Kidney allograft failure in the steroid‐free immunosuppression era: A matched case‐control study

Abstract

We studied the causes and predictors of death-censored kidney allograft failure among 1670 kidney recipients transplanted at our center in the corticosteroid-free maintenance immunosuppression era. As of January 1, 2012, we identified 137 recipients with allograft failure; 130 of them (cases) were matched 1-1 for recipient age, calendar year of transplant, and donor type with 130 recipients with functioning grafts (controls). Median time to allograft failure was 29 months (interquartile range: 18-51). Physician-validated and biopsy-confirmed categories of allograft failure were as follows: acute rejection (21%), glomerular disease (19%), transplant glomerulopathy (13%), interstitial fibrosis tubular atrophy (10%), and polyomavirus-associated nephropathy (7%). Graft failures were attributed to medical conditions in 21% and remained unresolved in 9%. Donor race, donor age, human leukocyte antigen mismatches, serum creatinine, urinary protein, acute cellular rejection, acute antibody-mediated rejection, BK viremia, and CMV viremia were associated with allograft failure. Independent predictors of allograft failure were acute cellular rejection (odds ratio: 18.31, 95% confidence interval: 5.28-63.45) and urine protein ≥1 g/d within the first year post-transplantation (5.85, 2.37-14.45). Serum creatinine ≤1.5 mg/dL within the first year post-transplantation reduced the odds (0.29, 0.13-0.64) of allograft failure. Our study has identified modifiable risk factors to reduce the burden of allograft failure.

Identification of Biomarkers for Predicting Allograft Rejection following Kidney Transplantation Based on the Weighted Gene Coexpression Network Analysis

“…Increasing evidence has demonstrated that kidney transplantation can effectively improve the quality of life and survival rates of patients with chronic kidney disease and end-stage kidney disease [ 3 ]. However, the occurrence of allograft rejection following kidney transplantation greatly limits the success rate by resulting in degradation of kidney function and graft loss [ 4 , 5 ]. Although the current advancements in the development of immunosuppressive medications targeting T cell-mediated immunity have effectively inhibited the occurrence of rejection reaction [ 6 ], the currently available immunosuppressive medications are ineffective against the adaptive humoral immune response.…”

Landscape of innate immune system transcriptome and acute T cell–mediated rejection of human kidney allografts

“…Immunological injury to the allograft results from the interactions between the donor and recipient genomes. Acute allograft rejection (AR) is a major risk factor for long-term graft failure (5,6). While the clinical application of potent immunosuppressive and anti-infective prophylactic drugs is a major reason for the current success rates, there is continuing need for better understanding of the alloimmune response to further optimize patient outcomes.…”

Detection of Infiltrating Fibroblasts by Single-Cell Transcriptomics in Human Kidney Allografts

“…Immune rejection of the allograft remains a signi cant challenge despite the use of potent immunosuppressive drugs [7][8][9] . Rejection episodes restrict the bene ts of transplantation and has a documented negative effect on long-term kidney allograft survival 10 .…”