The Impact of Organ Procurement Injury on Transplant Organ Availability.

Patients on the transplant waiting list continue to have a significant wait time as organ supply remains low. Many initiatives have been undertaken in the last few years to attempt to increase the organ allograft supply. As organ procurement organizations have attempted to increase their procurement of organs from deceased donors, emphasis has been placed on avoidance of injury to organs during procurement. To analyze the success of this attention, data were collected from 29 of 57 organ procurement organizations in the United States. Data collection was from November 2017 to January 2020. Total injury rate ranged from 6% (donation after brain death) to 8.4% (donation after circulatory death). Level 3 injuries, those resulting in loss of the allograft, ranged from 1.1% in donation after brain death to 1.6% in donation after circulatory death. The most likely injured organ resulting in loss of viability (level 3 injury) during procurement was the right kidney. We noted that among donors with procurement injuries, a higher number had no previous abdominal surgery and there were more injuries noted from attending surgeons (compared to trainees). Deceased donor procurement organ injuries, though rare, lead to substantial loss of transplantable organs every year. Given that the United Network for Organ Sharing has recorded >10,000 deceased donors yearly for the past few years, such injuries can result in hundreds of transplantable organs lost. In this article we detailed the incidence and degree of injury and some variables that may be associated with these injuries.

Vasopressin for Post-kidney Transplant Hypotension.

Introduction: Hypotension after deceased donor kidney transplant (DDKT) is a risk factor for delayed graft function (DGF) and poor graft survival (GS). We hypothesize that vasopressin use in hypotensive DDKT recipients (DDKTRs) to increase blood pressure (BP) reduces DGF rates and is safe without increasing mortality. Methods: Group with vasopressin "study group" (n = 45) was defined as DDKTRs between 2012 and 2017 who required vasopressin for hypotension systolic BP (SBP) <120 mm Hg or diastolic BP (DBP) <60 mm Hg. DDKTRs with no-vasopressin "comparison group" (n = 90) were propensity score-matched DDKTRs between 2012 and 2017 without vasopressin use. Primary outcomes were GS, creatinine and allograft biopsy rate at 1 year, DGF rate, and death during transplant hospitalization. Results: Vasopressin group had lower mean maximum and minimum SBP and DBP in the operating room (OR). Median vasopressin start time post-DDKT was 2 hours (interquartile range [IQR] 1-6), and duration of use was 42 hours (IQR 24-63). DGF, creatinine at 1 year, and allograft biopsy rates were comparable. No deaths occurred during transplant hospitalization. Multivariable analysis did not find an effect of vasopressin use on GS. Conclusion: Treatment of hypotensive DDKTRs with vasopressin is safe and facilitated similar graft function and survival with that of nonhypotensive patients. In the absence of a randomized control trial, our study supports the safety of vasopressin therapy to prevent the adverse effects of hypotension.

Nondirected Living Kidney Donation and Recipient Outcomes in the United States: A 20-Year Review.

Introduction: Nondirected donation (NDD) of the kidneys is a growing practice where donors who do not have any genetic or emotional relationship are selected to donate to a wide variety of recipients with a range of selection criteria and decisions which are left up to individual transplant centers. Methods: We review all adult living kidney donor-recipient (DR) pairs and outcomes from NDDs who were recorded in United Network for Organ Sharing (UNOS) database as code 10 (anonymous) from October 1997 to September 2017 for demographics and outcomes. Results: A total of 2174 DR pairs were identified. The number of NDDs increased from 18 in 2000 to 256 in 2016. Survival analysis showed higher death-censored-graft survival (DC-GS) when recipient was 20 years or more older than donor followed by recipient-donor within 20 years of age and lowest when donor was 20 years or more older than recipient (P = 0.0114). Conclusion: Overall, the number of NDDs has increased significantly in the 20-year review period. Transplants from NDDs have excellent long-term outcomes. Better matching of controllable DR factors, such as age and body mass index (BMI), could further improve GS. Further research is needed to incorporate these DR factors into paired kidney donation programs potentially enhancing the utility and beneficence of this invaluable donation.

Patient and Graft Survival Outcomes During 2 Eras of Immunosuppression Protocols in Kidney Transplantation: Indiana University Retrospective Cohort Experience.

BACKGROUND: Since 1964 when Indiana University performed its first kidney transplant, immunosuppression protocol was steroid-based until 2004 when steroid-free immunosuppression protocol was adopted. We describe clinical outcomes on our patients administered early steroid withdrawal (ESW) protocol (5 days) compared with our historical cohort (HC), who were on chronic steroid-based immunosuppression. METHODS: We performed a retrospective study evaluating kidney transplant recipients between 1993 and 2003 (HC, n = 1689) and between 2005 and 2016 (ESW cohort, n = 2097) at the Indiana University program, with a median follow-up of 10.5 years and 6.1 years, respectively. Primary outcomes were patient and death-censored graft survival at 1, 3, and 5 years in both study cohorts. Secondary outcomes were 1-year rates of biopsy-proven acute rejection; graft function at 1, 3, and 5 years; and risk of post-transplant infection (BK virus and cytomegalovirus) in the ESW cohort. Cox proportional model and Kaplan-Meier estimates were used to estimate survival probabilities. Fisher exact tests were used to compare episodes of acute rejection in the ESW cohort. RESULTS: No difference was observed in patient survival between the ESW and HC cohorts (P = .13). Compared with the ESW cohort, death-censored graft survival was significantly worse in the HC (5 year: 86.4% vs 90.6%, log-rank P < .001). One-year acute rejection reported in the ESW cohort alone was 15.7% and significantly worse in Black patients and younger patients (P < .05). CONCLUSIONS: In this sizeable single-center cohort study with significant ethnic diversity, ESW is a viable alternative to steroid-based immunosuppression protocol in kidney transplant recipients.

A National Survey of Practice Patterns for Accepting Living Kidney Donors With Prior COVID-19.

INTRODUCTION: A critical question facing transplant programs is whether, when, and how to safely accept living kidney donors (LKDs) who have recovered from COVID-19 infection. The purpose of the study is to understand current practices related to accepting these LKDs. METHODS: We surveyed US transplant programs from 3 September through 3 November 2020. Center level and participant level responses were analyzed. RESULTS: A total of 174 respondents from 115 unique centers responded, representing 59% of US LKD programs and 72.4% of 2019 and 72.5% of 2020 LKD volume (Organ Procurement and Transplantation Network-OPTN 2021). In all, 48.6% of responding centers had received inquiries from such LKDs, whereas 44.3% were currently evaluating. A total of 98 donors were in the evaluation phase, whereas 27.8% centers had approved 42 such donors to proceed with donation. A total of 50.8% of participants preferred to wait >3 months, and 91% would wait at least 1 month from onset of infection to LD surgery. The most common reason to exclude LDs was evidence of COVID-19-related AKI (59.8%) even if resolved, followed by COVID-19-related pneumonia (28.7%) and hospitalization (21.3%). The most common concern in accepting such donors was kidney health postdonation (59.2%), followed by risk of transmission to the recipient (55.7%), donor perioperative pulmonary risk (41.4%), and donor pulmonary risk in the future (29.9%). CONCLUSION: Practice patterns for acceptance of COVID-19-recovered LKDs showed considerable variability. Ongoing research and consensus building are needed to guide optimal practices to ensure safety of accepting such donors. Long-term close follow-up of such donors is warranted.

Living Donor Gifted Lithiasis: Long-Term Outcomes in Recipients.

OBJECTIVES: Presence of nephrolithiasis in a living donor has been at least a relative contraindication to living donor nephrectomy. The concern for stone recurrence and outcomes has been one of the reasons for reluctance to consider these medically complex donors. We evaluate long-term outcomes in recipients of kidney grafts from donors with nephrolithiasis, or history of nephrolithiasis, and provide results from our experience at Indiana University. MATERIALS AND METHODS: We retrospectively reviewed 57 donor-recipient pairs, where the allograft was received from a living donor with symptomatic calculi, or with imaging evidence of kidney stones, between 2003 and 2018. This research study was done in compliance with the ethical standards set forth in the Helsinki Congress. RESULTS: The mean age of recipients was 46±19 years and 58% were male. Kidney recipients were followed for a median of 3.5 years and 59.6% of patients had follow-up imaging studies. None of the recipients had obstructing renal calculi or related infections. None of the recipients required any interventions for recurrent calculi and no stone episode lead to adverse event to the graft. Hyperoxaluria and hypercalciuria were the most common risk factors in 24-hour urine collections obtained from donors. CONCLUSIONS: Our findings from a single large center looking at kidney recipient outcomes over a long follow-up period found that gifted lithiasis is a safe procedure. Careful selection of "medically complex donors" with kidney stones based on appropriate guidelines is a key step. Further studies are needed to help develop consensus guidelines.

Organ recovery from deceased donors with prior COVID-19: A case series.

Although guidance documents have been published regarding organ donation from individuals with a prior history of COVID-19 infection, no data exist regarding successful recovery and transplantation from deceased donors with a history of or positive testing suggesting a prior SARS-CoV-2 infection. Here, we report a case series of six deceased donors with a history of COVID-19 from whom 13 organs were recovered and transplanted through several of the nation's organ procurement organizations (OPOs). In addition, at least two potential donors were authorized for donation but with no organs were successfully allocated and did not proceed to recovery. No transmission of SARS-CoV-2 was reported from the six donors to recipients, procurement teams, or hospital personnel. Although more studies are needed, organ donation from deceased donors who have recovered from COVID-19 should be considered.

Correlation and Prediction of Living-Donor Remaining Function by Using Predonation Computed Tomography-Based Volumetric Measurements: Role of Remaining Kidney Volume.

OBJECTIVES: Kidney volume in healthy living donors may serve as a surrogate marker of renal function. Here, we evaluated whether preserved kidney volume correlated with and could predict donor renal function at 2 years postdonation using the CKD-EPI estimated glomerular filtration rate equation. MATERIALS AND METHODS: Healthy living donors (n = 208) with computed tomography volume measurements were evaluated for renal function before and after donation. Preserved kidney volume was adjusted to body surface area. Demographic characteristics (including race/ethnicity and sex) and renal function variables of donors were analyzed for postdonation renal function. RESULTS: Donor mean age was 39.4 ± 10.7 years (36.2% males, 91.9% white). Median adjusted preserved kidney volume was 180.6 mL. At 2 years postdonation, median estimated glomerular filtration rate was 62.4 mL/min (interquartile range, 54.8-73.2 mL/min). Predonation estimated glomerular filtration rate, age, and adjusted preserved kidney volume were found to be inde-pendent predictors of 2-year estimated glomerular filtration rate (P < .001). We further analyzed data by stratifying preserved kidney volumes into tertiles. Mean 2-year estimated glomerular filtration rates were 57.9 ± 12, 65 ± 16, and 73 ± 17 mL/min for lowest to highest tertile groups, respectively (P < .05). The odds ratio of having a 2-year postdonation estimated glomerular filtration rate of < 60 mL/min for donors in the lowest tertile group was 3.51 (95% confidence interval, 1.9-6.4; P < .001), whereas the risk for donors in the highest tertile group was 0.23 (95% confidence interval, 0.12-0.44; P< .001). Sensitivity analysis result was 0.764 (95% confidence interval, 0.69-0.82; P = .005) for adjusted preserved kidney volume and estimated glomerular filtration rate of < 60 mL/min. CONCLUSIONS: Remaining kidney volume before donation correlated with and predicted estimated glomerular filtration rate after donation. Remaining kidney volume should be assessed when selecting kidneys from healthy donors.

Late pancreatic panniculitis in a simultaneous pancreas kidney transplant patient with failed allografts.

We present a rare case of pancreatic panniculitis in a 59-year-old male simultaneous pancreas-kidney (SPK) recipient with failed allografts. The patient presented with fever and painful erythematous nodules on his leg 1 month after stopping all immunosuppression. A thorough infectious and rheumatological workup was negative. He had pancreas rejection 4 years after SKP transplant and was restarted on dialysis after 14 years when his renal allograft failed due to chronic allograft nephropathy. His chronic immunosuppression (tacrolimus, azathioprine) was stopped and prednisone was weaned over 3 months at that time. A skin biopsy revealed saponification of the subcutaneous fat with inflammation pathognomonic of pancreatic panniculitis. Concurrent allograft pancreatitis confirmed with elevated lipase and a computed tomography scan finding of peripancreatic graft stranding and atrophic native pancreas. He was started on pulse steroid therapy for 3 days followed by oral taper. This resulted in dramatic resolution of all skin lesions and normalization of lipase levels within 1 week, followed by resumption of low-dose tacrolimus and azathioprine. This is an extremely rare occurrence of panniculitis in pancreas allograft after 10 years of pancreatic failure associated with stopping immunosuppression.

Steroid-free three-drug maintenance regimen for pancreas transplant alone: Comparison of induction with rabbit antithymocyte globulin +/- rituximab.

Graft survival following pancreas transplant alone (PTA) is inferior to other pancreas transplants. Steroid elimination is appealing, but a two-drug maintenance strategy may be inadequate. Additionally, recipients tend to have diabetic nephropathy and do not tolerate nephrotoxic medications. A three-drug maintenance strategy permits immunosuppression through different mechanisms as well as an opportunity to use lower doses of the individual medications. Induction consisted of five doses of rabbit antithymocyte globulin (1 mg/kg/dose). As of October 2007, a single dose of rituximab (150 mg/m2 ) was added. Maintenance consisted of tacrolimus, sirolimus and mycophenolate mofetil. From 2004 to 2017, 166 PTA were performed. Graft loss at 7 and 90 days were 4% and 5%, and 1-year patient and graft survival were 97% and 91%. Comparing induction without and with rituximab, there was no significant difference in 7- or 90-day graft loss, 1-year patient or graft survival, or in the rate of rejection or infection. Rabbit antithymocyte globulin induction and steroid withdrawal followed by a three-drug immunosuppression regimen is an excellent strategy for PTA recipients.

Kidney allograft survival outcomes in combined intestinal-kidney transplant: An analysis of the UNOS/OPTN database 2000-2014.

BACKGROUND AND OBJECTIVES: Intestinal transplants carry a high morbidity/mortality. Kidney allograft outcomes after combined intestinal (IT) with kidney transplant (CIKT) remain largely uninvestigated. MATERIALS AND METHODS: The UNOS STAR database was queried to identify all such combined organ transplants from 2000 to 2015. RESULTS: Out of a total 2215 (51.4% peds vs 48.6% adults) intestinal transplants, 111 (5.0%) CIKT were identified (32.4% peds vs 67.6% adults). Over the study period of CIKT, a total of 45.9% of these cases died with a functioning kidney graft. DGF rate was 9.0%. The 1-year reported kidney acute rejection rate was 6.3%. For the entire CIKT population over the entire study era, the 1-, 3-, and 5-year unadjusted kidney graft survival was 57%, 39%, and 34%, while death-censored kidney graft survival was 93%, 90%, and 86%, respectively. Overall conditional 5-year kidney graft survival (defined as 1-year kidney graft survival) was 58%. Overall, patient survival was significantly lower in recipients of CIKT compared to intestinal transplant (IT) (P < .005); However, the 5-year conditional (1 year kidney graft) patient survival in adults was not significantly different between IT and CIKT overall (P = .194). CONCLUSIONS: Kidney allograft survival is primarily dependent on 1-year patient survival. Guidelines regarding allocation of kidney allografts in CIKT need to take into consideration utility and urgency.

Isolated pancreas rejections do not have an adverse impact on kidney graft survival whereas kidney rejections are associated with adverse pancreas graft survival in simultaneous pancreas kidney transplantation.

BACKGROUND AND OBJECTIVES: Diabetic Kidney Disease is associated with excessive mortality and morbidity. Simultaneous pancreas kidney transplantation (SPK) significantly improves quality of life and increases life expectancy of uremic diabetic patients. It is not known whether pancreas and kidney rejections in these transplant patients is concordant or discordant. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We analyzed clinical data on all SPK transplants performed between 2003 and 2014 at Indiana University to assess the impact of isolated or combined pancreas and kidney rejections on patient and allograft outcomes. The primary outcome of interest was kidney graft rejection within 1 year of pancreatic rejection and kidney survival in SPK patients with and without pancreatic rejection. RESULTS: Mean age of patients was 44 ± 9 years; 61.9% were males; 88% were Caucasians. A total of 23.8% of cases had rejection [8.7% pancreatic rejection alone (PA), 4.4% had concordant pancreas and kidney (PK) rejection, and 10.7% had kidney rejection alone(KA)]. PK had a worse effect on kidney graft survival than PA (p = 0.019). Neither pancreas rejection nor kidney rejection had an adverse effect on patient survival. However, both pancreas graft failure and kidney graft failure adversely affected patient survival. Tacrolimus levels were not significantly different in all groups over a 10 year period (p = 0.4584). CONCLUSIONS: Concordant pancreas kidney rejection is synergistically deleterious to kidney graft survival. Graft failure, not graft rejection, is adversely associated with patient survival.

Outcomes of Hepatitis C-Positive Kidney Transplant Recipients Compared With Hepatitis C-Negative Recipients in Today's Era of Immunosuppression: A UNOS Database Analysis With Long-Term Follow-Up.

OBJECTIVES: Our objective was to study the clinico-pathologic correlations in BK virus nephropathy. MATERIALS AND METHODS: We conducted a retrospective study of all patients with biopsy-proven polyoma (BK) virus infection. We compared their survival and renal outcomes versus BK virus-negative patients with biopsy-proven graft rejection. Histopathologic characterization by a blinded nephropathologist was performed. RESULTS: BK nephropathy was found in 10 patients biopsied for graft dysfunction. All virus-positive patients received antithymocyte globulin induction therapy compared with only 59.3% of the BK-negative group (P = .06). The percentage of patients in the BK-negative group who received acyclovir was significantly higher than that in the BK-positive group (P = .01). After a mean observation period of 6.8 ± 3.2 years, 70% of the BK group had functioning grafts compared with 68% in the BK-negative group (P = .9) with similar 3-year graft survival in the 2 groups (80% and 90%; P = .8). Within the BK group, graft survival was better in the older group (P = .005) and in those with deceased donor kidney grafts (P = .016). Patients in the BK-negative group were heavier (mean weight of 64.3 ± 12.1 vs 46.7 ± 20.6 kg; P = .003). None of the histopathologic features studied had any effect on renal prognosis. CONCLUSIONS: The risk factors for developing BK nephropathy were use of antithymocyte globulin, lower weight, and not using acyclovir as early prophylaxis. Within the BK nephropathy group, better graft survival was observed in deceased donor kidney recipients and in older patients. The viral load and polyoma virus nephropathy stage did not affect graft survival in this small sample study.

Early Fatal Cutaneous Lower Extremity Angiosarcoma Associated with Deep Venous Thrombosis in a Renal Transplant Recipient.

Angiosarcomas are extremely rare malignant tumors of vascular origin. We describe a 63-year-old recipient after a kidney transplant who had an angiosarcoma in the lower extremity that presented after new-onset deep venous thrombosis and was not associated with any fistula. There was rapid progression to metastasis and death. We reviewed the literature of this rare malignant tumor in kidney transplant patients.

Deceased donor organ procurement injuries in the United States.

AIM: To determine the incidence of surgical injury during deceased donor organ procurements. METHODS: Organ damage was classified into three tiers, from 1-3, with the latter rendering the organ non-transplantable. For 12 consecutive months starting in January of 2014, 36 of 58 organ procurement organization's (OPO)'s prospectively submitted quality data regarding organ damage (as reported by the transplanting surgeon and confirmed by the OPO medical director) seen on the procured organ. RESULTS: These 36 OPOs recovered 5401 of the nations's 8504 deceased donors for calendar year 2014. A total of 19043 organs procured were prospectively analyzed. Of this total, 59 organs sustained damage making them non-transplantable (0 intestines; 4 pancreata; 5 lungs; 6 livers; 43 kidneys). The class 3 damage was spread over 22 (of 36) reporting OPO's. CONCLUSION: While damage to the procured organ is rare with organ loss being approximately 0.3% of procured organs, loss of potential transplantable organs does occur during procurement.

Re-transplants compared to primary kidney transplants recipients: a mate kidney paired analysis of the OPTN/UNOS database.

Outcomes of kidney re-transplant recipients (RTR) were compared to primary recipients (FTR) from paired donor kidneys. Organ Procurement and Transplantation Network (OPTN) database was used to identify deceased donors (n = 6266) who donated one kidney to an RTR and the mate kidney to an FTR between January 2000 to December 2010. As compared to FTR, RTR were younger (45 vs. 52 yr, p < 0.001) and had higher proportion of plasma reactive antibody >80 (25% vs 7%, p < 0.001). There were higher 0 mismatches in RTR (19% vs. 16%, p < 0.001). There were more pre-emptive transplants in RTR (24% vs. 21%, p = 0.002). Delayed graft function (28% vs. 25%, p = 0.007) was higher in RTR. Patient survival was similar in FTR and RTR groups at one, three, and five yr (95.7%, 90.2%, and 82.5% vs. 95.2%, 89.8% and 82.7%). Allograft survival rates were higher in FTR group compared to RTR group at one, three, and five yr (91.1%, 82.4%, and 70.9% vs. 87.8%, 77.4%, and 66.1% p < 0.001). Death-censored allograft survival rates were higher in FTR group at one, three, and five yr (91.3%, 82.7% and 71.4% vs. 88%, 77.7% and 66.5% p < 0.001). In today's era of modern immunosuppression, graft survival in RTR has improved but remains inferior to FTR when controlling for donor factors.