Improved Early Post-Transplant Outcomes and Organ Use in Kidney Transplant Using Normothermic Regional Perfusion for Donation after Circulatory Death: National Experience in the US.

BACKGROUND: Normothermic regional perfusion (NRP) is a technique that is intended to enhance organ transplant outcomes from donation circulatory death (DCD) donors. STUDY DESIGN: A retrospective analysis of data from the Scientific Registry of Transplant Recipients was performed. DCD donors were screened for inclusion based on date of donation 2020 or later, and whether the heart was also recovered for transplantation. We grouped donors as either donation after brain death or DCD. DCD donors were further divided into groups including those in which the heart was not recovered for transplant (Non-Heart DCD) and those in which it was, based on recovery technique (thoracoabdominal-NRP [TA-NRP] Heart DCD and Super Rapid Recovery Heart DCD). RESULTS: A total of 219 kidney transplant recipients receiving organs from TA-NRP Heart DCD donors were compared to 436 SRR Super Rapid Recovery DCD, 10,630 Super Rapid Recovery non-heart DCD, and 27,820 donations after brain death recipients. Kidney transplant recipients of TA-NRP DCD allografts experienced shorter length of stay, lower rates of delayed graft function, and lower serum creatinine at the time of discharge when compared with recipients of other DCD allografts. CONCLUSIONS: Our analysis demonstrates superior early kidney allograft function when TA-NRP is used for DCD organ recovery.

Factors Associated With Persistent Post-transplant Hyperparathyroidism After Index Renal Transplantation.

INTRODUCTION: Secondary hyperparathyroidism (SHP) is common in end-stage renal disease and may progress to persistent post-transplant hyperparathyroidism (PTHP) following renal transplantation (RT). We sought to describe the frequency and determine factors associated with the incidence of PTHP for patients undergoing RT at a single institution that restricts RT for patients with uncontrolled SHP with a parathyroid hormone (PTH) of >800pg/mL at time of initial transplant evaluation. METHODS: We conducted a single-institution retrospective study of adults undergoing index RT from 2012 to 2020 who had a calcium and PTH level within 12 mo prior to RT and at least 6 mo following RT. PTHP was defined as calcium of >10 mg/dL with an elevated PTH > 88pg/mL at six or more months following RT. Univariate analysis and multivariable logistic regression were performed for factors associated with developing PTHP. RESULTS: We identified 1110 patients with RT, 65 were excluded for prior RT, 549 did not have a pre-RT and post-RT calcium, and PTH laboratories for inclusion, yielding 496 for analysis. Following RT, 39 patients (7.9%) developed PTHP, compared to those who did not develop PTHP; these patients had significantly higher pre-RT PTH, pre-RT calcium, and frequency of calcimimetic therapy. In multivariable logistic regression factors significantly associated with PTHP were pre-RT calcium of more than 10 mg/dL with an odds ratio (OR) of 3.57 (95% confidence interval [CI] 1.52-8.39, P = 0.003) and pre-RT calcimimetic therapy with an OR 1.30 (95% CI 1.06-2.85, P = 0.041). Compared with patients who had a pre-RT PTH of less than 200 pg/mL, a PTH of 200-399 pg/mL increased risk of PTHP with an OR of 4.52 (95% CI 1.95-21.5, P = 0.048) and a PTH of > 400 pg/mL increased risk of PTHP with an OR of 7.17 (95% CI 1.47-34.9, P = 0.015). In this cohort, 11 patients (28.2%) with PTHP underwent parathyroidectomy (PTx) at a mean of 1.4 y post-RT (standard deviation 0.87). CONCLUSIONS: For patients required to have a PTH < 800pg/mL for initial transplant candidacy, the subsequent incidence of PTHP is relatively low at 7.9%. Risk factors for PTHP include higher pre-RT calcium and PTH levels and pre-RT calcimimetic therapy. PTx remains underused in the treatment of PTHP. Further study is warranted to determine the optimal PTH cutoff for transplant candidacy and recommendation for PTx in patients requiring calcimimetic therapy for SHP.

Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871.

Not as Rare as Initially Described: Transplant Ureter Incarceration Within Inguinal Hernia. Two Cases, Literature Review, and Management Algorithm.

BACKGROUND: Obstructive uropathy after kidney transplant can present as acute kidney injury, urosepsis, and more rarely kidney allograft failure. We present a recent series of 2 cases and a literature review of 1 late etiology of ureteric obstruction: incarceration of the transplant ureter within an inguinal hernia. METHODS: We reviewed 2 cases of patients with ureteric incarceration in an inguinal hernia after kidney transplant and conducted a contemporary structured literature review. Relevant patient factors, management decisions, operative approaches, and clinical outcomes were abstracted and summarized. RESULTS: Two cases of ureteric involvement in an inguinal hernia from 2 institutions as well as a literature review of 14 case reports are provided. The clinical features most commonly associated with this condition were male sex, obesity, and decade or more delay between kidney transplantation and presentation. Preoperative management with nephrostomy tube with or without antegrade ureteric stent was most frequently employed. Ultimately, most patients underwent surgical hernia repair, which occasionally required additional surgery for distal ureteric resection or re-anastomosis. CONCLUSIONS: Incarceration of a transplant allograft ureter in inguinal hernia is likely not as rare as initially described, although a true incidence rate has not been established. This surgically correctible condition most frequently presents as a late complication after kidney transplantation. We present a management algorithm that can be used for the workup and treatment of patients with history of kidney transplant who present with ureteric obstruction owing to incarceration within an inguinal hernia.

Transverse Colonic Perforation in Renal Transplant Recipients During the Early Postoperative Period: A Case Series.

There are very few cases of nondiverticulitis episodes of colonic perforation in the acute postoperative period following kidney transplantation described in the literature. Various nondiverticular causes of colonic perforations include ischemia, malignancy, cytomegalovirus (CMV) enterocolitis, and nonobstructive colonic dilatation. Immunosuppressive medication can contribute to colonic perforation, placing kidney recipients at risk for these complications. Since 2011, there have been 2 cases of transverse colonic perforation in the early postoperative period following renal transplantation at our institution. Both patients underwent urgent exploratory laparotomy with resection of perforated transverse colon and creation of a proximal colostomy. The aim of this study is to review the cases of colonic perforation following renal transplantation to gain a greater understanding of this rare occurrence. Despite the lack of a clear cause of perforation, it is imperative to have a high index of suspicion for colonic perforations in these immunocompromised patients to provide prompt surgical management and improved outcomes.

The impact of multi-organ transplant allocation priority on waitlisted kidney transplant candidates.

Kidney-alone transplant (KAT) candidates may be disadvantaged by the allocation priority given to multi-organ transplant (MOT) candidates. This study identified potential KAT candidates not receiving a given kidney offer due to its allocation for MOT. Using the Organ Procurement and Transplant Network (OPTN) database, we identified deceased donors from 2002 to 2017 who had one kidney allocated for MOT and the other kidney allocated for KAT or simultaneous pancreas-kidney transplant (SPK) (n = 7,378). Potential transplant recipient data were used to identify the "next-sequential KAT candidate" who would have received a given kidney offer had it not been allocated to a higher prioritized MOT candidate. In this analysis, next-sequential KAT candidates were younger (p < .001), more likely to be racial/ethnic minorities (p < .001), and more highly sensitized than MOT recipients (p < .001). A total of 2,113 (28.6%) next-sequential KAT candidates subsequently either died or were removed from the waiting list without receiving a transplant. In a multivariable model, despite adjacent position on the kidney match-run, mortality risk was significantly higher for next-sequential KAT candidates compared to KAT/SPK recipients (hazard ratio 1.55, 95% confidence interval 1.44, 1.66). These results highlight implications of MOT allocation prioritization, and potential consequences to KAT candidates prioritized below MOT candidates.

Double Obstruction Following Third Renal Transplant: A Case Report.

As the field of transplant evolves and patients with chronic disease live longer, retransplant for end-stage renal disease becomes more common because kidney allografts have a limited lifespan. In renal retransplant, graft and patient survival is near equivalent to first-time transplant; however, these procedures present a unique surgical risk profile, especially third and subsequent transplants, which are reviewed in this manuscript. The risk of bowel obstruction in primary kidney transplant recipients is much lower than patients who have undergone laparotomy for second or third transplant because of the retroperitoneal location of the transplanted kidney. Internal hernia is an uncommon cause of small bowel obstruction, particularly after kidney transplant, and often diagnosis and intervention are delayed because of diagnostic uncertainty. We report a case of a 34-year-old man with acute kidney injury and bowel obstruction, whose final diagnosis was an internal hernia around the transplanted ureter of an intra-abdominally placed third renal transplant resulting in ureteric obstruction associated with small bowel obstruction-a case of double obstruction.

Fortuitous benefits of living kidney donation: Diagnosis of serious medical conditions during the living donor evaluation.

BACKGROUND: All living kidney donors are counseled about the possible surgical and medical risks associated with donation. Only a minority of transplant centers discuss the potential benefit of discovering undiagnosed medical conditions in the donor during evaluation, as part of their consent process. METHODS: We retrospectively investigated all potential living kidney donors evaluated over a 10-year period at a single center to characterize incidentally diagnosed serious medical conditions. RESULTS: Sixty-five of the 762 potential donors (8.5%) were not approved for donation because of a newly diagnosed serious medical condition discovered during their evaluation. This included six patients diagnosed with malignancies, five of which required operative intervention, six patients diagnosed with transmittable diseases requiring follow-up and treatment, four patients were found to have bilateral renal stones with significant stone burden, and two patients diagnosed with IgA nephropathy. Additionally, four patients were diagnosed with significant heart disease, and one of those patients subsequently required a coronary artery bypass surgery. CONCLUSIONS: The evaluation process can diagnose serious medical conditions in a significant minority of donors that would have otherwise been unrecognized. The benefit associated with the donor evaluation should be considered an important part of the consent process.

Is bacteremic sepsis associated with higher mortality in transplant recipients than in nontransplant patients? A matched case-control propensity-adjusted study.

BACKGROUND: Sepsis is a serious complication of solid organ transplant (SOT). Evidence on survival differences between SOT recipients and non-SOT patients with sepsis is lacking. METHODS: This was a matched, case-control propensity-adjusted study. Conditional logistic regression was performed for risk factor analysis, and Cox proportional hazards regression for survival analysis. RESULTS: Three hundred sixty-nine patients (123 cases; 246 controls) diagnosed with blood culture-proven sepsis were matched 1:2 by age, sex, and hospital location. The distribution of allografts was 36.6% kidney, 34.1% liver, 13% kidney-pancreas, 7.3% small bowel/liver, 5.7% heart/lung, and 3.3% multivisceral. The conditional logistic regression showed that the following factors were significantly more frequently associated with SOT compared to non-SOT: higher number of comorbidities (odds ratio [OR] = 8.2 [95% confidence interval {CI}, 1.48-45.44], P = .016); higher Sepsis-related Organ Failure Assessment score (OR = 1.2 [95% CI, 1.07-1.32], P = .001); presence of nosocomial infection (OR = 36.3 [95% CI, 9.71-135.96], P < .0001); appropriate initial antibiotics (OR = 0.04 [95% CI, .006-.23], P < .0001); and lower white blood cell count (OR = 0.93 [95% CI, .89-.97], P < .0001). Cox proportional hazards regression showed that after all adjustments for clinical presentation, severity of illness, and types of infection, SOT recipients with sepsis had a significantly lower risk of death at 28 days (hazard ratio [HR] = 0.22 [95% CI, .09-.54], P = .001) and at 90 days (HR = 0.43 [95% CI, .20-.89], P = .025). CONCLUSIONS: The 28-day and 90-day mortality were significantly decreased for transplant recipients compared with nontransplant patients. These findings suggest that the immunosuppression associated with transplantation may provide a survival advantage to transplant recipients with sepsis through modulation of the inflammatory response.

Biliary complications adversely affect patient and graft survival after liver retransplantation.

Inferior outcomes are consistently observed for recipients of liver retransplantation (re-LT) versus recipients of primary transplants. Few studies have examined the incidence and impact of biliary complications (BCs) on outcomes after re-LT. The aim of this study was to compare patient and graft survival for re-LT recipients with BCs (BC(+) ) and re-LT recipients without BCs (BC(-) ). Additional aims were to determine the impact of biliary reconstruction on the incidence of BCs and to identify risk factors for BCs after re-LT. A single-center, retrospective analysis of all re-LT recipients over a decade was performed. Univariate analyses were performed, and survival was compared with the log-rank method. A multivariate Cox regression analysis was performed to determine independent predictors of death and graft failure. The BC rate was 20.9% (n = 23) for 110 re-LT cases. The average follow-up was 55 months. The survival rates for BC(-) recipients at 3 months and 1, 3, and 5 years were 95.3%, 91.7%, 85.4%, and 80.9%, respectively, whereas BC(+) patients had survival rates of 64.3%, 49.7%, 34.8%, and 29.8%, respectively (P < 0.001, log-rank). The graft survival rates at 3 months and 1, 3, and 5 years were 92.0%, 88.5%, 82.4%, and 78.0%, respectively, for the BC(-) group and 60.9%, 43.5%, 30.4%, and 26.1%, respectively, for the BC(+) group (P < 0.001, log-rank). BCs, a length of stay ≥ 12 days, and donor age were strongly associated with death and graft failure in a regression analysis, whereas retransplant indications other than chronic rejection and recurrent disease also affected graft failure. In conclusion, BCs significantly affected both patient and graft survival, with an increased risk of death and graft loss among BC(+) recipients. Early recognition, appropriate interventions, and preventative measures for BCs are critical in the clinical management of re-LT recipients.