The Independent Effects of Kidney Length and Vascular Plaque on Ten-Year Outcomes of Extended Criteria Donor Kidney Transplants.

The independent effects of deceased donor kidney length and vascular plaque on long-term graft survival are not established. Utilizing DonorNet attachments from 4,480 expanded criteria donors (ECD) recovered between 2008 and 2012 in the United States with at least one kidney biopsied and transplanted, we analyzed the relationship between kidney length and vascular plaques and 10-year hazard of all-cause graft failure (ACGF) using causal inference methods in a Cox regression framework. The composite plaque score (range 0-4) and the presence of any plaque (yes, no) was also analyzed. Kidney length was modeled both categorically (<10, 10-12, >12 cm) as well as numerically, using a restricted cubic spline to capture nonlinearity. Effects of a novel composite plaque score 4 vs. 0 (HR 1.08; 95% CI: 0.96, 1.23) and the presence of any vascular plaque (HR 1.08; 95% CI: 0.98, 1.20) were attenuated after adjustment. Likewise, we identified a potential nonlinear relationship between kidney length and the 10-year hazard of ACGF, however the strength of the relationship was attenuated after adjusting for other donor factors. The independent effects of vascular plaque and kidney length on long-term ECD graft survival were found to be minimal and should not play a significant role in utilization.

The Independent Effects of Procurement Biopsy Findings on 10-Year Outcomes of Extended Criteria Donor Kidney Transplants.

Introduction: The role of procurement biopsies in deceased donor kidney evaluation is debated in light of uncertainty about the influence of biopsy findings on recipient outcomes. The literature is filled with conflicting and ambiguous findings typically derived from small studies focused on short-term outcomes or reliant on biopsies prepared by methods impractical in the time-sensitive context of organ procurement. Methods: After manual data entry of DonorNet attachments from 4480 extended criteria donors (ECDs) recovered in the United States from 2008 to 2012, we applied causal inference methods in a Cox regression framework to estimate independent effects of glomerulosclerosis (GS), interstitial fibrosis, and vascular changes on long-term kidney graft survival. Kidney discard rates from 2018 to 2019 were evaluated to characterize contemporary kidney utilization patterns. Results: Effects of interstitial fibrosis and vascular changes were largely attenuated after adjusting for potentially confounding donor and recipient variables, although conclusions are less certain for severe levels due to smaller sample sizes. By contrast, significant effects of GS (>10% vs. 0%-5%) persisted even after adjustment (all-cause, hazard ratio [HR] 1.18; 95% CI 1.06, 1.28; death-censored, HR 1.28; 95% CI 1.08, 1.46) but plateaued beyond 10%. By contrast, kidney discard rates increased precipitously as GS rose >10%. Conclusion: Despite being obtained under less than ideal conditions, estimated GS from a procurement biopsy is independently associated with long-term graft survival, above and beyond standard clinical parameters, in ECD transplants. However, the disproportionately high likelihood of discard for kidneys with GS >10% is unjustified. The outsized effect of GS on kidney utilization should be tempered and commensurate with its effect on outcomes.

Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies.

BACKGROUND: Circulating donor-derived cell-free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The molecular microscope diagnostic system (MMDx) tissue gene expression platform may provide increased precision to traditional histology. METHODS: In this single-center prospective study of 208 biopsies (median = 5.8 mo) posttransplant, we report on the calibration of cfDNA with simultaneous biopsy assessments using MMDx and histology by area under the curve (AUC) analyses for optimal criterion, as well as for, previously published cfDNA cutoffs ≤ 0.21% to "rule-out" rejection and ≥1% to "rule-in" rejection. RESULTS: There were significant discrepancies between histology and MMDx, with MMDx identifying more antibody-mediated rejection (65; 31%) than histology (43; 21%); the opposite was true for T cell-mediated rejection [TCMR; histology: 27 (13%) versus MMDx: 13 (6%)]. Most of the TCMR discrepancies were seen for histologic borderline/1A TCMR. AUC for cfDNA and prediction of rejection were slightly better with MMDx (AUC = 0.80; 95% CI: 0.74-0.86) versus histology (AUC = 0.75; 95% CI: 0.69-0.81). A cfDNA ≤ 0.21% had similar sensitivity (~91%) to "rule-out" rejection by histology and MMDx. Specificity was slightly higher with MMDx (92%) compared with histology (85%) to "rule-in" rejection using cfDNA criterion ≥1%. Strong positive quantitative correlations were observed between cfDNA scores and molecular acute kidney injury for both "rejection" and "nonrejection" biopsies. CONCLUSIONS: Molecular diagnostics using tissue gene expression and blood-based donor-derived cell-free DNA may add precision to some cases of traditional histology. The positive correlation of cfDNA with molecular acute kidney injury suggests a dose-dependent association with tissue injury irrespective of rejection characteristics.

Outcomes of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants.

Trials describing 4- to 12-week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R- transplants) may be limited in "real-world" application by costs and delayed access to DAAs. We previously reported HCV transmission of 13% among D+/R- transplants with 2- to 4-day pangenotypic sofosbuvir/velpatasvir (SOF/VEL) perioperative prophylaxis, where one patient with HCV transmission was a nonresponder to first-line full-course DAA. Here, we report new data with a 7-day prophylaxis protocol (N = 50), as well as cumulative treatment and outcome data on all HCV D+/R- transplants (N = 102). Overall, nine patients (9/102; 9%; 95% CI: 5%-16%) developed HCV transmission, with a significant decline noted in the 7-day group (2/50; 4%; 95% CI: 0%-13%) compared with 2- to 4-day prophylaxis (7/52; 13%; 95% CI: 5%-25%). All patients with HCV transmission achieved sustained virologic response post full-course therapy (including one nonresponder from initial trial). A 1:1 matched analysis (N = 102) with contemporary HCV D-/R- transplants (controls) showed that although the pretransplant wait time was significantly shorter for D+/R- compared with D-/R- (mean: 1.8 vs. 4.4 years; p < .001), there were no differences in infections, rejection, development of de novo donor-specific antibody, or transplant outcomes up to 6 months of transplant.

Impact of Belatacept Conversion on Renal Function, Histology, and Gene Expression in Kidney Transplant Patients With Chronic Active Antibody-mediated Rejection.

BACKGROUND: Here, we present our initial experience with a prospective protocol of belatacept conversion in patients with chronic active antibody-mediated rejection (caAMR) and a high degree of chronicity at the time of diagnosis. METHODS: We converted 19 patients (mean age, 45 ± 12 y) with biopsy-proven caAMR from tacrolimus to belatacept at a median of 44 months post-kidney transplant. RESULTS: At a median of 29 months (interquartile range, 16-46 mo) postconversion, death-censored graft and patient survivals were 89% and 95%, respectively. When compared to a 1:2 propensity-matched control cohort from the INSERM U970 registry maintained on calcineurin inhibitor, the belatacept group had progressive improvement (P = 0.02) in estimated glomerular filtration rate from a mean of 33.9 ± 10 at baseline to 37.8 ± 13 at 6 months and 38.5 ± 12 mL/min/1.73 m2 at 12 months postconversion, as compared to a steady decline noted in the controls (36.2 [baseline] → 33.1 [6 mo] → 32.7 mL/min/1.73 m2 [12 mo] of follow-up). A paired histologic comparison of preconversion and postconversion (performed at median 9.5 mo postconversion) biopsies showed no worsening in microvascular inflammation or chronicity. The paired tissue gene expression analysis showed improved mean total rejection score (0.68 ± 0.26-0.56 ± 0.33; P = 0.02) and a trend toward improved antibody-mediated rejection score (0.64 ± 0.34-0.56 ± 0.39; P = 0.06). CONCLUSIONS: Here, we report that in patients diagnosed with caAMR who were not subjected to intensive salvage immunosuppressive therapies, isolated belatacept conversion alone was associated with stabilization in renal function. These results are bolstered by molecular evidence of improved inflammation.

Coronavirus Disease 2019 Viremia, Serologies, and Clinical Course in a Case Series of Transplant Recipients.

Here we report a single-center cohort of 6 patients (4 kidney only, and 2 simultaneous liver/kidney transplants) diagnosed with COVID-19 at a median of 1.9 years (range = 0.2-9.3 years) post transplant. Five (of 6) patients required inpatient admission, 2 patients (mortality = 33%) died. Among those with mortality, an increased concentration of inflammatory biomarkers (interleukin-6 and C-reactive protein) was noted with a lack of response to interleukin-6 blockade, remdesivir, and/or convalescent plasma. None of the kidney-only transplants (4/6; 67%) had elevation in plasma donor-derived cell-free DNA above the previously published cut-off of 1%, suggesting absence of significant allo-immune injury. Four (of 5) admitted patients had detectable SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) in blood on samples obtained at/during hospitalization. Of the 4 discharged patients, 2 patients with undetectable virus on repeat nasopharyngeal swabs had seroconversion with positive SARS-CoV-2 IgG formation at 30 to 48 days post infection. One patient had prolonged shedding of virus on nasopharyngeal swab at 28 days post discharge despite lack of symptoms. In this preliminary report, we find that immunocompromised transplant patients had higher rates of RNAemia (67%) than reported in the general population (15%), seeming absence of allo-immune injury despite systemic inflammation, and formation of IgG overtime after recovery from infection.

Impact of belatacept conversion on kidney transplant function, histology, and gene expression - a single-center study.

Prior studies on belatacept conversion from calcineurin inhibitor (CNI) have been limited by an absence of postconversion surveillance biopsies that could underestimate subclinical rejection, or a case-controlled design. A total of 53 adult patients with allograft dysfunction underwent belatacept conversion (median: 6 months) post-transplant. At a median follow-up = 2.5 years, patient survival was 94% with a death-censored graft survival of 85%. Seven (13%) patients had acute rejection (including 3 subclinical) at median 6 months postconversion. Overall, eGFR improved (P = <0.001) from baseline = 31±15 to 40.2 ± 17.6 ml/min/1.73m2 by 6 months postconversion, but then stayed stable. This improvement was also observed (P < 0.001) in comparison with a propensity matched control cohort on CNI, where eGFR stayed stable (mean ~ 32ml/min/1.72m2 ) over 2-year follow-up. Patients converted < 6 months post-transplant were more likely to have a long-term improvement in kidney function. Paired gene expression analysis of 30 (of 53) consecutive pre- and postconversion surveillance biopsies did not reveal changes in inflammation/acute injury; although atrophy-fibrosis score worsened (mean = 0.28 to 0.44; P = 0.005). Thus, improvement in renal function with belatacept conversion occurred early and then sustained in comparison with controls where renal function remained unchanged overtime. We were unable to show molecular signals that could be related to CNI administration and regressed after withdrawal.

Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case Series.

Background: Traditional therapies for caAbMR have unclear efficacy with significant side effects in recipients of kidney transplants (KTs). A recent single-center case series suggested tocilizumab (TCZ) could stabilize renal function and improve microvascular inflammation. Here we report our findings of the use of TCZ in patients with caAbMR. Methods: Ten adult recipients of KTs with biopsy-proven caAbMR were treated with TCZ at 8 mg/kg per month. Patients were monitored for adverse events, and therapy was interrupted in the setting of serious infections. Six patients (60%) underwent post-treatment biopsies. Results: Patients (mean age of 43 years) were initiated on TCZ at a median of 36 months post-KT. A majority of patients were black (70%), underwent regrafts (40%), and were sensitized (mean cPRA=41%). Patients received a median of six doses of TCZ (range=3-10). At a median follow-up of 12 months (range=8-24 months), renal function did not show improvement (mean eGFR, 42±18 ml/min per 1.73 m2 to 37±24 ml/min per 1.73 m2; P=0.27). The slope of decline in eGFR remained unchanged (-0.14±0.9 to -0.33±1.1; P=0.25). There was no improvement in mean MVI (g+ptc) (4.8±1.4 to 4.2±2.0; P=0.39) scores or Molecular Microscope Diagnostic System (MMDx) AbMR scores (0.79±0.17 to 0.78±0.26; P=0.86). There was a numeric worsening of chronicity (ci+ct) scores (2.5±0.8 to 3.3±1.7; P=0.38) and MMDx atrophy fibrosis scores (0.36±0.24 to 0.58±0.15; P=0.21). Patient survival was 90%, with one patient death due to complications from a hip infection. Overall death-censored graft survival was 80%, with two graft losses in patients who had recurrent infections requiring hospitalization. Conclusions: In this early experience, we report a lack of efficacy and toxicity with the use of TCZ for caAbMR. Prospective clinical trials are needed to clarify the role of IL-6 blockade and the possibility of increased incidence of infections in patients with caAbMR who are treated with TCZ.

Impact of Induction Immunosuppression Strategies in Simultaneous Liver/Kidney Transplantation.

BACKGROUND: There is scant data on the use of induction immunosuppression for simultaneous liver/kidney transplantation (SLKT). METHODS: We analyzed the Organ Procurement and Transplant Network registry from 1996 to 2016 to compare outcomes of SLKT, based on induction immunosuppression. RESULTS: Of 5172 patients, 941 (18%) received T-cell depletion induction, 1635 (32%) received interleukin 2 receptor antagonist (IL2-RA), and 2596 (50%) received no induction (NI). At 5 years, patient survivals were 68% in the T-cell group, 74% in the IL2-RA group, and 71% in the NI group (P = 0.0006). Five-year liver and kidney allograft survivals were 67% and 64% in the T-cell group, 73% and 70% in the IL2-RA group, and 70% and 68% in the NI group (P = 0.001 and 0.003), respectively. On multivariate analysis, the type of induction had no impact on patient or allograft survival. Maintenance steroids and calcineurin inhibitors (CNIs) at discharge were associated with improved patient and graft survival (steroids: patient survival hazard ratio [HR] 0.37 [0.27-0.52], liver survival HR 0.43 [0.31-0.59], kidney survival HR 0.46 [0.34-0.63]; P < 0.0001, CNI: patient survival HR 0.3 [0.21-0.43], liver survival HR 0.3 [0.2-0.44], kidney survival HR 0.4 [0.26-0.59]; P < 0.0001). CNI maintenance in patients who received T-cell induction was associated with decreased patient, liver, and kidney allograft survivals (respective HR: 1.4 [1.1, 1.8]; 1.5 [1.1, 1.9]; 1.3 [1.08, 1.7]; P < 0.05) CONCLUSION.: Induction immunosuppression had no impact on patient and allograft survival in SLKT, while maintenance steroids and CNI were associated with improved patient and graft survivals. Given the inherent limitations of a registry analysis, these findings should be interpreted with caution.

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients.

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R - transplants.

Young donors with severe acute kidney injury offer an opportunity to expand the donor pool.

BACKGROUND: This study assessed our experience transplanting kidneys from young donors with severe acute kidney injury. METHODS: We performed a single center retrospective analysis of 315 kidney transplants between 1/1/2014-12/31/2016. Donor kidneys were classified according to the Acute Kidney Injury Network (AKIN) criteria. A case-matched cohort was created using recipient age, history of diabetes, donor specific antibody, donor age and donor after cardiac death. Primary endpoints were graft function measured by eGFR at 90 days and at 1-year. RESULTS: Stage 3 AKIN recipients had significantly greater eGFR at one year (63.9 ml/min v. 51.2 ml/min, p < 0.001) compared to those with Stage 0 AKIN. This difference was abrogated when compared to a case matched cohort (eGFR at 90 days or 1 year; p > 0.05). Donor and recipient characteristics on eGFR at 1 year were analyzed using linear and logistic regression. Only donor age had a significant impact on recipient eGFR. CONCLUSIONS: Donor kidneys with severe acute injury can achieve optimal 1-year outcomes. Donor age is the most significant predictor of eGFR >45 ml/min after transplant.

Hospital readmissions in diabetic kidney transplant recipients with peripheral vascular disease.

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.

Improving pancreas graft utilization through importation.

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.

Safety and Efficacy of Treatment of Hepatitis C in Kidney Transplant Recipients With Directly Acting Antiviral Agents.

BACKGROUND: With the development of all oral, interferon-free directly acting antiviral (DAA) medications, treatment of hepatitis C virus (HCV) infection in renal transplant recipients is possible, but limited data exists on its safety and efficacy. METHODS: We performed a retrospective cohort analysis of patients transplanted at our center with HCV who have been started on DAAs. Primary endpoints included sustained virologic response as defined as negative viral load at 12 weeks postcompletion of therapy and allograft function. RESULTS: A total of 31 patients met inclusion criteria. The most commonly used regimen was sofosbuvir and ledipasvir (n = 21). Of the treated patients, 100% had undetectable viral load at the completion of therapy. Of the 31 patients treated, 30 (97%) achieved sustained virologic response. Both graft and patient survivals at most recent follow-up was 100%. There was no significant change in glomerular filtration rate (GFR) before or after therapy (64.2 ± 16.5 mL/min per body surface area before vs. 58.9 ± 17.5 mL/min per body surface area after therapy; P = 0.22); however, 3 patients now have GFR less than 20. A total of 6 (19.3%) of 31 patients had worsening proteinuria during or shortly after therapy. Patients with more than 500 mg/g of proteinuria at the start of treatment were significantly more likely to develop worsening proteinuria than those with less than 500 mg/g of proteinuria at the start of therapy (P < 0.001). Retrospective review of 20 untreated HCV patients did not demonstrate worsening allograft function and proteinuria during a median follow-up time of 1386 days (range, 332-6254). CONCLUSIONS: Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.

Increased access to transplantation of highly sensitized patients under the new kidney allocation system. A single center experience.

We aimed to investigate the impact of the new kidney allocation system (KAS) on the rate of transplantation of sensitized patients at our center. Pre-KAS and post-KAS intervals were Jan 1st to Dec 3rd 2014 and Jan 1st 2015 to Dec 3rd 2015, respectively. The number of deceased-donor crossmatches performed by flow cytometry increased from 715 pre-KAS to 1188 post-KAS. The percent of crossmatches performed for sensitized patients with calculated panel reactive antibody (cPRA)>0% increased from 19% pre-KAS to 26% post-KAS (p<0.0001). The number of deceased-donor kidney transplants performed at our center increased from 115 pre-KAS to 125 post-KAS (9% increase). There was a significant increase in the percentage of deceased-donor kidney transplants received by sensitized candidates (from 14% to 26% pre- and post-KAS, respectively; p<0.0001). The highest increase was seen in the patients with cPRA>98%, from 0% to 9%, followed by the group with cPRA 50-79%, from 5% to 8%. This increase was balanced by a decrease of 12% in the percentage of non-sensitized recipients, and a modest decrease of 1% in the group with cPRA 1-49%. In conclusion, transplant rate has increased in sensitized patients after KAS. The highest increase was observed among highly sensitized patients (cPRA>98%).

Pregnancy in sensitized kidney transplant recipients: a single-center experience.

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.

Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies.

The diagnostic criteria for antibody-mediated rejection (AMR) are continuously evolving. Here we investigated the clinical and molecular significance of different Banff microvascular inflammation (MVI) scores in transplant kidney biopsies. A total of 356 patients with clinically indicated kidney transplant biopsies were classified into three groups based on MVI scores of 0, 1, 2, or more for Groups 1-3, respectively. Gene expression profiles were assessed using arrays on a representative subset of 93 patients. The incidence of donor-specific anti-HLA antibodies was increased from 25% in Group 1 to 36% in Group 2 and to 54% in Group 3. Acute and chronic AMR were significantly more frequent in Group 3 (15% and 35%) compared with the Group 2 (3% and 15%) and Group 1 (0% and 5%), respectively. Gene expression profiles showed increased interferon-γ and rejection-induced, cytotoxic and regulatory T-cell, natural killer cell-associated and donor-specific antibody (DSA)-selective transcripts in Group 3 compared with Groups 1 and 2. There was no significant difference in gene expression profiles between the Groups 1 and 2. Increased intragraft expression of DSA-selective transcripts was found in the biopsies of C4d- Group 3 patients. Thus, an MVI score of 2 or more was significantly associated with a histological diagnosis of acute and chronic antibody-mediated rejection. Hence, increased intragraft DSA-selective gene transcripts may be used as molecular markers for AMR, especially in C4d- biopsies.

Kidney transplantation in patients with severe preoperative hypertension.

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.