Beta-2 microglobulin and all-cause mortality in the era of high-flux hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Beta-2 microglobulin (ß2M) accumulates in hemodialysis (HD) patients, but its consequences are controversial, particularly in the current era of high-flux dialyzers. High-flux HD treatment improves ß2M removal, yet ß2M and other middle molecules may still contribute to adverse events. We investigated patient factors associated with serum ß2M, evaluated trends in ß2M levels and in hospitalizations due to dialysis-related amyloidosis (DRA), and estimated the effect of ß2M on mortality. METHODS: We studied European and Japanese participants in the Dialysis Outcomes and Practice Patterns Study. Analysis of DRA-related hospitalizations spanned 1998-2018 (n = 23 976), and analysis of ß2M and mortality in centers routinely measuring ß2M spanned 2011-18 (n = 5332). We evaluated time trends with linear and Poisson regression and mortality with Cox regression. RESULTS: Median ß2M changed nonsignificantly from 2.71 to 2.65 mg/dL during 2011-18 (P = 0.87). Highest ß2M tertile patients (>2.9 mg/dL) had longer dialysis vintage, higher C-reactive protein and lower urine volume than lowest tertile patients (≤2.3 mg/dL). DRA-related hospitalization rates [95% confidence interval (CI)] decreased from 1998 to 2018 from 3.10 (2.55-3.76) to 0.23 (0.13-0.42) per 100 patient-years. Compared with the lowest ß2M tertile, adjusted mortality hazard ratios (95% CI) were 1.16 (0.94-1.43) and 1.38 (1.13-1.69) for the middle and highest tertiles. Mortality risk increased monotonically with ß2M modeled continuously, with no indication of a threshold. CONCLUSIONS: DRA-related hospitalizations decreased over 10-fold from 1998 to 2018. Serum ß2M remains positively associated with mortality, even in the current high-flux HD era.

Anemia and iron deficiency among chronic kidney disease Stages 3-5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated.

BACKGROUND: International variation in anemia assessment and management practices in chronic kidney disease (CKD) is poorly understood. METHODS: We performed a cross-sectional analysis of anemia laboratory monitoring, prevalence and management in the prospective Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps). A total of 6766 participants with CKD Stages 3a-5ND from nephrology clinics in Brazil, France, Germany and the USA were included. RESULTS: Among patients with anemia (hemoglobin <12 g/dL), 36-58% in Brazil, the USA and Germany had repeat hemoglobin measured and 40-61% had iron indices measured within 3 months of the index hemoglobin measurement. Anemia was more common in the USA and Brazil than in France and Germany across CKD stages. Higher ferritin and lower iron saturation (TSAT) levels were observed with lower hemoglobin levels, and higher ferritin with more advanced CKD. The proportion of anemic patients with ferritin <100 ng/mL or TSAT <20% ranged from 42% in Brazil to 53% in France and Germany, and of these patients, over 40% in Brazil, Germany and the USA, compared with 27% in France, were treated with oral or intravenous iron within 3 months after hemoglobin measurement. The proportion of patients with hemoglobin <10 g/dL treated with erythropoiesis-stimulating agents ranged from 28% in the USA to 57% in Germany. CONCLUSIONS: Hemoglobin and iron stores are measured less frequently than per guidelines. Among all regions, there was a substantial proportion of anemic patients with iron deficiency who were not treated with iron, highlighting an area for practice improvement in CKD care.

Evaluating the effectiveness of IV iron dosing for anemia management in common clinical practice: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Anemia management protocols in hemodialysis (HD) units differ conspicuously regarding optimal intravenous (IV) iron dosing; consequently, patients receive markedly different cumulative exposures to IV iron and erythropoiesis-stimulating agents (ESAs). Complementary to IV iron safety studies, our goal was to gain insight into optimal IV iron dosing by estimating the effects of IV iron doses on Hgb, TSAT, ferritin, and ESA dose in common clinical practice. METHODS: 9,471 HD patients (11 countries, 2009-2011) in the DOPPS, a prospective cohort study, were analyzed. Associations of IV iron dose (3-month average, categorized as 0, <300, ≥300 mg/month) with 3-month change in Hgb, TSAT, ferritin, and ESA dose were evaluated using adjusted GEE models. RESULTS: Relative change: Monotonically positive associations between IV iron dose and Hgb, TSAT, and ferritin change, and inverse associations with ESA dose change, were observed across multiple strata of prior Hgb, TSAT, and ferritin levels. Absolute change: TSAT, ferritin, and ESA dose changes were nearest zero with IV iron <300 mg/month, rather than 0 mg/month or ≥300 mg/month by maintenance or replacement dosing. Findings were robust to numerous sensitivity analyses. CONCLUSIONS: Though residual confounding cannot be ruled out in this observational study, findings suggest that IV iron dosing <300 mg/month, as commonly seen with maintenance dosing of 100-200 mg/month, may be a more effective approach to support Hgb than the higher IV iron doses (300-400 mg/month) often given in many European and North American hemodialysis clinics. Alongside studies supporting the safety of IV iron in 100-200 mg/month dose range, these findings help guide the rational dosing of IV iron in anemia management protocols for everyday hemodialysis practice.

International Comparisons to Assess Effects of Payment and Regulatory Changes in the United States on Anemia Practice in Patients on Hemodialysis: The Dialysis Outcomes and Practice Patterns Study.

For years, erythropoiesis-stimulating agent (ESA) use among patients on dialysis was much higher in the United States than in Europe or Japan. Sweeping changes to dialysis reimbursement and regulatory policies for ESA in the United States in 2011 were expected to reduce ESA use and hemoglobin levels. We used the Dialysis Outcomes and Practice Patterns Study (DOPPS) data from 7129 patients in 223 in-center hemodialysis facilities (average per month) to estimate and compare time trends in ESA dose and hemoglobin levels among patients on hemodialysis in the United States, Germany, Italy, Spain, the United Kingdom, and Japan. From 2010 to 2013, substantial declines in ESA use and hemoglobin levels occurred in the United States but not in other DOPPS countries. Between August of 2010 and April of 2013, mean weekly ESA dose in the United States decreased 40.4% for black patients and 38.0% for nonblack patients; mean hemoglobin decreased from 11.5 g/dl in black patients and 11.4 g/dl in nonblack patients to 10.6 g/dl in both groups. In 2010 and 2013, adjusted weekly ESA doses per kilogram were 41% and 11% lower, respectively, in patients in Europe and 60% and 18% lower, respectively, in patients in Japan than in nonblack patients in the United States. Adjusted hemoglobin levels in 2010 and 2013 were 0.07 g/dl lower and 0.56 g/dl higher, respectively, in patients in Europe and 0.93 and 0.01 g/dl lower, respectively, in patients in Japan than in nonblack patients in the United States. In conclusion, ESA dosing reductions in the United States likely reflect efforts in response to changes in reimbursement policy and regulatory guidance.

Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing.

BACKGROUND AND OBJECTIVES: Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time. RESULTS: Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period. CONCLUSIONS: In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation.

On a preference-based instrumental variable approach in reducing unmeasured confounding-by-indication.

Treatment preferences of groups (e.g., clinical centers) have often been proposed as instruments to control for unmeasured confounding-by-indication in instrumental variable (IV) analyses. However, formal evaluations of these group-preference-based instruments are lacking. Unique challenges include the following: (i) correlations between outcomes within groups; (ii) the multi-value nature of the instruments; (iii) unmeasured confounding occurring between and within groups. We introduce the framework of between-group and within-group confounding to assess assumptions required for the group-preference-based IV analyses. Our work illustrates that, when unmeasured confounding effects exist only within groups but not between groups, preference-based IVs can satisfy assumptions required for valid instruments. We then derive a closed-form expression of asymptotic bias of the two-stage generalized ordinary least squares estimator when the IVs are valid. Simulations demonstrate that the asymptotic bias formula approximates bias in finite samples quite well, particularly when the number of groups is moderate to large. The bias formula shows that when the cluster size is finite, the IV estimator is asymptotically biased; only when both the number of groups and cluster size go to infinity, the bias disappears. However, the IV estimator remains advantageous in reducing bias from confounding-by-indication. The bias assessment provides practical guidance for preference-based IV analyses. To increase their performance, one should adjust for as many measured confounders as possible, consider groups that have the most random variation in treatment assignment and increase cluster size. To minimize the likelihood for these IVs to be invalid, one should minimize unmeasured between-group confounding.

Association between allopurinol and mortality among Japanese hemodialysis patients: results from the DOPPS.

PURPOSE: Allopurinol, for treating hyperuricemia, is associated with lower mortality among hyperuricemic patients without chronic kidney disease (CKD). Greater allopurinol utilization in hemodialysis (HD) in Japan versus other countries provides an opportunity for understanding allopurinol-related HD outcomes. METHODS: Data from 6,252 Japanese HD patients from phases 1-3 of the Dialysis Outcomes and Practice Patterns Study (1999-2008) at ~60 facilities per phase were analyzed. Mortality was compared for patients prescribed (25 %) versus not-prescribed allopurinol using Cox regression, overall, and in patient subgroups. RESULTS: Patients prescribed allopurinol were more likely to be younger, male, and non-diabetic, and had higher serum creatinine and lower (treated) serum uric acid levels (mean = 7.0 vs. 8.0 mg/dL, p < 0.001). The inverse association between allopurinol prescription and mortality in unadjusted analyses (HR 0.65, 95 % CI 0.52-0.81) was attenuated by covariate adjustment (HR 0.84, 0.66-1.06). In subgroup analyses, allopurinol was associated with lower mortality among patients with no history of cardiovascular disease (CVD) (HR 0.48, 0.28-0.83), but not among patients with CVD (HR 1.00, 0.76-1.32). A similar pattern was seen outside Japan and for cardiovascular (CV)-related mortality. CONCLUSIONS: Allopurinol prescription was not significantly associated with case-mix-adjusted mortality in Japanese HD patients overall, but was associated with lower all-cause and CV-related mortality in the subgroup of patients with no prior CVD history. These findings in HD patients may be related to findings in non-dialysis CKD patients showing lower CV event rates and mortality, and improved endothelial function with allopurinol prescription. These results are useful for designing future trials of allopurinol use in HD patients.

Facility-level interpatient hemoglobin variability in hemodialysis centers participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS): Associations with mortality, patient characteristics, and facility practices.

BACKGROUND: Hemodialysis patients with larger hemoglobin level fluctuations have higher mortality rates. We describe facility-level interpatient hemoglobin variability, its relation to patient mortality, and factors associated with facility-level hemoglobin variability or achieving hemoglobin levels of 10.5-12.0 g/dL. Facility-level hemoglobin variability may reflect within-patient hemoglobin variability and facility-level anemia-control practices. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS; 26,510 hemodialysis patients, 930 facilities, 12 countries, 1996-2008) and from the Centers for Medicare & Medicaid Services (CMS; 193,291 hemodialysis patients, 3,741 US facilities, 2002). PREDICTORS: Standard deviation (SD) in single-measurement hemoglobin levels in hemodialysis patients in facility cross-sections (facility-level hemoglobin SD); patient characteristics; facility practices. OUTCOMES: Patient-level mortality; additionally, facility practices correlated with facility-level hemoglobin SD or patient hemoglobin levels of 10.5-12.0 g/dL. RESULTS: Facility-level hemoglobin SD varied more than 5-fold across DOPPS facilities (range, 0.5-2.7 g/dL; mean, 1.3 g/dL) and by country (range, 1.1 in Japan-DOPPS [2005/2006] to 1.7 g/dL in Spain-DOPPS [1998/1999]), with substantial decreases seen in many countries from 1998 to 2007. Facility-level hemoglobin SD was related inversely to patient age, but was associated minimally with more than 30 other patient characteristics and facility mean hemoglobin levels. Several anemia management practices were associated strongly with facility-level hemoglobin SD and having a hemoglobin level of 10.5-12.0 g/dL. When examined in CMS data, facility-level hemoglobin SD was positively associated with within-patient hemoglobin SD during the prior 6 months. Patient mortality rates were higher with greater facility-level hemoglobin SD (DOPPS: HR, 1.08 per 0.5-g/dL greater facility-level hemoglobin SD [95% CI, 1.02-1.15; P = 0.006]; CMS: HR, 1.16 per 0.5-g/dL greater facility-level hemoglobin SD [95% CI, 1.11-1.21; P < 0. 001]). LIMITATIONS: Residual confounding. CONCLUSIONS: Facility-level hemoglobin SD was associated strongly and positively with patient mortality, not tightly linked to numerous patient characteristics, but related strongly to facility anemia management practices. Facility-level hemoglobin variability may be modifiable and its optimization may improve hemodialysis patient survival.

Naturally occurring higher hemoglobin concentration does not increase mortality among hemodialysis patients.

A small percentage of hemodialysis patients maintain higher hemoglobin concentrations without transfusion or erythropoietic therapy. Because uncertainty exists regarding the effects of higher hemoglobin concentration on mortality and quality of life among hemodialysis patients, studying this group of patients with sufficient endogenous erythropoietin may provide additional insights. The prospective, observational Dialysis Outcomes and Practice Patterns Study provides an opportunity to investigate this group. Among 29,796 patients in 12 nations, 545 (1.8%) maintained hemoglobin concentrations >12 g/dl for 4 months without erythropoietic support. This subset tended to be male, to have a longer duration of end-stage renal disease, and to not dialyze via a catheter. Cystic disease as the underlying cause of renal failure was over-represented in this group but was present in only 25%. Lung disease, smoking, and cardiovascular disease were associated with increased likelihood of naturally higher hemoglobin concentration. Quality-of-life scores were not higher among this subset compared with the other patients. Unadjusted mortality risk for patients with hemoglobin >12 g/dl and no erythropoietic therapy was lower than for the other patients, but after thorough adjustment for case mix, there was no difference between groups (relative risk, 0.98; 95% CI 0.80 to 1.19). These data show that naturally occurring hemoglobin concentration >12 g/dl does not associate with increased mortality among hemodialysis patients.

Hemodialysis vascular access training and practices are key to improved access outcomes.

Recognizing that autologous arteriovenous fistula use was associated with improved outcomes in hemodialysis patients, the 1997 Dialysis Outcomes Quality Initiative (DOQI) vascular access practice guidelines from the National Kidney Foundation stressed fistulas as the optimal means of dialysis vascular access. In the United States, this emphasis has continued with the Fistula First Breakthrough Initiative. Much of the data supporting fistulas for dialysis access are derived from longitudinal cohorts, including the Dialysis Outcomes and Practice Patterns Study (DOPPS), dialysis provider databases, and other sources. This article reviews major findings from these data sources, focusing on specific practices and characteristics associated with greater arteriovenous fistula use in dialysis facilities worldwide. Important and often overlooked characteristics that are discussed in detail include specific preferences of dialysis staff regarding access type and the emphasis placed on fistula primacy and the number of fistulas created during surgical training. For example, in the DOPPS, the risk of initial fistula failure was 34% lower when fistulas were placed by surgeons who had created at least 25 fistulas during training (P = 0.002). It is imperative that dialysis clinicians advocate actively for specific dialysis access types on behalf of individual patients. Vascular surgery teaching programs must supervise adequate numbers of fistula procedures for every trainee.

The organization and financing of end-stage renal disease treatment in Japan.

End-stage renal disease (ESRD) affects 230,000 Japanese, with about 36,000 cases diagnosed each year. Recent increases in ESRD incidence are attributed mainly to increases in diabetes and a rapidly aging population. Renal transplantation is rare in Japan. In private dialysis clinics, the majority of treatment costs are paid as fixed fees per session and the rest are fee for service. Payments for hospital-based dialysis are either fee-for-service or diagnosis-related. Dialysis is widely available, but reimbursement rates have recently been reduced. Clinical outcomes of dialysis are better in Japan than in other countries, but this may change given recent ESRD cost containment policies.

Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Mortality risk among hemodialysis (HD) patients may be highest soon after initiation of HD. A period of elevated mortality risk was identified among US incident HD patients, and which patient characteristics predict death during this period and throughout the first year was examined using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS; 1996 through 2004). A retrospective cohort study design was used to identify mortality risk factors. All patient information was collected at enrollment. Life-table analyses and discrete logistic regression were used to identify a period of elevated mortality risk. Cox regression was used to estimate adjusted hazard ratios (HR) measuring associations between patient characteristics and mortality and to examine whether these associations changed during the first year of HD. Among 4802 incident patients, risk for death was elevated during the first 120 d compared with 121 to 365 d (27.5 versus 21.9 deaths per 100 person-years; P = 0.002). Cause-specific mortality rates were higher in the first 120 d than in the subsequent 121 to 365 d for nearly all causes, with the greatest difference being for cardiovascular-related deaths. In addition, 20% of all deaths in the first 120 d occurred subsequent to withdrawal from dialysis. Most covariates were found to have consistent effects during the first year of HD: Older age, catheter vascular access, albumin <3.5, phosphorus <3.5, cancer, and congestive heart failure all were associated with elevated mortality. Pre-ESRD nephrology care was associated with a significantly lower risk for death before 120 d (HR 0.65; 95% confidence interval 0.51 to 0.83) but not in the subsequent 121- to 365-d period (HR 1.03; 95% confidence interval 0.83 to 1.27). This care was related to approximately 50% lower rates of both cardiac deaths and withdrawal from dialysis during the first 120 d. Mortality risk was highest in the first 120 d after HD initiation. Inadequate predialysis nephrology care was strongly associated with mortality during this period, highlighting the potential benefits of contact with a nephrologist at least 1 mo before HD initiation.

Peripheral arterial disease in patients with end-stage renal disease: observations from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Patients with end-stage renal disease are at high risk for cardiovascular morbidity and mortality. The aims of the present study were to describe the prevalence of peripheral arterial disease (PAD) and its effects on prognosis and health-related quality of life (HRQOL) in an international cohort of patients on hemodialysis. METHODS AND RESULTS: Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, international, observational study of hemodialysis patients (n=29,873), were analyzed. Associations between baseline clinical variables and PAD were evaluated by logistic regression analysis. Cox regression models were used to test the association between PAD and risk for all-cause mortality, cardiac mortality, and hospitalization. PAD was diagnosed in 7411 patients (25.3%) with significant geographic variation. Traditional cardiovascular risk factors including age, male sex, diabetes, hypertension, and smoking were identified, together with the duration of hemodialysis, as significant correlates of PAD. Diagnosis of PAD was associated with increased all-cause mortality (hazard ratio [HR]=1.36; P<0.0001), cardiac mortality (HR=1.43; P<0.0001), all-cause hospitalization (HR=1.19; P<0.0001), and hospitalization for a major adverse cardiovascular event (HR=2.05; P<0.0001). HRQOL questionnaires revealed physical health scores that were significantly lower in PAD compared with non-PAD patients (P<0.0001). CONCLUSIONS: PAD is common in hemodialysis patients and is associated with increased risk of cardiovascular mortality, morbidity, and hospitalization and reduced HRQOL.

Haemodialysis vascular access problems in Canada: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS II).

BACKGROUND: The optimal vascular access for chronic maintenance haemodialysis (HD) is the native arteriovenous fistula (AVF). Vascular access practice patterns are reported for a Canadian cohort of patients from the Dialysis Outcomes and Practice Patterns Study (DOPPS II). METHODS: DOPPS II is a prospective, observational study in 12 countries, including Canada. A representative random sample of 20 Canadian HD facilities and patients within those units were studied during 2002-2004. Canadian results were compared with those found in Europe and the USA. RESULTS: AVF use in Canadian prevalent (53%) and incident (26%) patients was lower than Canadian guidelines recommend (60%), and lower than in Europe [prevalent (74%), incident (50%)]. Despite 85% of Canadian HD patients having seen a nephrologist for > 1 month prior to starting dialysis, central venous catheter use in Canada (33% in prevalent patients, 70% in incident patients) was much higher than in Europe (prevalent 18%, incident 46%) and slightly higher than in the USA (prevalent 25%, incident 66%). This pattern is contrary to the preferences of Canadian medical directors and vascular access surgeons. The typical time from referral until permanent vascular access creation is substantially longer in Canada (61.7 days) than in Europe (29.4 days) or the USA (16 days). This longer delay time and higher catheter use in Canada may be a consequence of the significantly lower number of access surgeons per 100 HD patients in Canada (2.9) compared with the USA (8.1) and Europe (4.6). Furthermore, the median hours per week devoted to vascular access-related surgery per 100 patients is substantially lower in Canada (0.027 h) compared with the USA (0.082 h) and Europe (0.059 h). CONCLUSION: These findings suggest that Canadian chronic HD patients often rely on central venous catheters for vascular access, despite their known association with numerous detrimental outcomes in HD. Nephrologists, vascular access surgeons, interventional radiologists, other physicians and health care funding bodies must be more broadly educated about the priority of AVF creation as the preferred vascular access for chronic HD patients. They must work together to secure both the human and financial resources and other health care system enhancements to increase AVF creation rates in a timely manner.

Hepatitis C is a risk factor for death after liver retransplantation.

Retransplantation for liver allograft failure associated with hepatitis C virus (HCV) has been increasing due to nearly universal posttransplant HCV recurrence and has been demonstrated to be associated with poor outcomes. We report on the risk factors for death after retransplantation among liver recipients with HCV. A retrospective cohort of liver transplant recipients who underwent retransplantation between January 1997 and December 2002 was identified in the Scientific Registry of Transplant Recipients database. Cox regression was used to assess the relative effect of HCV diagnosis on mortality risk after retransplantation and was adjusted for multiple covariates. Of 1,718 liver retransplantations during the study period, 464 (27%) were associated with a diagnosis of HCV infection. Based on Cox regression, retransplant recipients with HCV had a 30% higher covariate-adjusted mortality risk than those without HCV diagnosis (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.54; P = 0.002). Other covariates associated with significant relative risk of death after retransplantation included older recipient age, presence in an intensive care unit (ICU), serum creatinine, and donor age. Additional regression analysis revealed that the increase in mortality risk associated with HCV was concentrated between 3 and 24 months postretransplantation, among patients age 18 to 39 at retransplant, and in patients retransplanted during the years 2000 to 2002. In conclusion, HCV liver recipients account for a considerable proportion of all retransplantations performed. Surprisingly, younger age predicted a higher mortality for recipients with HCV undergoing liver retransplantation. This may reflect a willingness to retransplant younger patients with an increased severity of illness or a more virulent HCV infection in this population. Although HCV was predictive of an increased risk of death, consideration of other characteristics of HCV patients, including donor and recipient age and need for preoperative ICU care may identify those at significantly higher risk.

Screening for depression in hemodialysis patients: associations with diagnosis, treatment, and outcomes in the DOPPS.

BACKGROUND: Depressive symptoms and depression are the most frequent psychologic problems reported by hemodialysis patients. We assessed the prevalence of depressive symptoms and physician-diagnosed depression, their variations by country, and associations with treatment by antidepressants among hemodialysis patients. We also assessed whether depressive symptoms were independently associated with mortality, hospitalization, and dialysis withdrawal. METHODS: The sample was represented by 9382 hemodialysis patients randomly selected from dialysis centers of 12 countries enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS II). Depressive symptoms were assessed by the short version of the Center for Epidemiological Studies Depression Screening Index (CES-D), using > or =10 CES-D score as the cut-off value. RESULTS: Overall prevalence of physician-diagnosed depression was 13.9%, and percentage of CES-D score > or =10 43.0%. While the smallest prevalence of physician-diagnosed depression was observed in Japan (2.0%) and France (10.6%), the percentage of CES-D score > or =10 in these counties was similar to the whole sample. Patients on antidepressants also varied by country, 34.9% and 17.3% among those with physician-diagnosed depression and CES-D scores > or =10, respectively. In Cox models adjusted for several comorbidities, CES-D scores > or =10 were associated with significantly higher relative risks (RR) of death (RR = 1.42; 95% CI = 1.29 to 1.57), hospitalization (RR = 1.12; 95% CI = 1.03 to 1.22), and dialysis withdrawal (RR = 1.55; 95% CI = 1.29 to 1.85). CONCLUSION: The data suggest that depression is underdiagnosed and undertreated among hemodialysis patients. CES-D can help identify hemodialysis patients who are at higher risk of death and hospitalization. Interventions should target these patients with the goal to improve survival and reduce hospitalizations.

Immunosuppression and the risk of post-transplant malignancy among cadaveric first kidney transplant recipients.

The success of renal transplantation may be counterbalanced by serious adverse medical events. The effect of immunosuppression on the incidence of de novo neoplasms among kidney recipients should be monitored continuously. Using data from the Scientific Registry of Transplant Recipients, we studied the association of induction therapy by immunosuppression with antilymphocyte antibodies, with the development of de novo neoplasms. The study population included more than 41 000 recipients who received a cadaveric first kidney transplant after December 31, 1995, and were followed through February 28, 2002. Using Cox regression models, we estimated time to development of two types of malignancy: de novo solid tumors and post-transplant lymphoproliferative disorder (PTLD). We made adjustments for several patient demographic factors and comorbidities. Induction therapy was significantly associated with a higher relative risk (RR) of PTLD (RR = 1.78, p < 0.001), but not with a greater likelihood of de novo tumors (RR = 1.07, p = 0.42). Treatment with maintenance tacrolimus vs. cyclosporine showed a significantly different RR of developing de novo tumors for recipients with induction than for those not receiving induction (p = 0.024). These new estimates of the magnitude of malignancy risk associated with induction therapy may be useful for clinical practice.

Mortality and hospitalization in haemodialysis patients in five European countries: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Mortality and hospitalization rates are reported for nationally representative random samples of haemodialysis patients treated at randomly selected dialysis facilities in five European countries participating in the Dialysis Outcomes and Practice Pattern Study (DOPPS) (France, Germany, Italy, Spain and the UK). RESULTS: In the UK, 28.1% of haemodialysis patients received prior peritoneal dialysis treatment compared with 4.2-8.3% in other countries. Kidney transplantation rates ranged from 3.3 (per 100 patient years) in Italy to 11.6 in Spain. The relative risk (RR) of mortality, adjusted for age, sex and diabetes status was significantly higher in the UK (RR = 1.39, P = 0.02) compared with Italy (reference) and increased in association with age (RR = 1.60 for every 10 years older, P <0.001), diabetes as cause of end-stage renal disease (ESRD) (RR = 1.55, P < 0.001), male patients <65 years (RR = 1.29, P = 0.02) and peritoneal dialysis in the 12 months prior to starting haemodialysis (RR = 1.72, P = 0.06). Hospitalization for cardiovascular disease was highest in France and Germany (0.40 and 0.43 hospitalizations per patient year, respectively) and lowest in the UK (0.19), although cardiovascular comorbidity was similar in the UK and France. Hospitalization rates for vascular access-related infection ranged from 0.01 hospitalizations per patient year in Italy to 0.08 in the UK, consistent with the higher dialysis catheter use in the UK (25%) vs Italy (5%). Hospitalization risk was significantly higher in France than in other Euro-DOPPS countries and was significantly (P < 0.05) associated with prior peritoneal dialysis therapy, peripheral vascular disease, gastrointestinal bleeding in the prior 12 months, diabetes, cancer, cardiac disease, psychiatric disease and recent onset of ESRD (within 30 days of study entry). CONCLUSIONS: The large differences in haemodialysis practice and outcomes in the Euro-DOPPS countries suggest opportunities for improvement in patient care.

Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, observational study based on data collected from nationally representative samples of haemodialysis facilities. The burden of anaemia in haemodialysis patients is substantial, leading to considerable morbidity, mortality and reduced quality of life. This study examines anaemia management and outcomes based on data from five European countries participating in the DOPPS: France, Germany, Italy, Spain and the UK. METHODS: Baseline data on demographics, co-morbidities and anaemia management in 4591 haemodialysis patients from 101 nephrology facilities were collected in 1998-2000. Using multivariate Cox survival analyses to adjust for patient characteristics, relationships between haemoglobin concentration at study entry and rates of mortality and hospitalization were evaluated. RESULTS: For a year 2000 sample of prevalent patients on haemodialysis >180 days, mean haemoglobin concentration was 11.0 g/dl; 53% had a haemoglobin concentration > or = 11 g/dl [1998-1999 = 44% (P < 0.05)]. In 2000, 84% of prevalent patients were prescribed recombinant human erythropoietin (rHuEpo). Higher haemoglobin concentrations were associated with decreased relative risk (RR) for mortality (RR = 0.95 for every 1 g/dl higher haemoglobin, P = 0.03) and hospitalization (RR = 0.96, P = 0.02). Patients with haemoglobin <10 g/dl were 29% more likely to be hospitalized than patients with haemoglobin 11-12 g/dl (P < 0.001). CONCLUSION: Even after adjustment, lower haemoglobin concentrations were associated with higher morbidity and mortality in European haemodialysis patients. A trend to increased haemoglobin concentrations was observed following publication of the European Best Practice Guidelines (EBPG) on anaemia management for chronic kidney disease patients, but efforts must continue to achieve EBPG goals.