J. Huskey

De novo donor-specific human leukocyte antigen antibodies early after kidney transplantation

Background Our aim was to determine the incidence of de novo donor-specific human leukocyte antigen (HLA) antibody (dnDSA) during the first year after kidney transplantation and the impact of early dnDSA on acute rejection and protocol biopsy findings. Methods We selected all patients who received a kidney transplant at our center between July 2010 and March 2012. Single antigen bead assay was performed at 1, 4 and 12 months after transplantation. Only DSAs with a mean fluorescence intensity (MFI) of greater 999 were included. Results We included 245 kidney transplant recipients who did not have a DSA before transplantation. At 12 months, 8.2% of the patients developed dnDSA; 2.4% of them were to HLA class I and 6.5% to HLA class II. Of the 32 patients with a dnDSA at 1 or 4 months, only 8 (25%) persisted at 12 months. The risk of antibody-mediated rejection (AMR) was higher in the dnDSA group. For the dnDSA group with MFI of 3,000 or greater (compared with the group with MFI<3,000), the hazard ratio for AMR was 10.6 (95% confidence interval, 2.27–49.5). The cumulative incidence of AMR or mixed rejection at 1 year was 30% in the group with dnDSA MFI level of 3,000 or greater but only 4% for the group with dnDSA with MFI less than 3,000. On 1-year protocol biopsies, the dnDSA group showed more interstitial inflammation, tubulitis, and glomerulitis. Conclusion We conclude that dnDSA occurring during the first posttransplantation year may be transient, and the risk of AMR is higher in patients with a dnDSA MFI level that is greater than 3,000.

Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury

Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin‐fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non‐AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p‐value <0.005; FDR <10%), but by 4 months there were no differences. Transplanting selected kidneys from deceased donors with AKI is safe and has excellent outcomes.

Rapid Resolution of Donor-Derived Glomerular Fibrin Thrombi after Deceased Donor Kidney Transplantation

The aim of this study was to determine the clinical and histologic outcomes related to transplanting kidneys from deceased donors with glomerular fibrin thrombi (GFT). We included all cases transplanted between October 2003 and October 2014 that had either a preimplantation biopsy or an immediate postreperfusion biopsy showing GFT. The study cohort included 61 recipients (9.9%) with GFT and 557 in the control group without GFT. Delayed graft function occurred in 49% of the GFT group and 39% in the control group (p = 0.14). Serum creatinine at 1, 4, and 12 months and estimated GFR at 12 months were similar in the two groups. Estimated 1‐year graft survival was 93.2% in the GFT group and 95.1% in the control group (p = 0.22 by log‐rank). Fifty‐two of the 61 patients in the GFT group (85%) had a 1‐month protocol biopsy, and only two biopsies (4%) showed residual focal glomerular thrombi. At the 1‐year protocol biopsy, the prevalence of moderate to severe interstitial fibrosis and tubular atrophy was 24% in the GFT group and 30% in the control group (p = 0.42). We concluded that GFT resolves rapidly after transplantation and that transplanting selected kidneys from deceased donors with GFT is a safe practice.

Cardiorespiratory fitness (peak oxygen uptake): Safe and effective measure for cardiovascular screening before kidney transplant

Background Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO2peak), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. Methods and Results We outlined a pre–renal transplant screening algorithm to incorporate VO 2peak testing among a population of asymptomatic high‐risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO 2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO 2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all‐cause mortality. We report a high (>90%) negative predictive value, indicating that VO 2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all‐cause mortality. However, lower VO 2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈

Clinical outcomes of hepatitis C treatment before and after kidney transplantation and its impact on time to transplant: A multicenter study

272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. Conclusions We conclude that incorporating an objective measure of cardiorespiratory fitness with VO 2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher‐risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.

Early Conversion to Belatacept in Kidney Transplant Recipient with Low Glomerular Filtration Rate

Waitlist time for kidney transplantation is long but may be shortened with the utilization of hepatitis C positive allografts. We retrospectively reviewed the course of 36 hepatitis C positive patients awaiting kidney transplantation at 2 large centers within the same health system, with near‐identical care delivery models with the exception of timing of hepatitis C treatment, to determine the impact of timing of hepatitis C treatment on access to transplant, waitlist time, and treatment efficacy and tolerability. The majority of patients had hepatitis C genotype 1a or 1b, and all received direct acting antiviral therapy with 100% treatment response. One patient underwent transplantation in the pretransplant treatment group. The 1‐year transplantation rate was 12.5% vs 67.9% (P = .0013) in those treated posttransplantation. The median waitlist time in the posttransplant group was 122 (interquartile range [IQR] 21.5, 531.0) days, which was significantly shorter than the center’s regional and national wait time. Pathologic review revealed no difference in allograft quality. Overall treatment related adverse events were not different between the 2 groups. A strategy of posttransplant hepatitis C treatment increased access to transplant and reduced waitlist time. Delaying treatment until after transplant did not appear to adversely affect recipients’ kidney allograft or overall survival.

Glucose homeostasis after simultaneous pancreas and kidney transplantation: a comparison of subjects with C-peptide-positive non-type 1 diabetes mellitus and type 1 diabetes mellitus.

Background Our aim was to determine the impact of converting from tacrolimus to belatacept in patients with stable low estimated glomerular filtration rate (eGFR) early after kidney transplant. Methods This is a single-center retrospective case control study. During this study period, we had a clinical protocol to convert patients to belatacept if they had a stable but low GFR and they were at least 1-month posttransplant. Eligible patients had stable but low eGFR usually < 40 mL/min per 1.73 m2. We used direct matching to select 1 control case for each patient converted to belatacept. The primary outcome was the change in eGFR from the point of belatacept conversion to 4 months postconversion (delta eGFR). Results There were 30 patients in the conversion group and 30 in a direct matched control group. The median preconversion eGFR for the entire cohort was 23.0 mL/min per 1.73 m2 with an interquartile range of 15.7 to 31.4. The delta eGFR was 11.0 (12.9) mL/min per 1.73 m2 in belatacept group and 4.8 (10.5) mL/min per 1.73 m2 in the control group (P = 0.045). Acute rejection postconversion occurred in 5 (16.7%) in the conversion group and none of the control group (P = 0.052). Although the delta improvement in eGFR was about 6 mL/min better in the Belatacept group, there was no difference in the slope of inverse creatinine during the 12-month period after conversion between the groups. Conclusions We conclude that early belatacept conversion in kidney transplant recipients with stable low eGFR may only result in a modest increase in GFR.

Excellent Outcome Following Transplantation Using Kidneys From Deceased Donors With Severe Acute Kidney Injury (AKI).: Abstract# 2869

While simultaneous pancreas kidney transplant (SPKTx) is a therapeutic option for patients with type 1 diabetes (T1DM) and renal failure, few centers offer SPKTx to “select” non‐T1DM patients. To address concerns that existing insulin resistance may limit the benefits of the pancreas allograft among non‐T1DM, we compared several indices of glucose homeostasis, in “select” non‐T1DM and T1DM patients who received SPKTx.

Possible Transmission of St. Louis Encephalitis Virus Through Blood Transfusion — Arizona, 2015

2870 Finding the “Diamond in the Rough” Kidneys Amongst Deceased Donors With a High Terminal Creatinine (hiCr). B. Philosophe, N. Desai, A. Singer, R. Munivenkatappa. Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. The Maryland Aggregate Pathology Index is a published pre-implantation scoring tool that predicts graft outcome is refl ective of donor renal pathology. A low(Lo) score (MAPI 0-7) indicates little donor disease, whereas a high(Hi) score (MAPI 12-15) indicates severe donor disease (Intermediate(In) is 8-11). As MAPI has been useful to further risk stratify ECD and older kidneys, we investigated whether MAPI can do the same for deceased donor(DD) kidneys with a hiCr. Methods: We analyzed 205 DDs transplants with a mean follow up of 683 days. 35 DDs with a hiCr (>2.0 mg/dl) were used due to favorable donor clinical parameters. Results: The hiCr gp was younger (41 yrs vs. 53 yrs, p<0.001), were less likely to have HTN (23% vs. 60%, p<0.04), and likely to have a shorter cold ischemia time (20 hrs vs. 24 hrs, p=0.047). Otherwise, this gp was similar to the low creatinine gp (loCr). The 4 yr survival for the loCr gp was 70% compared to 43.9% for the hiCr gp (p=0.8). Within each MAPI gp, there was no difference in 4 yr survival between the loCr or hiCr gps. MAPI DTSCr 1 yr 4 yr p Lo <2 90% 82.3% 0.2 >2 100% 93.3% In+Hi <2 73.3% 45.90% 0.5 >2 71.4% 14.% Hi & In MAPI kidneys faired worse regardless of the donor terminal creatinine. Conversely, within either the loCr and hiCr gps, the graft survival was signifi cantly infl uenced by the MAPI score. For the loCr gp, the 4 yr survival was 84% for the Lo MAPI kidneys vs. 45% for the In & Hi MAPI kidneys combined, p<0.001. Similarly, in the hiCr gp, the 4 yr survival was 93% for Lo MAPI kidneys vs 14% for the In & Hi MAPI kidneys combined, p=0.001. By both uni and multivariate analysis, clinical donor parameters were poor predictors of graft outcome. MAPI score on the other hand, was the best predictor of graft function (p<0.001). hiCr had no signifi cant impact. Conclusion: Although the use of hiCr donor kidneys can have good results, it is important to risk stratify within that group. As a pre-implantation scoring tool, MAPI successfully segregated the hiCr kidneys; Lo MAPI kidneys within that gp had excellent outcomes and were equivalent to Lo MAPI kidneys from the loCr group. Abstract# 2871 Two High KDPI Kidneys Are Better Than One: Opportunities to Expand Dual Kidney Transplantation to Reduce Discard Rates. D. Stewart,1 A. Kucheryavaya,1 W. Cherikh,1 G. Boyle,1 M. Aeder,2 R. Formica.3 1UNOS, Richmond, VA; 2Univ Hosp Case Med Ctr, Cleveland, OH; 3Yale, New Haven, CT. Background: OPTN policy permits both kidneys to be allocated to the same patient if at least two of the following donor criteria are met: age>60, eCrCl<65 ml/min based on admission creatinine (Cr), rising Cr (>2.5mg/dl), longstanding hypertension or diabetes, 15%<glomerulosclerosis<50%. The OPTN Kidney Transplantation Committee (KTC) is evaluating data to assess whether changes to this policy would help increase organ utilization. Methods: Cox models for graft survival adjusting for log(KDRI), recip age, diabetes status, and procedure type (single vs. dual) were estimated using solitary, primary, adult, deceased donor kidney recipients from 2000-2007 per the OPTN database. Organ allocation and disposition data from 2012 were also assessed. (En bloc tx were analyzed separately but not included here.) Results: In 2012, OPOs reported that only 207 (3%) kidney donors were eligible for dual allocation under current policy, and only 87 dual tx occurred. The frequency of dual tx has decreased in recent years (170 were performed in 2005). Yet dual tx confers substantially lower risk of graft failure (HR=0.82, p<0.001), with an improved survival most pronounced for high KDPI kidneys. 2871 Two High KDPI Kidneys Are Better Than One: Opportunities to Expand Dual Kidney Transplantation to Reduce Discard Rates. D. Stewart,1 A. Kucheryavaya,1 W. Cherikh,1 G. Boyle,1 M. Aeder,2 R. Formica.3 1UNOS, Richmond, VA; 2Univ Hosp Case Med Ctr, Cleveland, OH; 3Yale, New Haven, CT. Background: OPTN policy permits both kidneys to be allocated to the same patient if at least two of the following donor criteria are met: age>60, eCrCl<65 ml/min based on admission creatinine (Cr), rising Cr (>2.5mg/dl), longstanding hypertension or diabetes, 15%<glomerulosclerosis<50%. The OPTN Kidney Transplantation Committee (KTC) is evaluating data to assess whether changes to this policy would help increase organ utilization. Methods: Cox models for graft survival adjusting for log(KDRI), recip age, diabetes status, and procedure type (single vs. dual) were estimated using solitary, primary, adult, deceased donor kidney recipients from 2000-2007 per the OPTN database. Organ allocation and disposition data from 2012 were also assessed. (En bloc tx were analyzed separately but not included here.) Results: In 2012, OPOs reported that only 207 (3%) kidney donors were eligible for dual allocation under current policy, and only 87 dual tx occurred. The frequency of dual tx has decreased in recent years (170 were performed in 2005). Yet dual tx confers substantially lower risk of graft failure (HR=0.82, p<0.001), with an improved survival most pronounced for high KDPI kidneys. Of the 2,759 kidneys discarded in 2012, 2,126 (77%) were recovered from the same donor. Of these, 1,004 were from the same KDPI>85% donor. While relatively few of the 1,004 were reported discarded due to anatomical abnormalities (6%), diseased organ (4%), vascular damage (1%), organ trauma (1%), or infection (0%), more than two thirds were discarded due to “biopsy fi ndings” (42%) or “list exhausted” (26%). Conclusions: These results show that dual tx appears to lessen the detrimental effect