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Background: Allograft biopsies with lesions of Antibody-Mediated Rejection (ABMR) with Microvascular Inflammation (MVI) have shown heterogeneous etiologies and outcomes., Methods: To examine factors associated with outcomes in biopsies that meet histologic ABMR criteria, we retrospectively evaluated for-cause biopsies at our center between 2011 and 2017. We included biopsies that met the diagnosis of ABMR by histology, along with simultaneous evaluation for anti-Human Leukocyte Antigen (HLA) donor-specific antibodies (DSA). We evaluated death-censored graft loss (DCGL) and used a principal component analysis (PCA) approach to identify key predictors of outcomes., Results: Out of the histologic ABMR cohort (n = 118), 70 were DSA-positive ABMR, while 48 had no DSA. DSA(+)ABMR were younger and more often female recipients. DSA(+)ABMR occurred significantly later post-transplant than DSA(-)ABMR suggesting time-dependence. DSA(+)ABMR had higher inflammatory scores (i,t), chronicity scores (ci, ct) and tended to have higher MVI scores. Immunodominance of DQ-DSA in DSA(+)ABMR was associated with higher i+t scores. Clinical/histologic factors significantly associated with DCGL after biopsy were inputted into the PCA. Principal component-1 (PC-1), which contributed 34.8% of the variance, significantly correlated with time from transplantation to biopsy, ci/ct scores and DCGL. In the PCA analyses, i, t scores, DQ-DSA, and creatinine at biopsy retained significant correlations with GL-associated PCs., Conclusions: Time from transplantation to biopsy plays a major role in the prognosis of biopsies with histologic ABMR and MVI, likely due to ongoing chronic allograft injury over time., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

An unprecedented global pandemic caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has quickly overwhelmed the health care systems worldwide. While there is an absence of consensus among the community in how to manage solid organ transplant recipients and donors, a platform provided by the American Society of Transplantation online community "Outstanding Questions in Transplantation," hosted a collaborative multicenter, multinational discussions to share knowledge in a rapidly evolving global situation. Here, we present a summary of the discussion in addition to the latest published literature., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

The advent of direct-acting antivirals (DAAs) has provided the impetus to transplant kidneys from hepatitis C virus-positive donors into uninfected recipients (D+/R-). Thirty D+/R- patients received DAA treatment. Sustained virologic response (SVR12) was defined as an undetectable viral load in 12 weeks after treatment. An age-matched cohort of uninfected donor and recipient pairs (D-/R-) transplanted during same time period was used for comparison. The median day of viral detection was postoperative day (POD) 2. The detection of viremia in D+/R- patients was 100%. The initial median viral load was 531 copies/μL (range: 10-1 × 10 8 copies/μL) with a median peak viral load of 3.4 × 10 5 copies/μL (range: 804-1.0 × 10 8 copies/μL). DAAs were initiated on median POD 9 (range: 5-41 days). All 30 patients had confirmed SVR12. During a median follow-up of 10 months, patient and graft survival was 100%, and acute rejection was 6.6% with no major adverse events related to DAA treatment. Delayed graft function was significantly decreased in D+/R- patients as compared to the age-matched cohort (27% vs 60%; P = .01). D+/R- transplantation offers patients an alternative strategy to increase access., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We investigated clinical outcomes and molecular signatures of transplant glomerulopathy (TG) stratified by microvascular inflammation (MVI) and donor-specific antibody (DSA) status., Methods: We performed a retrospective review of 749 kidney transplant patients who received a for-cause kidney biopsy from 2009 to 2014. We classified TG as MVI positive (MVI+) or MVI negative (MVI-), and with or without DSA. We obtained gene expression profiles for 44 biopsies by Affymetrix HuGene 1.0 ST expression arrays., Results: A total of 100 patients had TG; 49 were MVI+, and 51 were MVI-. After a median post-biopsy follow-up of 2.08 years (range 0.43-4.59), Kaplan-Meier survival analysis demonstrated worse allograft survival in MVI+ TG patients compared with MVI- TG patients (P = 0.01), and time to graft failure was significantly shorter in MVI+ patients (1.08 ± 1.01 years vs 2.3 ± 1.8 years; P = 0.002). DSA status did not affect graft survival within MVI+ or MVI- groups. Analysis of pathogenesis-based transcripts (PBT) showed that MVI+ TG biopsies had increased expression of gamma interferon and rejection (GRIT) and DSA-associated transcripts (DSAST), as observed in antibody-mediated rejection. MVI- TG biopsies had increased expression of cytotoxic and regulatory T cell- and B cell-associated transcripts but not GRIT or DSAST. DSA status had no effect on expression of any PBTs studied in MVI- TG biopsies., Conclusions: Graft survival in TG is significantly worse in the presence of MVI. Gene expression profiles of MVI+ TG resemble antibody-mediated rejection while gene expression profiles of MVI- TG resemble cell-mediated rejection regardless of DSA status., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The benefits of kidney transplantation in diabetic patients with peripheral vascular disease (PVD) are unclear. While patients may have improved survival compared to dialysis, the burden of care after transplant has not been assessed., Methods: We performed a retrospective review of adult diabetic kidney-only transplant recipients with and without PVD transplanted from January 2012 until June 30, 2015., Results: Of 203 diabetic kidney transplant recipients, 56 (27.6%) had PVD and 147 (72.4%) had no PVD. At a median of 3.14 years follow-up, there were no significant differences in 30-, 90-, or 1-year readmission rates. At 1 year after transplant, PVD patients were significantly more likely to have a greater sum of unplanned inpatient days (44.6% vs 27.9% with ≥10 inpatient days, P = .03) and at least 1 reoperation (28.6% vs. 8.7%, P < .01). At 1 year post-transplant, there were similar rates of graft-related reoperations; however, patients with PVD had significantly increased rates of non-graft-related operations of which 31.2% were PVD-related., Conclusions: Diabetic patients with PVD utilize more resources after kidney transplant, spending more time in the hospital and undergoing more post-transplant operations. The causes of readmission are predominantly related to progression of PVD rather than allograft complications., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We analyze our outcomes utilizing imported allografts as a strategy to shorten wait list time for pancreas transplantation., Methods: This is an observational retrospective cohort of 26 recipients who received either a locally procured (n = 16) or an imported pancreas graft (n = 10) at our center between January 2014 and May 2017. Wait list times of this cohort were compared to UNOS Region 9 (New York State and Western Vermont). Hospital financial data were also reviewed to analyze the cost-effectiveness of this strategy., Results: Imported pancreas grafts had significantly increased cold ischemia times (CIT) and peak lipase (PL) levels compared to locally procured grafts (CIT 827 vs 497 minutes; P = .001, PL 563 vs 157 u/L; P = .023, respectively). There were no differences in graft or patient survival. The median wait time was significantly lower for simultaneous kidney-pancreas transplants at our center (518 days, n = 21) compared to Region 9 (1001 days, n = 65) P = .038. Despite financial concerns, the cost of transport for imported grafts was offset by lower standard acquisition costs., Conclusions: Imported pancreas grafts may be a cost-effective strategy to increase organ utilization and shorten wait times in regions with longer waiting times., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We aimed to examine the clinical outcomes of sensitized pregnant kidney transplant recipients., Methods: A retrospective cohort study of female patients who received kidney transplant at Montefiore transplant center between June 1, 2009 through December 31, 2014 and had a documented pregnancy in our system., Results: We found that 11 women had pregnancies during this period with a median age of 36 yr (range 22, 39). Pregnancies occurred at a median of 3.1 yr (1.1, 8.7) after transplantation. Pre-pregnancy patients' median serum creatinine levels and spot urine protein/creatinine ratio were 1.1 mg/dL (1.1, 2.1) and 0.55 g/d (0, 1.2), respectively. Eight patients were sensitized with panel reactive antibody (PRA) levels > 0% and three had PRA of 0%. The sensitized group had a higher incidence of adverse pregnancy outcomes; one stillbirth and two second trimester miscarriage. During a median follow-up of 2.3 yr (1.2, 4) after delivery, three high PRA patients (37%) developed antibody-mediated rejection that led to graft loss., Conclusions: We observed an increased risk of rejection, graft loss, and adverse pregnancy outcomes in sensitized kidney recipients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Severe systemic hypertension (HTN) is a risk factor for perioperative cardiovascular complications; however, its impact at the time of kidney transplantation (KTX) is not well defined., Methods: A retrospective cohort study of adult kidney-only transplant recipients between October 2009 and December 2012 was performed to examine outcomes between patients with (n = 111) and without (n = 98) severe preoperative HTN defined as SBP > 180 or DBP > 110 mmHg., Results: Recipients with severe HTN were older (56.7 ± 13.0 vs. 53.5 ± 12.4 yr, p = 0.07) and significantly more likely to receive an expanded criteria donor kidney (32.7% vs. 12.2%, p = 0.02). No patients developed hypertensive crisis, intracranial hemorrhage, or life threatening ventricular arrhythmias within 30 d post-transplantation; however, three patients with severe HTN had cardiac events: two with demand ischemia and one with decompensate heart failure. Two patients in the control group had decompensated heart failure. There were no differences between the groups in terms of cardiac event (2.7% vs. 2.0%, p = 0.75), one-yr patient survival (98.2% vs. 98.0%, p = 0.90) or graft survival (90.1% vs. 92.9%, p = 0.48), nadir creatinine > 2 mg/dL (4.6% vs. 6.2%, p = 0.62), length of stay > 6 d (37.8% vs. 35.7%, p = 0.75), and DGF (52.3% vs. 63.3%, p = 0.11)., Conclusions: Our results suggest that severe preoperative HTN should not be considered an absolute contraindication to kidney transplant in patients who are otherwise clinically stable., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: It is estimated that approximately 50% of males over 50 have benign prostatic hypertrophy (BPH). BPH is underappreciated in anuric patients with end stage renal disease, and failure of diagnosis in this population can lead to complications after kidney transplantation., Methods: A single-center retrospective review of male patients over 50 yr of age transplanted from January 1, 2010, until September 30, 2013, was performed. Outcomes assessed were as follows: graft survival, urinary retention, discharge with Foley catheter, and urinary tract infection (UTI)., Results: Of 147 patients, 17.0% were diagnosed with BPH before transplant, 19.0% received a BPH diagnosis after transplant, and 64% did not have BPH. Compared to those without BPH, a post-transplant BPH diagnosis was associated with urinary retention during the transplant admission (0% vs. 46.4%, p < 0.01), discharge with Foley catheter (0% vs. 21.4%, p < 0.01), readmission related to urinary retention (0% vs. 46.4%, p < 0.01), and UTI (18.0% vs. 64.3%, p < 0.01). Patients with prior diagnosis of BPH and on therapy had similar outcomes to those without BPH., Conclusions: Following kidney transplant, urinary tract complications are more common in patients with BPH; however, being on medical therapy prior to transplantation diminishes the incidence of these complications significantly., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Limited data exist on the effect of intravenous immunoglobulin (IVIg) on anti-HLA antibodies as determined by solid-phase assays. We reviewed our experience treating sensitized wait-listed kidney transplant recipients with IVIg as a method for desensitization and report our results utilizing Luminex single antigen (LSA) bead assay to quantify antibody reactivity (MFI). Fifteen patients with a cPRA > 40% received 2 g/kg IVIg per month for four months or until transplanted. LSA testing was performed before and after IVIg. Median MFI for anti-class I antibodies fell in 11 (73%) and increased in 4 (27%) patients after IVIg. Similar significant changes in MFI for anti-class II antibodies were observed in 10 patients (66%). Administration of IVIg was associated with a modest decrease in reactivity to both class I and II HLA antigens (median MFI change 493 and 1110, respectively; p < 0.0001) but did not significantly alter mean cPRA (85% before IVIg vs. 80% after IVIg; p = 0.1). Our data suggest a smaller effect of IVIg on HLA antibody reactivity than previously described, leading us to question how best to measure the efficacy of a desensitization protocol in current practice., (© 2012 John Wiley & Sons A/S.)

Introduction: The aim of this study is to investigate the prevalence, predictors, and clinical outcomes of acute antibody-mediated rejection (AAMR)., Methods: Retrospective analysis of 833 adult patients who received kidney transplantation between 1/1/2001 and 8/15/2007., Results: The prevalence of AAMR and acute cellular rejection was 2% and 8.2%, respectively. Eight patients had type I, seven type II, and two type III AAMR. All patients had at least one strong donor-specific anti-HLA antibodies (DSA) with a median fluorescence intensity (MFI) value of over 6000 and the mean number of strong DSAs was 2.0 +/- 0.7. Fifteen of 17 patients received pre-transplant desensitization treatment. During a median 28 months of follow-up (range: 12-38 months), two patients died (88% patient survival), and nine lost their allografts (35% graft survival). While all type I AAMR patients responded to treatment, all type III patients, and four of seven patients with type II AAMR lost their allografts earlier, and three type II AAMR patients later due to transplant glomerulopathy., Conclusions: AAMR is mainly seen in patients with pre-transplant strong DSAs. There is a striking difference in clinical outcomes of AAMR that types II and III AAMR patients have poor prognosis compared to type I AAMR patients.

Background: Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C(2)) has been shown to be the most reliable, single-point surrogate marker for AUC. The objective of this study was to measure renal function beyond month 2 post-transplant using two different C(2) maintenance targets in combination with enteric-coated mycophenolate sodium (EC-MPS), corticosteroids, and basiliximab induction., Methods: In this open-label, multicenter trial, renal transplant recipients entered one of two randomized groups at day 61 post-transplant: group A (higher-C(2) range) or group B (lower-C(2) range)., Results: Patients (164) were recruited, and 141 patients were entered the randomized groups (group A, n = 66; group B, n = 75). At 12 months, the mean calculated creatinine clearance was significantly greater in group B than in group A (79.2 vs. 71.0 mL/min, p < 0.05). Biopsy-proven acute rejection occurred in 14.7% patients in group B and in 24.2% patients in group A (n.s.). During the 12-month trial, 17.7% patients discontinued EC-MPS because of adverse events. Group B (44.0%) had fewer serious adverse events when compared with group A (62.1%; p = 0.04). Overall patient and graft survival were 99.4% and 95.7% respectively. Among 99 high-risk patients (i.e., African-American race, previous transplant, PRA >35% or >4 HLA mismatches), mean creatinine clearance at 12 months was 65.6 mL/min and biopsy-proven rejection occurred in 20.2% patients., Conclusions: Low cyclosporine C(2) levels are associated with improved renal function compared with higher C(2) levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C(2) levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.

Hepatitis B virus core antibody (HBcAb) or surface antigen (HBsAg)-positive organ donors have the potential to transmit infection to transplant recipients. We investigated the safety of using HBcAb(+) or HBsAg(+) donors in kidney or pancreas transplant recipients with 1 yr lamivudine prophylaxis. While HBsAb(-) recipients of HBcAb(+) donors received prophylaxis, HBsAb(+) recipients did not. HBsAg(+) organs were only used in patients who were both HBcAb and HBsAb(+). Forty-six patients received HBcAb(+) and four received HBsAg(+) organs (47 kidney, two pancreas, and one kidney/pancreas). All but one recipient were HBsAg(-), 25 were HBsAb(+), and 19 HBcAb(+). During a median 36 months of follow-up (range 6-66 months), with 43 of a total 50 patients having at least 1 yr follow-up and were off lamivudine, and none of the patients developed hepatitis B viremia or seroconversion to HBsAg or HBsAb(+). These results suggest that HBcAb(+) or HBsAg(+) organs can be used safely in selected recipients with lamivudine prophylaxis without requiring hepatitis B immunglobulin.

The effects of rapid steroid withdrawal (SW) on kidney transplantation (KT) outcome were investigated in 12 HCV+ patients in a prospective cohort study. These results were compared with 17 HCV+ patients who received KT in the prior 2 yr and treated with a standard prednisone taper protocol. SW patients received only 6 d of steroid treatment after transplantation. Eleven received Thymoglobulin and one Basiliximab induction treatment along with a calcineurin inhibitor and mycophenolate mofetil. Patient and graft survival was 92% in SW group (median follow-up 12 months, range 6-17), and 92 and 82% in the historic control group respectively (median follow-up 21 months, range 11-27). In the SW and control group, acute rejection rates were 9 and 18%, and mean creatinine levels at last follow-up 1.30 +/- 0.36 and 1.68 +/- 0.58 mg/dL respectively. Only two SW patients had an increase in liver function tests during follow-up (18%), compared with six patients in the control group (43%). This study demonstrates that rapid SW is safe for HCV+ KT recipients, without an increase in acute rejection episodes or liver function abnormalities in the short term.

Background: Acute renal failure (ARF) occurs in 5-50% of patients undergoing orthotopic liver transplantation (OLT). The aim of this study was to determine factors that might predict the development of end stage renal disease (ESRD) in patients who had ARF after OLT., Methods: We studied all OLT recipients between 9/1/1988 through 12/31/2000., Results: A total of 1602 patients underwent OLT during the study period. About 350 patients (22%) developed ARF requiring dialysis post-operatively. One hundred and twenty-three (39.8%) died within a year after OLT. Median follow up was 5.8 yr (range 1-12 yr). Forty-three patients (23%) developed ESRD over median of 3.79 yr (range 1-8 yr). Multivariate logistic regression analysis revealed creatinine levels > 1.7 mg/dL at 1 yr (p < 0.001), cyclosporine as immunosuppression (p = 0.026), and the presence of diabetes pre-OLT (p < 0.001) to be associated with the development of ESRD. The development of ESRD did not decrease patient survival (p = 0.111). ESRD patients who received subsequent kidney transplantation had significantly improved survival rates (p = 0.005)., Conclusions: Serum creatinine levels at 1 yr, cyclosporine as immunosuppression, and the presence of diabetes pre-OLT are independent predictive factors for the development of ESRD. ESRD patients who received kidney transplantation had higher 10-yr survival rates when compared with patients maintained on dialysis.