Risk Factor For Allograft Loss Research Articles

Concurrent Acute Cellular Rejection Is an Independent Risk Factor for Renal Allograft Failure in Patients With C4d-Positive Antibody-Mediated Rejection

Identification of risk factors for renal allograft failure after an episode of acute antibody-mediated rejection (AMR) may help the outcome of this difficult-to-treat complication. During December 2003 to February 2011, 833 kidney graft recipients underwent 1120 clinically indicated biopsies at our center. We reviewed the biopsy results and identified 87 biopsy specimens from 87 patients positive for the degradation product of complement component 4 (C4d) and acute AMR. We generated Kaplan-Meier survival curves and performed a multivariable analysis using the Cox proportional hazards regression model to identify risk factors for allograft failure after C4d+ acute AMR. Among the 87 patients, 26 had a diagnosis of acute AMR according to the Banff '09 classification schema, 29 had acute AMR and chronic active AMR, 18 had acute AMR and acute T-cell mediated rejection (TCMR), and 14 had acute AMR, chronic active AMR, and acute TCMR. Kaplan-Meier survival estimates showed that concurrent acute TCMR (P=0.001, Mantel-Cox log-rank test), concurrent chronic active AMR (P=0.03), and time to biopsy (P=0.04) are associated with graft survival. The Cox proportional hazards regression analysis identified that concurrent acute TCMR (hazard ratio, 2.59 [95% confidence interval, 1.21-5.55]; P=0.01) and estimated glomerular filtration rate (hazard ratio, 0.65 [95% confidence interval, 0.48-0.88]; P=0.01) are independent risk factors for allograft loss. Concurrent chronic active AMR or time to biopsy was not associated with graft failure by the multivariable Cox analysis. Our single-center study has elucidated that concurrent acute TCMR in kidney transplant recipients with C4d+ acute AMR is an independent risk factor for graft failure. Level of allograft function at the time of diagnosis was also an independent predictor of graft loss.

Intra‐patient variability in tacrolimus trough concentrations and renal function decline in pediatric renal transplant recipients

High intra-patient variability in TCL exposure is a risk factor for allograft loss and late acute rejection. We hypothesized that a higher intra-patient variability leads to a faster decline in GFR in pediatric renal transplant patients and that adolescents have a higher intra-patient variability due to poorer adherence. We included 69 children aged 3.5-18 yr who had undergone renal transplantation between April 1996 and May 2009 in two pediatric nephrology centers in the Netherlands. We analyzed TCL trough concentrations over a period of one yr and calculated TCL trough concentrations variability using VC. We investigated the correlation between the TCL trough concentrations variability and the decline in estimated GFR over four yr. The median intra-patient variability in TCL concentrations was 30.1% (range 8.6-77.6) and the mean GFR slope -3.8 mL/min/1.73 m(2) /yr. The VC correlated neither with the GFR slope, nor with the patients' age. However, children with late acute rejection had higher VC (p = 0.045). We were unable to provide evidence that a high variability in TCL exposure leads to a faster decline in renal function, although children with late acute rejection have a higher variability in TCL exposure. Adolescents do not have a higher intra-patient variability in TCL trough concentrations than younger children.

Glomerular damage as a predictor of renal allograft loss

Interstitial fibrosis and tubular atrophy (IF/TA) are the most common cause of renal graft failure. Chronic transplant glomerulopathy (CTG) is present in approximately 1.5-3.0% of all renal grafts. We retrospectively studied the contribution of CTG and recurrent post-transplant glomerulopathies (RGN) to graft loss. We analyzed 123 patients with chronic renal allograft dysfunction and divided them into three groups: CTG (N = 37), RGN (N = 21), and IF/TA (N = 65). Demographic data were analyzed and the variables related to graft function identified by statistical methods. CTG had a significantly lower allograft survival than IF/TA. In a multivariate analysis, protective factors for allograft outcomes were: use of angiotensin-converting enzyme inhibitor (ACEI; hazard ratio (HR) = 0.12, P = 0.001), mycophenolate mofetil (MMF; HR = 0.17, P = 0.026), hepatitis C virus (HR = 7.29, P = 0.003), delayed graft function (HR = 5.32, P = 0.016), serum creatinine > or =1.5 mg/dL at the 1st year post-transplant (HR = 0.20, P = 0.011), and proteinuria > or =0.5 g/24 h at the 1st year post-transplant (HR = 0.14, P = 0.004). The presence of glomerular damage is a risk factor for allograft loss (HR = 4.55, P = 0.015). The presence of some degree of chronic glomerular damage in addition to the diagnosis of IF/TA was the most important risk factor associated with allograft loss since it could indicate chronic active antibody-mediated rejection. ACEI and MMF were associated with better outcomes, indicating that they might improve graft survival.

Risk factors and impact of recurrent lupus nephritis in patients with systemic lupus erythematosus undergoing renal transplantation: Data from a single US institution

To determine the risk factors for recurrent lupus nephritis, allograft loss, and survival among patients with systemic lupus erythematosus (SLE) undergoing kidney transplantation. The archival records of all kidney transplant recipients with a prior diagnosis of SLE (according to the American College of Rheumatology criteria) from June 1977 to June 2007 were reviewed. Patients who had died or lost the allograft within 90 days of engraftment were excluded. Time-to-event data were examined by univariable and multivariable Cox proportional hazards regression analyses. Two hundred twenty of nearly 7,000 renal transplantations were performed in 202 SLE patients during the 30-year interval. Of the 177 patients who met the criteria for study entry, the majority were women (80%) and African American (65%), the mean age was 35.6 years, and the mean disease duration was 11.2 years. Recurrent lupus nephritis was noted in 20 patients (11%), allograft loss in 69 patients (39%), and death in 36 patients (20%). African American ethnicity was found to be associated with a shorter time-to-event for recurrent lupus nephritis (hazard ratio [HR] 4.63, 95% confidence interval [95% CI] 1.29-16.65) and death (HR 2.47, 95% CI 0.91-6.71), although, with the latter, the association was not statistically significant. Recurrent lupus nephritis and chronic rejection of the kidney transplant were found to be risk factors for allograft loss (HR 2.48, 95% CI 1.09-5.60 and HR 2.72, 95% CI 1.55-4.78, respectively). In patients with recurrent lupus nephritis, the lesion in the engrafted kidney was predominantly mesangial, compared with a predominance of proliferative or membranous lesions in the native kidneys. African American ethnicity was independently associated with recurrent lupus nephritis. Allograft loss was associated with chronic transplant rejection and recurrence of lupus nephritis. Recurrent lupus nephritis is infrequent and relatively benign, without influence on a patient's survival.

Racial Disparities in Renal Allograft Survival: A Public Health Issue?

Racial disparities in renal transplantation outcomes have been documented with inferior allograft survival among African Americans compared with non-African Americans. These differences have been attributed to a variety of factors, including immunologic hyperresponsiveness, socioeconomic status, compliance, HLA matching, and access to care. The purpose of this study was to examine both immunologic and nonimmunologic risk factors for allograft loss with a goal of defining targeted strategies to improve outcomes among African Americans. We retrospectively analyzed all primary deceased-donor adult renal transplants (n = 2,453) at our center between May 1987 and December 2004. Analysis included the impact of recipient and donor characteristics, HLA typing, and immunosuppressive regimen on graft outcomes. Data were analyzed using standard Kaplan-Meier actuarial techniques and were explored with nonparametric and parametric methods. Multivariable analyses in the hazard-function domain were done to identify specific risk factors associated with graft loss. The 1-year allograft survival in recipients improved substantially throughout the study period, and 3-year allograft survival also improved. Risk factor analyses are shown by type of allograft and according to specific time periods. Risk of immunologic graft loss (acute rejection) was most prominent during the early phase. During late-phase, immunologic risk persists (chronic rejection), but recurrent disease, graft quality, and recipient's comorbidities have an increasingly greater role. Advances in immunosuppression regimens have contributed to allograft survival in both early and late (constant) phases throughout all eras, but improvement in longterm outcomes for African Americans continues to lag behind non-African Americans. The disparity in renal allograft loss between African Americans and non-African Americans over time indicates that beyond immunologic risk, the impact of nonimmunologic variables, such as time on dialysis pretransplantation, diabetes, and access to medical care, can be key issues.

Multivariate analysis of risk factors for allograft loss in black and white recipients of renal allografts

Multivariate analysis of risk factors for allograft loss in black and white recipients of renal allografts