Jeffrey Petersen

Sensitization from transfusion in patients awaiting primary kidney transplant

BACKGROUND Sensitization to human leukocyte antigen (HLA) from red blood cell (RBC) transfusion is poorly quantified and is based on outdated, insensitive methods. The objective was to evaluate the effect of transfusion on the breadth, magnitude and specificity of HLA antibody formation using sensitive and specific methods. METHODS Transfusion, demographic and clinical data from the US Renal Data System were obtained for patients on dialysis awaiting primary kidney transplant who had ≥ 2 HLA antibody measurements using the Luminex single-antigen bead assay. One cohort included patients with a transfusion (n = 50) between two antibody measurements matched with up to four nontransfused patients (n = 155) by age, sex, race and vintage (time on dialysis). A second crossover cohort (n = 25) included patients with multiple antibody measurements before and after transfusion. We studied changes in HLA antibody mean fluorescence intensity (MFI) and calculated panel reactive antibody (cPRA). RESULTS In the matched cohort, 10 of 50 (20%) transfused versus 6 of 155 (4%) nontransfused patients had a ≥ 10 HLA antibodies increase of >3000 MFI (P = 0.0006); 6 of 50 (12%) transfused patients had a ≥ 30 antibodies increase (P = 0.0007). In the crossover cohort, the number of HLA antibodies increasing >1000 and >3000 MFI was higher in the transfused versus the control period, P = 0.03 and P = 0.008, respectively. Using a ≥ 3000 MFI threshold, cPRA significantly increased in both matched (P = 0.01) and crossover (P = 0.002) transfused patients. CONCLUSIONS Among prospective primary kidney transplant recipients, RBC transfusion results in clinically significant increases in HLA antibody strength and breadth, which adversely affect the opportunity for future transplant.

An update on the impact of pre-transplant transfusions and allosensitization on time to renal transplant and on allograft survival

BackgroundBlood transfusions have the potential to improve graft survival, induce sensitization, and transmit infections. Current clinical practice is to minimize transfusions in renal transplantation candidates, but it is unclear if the evidence continues to support pre-transplant transfusion avoidance. Changes in the Medicare prospective payment system may increase transfusion rates. Thus there is a need to re-evaluate the literature to improve the management options for renal transplant candidates.MethodsA review applying a systematic approach and conducted using MEDLINE®, Embase®, and the Cochrane Library for English-language publications (timeframe: 01/1984–03/2011) captured 180 studies and data from publically available registries and assessed the impact of transfusions on allosensitization and graft survival, and the impact of allosensitization on graft survival and wait time.ResultsBlood transfusions continued to be a major cause of allosensitization, with allosensitization associated with increased rejection and graft loss, and longer wait times to transplantation. Although older studies showed a beneficial effect of transfusion on graft survival, this benefit has largely disappeared in the post-cyclosporine era due to improved graft outcomes with current practice. Recent data suggested that it may be the donor-specific antibody component of allosensitization that carried the risk to graft outcomes.ConclusionsResults of this review indicated that avoiding transfusions whenever possible is a sound management option that could prevent detrimental effects in patients awaiting kidney transplantation.

Red blood cell transfusions and the risk of allosensitization in patients awaiting primary kidney transplantation.

Background Most studies of HLA sensitization after red blood cell transfusion in transplant candidates were done before widespread use of leukoreduced blood and based on relatively insensitive, nonspecific antibody assays. We evaluated the effect of transfusion on the breadth and magnitude of HLA antibody formation using current, sensitive, HLA-specific immunoassays. Methods Serial HLA antibody data were merged with transfusion data from the US Renal Data System for 1324 patients on the kidney transplant waitlist (2004–2010). Two study groups were identified: a matched cohort consisting of 89 patients who received transfusion and 251 patients who did not receive transfusion and a crossover cohort consisting of 69 patients. Changes in antibody levels and calculated panel-reactive antibody (CPRA) were compared using &khgr;2 and Sign tests, respectively. Logistic regression was used to estimate the relative risk of antibody responses. Results Among the matched cohort, 20% of those who received transfusion compared to 3% of those who did not receive transfusion exhibited an antibody response (P=0.001), whereas in the crossover cohort, 19% exhibited a response in those who received transfusion compared to 1% of those who did not receive transfusion (P=0.0001). Moreover, 26.3% of those who received transfusion had increased CPRA compared to 5.8% of those who did not receive transfusion . These effects were greater in women and blacks compared to men and whites, respectively. Importantly, patients who received transfusion were at an increased risk of a potentially crossmatch positive response (odds ratio=9.6, 95% confidence interval=3.0–30.7). Conclusions Sensitization from transfusion can occur in up to 20% of transplant candidates, resulting in higher antibody levels and CPRA values that adversely impact access to transplantation. These results support transfusion avoidance whenever possible.

Red blood cell transfusion use in patients with chronic kidney disease

BACKGROUND There is limited data available on the use of red blood cell (RBC) transfusions in younger chronic kidney disease patients not on dialysis (CKD-ND), for whom the consequences of developing antibodies to foreign antigens (allosensitization) may be particularly relevant. METHODS We used the Ingenix medical claims database, comprising data on ∼40 million commercially insured US individuals, to identify annual (2002-08) cohorts of patients 18-64 years of age with newly diagnosed CKD. We followed each cohort for 1 year to estimate RBC transfusion rates and used Cox proportional hazards regression to identify patient characteristics associated with time to first transfusion. RESULTS We identified 120 790 newly diagnosed CKD patients for the years 2002-08; 54% were 50-64 years of age. Overall, the transfusion rate was 2.64/100 person-years (PYs) (95% CI: 2.52-2.77). Rates were higher among those with diagnosed anemia [9.80/100 PYs (95% CI: 9.31-10.3)] and among those who progressed to end-stage renal disease (ESRD) [28.0/100 PYs (95% CI: 23.7-33.0)]. For those progressing to ESRD, transfusion rates more than doubled between 2002 and 2008. Of the factors evaluated, transfusion history and the presence of heart failure and diabetes were most strongly associated with a receipt of a transfusion. CONCLUSIONS RBC transfusions are relatively common and on the rise among younger CKD-ND patients who are anemic and progress to ESRD. Efforts to decrease the use of transfusions may be important for potential transplant candidates who progress to ESRD.

Estimate of maintenance EPO to darbepoetin alfa dose conversion ratio in a hospital-based dialysis patient population

Abstract Background: Epoetin alfa (EPO) and darbepoetin alfa are erythropoiesis-stimulating agents (ESAs) used to treat anemia in patients with chronic kidney disease. EPO and darbepoetin alfa have a non-proportional dose conversion relationship across the dosing spectrum. However, reports comparing the dose relationship between the two ESAs do not adjust for the non-proportional dose relationship or for population differences. Because drug cost is directly related to dosage, appropriate methods to assess the dose relationship between the two ESAs are important to understand the economic implications of converting patient populations from one ESA treatment to another. Objective: To describe dose conversion methods that take into account the non-proportional dose relationship between EPO and darbepoetin alfa, and calculate the dose conversion ratio (DCR) between the two ESAs in a hospital-based dialysis patient population. Methods: This was a retrospective observational study where longitudinal data from medical charts were collected for chronic hemodialysis patients being treated at hospital-based dialysis centers. Mean maintenance DCRs were calculated at the population level for hemodialysis patients converted from EPO to darbepoetin alfa treatment and subsequently maintained on darbepoetin alfa. Two methods were used to determine the DCRs: a regression-based method using ordinary least squares regression, and ratio-based method using an arithmetic mean. Results: The estimated population mean maintenance DCR for the population in this analysis was 320:1 (Units EPO:µg darbepoetin alfa) using the regression-based method, and 350:1 using the ratio-based method. Sensitivity analysis yielded DCRs ranging from 311 to 333:1. Conclusions: The two methods in estimating the DCR presented here provide payers with an empirical way of comparing ESA utilization for pharmacoeconomic evaluation. DCR results may vary according to patient characteristics; however, mean DCRs of greater than 300:1 were obtained in this analysis. Exclusion of other patient-related factors that may influence ESA dose is a possible limitation of the study.

Transfusion burden in non-dialysis chronic kidney disease patients with persistent anemia treated in routine clinical practice: a retrospective observational study

BackgroundTransfusion patterns are not well characterized in non-dialysis (ND) chronic kidney disease (CKD) patients. This study describes the proportion of patients transfused, units of blood transfused and trigger-hemoglobin (Hb) levels for transfusions in severe anemic, ND-CKD patients in routine practice.MethodsA retrospective cohort study of electronic medical record data from the Henry Ford Health System identified 374 adult, ND-CKD patients with severe anemia (Hb < 10 g/dL and subsequent use of erythropoiesis-stimulating agents [ESA] therapy, blood transfusions, or a second Hb < 10 g/dL) between January 2004 and June 2008. Exclusions included those with prior diagnoses of cancer, renal or liver transplant, end-stage renal disease, acute bleeding, trauma, sickle cell disease, or aplastic anemia. A gap of ≥ 1 days between units of blood transfused was counted as a separate transfusion.ResultsAt least 1 transfusion (mean of 2 units; range, 1-4) was administered to 20% (75/374) of ND-CKD patients with mean (± SD) follow-up of 459 (± 427) days. The mean (± SD) Hb level closest and prior to a transfusion was 8.8 (± 1.5) g/dL. Patients who were hospitalized in the 6 months prior to their first anemia diagnosis were 6.3 times more likely to receive a blood transfusion than patients who were not hospitalized (p < 0.0001). Patients with peripheral vascular disease (PVD) were twice as likely to have a transfusion as patients without PVD (p = 0.04).ConclusionsTransfusions were prevalent and the trigger hemoglobin concentration was approximately 9 g/dL among ND-CKD patients with anemia. To reduce the transfusion burden, clinicians should consider other anemia treatments including ESA therapy.

Red blood cell transfusion, hyperkalemia, and heart failure in advanced chronic kidney disease

In recent years, the use of red blood cell (RBC) transfusion for the treatment of chronic kidney disease (CKD)‐related anemia has increased. We used the OptumInsight medical claims database to study the association between receiving a transfusion and hyperkalemia and heart failure events.

Hemoglobin Stability and Patient Compliance With Darbepoetin Alfa in Peritoneal Dialysis Patients After the Implementation of the Prospective Payment System

PURPOSE Since the Centers for Medicare & Medicaid Services implemented the End-Stage Renal Disease Prospective Payment System, dialysis providers have increasingly focused on balancing resource utilization and quality outcomes for the treatment of anemia in patients undergoing peritoneal dialysis. Limited data exist regarding anemia management outcomes for these patients in US-based dialysis centers after the implementation of the new payment system. METHODS This was a retrospective, observational, cohort study of stable PD patients with end-stage renal disease who received darbepoetin alfa for anemia management over a 15-month period (April 1, 2011-June 29, 2012). The medication was administered by staff in the home-training unit instead of being self-administered at home. The primary end point was mean quarterly hemoglobin (Hb) levels. Variability in Hb levels was assessed over the 5 quarters by using repeated measures ANOVA to test for differences in the observed mean SDs. FINDINGS In the 139 adult patients on stable peritoneal dialysis and meeting the eligibility criteria, mean (SD) Hb level by quarter was 10.8 (1.2) g/dL in quarters 2 and 3 of 2011, 10.5 (1.1) g/dL in quarter 4 of 2011, and 10.4 (1.1) g/dL in quarters 1 and 2 of 2012. Hb levels were stable (mean SDs, 0.58-0.72) over the 5 quarters of the study. Patient compliance with attendance for all scheduled home training unit visits was 84%. IMPLICATIONS PD patients who underwent darbepoetin alfa administration and twice-monthly laboratory testing in the home-training unit had stable Hb levels. Despite more frequent center visits compared with a home-administered approach, patient compliance was high.