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Kidney transplantation is the best health option for patients with end-stage kidney disease. Ideally, a kidney transplant would last for the lifetime of each recipient. However, depending on the age of the recipient and details of the kidney transplant, there may be a need for a second, third, fourth, or even more kidney transplants. In this overview, the outcome of multiple kidney transplants for an individual is presented. Key issues include surgical approach and immunologic concerns. Included in the surgical approach is an analysis of transplant nephrectomy, with indications, timing, and immunologic impact. Allograft thrombosis, whether related to donor or recipient factors merits investigation to prevent it from happening again. Other posttransplant events such as rejection, viral illness (polyomavirus hominis type I), recurrent disease (focal segmental glomerulosclerosis), and posttransplant lymphoproliferative disease may lead to the need for retransplantation. The pediatric recipient is especially likely to need a subsequent kidney transplant. Finally, noncompliance/nonadherence can affect both adults and children. Innovative approaches may reduce the need for retransplantation in the future.

BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation (DDKT) to address the high incidence of kidney failure. Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients; thus the identification of modifiable risk factors associated with poor outcomes is paramount. AIM To identify risk factors associated with delayed graft function (DGF). METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients. The primary outcome was the occurrence of DGF. RESULTS The incidence of DGF was 27%. Under logistic regression, eight independent risk factors for DGF were identified including recipient body mass index ≥ 30 kg/m2, baseline mean arterial pressure < 110 mmHg, intraoperative phenylephrine administration, cold storage time ≥ 16 h, donation after cardiac death, donor history of coronary artery disease, donor terminal creatinine ≥ 1.9 mg/dL, and a hypothermic machine perfusion (HMP) pump resistance ≥ 0.23 mmHg/mL/min. CONCLUSION We delineate the association between DGF and recipient characteristics of pre-induction mean arterial pressure below 110 mmHg, metabolic syndrome, donor-specific risk factors, HMP pump parameters, and intraoperative use of phenylephrine.

Objetives ECMO is progressively being adopted as a last resort to stabilize patients receiving cardiopulmonary resuscitation (ECMO CPR). A significant number of these patients will present recovery of end-organ function, but evolve with brain death, accounting for only 30% of patients discharged from the hospital alive. Harvesting organs from donors on VA ECMO has recently been proposed as a strategy to expand the pool of available organs for transplantation. Methods We present a case of combined heart and kidney transplantation from a brain death donor with recent out of hospital cardiac arrest rescued with eCPR. Results A 31 year old male patient was admitted to local hospital with diagnosis of drowning after seizure episode. Patient received two rounds of CPR for 8 and 30 minutes respectively, and required emergency insertion of VA ECMO. Patient developed compartment syndrome of right lower extremity (RLE) with CPK = 30,720, prompting discontinuation of ECMO support within 48 hours as cardiac function had recovered, reflected on echocardiographic and enzymatic parameters. Patient was declared brain death and became organ donor. Multiple organ procurement was performed. Combined heart and right kidney transplant was then performed on a 61-year-old male with uneventful course, and with normal function of all implanted allografts at 3 months follow up. Conclusion Our experience supports the concept that VA ECMO is not a contraindication for solid organ donation. Individual evaluation of organ function can lead to successful transplantation of multiple organs from donors with recent history of VA ECMO support.

Background: Contrasting results have emerged from limited studies investigating the role of prophylactic surgical drainage in preventing wound morbidity after liver and kidney transplantation. This retrospective study analyzes the use of surgical drain and the incidence of wound complications in combined liver and kidney transplantation (CLKTx).Methods: A total of 55 patients aged ≥18 years were divided into two groups: the drain group (D) (n = 35) and the drain-free group (DF) (n = 20). Discretion to place a drain was based exclusively on surgeon preference. All deceased donor kidneys were connected to the LifePort Renal Preservation Machine® prior to transplantation, in both simultaneous and delayed technique of implantation of the renal allograft. The primary outcome was the development of superficial/deep wound complications during the study follow-up. Secondary outcomes included the development of delayed graft function (DGF) of the transplanted kidney, primary non-function (PNF) and early allograft dysfunction (EAD) of the transplanted liver, graft failure, graft and patient survival, overall post-operative morbidity rate and length of hospital stay.Results: With a median follow-up of 14.4 months after transplant, no difference in the incidence of superficial/deep wound complications, except for hematomas, in collections size, intervention rate, PNF, EAD, graft failure and patient survival, was observed between the 2 groups. Significantly lower level of platelets, higher INR values, DGF, morbidity rates and length of hospital stay were reported post-operatively in the D group. Pre-operative hypoalbuminemia and longer CIT were included in the propensity score for receiving a drain and were associated with a significantly higher rate of developing a hematoma post-transplant.Conclusions: Absence of the surgical drain did not appear to adversely affect wound morbidity compared to the prophylactic use of drains in renal transplant patients during CLKTx.

Simultaneous pancreas-kidney transplantation (SPKT) is an important option for patients with type 1 diabetes (T1D) and end-stage renal disease. While most SPKT recipients experience long-term euglycemia, about 5% return to insulin therapy, 5–20 years after transplantation due to T1D recurrence (T1DR). Over the last two decades, we have assessed autoimmunity in our patients, evaluating autoantibodies (GAD65, IA2, and ZnT8), autoreactive T cells, and pancreas transplant biopsies. Most patients demonstrate seroconversion for multiple autoantibodies. Autoreactive memory T cells have been identified in the peripheral blood, pancreas transplant, and peri-pancreas transplant tissues. Biopsies generally exhibit insulitis, the typical lesion of T1D, affecting pancreatic islets in the pancreas transplant, and lack of rejection in the pancreas and kidney transplants. In addition to membrane expression of memory markers, we have identified other biomarkers, including CXCR3, on circulating and infiltrating autoreactive memory T cells. We hope that this work will lead to therapeutic intervention in our patients with T1DR, and that this will translate to effective treatment for T1D.

Background Outcomes of COVID-19 have been reported in deceased donor kidney transplant (DDKT) recipients. However, data is limited in patients that underwent recent DDKT. Methods This single-center retrospective study evaluated the differences in demographics and post-transplant outcomes between those who tested positive and negative for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by polymerase chain reaction, after undergoing recent DDKT. The treatments and outcomes for the SARS-CoV-2-positive patients were assessed. Patients who underwent DDKT from 3/2020 to 8/2020 were included and followed until 9/2020. Results 201 DDKT recipients were analyzed [14(7%) SARS-CoV-2-positive and 187(93%) negative]. There was no difference in delayed graft function and biopsy-proven rejection between both groups. The patient survival at the end of the study follow-up was lower among SARS-CoV-2-positive patients (Table 1). The median time from DDKT to COVID-19 diagnosis was 45 (range: 8-90) days; 5(36%) patients required intensive care unit and 4(29%) required mechanical ventilation; steroids were used in all the patients, therapeutic plasma exchange (TPE) and convalescent plasma (CP) in 7(50%) patients each, remdesivir in 6(43%) and tocilizumab in 1(7%); 9(64%) patients recovered, 3(21%) died and two were still requiring mechanical ventilation at the end of the follow-up. Conclusion Our cohort demonstrated a lower survival rate among SARS-CoV-2-positive patients, which highlights the vulnerability of the transplant population. Transplant patients must comply with the CDC recommendations to prevent COVID-19. Disclosures All Authors: No reported disclosures

Simultaneous pancreas-kidney transplantation (SPKT) is an important option for patients with type 1 diabetes (T1D) and end-stage renal disease. While most SPKT recipients experience long-term euglycemia, about 5%, return to insulin therapy, 5–20 years after transplantation due to T1D recurrence (T1DR). Over the last two decades, we have assessed autoimmunity in our patients, evaluating T1D-associated autoantibodies (GAD65, IA2, and ZnT8), autoreactive T cells against islet antigens, and pancreas transplant biopsies. Most patients with T1DR demonstrate seroconversion for multiple autoantibodies. Autoreactive memory T cells have been identified in their peripheral blood, pancreas transplant, and peripancreas transplant tissues. Biopsies generally exhibit insulitis, the typical lesion of T1D, affecting pancreatic islets in the pancreas transplant. In addition to membrane surface expression of memory markers, we have identified other biomarkers, including CXCR3, on circulating and infiltrating autoreactive memory T cells. We hope that this work will lead to therapeutic intervention in our patients with T1DR, and that this will translate to effective treatment for T1D.

Pancreas transplant achieves consistent long-term euglycemia in type 1 diabetes. Allograft thrombosis (AT) causes the majority of early graft failure. We compared outcomes of four anticoagulation regimens administered to 95 simultaneous kidney-pancreas or isolated pancreas transplanted between 1/1/2015 and 11/20/2018. Early postoperative anticoagulation regimens included the following: none, subcutaneous heparin/aspirin, with or without dextran, and heparin infusion. The regimens were empirically selected based on each surgeon's assessment of hemostasis of the operative field and personal preference. A sonographic-based global scoring system of AT is presented. The 47-month recipients and graft survival were 95% and 86%, respectively. Recipients with or without AT had similar survival. Five and four grafts were lost due to death and AT, respectively. Outcomes of prophylaxis regimens correlated with intensity of anticoagulation. Compared with no anticoagulation, an increase in hemorrhagic complications occurred exclusively with iv heparin. The higher arterial AT score found in regimens lacking antiplatelet therapy highlights the importance of early antiaggregants therapy. Abnormal fibrinolysis was associated with an increase in AT score. Platelet dysfunction, warm ischemia time, and enteric drainage were predictive of AT and, along with other known risk factors, were incorporated into an algorithm that matches intensity of early postoperative anticoagulation to the thrombotic risk.

Background Previous studies have demonstrated inferior patient and graft survival following kidney transplant (KT) in HIV+/HCV+ coinfected patients compared to HIV+/HCV- recipients. However, these studies were conducted prior to the availability of direct-acting antiviral (DAA) agents and data in the modern era are lacking. Methods Single center retrospective study of HIV+/HCV+ coinfected KT recipients (2007-2017). Outcomes were assessed for the pre-DAA and post-DAA (ie, after December 2013) eras including 1-year patient survival, death-censored graft survival, and acute rejection; and serious infections (defined as infections requiring admission to the intensive care unit during initial transplant hospitalization or re-admission to the hospital after discharge) within the first 6 months post-transplant. Results A total of 13 consecutive HIV+/HCV+ recipients were identified. Median time of post-transplant follow-up was 722 days. Seven patients were transplanted in the DAA era; five of them had anti-HCV Ab+ donors, with two donors being HCV NAT positive; all received DAA therapy, six of them post-transplant (median time from KT to DAA: 83 days; IQR, 54-300). All the patients in the pre-DAA era were on a protease inhibitor-containing ART regimen. One-year patient and death-censored graft survivals were 83% and 67%, respectively, for the patients transplanted in the pre-DAA era, and 100% for both outcomes in the subgroup of patients transplanted in the post-DAA era (P > 0.05). Compared to patients in the post-DAA era, those in the pre-DAA era had higher incidence of serious infections (0 vs 67%; P = 0.02). Acute rejection exclusively occurred in the pre-DAA group (n = 1; 17%). Conclusions Outcomes of HIV+/HCV+ KT recipients, including HIV-/HCV+ to HIV+/HCV+ transplants, in the DAA era were excellent in this small cohort. Larger studies are needed.

The safety and efficacy of renal and liver transplantation has been reported for Jehovah's Witness (JW) patients, with patient, and graft survival similar to that of non-JW patients. We report our experience in five JW recipients of simultaneous pancreas-kidney transplants. None of the patients received transfusion of blood or blood products, either before or after transplant. Like the other solid organ transplants, patient, and graft survival was similar to that of the non-JW group. Specific technical issues related to the operative procedure include the use of the cell saver until the donor duodenum is opened (enteric contamination). Post-operatively, care should be taken to minimize drawing of blood and optimize erythrocyte synthesis with erythropoetin, folic acid, vitamin B12, and iron. Finally, it is critical that the pre-operative evaluation demonstrates sufficient cardiac reserve to allow the JW patient to tolerate a possible temporary anemic state.

Diabetic muscle infarction (DMI) is a rare entity that occurs in patients with long-standing type 1 insulin dependent diabetes mellitus (IDDM). We describe DMI occurring on an average of 5 months after SPK in four patients with IDDM and end stage renal disease (ESRD). These patients had evidence of other long-term diabetic complications including retinopathy and neuropathy, as well as microangiopathy and hypercoagulability, both of which are pre-disposing factors for DMI. The etiology of DMI is not well understood. Despite establishment of normoglycemia after kidney-pancreas transplantation, DMI may occur as a result of tissue damage/fragility secondary to the pre-existing long-term labile glycemic control and hypertension. This may be exacerbated by the pro-coagulant effects of the calcineurin-inhibitors and the use of steroids as part of the immunosuppressive regimen.

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV+ kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV- to HIV+ adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% (p=0.06) and 82% vs. 100% (p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV+ kidney transplant recipients.

We report 2 cases of sensitized patients who were successfully treated with bortezomib therapy resulting in reduction of donor-specific antibodies (DSA). Our cases illustrate the synergistic effects of combination therapy that includes bortezomib on prevention and treatment of AMR in highly sensitized patients. Moving forward, long-term data on sensitized patients treated with bortezomib are needed to fully evaluate the impact of this therapy.

Background: The clinical consequences of type 1 diabetes mellitus (IDDM) include diabetic triopathy: retinopathy, nephropathy, and neuropathy, as well as microangiopathy, accelerated atherosclerotic disease, and hypercoagulability. The etiology of the hypercoagulability is multifactorial, involving various clotting factors or pathways (for example platelets, fibrinogen, individual components of the clotting system and/or fibrinolysis in different studies). The development of end-stage renal disease (ESRD), with the uremia-related platelet effect has the potential to protect from the existing hypercoagulable state. This has important implications for surgery, particularly simultaneous pancreas–kidney (SPK) transplantation, where the pancreas has historically been prone to thrombosis. This has led us to perform intra-operative thromboelastograms (TEG's) to evaluate the patient's current coagulation status. Methods: A TEG was performed in 85 SPK recipients along with a control group of 54 non-diabetic kidney transplant (KT) recipients. Results: For each of the 4 TEG coagulation parameters, the SPK recipients were significantly more hypercoagulable than the non-diabetic KT recipients. The use of intra-operative heparin is based on the degree of hypercoagulability by TEG and degree of operative hemostasis. There has been one PT lost to thrombosis (1%) in the first week following transplantation during this time. Conclusion: The use of TEG is a helpful adjunct to SPK surgery, demonstrating the patient's current coagulation status. Nearly all SPK recipients (type 1 IDDM with ESRD) have been demonstrated to be hypercoagulable. The TEG allows the judicious use of anti-coagulation at the time of surgery, and beyond.

The safety and efficacy of renal and liver transplantation has been reported for Jehovah's Witness (JW) patients, with patient, and graft survival similar to that of non-JW patients. We report our experience in five JW recipients of simultaneous pancreas-kidney transplants. None of the patients received transfusion of blood or blood products, either before or after transplant. Like the other solid organ transplants, patient, and graft survival was similar to that of the non-JW group. Specific technical issues related to the operative procedure include the use of the cell saver until the donor duodenum is opened (enteric contamination). Post-operatively, care should be taken to minimize drawing of blood and optimize erythrocyte synthesis with erythropoetin, folic acid, vitamin B12, and iron. Finally, it is critical that the pre-operative evaluation demonstrates sufficient cardiac reserve to allow the JW patient to tolerate a possible temporary anemic state.

Diabetic muscle infarction (DMI) is a rare entity that occurs in patients with long-standing type 1 insulin dependent diabetes mellitus (IDDM). We describe DMI occurring on an average of 5 months after SPK in four patients with IDDM and end stage renal disease (ESRD). These patients had evidence of other long-term diabetic complications including retinopathy and neuropathy, as well as microangiopathy and hypercoagulability, both of which are pre-disposing factors for DMI. The etiology of DMI is not well understood. Despite establishment of normoglycemia after kidney-pancreas transplantation, DMI may occur as a result of tissue damage/fragility secondary to the pre-existing long-term labile glycemic control and hypertension. This may be exacerbated by the pro-coagulant effects of the calcineurin-inhibitors and the use of steroids as part of the immunosuppressive regimen.

Fulminant hepatic failure is associated with high mortality. Liver transplantation is an effective therapy that improves survival, and because of donor organ shortage and urgency, a bioartificial liver could act as an effective bridge to liver transplantation in patients with fulminant hepatic failure. We discuss the place of the bioartificial liver in the treatment of other causes of liver failure.