Risk Of Death-censored Graft Failure Research Articles

Completely HLA Mismatched Living Donor Kidneys Have Comparable Results to the Best Matched Deceased Donor Kidneys

Background: HLA mismatches as a categorical variable is known to influence graft survival in deceased donor kidney transplantation. We studied the effect of HLA-A, -B, and -DR mismatches in a population with deceased and living donor kidney transplantations. Methods: All 1821 transplantations performed in our center from 1990 until 2010 were included in the analysis. Univariate and multivariate Cox proportional hazard analyses were performed. Three analyses were performed: HLA mismatches were included as a continuous variable, as a categorical variable (total number of mismatches), and as a binary variable (zero versus non-zero mismatches). Other variables included were year of transplantation, number of previous transplantations, pre-treatment, maximum PRA, current PRA, recipient gender and age, and donor type, gender and age. Results: 941 patients received a deceased donor kidney and 880 a living donor kidney. There were 494 failures, 337 in recipients of deceased donor kidneys and 157 in recipients of living donor kidneys. In multivariate Cox analysis, donor type and age, current PRA, and recipient age were found to have a significant influence on graft failure, censored for death. Number of HLA mismatches had a significant influence in all analyses. There was no interaction between donor type and HLA mismatches. Conclusion: Number of HLA mismatches has a significant influence on death-censored graft survival. This holds true for both deceased and living donor kidney transplantation. However, the risk of death-censored graft failure of a 2-2-2 mismatched living donor kidney is comparable to that of a 0-0-0 mismatched deceased donor kidney (figure 1).[Figure 1]

Association Between Age and Graft Failure Rates in Young Kidney Transplant Recipients

Age at transplant and graft failure risk are associated in young kidney transplant recipients. The risk of graft failure may also vary by current age, irrespective of age at transplant. We sought to estimate age-specific graft failure rates in young kidney transplant recipients and to estimate the relative hazards of graft failure at different ages, compared with at the age of 25 to 29 years. We evaluated 90,689 patients recorded in the United States Renal Data System database who received a first transplant when younger than 40 years (1988-2009); 18,310 were younger than 21 years at transplant. Time-dependent Cox models with time-varying covariates were used to estimate the association between age (time-dependent) and death-censored graft failure risk, adjusted for time since transplant and other potential confounders. There were 31,857 graft failures over a median follow-up of 5.9 years (interquartile range, 2.5-10.5 years; maximum, 21.8 years). Crude age-specific graft failure rates were highest in 19 year olds (6.6 per 100 person-years). Compared with individuals with the same time since transplant observed at 25 to 29 years of age, death-censored graft failure rates were highest in 17 to 24 year olds (hazard ratio, 1.20; [95% confidence interval 1.13, 1.27] for 17-20 year olds and 1.20 [1.13, 1.26] for 21-24 year olds; both P<0.0001) and lowest in 5 to 12 year olds (hazard ratio, 0.60; [0.53, 0.68] for 5-9 year olds and 0.56 [0.49, 0.64] for 10-12 year olds; both P<0.0001). Among first kidney transplant recipients younger than 40 years, older adolescents and young adults (17-24 years) have the highest risk of graft failure, irrespective of age at transplant.

Association of Pretransplant Glycemic Control With Posttransplant Outcomes in Diabetic Kidney Transplant Recipients

OBJECTIVEObservational studies have yielded inconsistent findings regarding the association of hemoglobin A1c (HbA1c) with survival in diabetic patients on dialysis. The association between pretransplant glycemic control and short- and long-term posttransplant outcomes in kidney transplant recipients is not clear.RESEARCH DESIGN AND METHODSLinking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 2,872 diabetic dialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (odds ratio), respectively.RESULTSPatients were 53 ± 11 years old and included 36% women and 24% African Americans. In our fully adjusted model, allograft failure–censored, all-cause death HR and 95% CI for time-averaged pretransplant HbA1c categories of 7 to <8%, 8 to <9%, 9 to 10%, and ≥10%, compared with 6 to <7% (reference), were 0.89 (0.59–1.36), 2.06 (1.31–3.24), 1.41 (0.73–2.74), and 3.43 (1.56–7.56), respectively; and graft failure–censored cardiovascular death HR was 0.38 (0.13–1.05), 1.78 (0.69–4.55), 1.59 (0.44–5.76), and 4.28 (0.85–21.64), respectively. We did not find any difference in risk of death-censored graft failure or DGF with different pretransplant HbA1c levels.CONCLUSIONSPoor pretransplant glycemic control appears associated with decreased posttransplant survival in kidney transplant recipients, whereas allograft outcomes may not be affected.

Lymphoproliferative Disorders After Adult Kidney Transplant: Epidemiology and Comparison of Registry Report With Claims-Based Diagnoses

Posttransplant lymphoproliferative disorder (PTLD) is a major complication of kidney transplant. Retrospective cohort study comparing PTLD incidence rates using US Medicare claims and Organ Procurement and Transplantation Network (OPTN) data, examining risk factors for PTLD in OPTN data, and studying recipient and graft survival after PTLD diagnosis. All adult first-transplant patients who underwent deceased or living donor kidney-only transplants in 2000-2006 (n = 89,485) followed up through 3 years posttransplant. Recipient and donor characteristics, HLA mismatches, viral serologic test results, and initial immunosuppression. OPTN-reported or Medicare claims-based PTLD diagnosis, recipient and graft survival after OPTN-reported PTLD diagnosis. Adjusted HRs for PTLD diagnosis estimated using a Cox proportional hazards model; probability of survival free of all-cause graft failure estimated using the Kaplan-Meier method. The incidence rate of PTLD during the first posttransplant year was 2-fold higher in Medicare claims (0.46/100 patient-years; 95% CI, 0.39-0.53) than in OPTN data (0.22/100 patient-years; 95% CI, 0.17-0.27). Factors associated with increased rates of PTLD included older age, white race (vs African American), induction with T-cell-depleting antibodies, Epstein-Barr virus seronegativity at the time of transplant, and cytomegalovirus seronegativity at the time of transplant. The adjusted risk of death with graft function was 17.5 (95% CI, 14.3-21.4) times higher after a report of PTLD, and the risk of death-censored graft failure was 5.5 (95% CI, 3.9-7.7) times higher. Shortcomings inherent in large databases, including inconsistencies in patient follow-up, reporting, and coding practices by transplant centers; insufficient registry data to analyze acute rejection episodes and antirejection treatment; no available data for potential effects of different types of PTLD treatment on patient outcomes. Despite the limitations of data collected by registries, PTLD clearly is an important complication; both mortality and death-censored graft failure increase after PTLD.

Associations of Renal Function at 1-Year After Kidney Transplantation With Subsequent Return to Dialysis, Mortality, and Healthcare Costs

Improved early kidney transplant outcomes limit the contemporary utility of standard clinical endpoints. Quantifying the relationship of renal function at 1 year after transplant with subsequent clinical outcomes and healthcare costs may facilitate cost-benefit evaluations among transplant recipients. Data for Medicare-insured kidney-only transplant recipients (1995-2003) were drawn from the United States Renal Data System. Associations of estimated glomerular filtration rate (eGFR) level at the first transplant anniversary with subsequent death-censored graft failure and patient death in posttransplant years 1 to 3 and 4 to 7 were examined by parametric survival analysis. Associations of eGFR with total health care costs defined by Medicare payments were assessed with multivariate linear regression. Among 38,015 participants, first anniversary eGFR level demonstrated graded associations with subsequent outcomes. Compared with patients with 12-month eGFR more than or equal to 60 mL/min/1.73 m, the adjusted relative risk of death-censored graft failure in years 1 to 3 was 31% greater for eGFR 45 to 59 mL/min/1.73 m (P<0.0001) and 622% greater for eGFR 15 to 30 mL/min/1.73 m (P<0.0001). Associations of first anniversary eGFR level with graft failure and mortality remained significant in years 4 to 7. The proportions of recipients expected to return to dialysis or die attributable to eGFR less than 60 mL/min/1.73 m over 10 years were 23.1% and 9.4%, respectively, and were significantly higher than proportions attributable to delayed graft function or acute rejection. Reduced eGFR was associated with graded and significant increases in health care spending during years 2 and 3 after transplant (P<0.0001). eGFR is strongly associated with clinical and economic outcomes after kidney transplantation.

Blood transfusions in kidney transplant candidates are common and associated with adverse outcomes

Surprisingly, there are no data regarding transfusion frequency, factors associated with transfusion administration in patients on the kidney transplant waiting list, or transfusion impact on graft and recipient outcomes. We used United States Renal Data System data to identify 43,025 patients added to the waiting list in 1999-2004 and followed through 2006 to assess the relative risk of post-listing transfusions. In 69,991 patients who underwent transplants during the same time period, we assessed the association between pre-transplant transfusions and level of panel-reactive antibody (PRA) at the time of transplant, and associations between PRA and patient outcomes. The three-yr cumulative incidence of transfusions was 26% for patients added to the waiting list in 1999, rising to 30% in 2004. Post-listing transfusions were associated with a 28% decreased likelihood of undergoing transplant, and a more than fourfold increased risk of death. There was a graded association between percent PRA at the time of transplant and adjusted risk of death-censored graft failure, death with function, and the combined event of graft failure and death. These data demonstrate that transfusions remain common and confirm the adverse association between transfusions and PRA, and high PRA and inferior graft and patient outcomes.

The association between recipient alcohol dependency and long-term graft and recipient survival

The causative role of alcohol consumption in renal disease is controversial, and its effect on renal graft and recipient survival has not been previously studied. We analysed the association between pre-transplant [at the time of end-stage renal disease (ESRD) onset] alcohol dependency and renal graft and recipient survival. The United States Renal Data System (USRDS) records of kidney transplant recipients 18 years or older transplanted between 1 January 1995 and 31 December 2002 were examined. We used Kaplan-Meier analysis and Cox regression models adjusted for covariates to analyse the association between pre-transplant alcohol dependency and graft and recipient survival. In an entire study cohort of 60 523, we identified 425 patients with a history of alcohol dependency. Using Cox models, alcohol dependency was found to be associated with increased risk of death-censored graft failure [hazard ratio (HR) 1.38, P < 0.05] and increased risk of transplant recipient death (HR 1.56, P < 0.001). Subgroup analysis demonstrated an association of alcohol-dependency with recipient survival and death-censored graft survival in males (but not in females), and in both white and non-white racial subgroups. We concluded that alcohol dependency at the time of ESRD onset is a risk factor for renal graft failure and recipient death.