Survival In Incident Dialysis Patients Research Articles

Mortality in Incident Maintenance Dialysis Patients Versus Incident Solid Organ Cancer Patients: A Population-Based Cohort

The mortality rate is high among dialysis patients, but how this compares with other diseases such as cancer is poorly understood. We compared the survival of maintenance dialysis patients with that for patients with common cancers to enhance the understanding of the burden of end-stage kidney disease. Population-based cohort study. 33,500 incident maintenance dialysis patients in Ontario, Canada, and 532,452 incident patients with cancer (women: breast, colorectal, lung, or pancreas; men: prostate, colorectal, lung, or pancreas) from 1997 to 2015 using administrative health care databases. Incident kidney failure treated with maintenance dialysis versus incident diagnoses of cancer. All-cause mortality. Kaplan-Meier product limit estimator was used to describe the survival of subgroups of study participants. Extended Cox regression with a Heaviside function was used to compare survival between patients with incident kidney failure treated with maintenance dialysis and individual diagnoses of various incident cancers. In men, dialysis had worse unadjusted 5-year survival (50.8%; 95% CI, 50.1%-51.6%) compared with prostate (83.3%; 95% CI, 83.1%-83.5%) and colorectal (56.1%; 95% CI, 55.7%-56.5%) cancer, but better survival than lung (14.0%; 95% CI, 13.7%-14.3%) and pancreas (9.1%; 95% CI, 8.5%-9.7%) cancer. In women, dialysis had worse unadjusted 5-year survival (49.8%; 95% CI, 48.9%-50.7%) compared with breast (82.1%; 95% CI, 81.9%-82.4%) and colorectal (56.8%; 95% CI, 56.3%-57.2%) cancer, but better survival than lung (19.7%; 95% CI, 19.4%-20.1%) and pancreas (9.4%; 95% CI, 8.9%-10.0%) cancer. After adjusting for clinical characteristics, similar results were found except when examining men and women with lung and pancreas cancer, for which dialysis patients had a higher rate of death 4 or more years after diagnosis. Women and men 70 years and older with incident kidney failure treated with maintenance dialysis had unadjusted 10-year survival probabilities that were comparable to pancreas and lung cancer. Cancer stage could be obtained for only a subpopulation. Survival in incident dialysis patients was lower than in patients with several different solid-organ cancers. These results highlight the need to develop interventions to improve survival on dialysis therapy and can be used to aid advance care planning for elderly patients beginning treatment with maintenance dialysis.

Pregnancy-associated plasma protein-A predicts survival in end-stage renal disease-confounding and modifying effects of cardiovascular disease, body composition and inflammation.

Background High pregnancy-associated plasma protein-A (PAPP-A) levels are linked to atherosclerosis and associate with increased mortality in prevalent dialysis patients. We investigated associations of PAPP-A, measured at dialysis initiation, with cardiovascular disease (CVD), CVD risk factors and mortality in incident dialysis patients, and explored if body composition and inflammation modulated these associations. Methods Baseline plasma PAPP-A levels, inflammation biomarkers and body composition, using dual-energy X-ray absorptiometry, were measured in 286 incident dialysis patients. Primary outcome was survival during 60 months follow-up. Quantile (median) regression was used for cross-sectional analysis and Kaplan-Meier diagrams and Cox proportional hazards regression for survival analysis. Results In cross-sectional analysis adjusted for age and sex, PAPP-A levels were associated with lean tissue index (LTI) and high-sensitivity C-reactive protein (hsCRP) but not with fat tissue index (FTI) or history of CVD. In a model also including diabetes mellitus (DM), the association with LTI did not remain statistically significant. When adjusted for cardiovascular risk factors and body composition, higher PAPP-A levels showed a moderate but significant association [hazard ratio (HR) = 1.2, 95% confidence interval (CI): 1-1.4, P = 0.04] with mortality. When also including hsCRP the association was attenuated (HR = 1.2, 95% CI: 0.99-1.4, P = 0.06). In survival analysis, interactions with PAPP-A on the multiplicative scale were found for hsCRP (HR = 1.6, 95% CI: 1.2-2.2, P = 0.004) and DM (HR = 1.6, 95% CI: 1.1-2.2, P = 0.01) and with DM and FTI on the additive scale. Conclusions Higher PAPP-A levels are associated with worse survival in incident dialysis patients following adjustment for established cardiovascular risk factors and body composition indices, but not clearly so when adjusted for hsCRP. Inflammation, body composition (FTI) and DM were found to be potential effect modifiers for the observed moderate association of PAPP-A with survival.

Pregnancy-associated plasma protein-A predicts survival in end-stage renal disease-confounding and modifying effects of cardiovascular disease, body composition and inflammation.

High pregnancy-associated plasma protein-A (PAPP-A) levels are linked to atherosclerosis and associate with increased mortality in prevalent dialysis patients. We investigated associations of PAPP-A, measured at dialysis initiation, with cardiovascular disease (CVD), CVD risk factors and mortality in incident dialysis patients, and explored if body composition and inflammation modulated these associations. Baseline plasma PAPP-A levels, inflammation biomarkers and body composition, using dual-energy X-ray absorptiometry, were measured in 286 incident dialysis patients. Primary outcome was survival during 60 months follow-up. Quantile (median) regression was used for cross-sectional analysis and Kaplan-Meier diagrams and Cox proportional hazards regression for survival analysis. In cross-sectional analysis adjusted for age and sex, PAPP-A levels were associated with lean tissue index (LTI) and high-sensitivity C-reactive protein (hsCRP) but not with fat tissue index (FTI) or history of CVD. In a model also including diabetes mellitus (DM), the association with LTI did not remain statistically significant. When adjusted for cardiovascular risk factors and body composition, higher PAPP-A levels showed a moderate but significant association [hazard ratio (HR) = 1.2, 95% confidence interval (CI): 1-1.4, P = 0.04] with mortality. When also including hsCRP the association was attenuated (HR = 1.2, 95% CI: 0.99-1.4, P = 0.06). In survival analysis, interactions with PAPP-A on the multiplicative scale were found for hsCRP (HR = 1.6, 95% CI: 1.2-2.2, P = 0.004) and DM (HR = 1.6, 95% CI: 1.1-2.2, P = 0.01) and with DM and FTI on the additive scale. Higher PAPP-A levels are associated with worse survival in incident dialysis patients following adjustment for established cardiovascular risk factors and body composition indices, but not clearly so when adjusted for hsCRP. Inflammation, body composition (FTI) and DM were found to be potential effect modifiers for the observed moderate association of PAPP-A with survival.

Institutional factors influencing regional differences in the 1-year survival of dialysis patients.

There are regional differences in the survival of incident dialysis patients, but few studies have investigated the reasons. We assessed the effect of institutional factors on factors on survival (by both cross-sectional assessment and after a 1-year investigation) in a cohort of the Japanese Society for Dialysis Therapy (JSDT). We investigated 20 institutional factors from 3958 dialysis institution data of the 47 prefectures in Japan in 2005 and the JSDT database of 102,011 patients who commenced dialysis during 2004-2006. Univariate regression analysis between 20 factors and 1-year survival rate, Kaplan-Meier method, log-rank test, and Cox's proportional hazard model between the upper 24 and the lower 23 prefectures of the significant factors were carried out. The age-adjusted 1-year survival rate was 0.832 ± 0.027. Deaths occurred in 15.0% in 24 upper survival prefectures and 18.7% in 23 lower survival prefectures (P < 0.0001, unadjusted hazard ratio [HR] of death in lower survival prefectures: 1.26, 95% confidence interval [CI]: 1.17-1.40). A total of five factors among males were significantly correlated with 1-year survival according to the univariate regression analysis. Among them, three factors (night-time center/total dialysis center ratio [males: P < 0.0001, age, genders, and presence of diabetes adjusted HR: 0.88, 95% CI: 0.81-0.93], number of full-time dialysis nurses [males: P = 0.0427, 0.94, 0.87-1.00], number of full-time dialysis dietitians [males: P = 0.0084, 0.92, 0.85-0.98], respectively) were significant in Kaplan-Meier analysis, log-rank test, and the Cox's model. Institutional factors were closely related to the survival of incident dialysis patients, and regional differences in the survival may be explained, at least partly, by these factors.

Myocardial SPECT Images in Incident Hemodialysis Patients Without Ischemic Heart Disease.

Cardiovascular disease is the leading cause of death in dialysis patients and is significantly associated with poor survival in incident dialysis patients. However, little is known about the pathogenesis of cardiovascular disease in these populations. (123) I-15-(p-iodophenyl)-3(R,S)- methylpentadecanoic acid (BMIPP) imaging is useful for detection of ischemic heart disease. We examined imaging characteristics to identify potential pathologies of cardiac disease, other than ischemic heart disease. The subjects were 42 incident dialysis patients without histories of ischemic heart disease such as acute coronary syndrome. All the patients underwent BMIPP imaging in addition to a screening examination. Patients with positive findings in BMIPP imaging underwent myocardial perfusion imaging within 2 weeks after BMIPP imaging to evaluate the possibility of ischemic heart disease. Twenty-two patients were BMIPP-positive and 10 of these patients had negative findings on perfusion imaging and were defined as mismatch cases. Compared with patients who were BMIPP- and perfusion-positive, the mismatch cases had higher parathyroid hormone (PTH), serum albumin, and alkaline phosphatase levels. The mismatch cases also formed the largest proportion in the highest PTH tertile. A histologic examination of a mismatch case with no stenotic lesions in the coronary artery revealed the presence of cardiac hypertrophy and fibrosis. These findings suggest that a perfusion-metabolism mismatch may be present in incident dialysis patients without a history of ischemic heart disease. This mismatch is associated with PTH, which suggests potential involvement of uremic cardiomyopathy in the pathology of cardiac disease in these patients.

High levels of circulating sclerostin are associated with better cardiovascular survival in incident dialysis patients: results from the NECOSAD study.

Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover, and it plays a role in cardiovascular calcification processes. Previous findings indicate that sclerostin regulation is disturbed in chronic kidney disease (CKD). The aim of this study was to assess the association of circulating sclerostin levels with mortality in dialysis patients. From a prospective cohort study of incident dialysis patients in the Netherlands, all patients with measured circulating sclerostin at 3 months after the start of dialysis (baseline) were included in the present analysis: n = 673, age 63 ± 14 years, mean serum sclerostin (ELISA) 1.24 ± 0.57 ng/mL. By Cox regression analyses, we assessed the association of sclerostin levels with cardiovascular and non-cardiovascular mortality both in the short (18 months) and long term (4-year follow-up). Serum sclerostin levels in the entire cohort correlated with intact parathyroid hormone levels (r = -0.25, P < 0.001), age (r = 0.16, P < 0.001) and serum alkaline phosphatase (r = -0.13, P = 0.001). After adjustment for various clinical and biochemical parameters, patients in the highest sclerostin tertile had a significantly lower risk of cardiovascular death [hazard ratio 0.29, 95% confidence interval (CI) 0.13-0.62] and for all-cause mortality (0.39, 95% CI 0.22-0.68) within 18 months compared with patients of the lowest tertile. The association of sclerostin levels with outcome was less pronounced for long-term cardiovascular mortality and absent for non-cardiovascular mortality. High levels of serum sclerostin are associated with lower short-term cardiovascular mortality in dialysis patients. The exact mechanisms of this association, e.g. how sclerostin influences or reflects uraemic vascular calcification, need to be investigated in further studies.

Coumarins and survival in incident dialysis patients

The benefit and risk of oral anticoagulation in dialysis patients are debated controversially. We prospectively followed 235 dialysis patients of the INVOR Study (Study of Incident Dialysis Patients in Vorarlberg) for up to 7 years and analysed the prevalence and incidence of atrial fibrillation (AF) and the impact of coumarin therapy on survival. Oral anticoagulation was monitored frequently. A total of 748 person-years were recorded with a median follow-up of 2.84 years. Twelve patients (5.1%) had AF at the start of dialysis. During follow-up, 40 patients (17.0%) developed AF, representing an incidence of 5.85 per 100 person-years. AF was positively associated with mortality (P = 0.004). Forty-six (19.6%) of the 235 patients were treated with coumarins. The majority (93.7%) had a clear indication for oral anticoagulation. In 65% of our patients, AF was the indication for coumarins. Patients without coumarins and without AF represented our reference group. The mortality risk of the coumarin-treated patients with AF or an alternative indication for coumarins was slightly lower compared to the reference group [hazard ratio (HR) 95% confidence interval (CI): 0.80 (0.28-2.29), P = 0.679 and 0.42 (0.16-1.10), P = 0.078, respectively]. No patient under sufficient oral anticoagulation experienced a stroke or a fatal bleeding event. Patients with AF and a contraindication for coumarins had a significantly higher mortality risk compared to the reference group [HR (95% CI): 3.90 (2.16-7.04), P < 0.001]. Our data suggest that coumarins might be less harmful than previously anticipated when clearly indicated and closely monitored.

An association between depressive symptoms and survival in incident dialysis patients

Depression in end-stage renal disease patients is detrimental to quality of life, and is also associated with adverse clinical outcomes. The aim of this study was to examine whether depression symptoms in 'incident dialysis' patients predicted survival. One hundred and sixty incident haemodialysis and peritoneal dialysis patients completed a self-report depression questionnaire (Beck Depression Inventory-II, BDI) at a point soon after dialysis initiation. Over the study period (May 2007-December 2009), patients were followed up with all-cause mortality recorded as the end point. The median follow-up time for the cohort was 511 days (min 47 days and max 1027 days). There were 27 deaths (16.9%). Depression symptoms were evaluated both as a continuous variable and using a defined cut-off for depressed patients (BDI ≥ 16). In a Cox proportional hazards model, adjusted for several covariates including albumin and extra renal comorbidity, depression score was an independent predictor of mortality (HR = 1.07, 95% CI 1.02-1.11, P = 0.002). In an additional adjusted model, a BDI score ≥ 16 was associated with a 2.7 times increase in the hazard for death (HR = 2.7, 95% CI 1.06-6.8, P = 0.037). The severity of depression symptoms following the start of dialysis treatment is an independent predictor of survival. Further studies will be required to determine whether the treatment of depression would alter health-related outcomes, including survival.

Survival in end stage renal disease: calcium carbonate vs. sevelamer

There is concern regarding long-term excess calcium intake in end-stage renal disease populations. Because calcium carbonate is an over-the-counter (OTC) medication, few studies have been able to track its use. The Veterans Health Administration (VA) tracks national pharmacy data for both OTC and prescription drugs. We thus compared survival in incident dialysis patients on sevelamer and calcium carbonate phosphate binders. This was a retrospective cohort study of veterans initiating haemodialysis using existing VA databases. Patients were divided into calcium only (n = 769) and sevelamer only (n = 608) groups, then followed for up to 2 years until FY03 end. Survival was modelled using Cox regression adjusting for age, gender, race, marital status, service-connected disability, region, diabetes, hypertension and Charlson index. Stability of findings was examined using propensity score analysis. Sevelamer only vs. calcium only subjects were younger (respective mean ages 59.6 and 63.0, P < 0.001) with fewer comorbidities (Charlson index 3.8 and 4.5, P < 0.001). By study end, 24% of sevelamer and 30% of calcium subjects had died. Comparing sevelamer to calcium, the unadjusted hazard ratio for death was 0.62 (95% CI 0.50-0.76); the adjusted hazard ratio was 0.67 (CI 0.54-0.84). Propensity score analysis revealed similar results, with a hazard ratio of 0.65 (CI 0.54-0.80). In a national incident dialysis cohort, sevelamer treatment was associated with improved survival compared with calcium carbonate. Further research should investigate whether the worse survival with calcium is a long-term consequence of increased calcium accumulation.

Body mass index and survival in incident dialysis patients: the answer depends on the question

Body mass index and survival in incident dialysis patients: the answer depends on the question

Comorbidity and its change predict survival in incident dialysis patients

Background: Few studies have performed a comprehensive comparison of the prognostic importance of comorbidity to that of other case-mix factors influencing incident dialysis patients' survival. Longitudinal change in the comorbid illness burden of incident dialysis patients has not been measured. Comorbidity severity and its change may serve as important prognostic markers of survival, independent of other case-mix factors. Methods: The Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Cohort Study used the Index of Coexistent Disease (ICED) to assess comorbidity at the initiation of chronic dialysis treatment (1,039 incident patients) and during follow-up (733 patients). Using proportional hazards regression analyses, the relationship to survival of baseline ICED level and change in ICED level was examined. Results: At the initiation of chronic dialysis treatment, 36% of patients were at ICED level 0 to 1 (least comorbidity severity); 35%, level 2; and 29%, level 3. After multivariable adjustment, baseline ICED level was the strongest predictor of subsequent mortality. Compared with ICED level 0 to 1, relative risks for mortality were 1.9 (95% confidence interval, 1.3 to 2.6) for ICED level 2 and 2.8 (95% confidence interval, 2.0 to 3.9) for ICED level 3. The prevalence and severity of most comorbid conditions increased during follow-up. After controlling for baseline ICED level and other factors, change in ICED level over time was significantly associated with mortality (P = 0.01). Conclusion: Indexing comorbidity when patients begin chronic dialysis therapy and recording the evolution of index scores yields a predictor of mortality risk that is independent of other case-mix factors. Am. J Kidney Dis 41:149-161. © 2003 by the National Kidney Foundation, Inc.