Achievement of renal anemia KDIGO targets by two different clinical strategies - a European hemodialysis multicenter analysis.

BACKGROUND: The optimal treatment algorithm for iron therapy and the use of erythropoiesis-stimulating agents (ESA) in anemic hemodialysis (HD) patients has not been established. Hemoglobin (Hb) target levels can be achieved through more frequent intravenous (IV) iron use with lower ESA dose, or with less iron dosing but higher ESA. ESA therapy to correct anemia may result in severe arterial and venous thrombotic complications and the evidence base evaluating hard clinical outcomes related to the use of IV iron is sparse. METHODS: A total of 1247 maintenance HD patients from 12 dialysis centers in Portugal (n = 730) and Poland (n = 517) were considered. We assessed achievement of KDIGO renal anemia targets with focus on treatment strategies, which typically differ between countries. In Poland the use and dose of IV iron was 35-72% higher than that in Portugal (p <  0.001) during three consecutive months; use and dose of ESA was 61% higher in Portugal (5034 vs 3133 IU (adjusted)/week, p <  0.001). RESULTS: Mean Hb concentration was similar (11.0 vs 11.0 g/dL) in patients treated in both countries and the proportion of patients within KDIGO anemia target was 69.5% in Poland vs 65.8% in Portugal (NS). Ferritin and TSAT levels and the proportion of patients with TSAT > 20 and > 50% were both significantly higher in patients in Poland (88.8 and 14.6%) than in Portugal (76.3 and 5.7% respectively, p <  0.001). Significantly more patients in Poland had a ferritin concentration > 800 µg/L (35.6%) compared to Portugal (15.8%, p <  0.001). The ESA resistance index (ERI) was significantly higher in patients treated in Portugal (p <  0.001). Correlation analyses showed confounding by treatment indication in unadjusted models. Multiple and logistic regression analyses showed that with ferritin within KDIGO recommended range of 200-800 µg/L the odds for Hb within guidelines increased significantly. Annual gross mortality was 16% in Poland and 13% in Portugal (NS); there were no differences in cause-specific mortality. CONCLUSIONS: Administration of high doses of IV iron in routine clinical HD practice may not be associated with considerable harm. However, large randomized controlled trials are needed to provide absolute evidence of iron safety.

Comorbidity ascertainment from the ESRD Medical Evidence Report and Medicare claims around dialysis initiation: a comparison using US Renal Data System data.

BACKGROUND: The end-stage renal disease Medical Evidence Report serves as a source of comorbid condition data for risk adjustment of quality metrics. We sought to compare comorbid condition data in the Medical Evidence Report around dialysis therapy initiation with diagnosis codes in Medicare claims. STUDY DESIGN: Observational cohort study using US Renal Data System data. SETTING & PARTICIPANTS: Medicare-enrolled elderly (≥66 years) patients who initiated maintenance dialysis therapy July 1 to December 31, 2007, 2008, or 2009. INDEX TESTS: 12 comorbid conditions ascertained from claims during the 6 months before dialysis therapy initiation, the Medical Evidence Report, and claims during the 3 months after dialysis therapy initiation. REFERENCE TEST: None. RESULTS: Comorbid condition prevalence according to claims before dialysis therapy initiation generally exceeded prevalence according to the Medical Evidence Report. The κ statistics for comorbid condition designations other than diabetes ranged from 0.06 to 0.43. Discordance of designations was associated with age, race, sex, and end-stage renal disease Network. During 23,930 patient-years of follow-up from 4 to 12 months after dialysis therapy initiation (8,930 deaths), designations from claims during the 3 months after initiation better discriminated risk of death than designations from the Medical Evidence Report (C statistics of 0.674 vs 0.616). Between the Medical Evidence Report and claims, standardized mortality ratios changed by >10% for more than half the dialysis facilities. LIMITATIONS: Neither the Medical Evidence Report nor diagnosis codes in claims constitute a gold standard of comorbid condition data; results may not apply to nonelderly patients or patients without Medicare coverage. CONCLUSIONS: Discordance of comorbid condition designations from the Medical Evidence Report and claims around dialysis therapy initiation was substantial and significantly associated with patient characteristics, including location. These patterns may engender bias in risk-adjusted quality metrics. In lieu of the Medical Evidence Report, claims during the 3 months after dialysis therapy initiation may constitute a useful source of comorbid condition data.

Guiding principles and checklist for population-based quality metrics.

The Centers for Medicare and Medicaid Services oversees the ESRD Quality Incentive Program to ensure that the highest quality of health care is provided by outpatient dialysis facilities that treat patients with ESRD. To that end, Centers for Medicare and Medicaid Services uses clinical performance measures to evaluate quality of care under a pay-for-performance or value-based purchasing model. Now more than ever, the ESRD therapeutic area serves as the vanguard of health care delivery. By translating medical evidence into clinical performance measures, the ESRD Prospective Payment System became the first disease-specific sector using the pay-for-performance model. A major challenge for the creation and implementation of clinical performance measures is the adjustments that are necessary to transition from taking care of individual patients to managing the care of patient populations. The National Quality Forum and others have developed effective and appropriate population-based clinical performance measures quality metrics that can be aggregated at the physician, hospital, dialysis facility, nursing home, or surgery center level. Clinical performance measures considered for endorsement by the National Quality Forum are evaluated using five key criteria: evidence, performance gap, and priority (impact); reliability; validity; feasibility; and usability and use. We have developed a checklist of special considerations for clinical performance measure development according to these National Quality Forum criteria. Although the checklist is focused on ESRD, it could also have broad application to chronic disease states, where health care delivery organizations seek to enhance quality, safety, and efficiency of their services. Clinical performance measures are likely to become the norm for tracking performance for health care insurers. Thus, it is critical that the methodologies used to develop such metrics serve the payer and the provider and most importantly, reflect what represents the best care to improve patient outcomes.

Association of pre-transplant erythropoiesis-stimulating agent responsiveness with post-transplant outcomes.

BACKGROUND: The role of pre-transplant erythropoiesis-stimulating agent (ESA) responsiveness in affecting post-transplant outcomes is not clear. METHODS: Linking the 5-year patient data of a large dialysis organization to the 'Scientific Registry of Transplant Recipients', we identified 8795 hemodialyzed patients who underwent first kidney transplantation. Mortality or graft failure, delayed graft function (DGF) and acute rejection risks were estimated by Cox regression [hazard ratio (HR)] and logistic regression, respectively. RESULTS: Patients were 48 ± 14 years old and included 38% women and 36% diabetics. Compared to renal allograft recipients who were in the first quartile of pre-transplant ESA responsiveness index (ERI), i.e. ESA dose divided by hemoglobin and weight, recipients in second, third and fourth quartiles had higher adjusted graft-censored death HR (and 95% confidence intervals) of 1.7 (1.0-2.7), 1.8 (1.1-2.9) and 2.3 (1.4-3.9) and higher death-censored graft failure HR of 1.6 (1.0-2.5), 2.0 (1.2-3.1) and 1.6 (0.9-2.6), respectively. No significant association between pre-transplant ERI and post-transplant DGF or acute rejection was detected. CONCLUSIONS: Higher pre-transplant ERI during the hemodialysis treatment period was associated with worse post-transplant long-term outcomes including increased all-cause death and higher risk of graft failure.

High platelet count as a link between renal cachexia and cardiovascular mortality in end-stage renal disease patients.

BACKGROUND: It is not clear why cardiac or renal cachexia in chronic diseases is associated with poor cardiovascular outcomes. Platelet reactivity predisposes to thromboembolic events in the setting of atherosclerotic cardiovascular disease, which is often present in patients with end-stage renal disease (ESRD). OBJECTIVES: We hypothesized that ESRD patients with relative thrombocytosis (platelet count >300 × 10(3)/µL) have a higher mortality rate and that this association may be related to malnutrition-inflammation cachexia syndrome (MICS). DESIGN: We examined the associations of 3-mo-averaged platelet counts with markers of MICS and 6-y all-cause and cardiovascular mortality (2001-2007) in a cohort of 40,797 patients who were receiving maintenance hemodialysis. RESULTS: The patients comprised 46% women and 34% African Americans, and 46% of the patients had diabetes. The 3-mo-averaged platelet count was 229 ± 78 × 10(3)/µL. In unadjusted and case-mix adjusted models, lower values of albumin, creatinine, protein intake, hemoglobin, and dialysis dose and a higher erythropoietin dose were associated with a higher platelet count. Compared with patients with a platelet count of between 150 and 200 × 10(3)/µL (reference), the all-cause (and cardiovascular) mortality rate with platelet counts between 300 and <350, between 350 and <400, and ≥400 ×10(3)/µL were 6% (and 7%), 17% (and 15%), and 24% (and 25%) higher (P < 0.05), respectively. The associations persisted after control for case-mix adjustment, but adjustment for MICS abolished them. CONCLUSIONS: Relative thrombocytosis is associated with a worse MICS profile, a lower dialysis dose, and higher all-cause and cardiovascular disease death risk in hemodialysis patients; and its all-cause and cardiovascular mortality predictability is accounted for by MICS. The role of platelet activation in cachexia-associated mortality warrants additional studies.

Association of dialysis facility-level hemoglobin measurement and erythropoiesis-stimulating agent dose adjustment frequencies with dialysis facility-level hemoglobin variation: a retrospective analysis.

BACKGROUND: A key goal of anemia management in dialysis patients is to maintain patients' hemoglobin (Hb) levels consistently within a target range. Our aim in this study was to assess the association of facility-level practice patterns representing Hb measurement and erythropoiesis-stimulating agent (ESA) dose adjustment frequencies with facility-level Hb variation. METHODS: This was a retrospective observational database analysis of patients in dialysis facilities affiliated with large dialysis organizations as of July 01, 2006, covering a follow-up period from July 01, 2006 to June 30, 2009. A total of 2,763 facilities representing 436,442 unique patients were included. The predictors evaluated were facility-level Hb measurement and ESA dose adjustment frequencies, and the outcome measured was facility-level Hb variation. RESULTS: First to 99th percentile ranges for facility-level Hb measurement and ESA dose adjustment frequencies were approximately once per month to once per week and approximately once per 3 months to once per 3 weeks, respectively. Facility-level Hb measurement and ESA dose adjustment frequencies were inversely associated with Hb variation. Modeling results suggested that a more frequent Hb measurement (once per week rather than once per month) was associated with approximately 7% to 9% and 6% to 8% gains in the proportion of patients with Hb levels within a ±1 and ±2 g/dL range around the mean, respectively. Similarly, more frequent ESA dose adjustment (once per 2 weeks rather than once per 3 months) was associated with approximately 6% to 9% and 5% to 7% gains in the proportion of patients in these respective Hb ranges. CONCLUSIONS: Frequent Hb measurements and timely ESA dose adjustments in dialysis patients are associated with lower facility-level Hb variation and an increase in proportion of patients within ±1 and ±2 g/dL ranges around the facility-level Hb mean.

Causes and consequences of inflammation on anemia management in hemodialysis patients.

Inflammation is common among hemodialysis patients, and evidence is accumulating to suggest that inflammation is a major contributor to morbidity and mortality. Several factors have been suggested as potential causes of inflammation, including infections and the atherosclerosis process, as well as etiologies directly related to kidney disease such as reduced renal function and dialysis. Among several inflammatory biomarkers investigated, serum C-reactive protein (CRP) is the most widely used. In hemodialysis patients, raised CRP levels have been shown to be predictive of cardiovascular events, hospitalization, and all-cause and cardiovascular mortality. Elevated CRP levels may correlate with comorbidities and intercurrent events, all of which may impact the response to erythropoiesis-stimulating agents (ESAs) and lead to higher ESA doses. Most dialysis facilities do not routinely measure CRP, despite recommendations by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative. Regular measurement of CRP levels may help providers to understand change in ESA dosing and identify patients at risk for cardiovascular events. This review explores the inter-relationships between inflammation, CRP levels, and anemia management in patients receiving hemodialysis.

Impact of elevated C-reactive protein levels on erythropoiesis- stimulating agent (ESA) dose and responsiveness in hemodialysis patients.

BACKGROUND: Inflammation in an ESRD patient may impact responsiveness to erythropoiesis-stimulating agent (ESA) therapy. We sought to investigate the association between C-reactive protein (CRP) levels and average per-administration epoetin alfa (EPO) dose over 3 months following a CRP measurement. METHODS: The study is a retrospective cohort study of hemodialysis patients >or=18 years of age receiving care at a Fresenius Medical Care-North America facility between 1 July 2000 and 30 June 2002 who had no history of peritoneal dialysis. All patients had >or=1 CRP measurement and >or=3 months of recorded information before the CRP measurement (entry period). We evaluated the association between CRP levels and average hemoglobin (Hb) and per-administration EPO dose over the 3 months following the CRP measurement. RESULTS: We identified 1754 patients with a CRP measurement; mean age was 62.6 years (SD 14.1), 51.5% were male, 56.2% were white and the median CRP value was 2.04 mg/dL (20.4 mg/L). Patients in the upper CRP quartiles were more likely to be older, recently hospitalized; have a catheter vascular access; have lower albumin, Hb and transferrin saturation levels and greater EPO doses. In the subsequent 3 months, EPO doses but not Hb levels were significantly higher for patients in the highest CRP quartile [3.21 mg/dL (32.1 mg/L)] (P = 0.01). CONCLUSIONS: Inflammation as measured by an elevated CRP level appears to be an independent predictor of greater ESA dose requirements. Patients with the highest CRP levels required significantly higher ESA doses to achieve comparable Hb levels even after controlling for potential confounding variables.

Greater epoetin alfa responsiveness is associated with improved survival in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Among hemodialysis patients, achieved hemoglobin is associated with Epoetin alfa dose and erythropoietin responsiveness. A prospective erythropoietin responsiveness measure was developed and its association with mortality evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from 321 participants were used and randomized to the hematocrit normalization arm of the Normal Hematocrit Cardiac Trial. Subjects were to receive a 50% Epoetin alfa dose increase at randomization. The prospective erythropoietin responsiveness measure was defined as the ratio of weekly hematocrit change (over the 3 wk after randomization) per Epoetin alfa dose increase (1000 IU/wk) corresponding to the mandated 50% dose increase at randomization. The distribution of responsiveness was divided into quartiles. Over a 1-yr follow-up, Cox proportional hazard modeling evaluated associations between this responsiveness measure and mortality. RESULTS: Erythropoietin responsiveness values ranged from -2.1% to 2.4% per week per 1000 IU. Although subjects were similar across response quartiles, mortality ranged between 14% and 34% among subjects in the highest and lowest response quartiles (P = 0.0004), respectively. After adjusting for baseline prognostic indicators, highest versus lowest responsiveness was associated with a hazard ratio of 0.41 (95% confidence interval, 0.20 to 0.87). CONCLUSION: Lower erythropoietin responsiveness is a strong, independent predictor of mortality risk and should be considered when evaluating associations between clinical outcomes and potential prognostic indicators, such as Epoetin alfa dose and achieved hemoglobin values.

Managing the anemia of end-stage renal disease after hospitalization.

Aggravation of pre-existing anemia is a common clinical manifestation in patients who return to the dialysis facility after being hospitalized. Many of them display persistent anemia, with Hb levels remaining below the NKF-K/DOQI minimum threshold of 11 g/dL for 6 months or more following hospitalization. Proactive management of anemia in the periods before, during, and after hospitalization can often minimize the severity of any decrease in Hb while shortening the time required to reachieve targeted Hb levels.

Preoperative care of patients with kidney disease.

Patients with chronic kidney disease often require surgical interventions for vascular access and for medical problems related to comorbid conditions. Perioperative morbidity and mortality rates are increased in these patients. Preoperative attention to common medical problems that occur in patients with impaired renal function can lower some surgical risks. Hyperkalemia can be temporarily improved by the intravenous administration of an insulin-dextrose combination or bicarbonate, and polystyrene binding resins or dialysis can remove excess stores of potassium. Increased bleeding related to uremic platelet dysfunction can be managed by the administration of desmopressin, cryoprecipitate, or estrogens, and by avoiding the use of medications with antiplatelet effects close to the time of surgery. Transfusions of red blood cells should be reserved for use in patients with clinically significant anemia, because antibody formation may decrease the likelihood of successful renal transplantation in the future. Cardiovascular disease is the most common cause of death in patients with renal disease. Patients with chronic kidney disease may have hypertension and hypoglycemia in the perioperative period. Preoperative testing may be necessary in patients with cardiac risk factors. If future vascular access grafting is contemplated, intravenous line placement and blood draws should be avoided in a patient's nondominant arm.