In kidney recipients from the same deceased donor, discordance in delayed graft function is associated with the worst outcomes.

INTRODUCTION: Delayed graft function (DGF) is a common complication among deceased donor kidney transplant recipients (DDKTs) and is associated with worse outcomes. The effect on outcomes of concordance versus discordance in DGF between two different recipients of kidneys from the same donor is largely unknown. METHODS: We reviewed all adult DDKTs for which both kidneys were transplanted to two different recipients at our center between 2014-2019. DDKTs were divided into four groups based on the DGF status: concordance no DGF (cc-no-DGF); discordance no DGF(dd-no-DGF); discordance DGF (dd-DGF) and concordance in DGF (cc-DGF). Acute rejection (AR) and death censored graft failure (DCGF) were outcomes of interest. RESULTS: A total of 578 DDKTs fulfilled our selection criteria, 280were in cc-no-DGF, 83 in dd-no-DGF, 83 in dd-DGF, and 132 in cc-DGF. Compared to cc-no-DGF, in univariate analysis, dd-DGF was associated with an increased risk of AR (HR: 1.60; 95% CI: 1.0-2.56) but cc-DGF was not (HR: 1.01; 95% CI: 0.63-1.62). dd-DGF was not associated with an increased risk of AR in multivariate analysis. In multivariate analysis, dd-DGF was associated with an increased risk of DCGF (HR: 2.70; 95% CI: 1.05-6.93) but cc-DGFwas not (HR: 2.36; 95% CI: 0.97-5.70). CONCLUSION: Discordance in DGF is associated with worse outcomes and may need closefollow-up and monitoring to improve the outcomes.

The Utility of Donor-specific Antibody Monitoring and the Role of Kidney Biopsy in Simultaneous Liver and Kidney Recipients With De Novo Donor-specific Antibodies.

BACKGROUND: There is limited information about the utility of donor-specific antibody (DSA) against HLA monitoring and the role of protocol kidney biopsy for de novo DSA (dnDSA) in simultaneous liver and kidney (SLK) transplant recipients. METHODS: We analyzed SLK transplant recipients transplanted between January 2005 and December 2017, who had DSA checked posttransplant. Patients were divided into 2 groups based on whether they developed dnDSA posttransplant (dnDSA+) or not (dnDSA-). Kidney graft rejection ±45 d of dnDSA and a kidney death-censored graft survival were the primary endpoints. RESULTS: A total of 83 SLK transplant recipients fulfilled our selection criteria. Of those, 23 were dnDSA+ and 60 were dnDSA-. Twenty-two of 23 dnDSA+ patients had DSA against class II HLA, predominantly against DQ. Fifteen recipients underwent kidney biopsy ±45 d of dnDSA. Six of these were clinically indicated due to kidney graft dysfunction. The other 9 had a protocol kidney biopsy only due to dnDSA, and 6 of these 9 had a rejection. Also, 3 recipients had sequential biopsies of both the kidney and liver grafts. Among those with sequential biopsies of both grafts, there was a difference between the organs in the rate and types of rejections. At last follow up, dnDSA was not associated with graft failure of either the kidney or liver. CONCLUSIONS: Although our study was limited by a small sample size, it suggests the potential utility of DSA monitoring and protocol kidney biopsy for dnDSA.

A Single-Center Assessment of Delayed Graft Function in Recipients of Simultaneous Liver and Kidney Transplant.

BACKGROUND: The effects of delayed graft function on long-term kidney allograft outcomes are poorly defined among simultaneous liver and kidney transplant recipients. METHODS: We analyzed data of all simultaneous liver and kidney recipients transplanted at the University of Wisconsin between 2010 and 2017. Risk factors for the development of delayed graft function, kidney graft failure, and patient mortality were outcomes of interest. RESULTS: There were a total of 60 simultaneous liver and kidney recipients; 28 (47%) had delayed graft function. After adjustment for multiple variables, we found that pretransplant dialysis >6 weeks (hazard ratio [HR] = 5.6, 95% CI: 1.23-25.59, P = .02), pretransplant albumin <3 g/dL (HR = 5.75, 95% CI: 1.76-16.94, P = .003), and presence of pretransplant diabetes (HR = 2.5, 95% CI: 0.97-4.77, P = .05) were significantly associated with delayed graft function. Multivariate analysis showed that pretransplant albumin <3 (HR = 4.86, 95% CI: 1.07-22.02, P = .02) was associated with a higher risk of all-cause kidney allograft failure, whereas the duration of delayed graft function (HR = 1.07 per day, 95% CI: 1.01-1.14, P = .01) was associated with a higher risk of death-censored kidney allograft failure. The presence of delayed graft function was not associated with all-cause or death-censored kidney or liver allograft failure. Similarly, the presence of delayed graft function was not associated with patient mortality. CONCLUSION: The incidence of delayed graft function was high in simultaneous liver and kidney recipients. However, with appropriate management, delayed graft function may not have a negative impact on patient or kidney allograft survival.

Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression.

BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Blessing and a curse of outpatient management of delayed graft function.

Delayed graft function (DGF) is a common complication occurring most often after deceased donor kidney transplant with several donor characteristics as well as immunologic factors that lead to its development post-transplant. These patients require dialysis and close kidney function monitoring until sufficient allograft function is achieved. This has resulted in limited options for DGF management, either prolonged hospitalization until graft function improves to the point where dialysis is no longer needed or discharge back to their home dialysis unit with periodic follow up in the transplant clinic. DGF is associated with a higher risk for acute rejection, premature graft failure, and 30-d readmission; therefore, these patients need close monitoring, immunosuppression management, and prompt allograft biopsy if prolonged DGF is observed. This may not occur if these patients are discharged back to their home dialysis unit. To address this issue, the University of Wisconsin-Madison created a clinic in 2011 specialized in outpatient DGF management. This clinic was able to successfully reduce hospital length of stay without an increase in 30-d readmission, graft loss, and patient death.

Donor-Specific Antibodies in the Absence of Rejection Are Not a Risk Factor for Allograft Failure.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Subclinical Antibody-mediated Rejection After Kidney Transplantation: Treatment Outcomes.

BACKGROUND: Antibody-mediated rejection (AMR) is a leading cause of morbidity and mortality after kidney transplantation. Early diagnosis and treatment of subclinical AMR based on the donor-specific antibody (DSA) testing may result in better outcomes. METHODS: We tested this hypothesis in 220 kidney transplant recipients who underwent an indication or DSA-based surveillance protocol biopsies between March 1, 2013 and December 31, 2016. Patients were divided into 3 groups: clinical AMR (n = 118), subclinical AMR (n = 25), or no rejection on protocol biopsy (controls; n = 77). RESULTS: Both clinical and subclinical AMR groups underwent similar treatment including plasmapheresis, pulse steroids, IVIG, and rituximab (P = ns). Mean follow-up after AMR was 29.5 ± 16.8 months. There were 2 (3%), 2 (8%), and 54 (46%) death-censored graft failures in the control, subclinical, and clinical AMR groups, respectively (P < 0.001). Graft outcomes were similar in the subclinical rejection and control groups. In adjusted Cox regression analysis, only clinical rejection (hazards ratio [HR], 4.31; 95% confidence interval [CI], 1.01-18.94; P = 0.05) and sum chronicity scores (HR, 1.16; 95% CI, 1.01-1.35; P = 0.03) were associated with increased risk of graft failure, while estimated glomerular filtration rate at time of biopsy (HR, 0.98; 95% CI, 0.96-0.99; P = 0.01) was associated with decreased risk of graft failure. CONCLUSIONS: Our study suggests that early diagnosis and treatment of subclinical AMR using DSA monitoring may improve outcomes after kidney transplantation.