consistent with prior studies and may be due to excessive blood pressure lowering during dialysis. The lowest risk facility systolic blood pressure of 130-159 mm Hg indicates this range may be optimal, but may have been influenced by unmeasured facility practices. While additional study is needed, our findings contrast with KDOQI blood pressure targets, and provide guidance on optimal blood pressure range in the absence of definitive clinical trial data.