The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy. To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications. In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy. We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy (IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy (TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR (40%), TG (17%), and IFTA (13%). Most grafts failed within two years of post-transplant (36%). Subsequently, approximately 10%-15% of grafts failed every two years: > 2-4 years (16%), > 4-6 years (13%), > 6-8 years (11%), > 8-10 years (9%) and > 10 years (16%). AR was the most common cause of graft failure in the first six years (48%), whereas TG was the most prevalent cause of graft failure after 6 years (32%) of transplant. In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.

Background.: Limited information exists about outcomes of HLA donor-specific antibody (DSA) negative (DSA−) microvascular inflammation (MVI). Methods.: We report our experience with 25 DSA− patients with MVI compared to 155 DSA+ patients who met Banff 2013 criteria for antibody-mediated rejection (AMR). We also compared outcomes to 228 DSA+ patients whose biopsies were negative for rejection and served as a negative control. Results.: There were no significant differences in the baseline characteristics between the DSA− MVI and DSA+ AMR groups. At the time of diagnosis, both groups had similar graft function. The DSA− group had higher MVI scores but lower C4d scores. At last follow-up, renal function was similar between the groups. There were 12 (48%) graft failures in the DSA− group and 59 (38%) graft failures in the DSA+ group, which was not statistically different. Similar results were found after matching for the MVI scores, C4d, and treatment between 2 groups. We also found similar outcomes between DSA− and DSA+ patients when only including those who would have met Banff 2017 criteria for AMR. In univariate Cox regression analyses, estimated glomerular filtration rate at time of biopsy, glomerulitis, rituximab, diabetes, v score, allograft glomerulopathy, fibrous intimal thickening, tubular atrophy, and interstitial fibrosis scores were associated with graft failure. In multivariate analysis, only estimated glomerular filtration rate was protective. Both groups had significantly worse outcomes than the DSA+-negative controls without AMR. Conclusions.: Our findings suggest that outcomes and response to treatment with HLA DSA− MVI patients are similarly poor to those with DSA+ MVI patients, supporting a critical role for MVI in the diagnosis of AMR.

Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are scarce data evaluating the association of recipient factors such as age, BMI, or pretransplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006 and 2017 with 1 year of follow-up at minimum, were assessed for potential relationship of pretransplant BMI and insulin requirements with posttransplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from posttransplant diabetes (94.7% T2D vs. 92.3% T1D at 1 yr, and 88.1% T2D vs. 81.1% T1D at 5 yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1 yr, and 89.7% T2D vs. 81.2% T1D at 5 yrs). There was no significant association between BMI or pretransplant insulin requirements with posttransplant diabetes occurrence in either T1D (p = .10, .43, respectively) or T2D (p = .12, .63) patients in the cohort; or with graft failure (T1D: p = .40, .09; T2D: p = .71, .28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D.

It is commonly assumed that in simultaneous kidney and pancreas (SPK) recipients, rejection of the two organs is concordant. As a result, concurrent biopsies of both organs are rarely performed and there are limited histological data on how often rejection is in fact discordant. We reviewed all SPK recipients transplanted at the University of Wisconsin between 01/01/2001 and 12/31/2016 that underwent biopsy of both organs. We included all patients whose biopsies were within 30 days. If patients were treated for rejection between biopsies, they were excluded if the biopsies were more than 4 days apart. 91 simultaneous biopsies were performed within 30 days of each other, and 40 met our inclusion criteria. 25 (62.5%) patients had concordance of biopsy findings: 11 had rejection of both organs and 14 had no rejection of either organ. The other 15 (37.5%) were discordant for rejection, with 10 having pancreas-only rejection and 5 kidney-only rejection. It was striking to find that 4 of the 11 patients with concordance for rejection (36%) had different types (AMR, ACR or mixed) of rejection in the two organs. This large series of simultaneous kidney and pancreas biopsies demonstrates the continued utility of performing biopsies of both organs.

Donor-specific antibodies (DSAs) are considered an important risk factor for graft injury and failure. However, there is limited information on long-term outcomes for kidney transplant recipients with positive DSAs in the absence of rejection on biopsy. We evaluated all patients at the University of Wisconsin who underwent a kidney allograft biopsy between January 1, 2013, and December 31, 2016. All patients with clinical indication or protocol biopsies that were negative for acute rejection and lacked significant acute pathological features were included in the study and divided into 2 groups based on DSAs at the time of biopsy. There were a total of 1102 kidney biopsies during the study period of which 587 fulfilled our selection criteria (DSA+, n = 192, and DSA-, n = 395). The incidence of subsequent rejection and death-censored graft failure (DCGF) were outcomes of interest. There was no difference in acute (i + t + v + c4d + ptc + g = 0 in both groups) or chronic (ci + ct + cv + cg = 2.4 ± 2.2 vs. 2.7 ± 2.4; cg = 0.12 ± 0.48 vs. 0.13 ± 0.48) Banff scores in the index biopsy. Patients were followed for a mean of 33.1 ± 16.8 months. Kaplan-Meier analyses demonstrated a higher incidence of DCGF in DSA- group (n = 83) but this was not observed for subsequent rejection (n = 76). In multivariate Cox regression analyses, the interval from transplant to biopsy, de novo DSA, and younger age remained independently associated with increased risk of subsequent rejection. Notably, there was no association between subsequent rejection or DSA (pretransplant, de novo, persistant, Class I/II, MFIsum, or MFImax) and graft failure. This study suggests that in the absence of biopsy-proven rejection and acute inflammation, human leukocyte antigen (HLA) DSAs are not associated with increased risk of graft failure.

Role of novel biomarkers in kidney transplantation