Simultaneous Pancreas-kidney Recipients Research Articles

Simultaneous Pancreas-Kidney Transplant Outcomes Stratified by Autoantibodies Status and Pretransplant Fasting C-peptide.

Pancreatic beta cell function and islet autoantibodies classically distinguish types of diabetes (type 1 diabetes mellitus [DM] or type 2 DM). Here, we sought to evaluate simultaneous pancreas-kidney (SPK) transplant outcomes stratified by the presence or absence of beta cell function and autoantibodies. SPK recipients were eligible if pretransplant autoantibodies were measured against insulin, islet cell, or glutamic acid decarboxylase 65-kD isoform. Recipients were categorized as A+ or A- based on the detection of ≥1 autoantibodies. Recipients were similarly categorized on the basis of detectable pretransplant fasting C-peptide of ≥2 ng/mL (β+) or <2 ng/mL (β-). Thus, recipients were categorized into 4 groups: A+β-, A-β-, A-β+, and A+β+. Outcomes of interest were overall pancreas graft failure (non-death-censored), death-censored pancreas, or kidney graft failure (death-censored pancreas graft failure [DCGF]; kidney DCGF), composite outcomes with any of the 3 outcomes as pancreas DCGF, use of an antidiabetic agent, or hemoglobin A1c >6.5. One hundred eighty-three SPK recipients were included: A+β- (n = 72), A-β- (n = 42), A-β+ (n = 49), and A+β+ (n = 20). We did not detect a statistical difference in non-death-censored pancreas graft failure for A+β- recipients compared with other groups: A-β- (adjusted hazard ratio [aHR]: 0.44; 95% confidence interval [CI], 0.14-1.42), A-β+ (aHR: 1.02; 95% CI, 0.37-2.85), and A+β+ (aHR: 0.67; 95% CI, 0.13-3.33) in adjusted analyses. Similar outcomes were observed for other outcomes. In SPK recipients, outcomes were similar among recipients with classic features of type 1 DM and various other types of DM.

Risk Factors for Early Post-transplant Weight Changes Among Simultaneous Pancreas-kidney Recipients and Impact on Outcomes.

There are limited data about the risk factors for weight changes and the association of significant weight changes with graft and metabolic outcomes after simultaneous pancreas and kidney (SPK) transplantation. We included all SPK recipients with both allografts functioning for at least 6 mo post-transplant and categorized them based on the weight changes from baseline to 6 mo post-transplant. We analyzed risk factors for significant weight gain (SWG) and significant weight loss (SWL) over 6 mo post-transplant, as well as outcomes including pancreas uncensored graft failure, pancreas death-censored graft failure (DCGF), composite pancreas graft outcomes of DCGF, use of an antidiabetic agent, or hemoglobin A1C >6.5%, and kidney DCGF. Of 280 SPK recipients, 153 (55%) experienced no significant weight change, 57 (20%) SWG, and 70 (25%) SWL. At 6 mo post-transplant, mean weight changes were 1.2% gain in the no significant weight change group, 13.4% gain in SWG, and 9.6% loss in the SWL groups. In multivariate analysis, the only factor associated with decreased risk for weight gain was older recipient age (aOR, 0.97; 95% confidence intervals, 0.95-0.99). Importantly, SWG or SWL were not associated with pancreas graft failure, P-DCGF, or K-DCGF. Interestingly in the adjusted model, SWG at 6 mo was associated with a lower risk for composite outcomes (HR, 0.35; 95% confidence intervals, 0.14-0.85). Forty-five percent of SPK recipients had significant weight changes by 6 mo post-transplant, but only 20% exhibited SWG. Likely because of proper management, weight changes were not associated with poor outcomes post-SPK transplant.

Pancreas transplantation: review.

Pancreas transplant (PTx) is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes types 1 and 2. The paper aims to review and analyze graft survival, patient survival, and the impact on diabetic complications. We describe that the graft survival was 82-98% at 1 year, 90% at 5 years, and 75-54% at 10 years for simultaneous pancreas-kidney recipient; 71% pancreas after kidney (PAK), and 62% PTx alone at 1 year. Patient survival: At 1 year for recipients was 96.9% simultaneous pancreas-kidney transplantation (SPK); for PAK transplantation recipients, 96.3%; and for PTx alone recipients, 98.3%. In general, the pancreas transplantation improves and reverses diabetic complications. Finally, the pancreatic transplant is a morbid procedure and emerges as a significant alternative in diabetes management, directly competing with conventional insulin therapies. Results so far suggest that the most effective transplant model is the SPK. While more patients could benefit from this procedure, surgical complications and the need for immunosuppression pose significant challenges.

Low-Dose Valganciclovir Prophylaxis Against Cytomegalovirus in Intermediate-Risk Liver and Dual-Abdominal Transplant Recipients.

Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies. The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min. This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant. Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease. Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

Donor Blood Tests do Not Predict Pancreas Graft Survival After Simultaneous Pancreas Kidney Transplantation; a National Cohort Study.

Simultaneous pancreas-kidney (SPK) transplantation improves quality of life and limits progression of diabetic complications. There is reluctance to accept pancreata from donors with abnormal blood tests, due to concern of inferior outcomes. We investigated whether donor amylase and liver blood tests (markers of visceral ischaemic injury) predict pancreas graft outcome using the UK Transplant Registry (2016-2021). 857 SPK recipients were included (619 following brainstem death, 238 following circulatory death). Peak donor amylase ranged from 8 to 3300U/L (median = 70), and this had no impact on pancreas graft survival when adjusting for multiple confounders (aHR = 0.944, 95% CI = 0.754-1.81). Peak alanine transaminases also did not influence pancreas graft survival in multivariable models (aHR = 0.967, 95% CI = 0.848-1.102). Restricted cubic splines were used to assess associations between donor blood tests and pancreas graft survival without assuming linear relationships; these confirmed neither amylase, nor transaminases, significantly impact pancreas transplant outcome. This is the largest, most statistically robust study evaluating donor blood tests and transplant outcome. Provided other factors are acceptable, pancreata from donors with mild or moderately raised amylase and transaminases can be accepted with confidence. The use of pancreas grafts from such donors is therefore a safe, immediate, and simple approach to expand the donor pool to reach increasing demands.

Local Postoperative Graft Inflammation in Pancreas Transplant Patients With Early Graft Thrombosis

Background. Graft thrombosis is the main cause of early graft loss following pancreas transplantation, and is more frequent in pancreas transplant alone (PTA) compared with simultaneous pancreas-kidney (SPK) recipients. Ischemia-reperfusion injury during transplantation triggers a local thromboinflammatory response. We aimed to evaluate local graft inflammation and its potential association with early graft thrombosis. Methods. In this observational study, we monitored 67 pancreas-transplanted patients using microdialysis catheters placed on the pancreatic surface during the first postoperative week. We analyzed 6 cytokines, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, interferon gamma-induced protein 10 (IP-10), macrophage inflammatory protein 1β (MIP-1β), IL-10, and the complement activation product complement activation product 5a (C5a) in microdialysis fluid. We compared the dynamic courses between patients with pancreas graft thrombosis and patients without early complications (event-free) and between PTA and SPK recipients. Levels of the local inflammatory markers, and plasma markers C-reactive protein, pancreas amylase, and lipase were evaluated on the day of thrombosis diagnosis compared with the first week in event-free patients. Results. IL-10 and C5a were not detectable. Patients with no early complications (n = 34) demonstrated high IL-1ra, IL-6, IL-8, IP-10, and MIP-1β concentrations immediately after surgery, which decreased to steady low levels during the first 2 postoperative days (PODs). Patients with early graft thrombosis (n = 17) demonstrated elevated IL-6 (P = 0.003) concentrations from POD 1 and elevated IL-8 (P = 0.027) concentrations from POD 2 and throughout the first postoperative week compared with patients without complications. IL-6 (P &lt; 0.001) and IL-8 (P = 0.003) were higher on the day of thrombosis diagnosis compared with patients without early complications. No differences between PTA (n = 35) and SPK (n = 32) recipients were detected. Conclusions. Local pancreas graft inflammation was increased in patients experiencing graft thrombosis, with elevated postoperative IL-6 and IL-8 concentrations, but did not differ between PTA and SPK recipients. Investigating the relationship between the local cytokine response and the formation of graft thrombosis warrants further research.

Pancreatic Allograft Thrombosis: Implementation of the CPAT-Grading System in a Retrospective Series of Simultaneous Pancreas-Kidney Transplantation.

Pancreatic graft thrombosis (PAT) is a major surgical complication, potentially leading to graft loss. The recently proposed Cambridge Pancreas Allograft Thrombosis (CPAT) grading system provides diagnostic, prognostic and therapeutic recommendations. The aim of the present study was to retrospectively assess computed tomography angiography (CTA) examinations performed routinely in simultaneous pancreas-kidney (SPK) recipients to implement the CPAT grading system and to study its association with the recipients' outcomes. We retrospectively studied 319 SPK transplant recipients, who underwent a routine CTA within the first 7 postoperative days. Analysis of the CTA scans revealed PAT in 215 patients (106 grade 1, 85 grade 2, 24 grade 3), while 104 showed no signs. Demographic data of the patients with and without PAT (thrombosis and non-thrombosis group) were not significantly different, except for the higher number of male donors in the thrombosis group. Pancreatic graft survival was significantly shorter in the thrombosis group. Graft loss due to PAT was significantly associated with grade 2 and 3 thrombosis, while it did not differ for recipients with grade 0 or grade 1 thrombosis. In conclusion, the CPAT grading system was successfully implemented in a large series of SPK transplant recipients and proved applicable in clinical practice.

The burden of coronary heart disease in simultaneous pancreas-kidney transplantation: coronary angiography as a diagnostic method for all? - a retrospective study.

Type 1 diabetes mellitus is associated with an increased risk of coronary artery disease, which is frequently asymptomatic. This risk increases significantly in those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols are still controversial for coronary artery disease in this population. We retrospectively analysed 99 simultaneous pancreas-kidney recipients from our centre from 2011 to 2018 and selected 77 patients who underwent coronary angiography during the pre-transplant evaluation. Our aim was to identify potential risk factors associated with significant lesions on coronary angiography. Almost half of our cohort of 77 candidates submitted to coronary angiography had coronary artery disease. Of these, nearly 30% underwent revascularization, although only one of them reported symptoms of myocardial ischemia. In a univariate analysis, the presence of smoking habits was the only risk factor for coronary artery disease. We also found that 20 or more years of type 1 diabetes mellitus was significantly associated with the presence of coronaropathy. Selection of diabetic candidates with acceptable cardiac risk before simultaneous pancreas-kidney transplantation is imperative. Given the impact of a correct diagnosis and a low procedural risk, we defend the routine use of coronary angiography as the initial screening method for coronary artery disease in this population. Particularly care must be taken in evaluating asymptomatic patients with long-term type 1 diabetes mellitus and smokers.

Outcomes of Primary Simultaneous Pancreas-kidney Transplants by Induction Agent in the United States.

Utilizing the Scientific Registry of Transplant Recipients, we examined all primary SPK transplants between 2000 and 2020, excluding crossmatch-positive recipients. We grouped recipients according to induction regimen into 3 groups: rabbit anti-thymocyte globulin (r-ATG) (n = 5678), alemtuzumab (n = 1199), and interleukin-2 receptor antagonist (IL-2RA; n = 1593). We analyzed the 10-y recipient and composite (kidney and pancreas) graft survival using the Kaplan-Meier survival function. Cox-proportion hazard models were generated to examine the association between induction type, the 10-y recipient, and graft survival. Models were adjusted for recipient age, sex, ethnicity, HLA-mismatch, diabetes type, dialysis dependency, cold-ischemia time, local versus imported organs, panel reactive antibody, steroid maintenance, and Pancreas Donor Risk Index. r-ATG was associated with the lowest 1-y kidney and pancreas rejection rates compared with other agents (P < 0.001). In the univariable analysis, induction type was not associated with recipient (log-rank P = 0.11) or graft survival (log-rank P = 0.36). In the multivariable model for the composite graft survival, alemtuzumab use was associated with 22% increased kidney or pancreas graft loss compared with r-ATG (adjusted hazard ratio, 1.22; 95% confidence interval, 1.05-1.42), whereas IL-2RA use was not a predictor of graft survival. Induction type did not influence recipient survival in the adjusted model. r-ATG use was associated with the lowest SPK rejection rates. Compared with r-ATG, alemtuzumab but not IL-2RA was associated with worse long-term death-censored SPK graft outcome. Our analysis supports the common use of r-ATG for induction in US primary SPK recipients.

Recipient and Graft Outcomes in Simultaneous Kidney and Pancreas Transplantation With Steroid Avoidance in the United States.

Steroid avoidance in kidney transplantation has been proven noninferior. Long-term outcome data on steroid avoidance in simultaneous pancreas-kidney (SPK) remains scant. Utilizing the Scientific Registry of Transplant Recipients between 2000 and 2020, we studied all primary crossmatch negative SPK recipients (N = 5683) who received antithymocyte globulin induction and were discharged alive with functioning grafts on tacrolimus and mycophenolate ± steroid maintenance. Recipients were grouped according to steroid use into 2 groups: steroid maintenance (n = 4191) and steroid avoidance (n = 1492). Kaplan-Meier curves censored at 10 y were generated for recipient and allograft survival by steroid maintenance. Predictors for recipient and graft survival were examined using Cox Proportional Hazards. Models were adjusted for age, body mass index, ethnicity, diabetes type, human leukocyte-antigen mismatches, cold ischemia time, transplant era, preemptive transplantation, and pancreas donor risk index with the transplant center included as a random effect. Steroid avoidance gained popularity over time, accounting for over one-fourth of the studied cohort. One-year acute rejection rates by steroid avoidance were comparable for kidney (8.6% versus 9%, P = 0.783); however, the pancreas rejection rate was lower in the steroid avoidance group (7.9% versus 10%; P = 0.035). After adjustment, steroid avoidance did not influence recipient survival (lower level of confidence interval, adjusted hazard ratio, upper level of confidence interval: 0.94, 1.15, 1.39), pancreas (0.75, 0.93, 1.16), or kidney (0.95, 1.18, 1.45) death-censored survival, compared with steroid maintenance. Accounting for the recipient and graft characteristics, steroid avoidance is associated with similar recipient, pancreas, and kidney graft outcomes compared with steroid maintenance in SPK recipients after antithymocyte globulin induction with tacrolimus and mycophenolate maintenance.

214.5: Long-term Outcomes in Primary Simultaneous Kidney and Pancreas Recipients Under Steroid Avoidance in the United States

Background: Steroid avoidance in kidney transplantation has been proven non-inferior. Data on steroid avoidance in simultaneous pancreas-kidney (SPK) is scant. Methods: We utilized the Scientific Registry of Transplant Recipients (SRTR) between 2000 and 2020 we studied all primary crossmatch negative SPK recipients (N=5683) who received anti-thymocyte globulin for induction and were discharged alive on tacrolimus and mycophenolate with or without steroid maintenance. Recipients were grouped according to steroid use into two groups: steroid maintenance n=4191 and steroid avoidance n=1492. Kaplan-Meier curves with generated for Recipient and allografts survival according to steroid maintenance censored at 10 years. Predictors for recipient and grafts survival were examined using Cox proportional Hazards. Models were adjusted for age, BMI, ethnicity, diabetes type, HLA-antigen mismatches, cold ischemia time, transplant era, preemptive transplantation, and PDRI with the transplant center included as a random effect. Results: Steroid avoidance gained popularity over the years, accounting for over one fourth of the studied cohort. One-year acute rejection rates by steroid avoidance were comparable for kidney (8.6 vs. 9%, P= 0.783, however pancreas rejection rate was lower in the steroid avoidance group (7.9 vs. 10%. P=0.035). In the Kaplan-Meier analysis for the pancreas death-censored graft survival (DCGS), steroid avoidance was associated with better pancreas graft survival (log-rank p =0.006). The kidney DCGS did not vary between groups (log-rank p=0.233). In the multivariable models, steroid avoidance did not influence recipient (LLCI, aHR, ULCI) (0.94, 1.15,1.39), death-censored pancreas graft survival (0.75, 0.93, 1.16) or kidney (0.95, 1.18, 1.45) compared to recipients on steroid maintenance. Conclusion: After multivariable adjustment for recipient and grafts characteristics, steroid avoidance is associated with similar patient, pancreas and kidney grafts outcomes when compared with steroid maintenance in SPK recipients following r-ATG induction and tacrolimus plus mycophenolate maintenance. The data reported here have been supplied by the Hennepin Healthcare Research Institute (HHRI) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government.

343.3: Outcomes of Primary Simultaneous Pancreas-Kidney Transplants by Induction Agent in the United States

Background: Induction immunosuppression choice for simultaneous pancreas-kidney (SPK) transplants varies widely in the United States. We examined the association between induction agents and outcomes of SPK recipients discharged on tacrolimus and mycophenolate. Methods: We used the Scientific Registry of Transplant Recipients to examine all primary SPK transplants between 2000 and 2020, excluding crossmatch positive recipients and those with other induction regimens. We grouped recipients according to induction regimen used into three groups: anti-thymocyte globulin (n=5678), alemtuzumab (n=1199) and IL-2 RA (1593). Delayed graft function, acute kidney and pancreas rejection rates were compared by type of induction. We analyzed the ten-year recipient and composite (kidney and pancreas) grafts survival using Kaplan-Meier survival function. Cox proportion hazard models were utilized to examine the association between induction type and the ten-year recipient and grafts survival. Models were adjusted for recipient age, sex, ethnicity, HLA-MM, diabetes type, dialysis dependency, cold ischemia time, local vs imported organs, PRA, steroid maintenance and PDRI. Results: Delayed graft function rate was observed in less than 6.5% of the recipients and did not differ between groups P=0.68. One-year kidney rejection rates were observed in 8.9% of the anti-thymocyte group, 9.5% of the IL-2RA group and 13% in the alemtuzumab group (p<0.001). Similarly, one-year pancreas rejection rates were observed in 9.5% of the anti-thymocyte group, 12.4% of the IL-2RA group and 14.1% in the alemtuzumab group (p<0.001). In the univariable analysis, induction type was not associated with recipient (log-rank p=0.11) or grafts survival (log-rank p=0.36). In the multivariable model for the composite grafts survival, alemtuzumab use was associated with 22% increased kidney or pancreas graft loss compared to anti-thymocyte globulin (LLCI, aHR, ULCI) (1.05, 1.22, 1.42), while IL-2RA use was not a predictor of worse grafts survival. Induction type didn’t influence recipient survival in the adjusted model. Conclusion: r-ATG use was associated with the lowest kidney and pancreas rejection rates. Compared to r-ATG, alemtuzumab but not IL-2RA was associated with worse long-term death-censored SPK grafts outcome. Our analysis supports the US national popularity of r-ATG induction in primary SPK recipients.

Factors affecting sensitization following kidney allograft failure.

Management of immunosuppression in a kidney transplant recipient with a failed allograft is complex; continuation carries infectious and metabolic risks, and discontinuation can lead to sensitization. We evaluated risk factors for sensitization in 89 kidney or simultaneous kidney-pancreas recipients, whose kidney transplant failed after January, 2013 and who were subsequently re-evaluated for kidney transplantation. Among recipients with pre graft failure cPRA<50%, calcineurin inhibitor (CNI) continuation (OR .11, P=.003) and steroid continuation (OR .17, P=.04) were associated with significantly lower odds of developing an absolute increase in cPRA of ≥50%. Each additional HLA mismatch was associated with OR of 2.16 (P=.02). CNI use was associated with OR of .09 (P=.001) for increase in cPRA to ≥80% if pre graft failure cPRA was <50%, and OR of .08 (P=.02) for increase in cPRA to ≥98% if pre graft cPRA was <80%. Anti-metabolites were continued more often among recipients who had a <50% increase (P=.006); however, the association was lost on multivariate analyses. Weaning off immunosuppression and higher number of HLA mismatches are associated with greater likelihood of sensitization. While both CNI and steroid continuation conferred some protection against increase in cPRA, CNI continuation was the only factor protecting against becoming highly sensitized.

406.2: Utility of Donor-derived Cell-free DNA in Assessing Simultaneous Pancreas-Kidney Transplantation Rejection

Introduction: Among solid organ transplants, pancreas transplantation has one of the highest rates of acute rejection within the first 12 months. Graft biopsy, the gold standard, is risky and often not available. Hence, a non-invasive biomarker with good predictive value, such as donor-derived cell free DNA (dd-cfDNA), may be useful in predicting risk of rejection. In this study we sought to analyze the performance of a dd-cfDNA test in patients with simultaneous pancreas kidney (SPK) transplant. Methods: A retrospective study was conducted from 2017 to 2020 on patients admitted for pancreas graft biopsy at the Hospital Clínic Barcelona. Plasma samples were collected on the day of biopsy. dd-cfDNA fraction was assessed using the ProsperaTM test, a SNP-based mmPCR methodology to predict risk of rejection (including T-cell mediated rejection [TCMR] and antibody mediated rejection [ABMR]). Results: Plasma samples (n=50) were obtained from 37 SPK recipients. Pancreas biopsies were collected from 30 patients. Of the 50 plasma samples, 36 were plasma-biopsy paired and per Banff criteria were categorized as no rejection (n=21) and acute rejection (aTCMR and aABMR; n=15). Median dd-cfDNA levels were significantly elevated in samples with graft rejection diagnosis: 1.11 [0.83–1.66] vs. no rejection 0.65 [0.28–1.00]; p=0.004),especially after 45 days post transplantation (AR: 0.83[0.67–1.59], NR:0.45[0.13–0.55], p=0.004) (Figure 1). The overall performance of the test after 45 days of transplant is as follows: sensitivity 71.4%, specificity 91.6%, PPV: 83.8%, NPV:84.6%. Conclusion: dd-cfDNA assay can accurately differentiate active rejection from non rejection through a non-invasive, simple blood test in SPK patients as early as 45 days post SPK transplant.Medical writing support was provided by Nour Al Haj Baddar, Ph.D. from Natera, Inc. at San Carlos, CA.

Neurogenic Orthostatic Hypotension: a Common Complication of Successful Pancreas Transplantation.

Background.Orthostatic hypotension (OH) is a poorly understood complication of simultaneous pancreas–kidney (SPK) transplantation. We sought to determine the incidence, timing, and relationship of OH to rapid glycemic control in the early posttransplant period.Methods.This was a nonrandomized retrospective single-center review of 75 SPK and 19 kidney-alone (KA) recipients with type 1 diabetes (DM).Results.OH occurred in 57 (76%) SPK versus 2 (10%) KA recipients (odds ratio [OR] 61.72, 95% confidence interval [CI], 9.69-393.01; P < 0.001). The median onset of OH was 12 (interquartile range [IQR] 9–18) days posttransplant and resolved in 85% of SPK recipients after a median of 2.5 (IQR 1.2–6.3) months. Among SPK recipients, independent risk factors for OH were a shorter duration of DM (OR 0.85, 95% CI, 0.73-0.98; P = 0.03) and rapid glycemic control in the early posttransplant period (OR 1.13, 95% CI, 1.01-1.27; P = 0.04), as evidenced by a larger percent change in hemoglobin A1c (HbA1c) from transplant to month 3. OH patients had a higher median baseline HbA1c [8.3% (IQR 7.2–10.0) versus 7.1% (IQR 6.8–8.3); P = 0.07], lower median 3-month HbA1c [4.8% (IQR 4.6–5.2) versus 5.2% (IQR 5.0–5.4); P = 0.02], and a larger reduction in HbA1c over time as compared to recipients without OH (P < 0.01).Conclusions.Our results show that OH is more likely to occur following SPK versus KA transplantation and is strongly associated with rapid glucose normalization within the early posttransplant period.

Pancreas-Kidney Transplantation: Do We Know the Frequency of Clinical Complications?

The objective of this study was to describe the most common medical complications in simultaneous pancreas-kidney recipients in our center. Retrospective and descriptive study of complications observed in a series of 73 simultaneous pancreas-kidney transplant recipients, which included 54 men and 19 women with an average age of 40.6 years, between February 2009 and April 2019. The study assessed the incidence of cytopenia, viral infections, tumors, and graft rejection. Frequency tables were created for each complication in the analysis. Cytopenia was the most common complication, either by itself or associated with a different complication, and it was found in 23.3% of all patients. The most common infection was cytomegalovirus, which was in 55.6% of all 9 patients who presented infections in spite of universal prophylaxis with valganciclovir, followed by herpes virus (11.1%), papillomavirus (11.1%), and polyoma BK virus (22.2%). Regarding tumors, the number of patients who presented this complication was low; 2 gynecologic tumors were detected (cervical intracellular neoplasia and one ovarian tumor), and 1 case of skin tumor was also observed. There were 3 cases of acute rejection, which represents 4.1% of all patients. Rejection was cellular and steroid-sensitive except for 1 case that was humoral, with good response to treatment. In spite of the doses of immunosuppressive drugs received by these patients, the incidence of infections was low, and cytomegalovirus was the most common infection. As a consequence of the drugs administered, virtually all patients developed cytopenia. The number of tumors observed in this series was low in spite of the immunosuppressive treatment.

SARS-CoV-2 Infection After Full Vaccination in Kidney Transplant Recipients.

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccines have been developed and approved for human use in the United States and Europe.1 In our center, coronavirus disease 2019 (COVID-19) vaccination of kidney transplant recipients (KTRs) started in February 2021, with about 800 KTRs fully vaccinated in May 2021. Among the different vaccines, mRNA vaccines BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna) have demonstrated an effectiveness of up to 95% in preventing COVID-19 in immunocompetent population. However, the effectiveness in KTRs to induce an immunological response has been reported to be significantly lower (up to 65%), and information about the risk and severity of a postvaccination COVID-19 is scarce in these patients.1-6 Herein, we describe 21 cases of KTRs (20 KTRs and 1 simultaneous pancreas-kidney recipient) who developed a polymerase chain reaction–proven COVID-19 after a full vaccination course. The study was approved by the ethics committee from our center. From the 21 KTRs, 2 patients (9%) received a 2-dose regimen of the BNT162b2 vaccine and 19 (91%) the mRNA-1273 vaccine. Only 1 patient (5%) developed SARS-CoV-2 immunoglobulin G antibodies after vaccination (which were assessed >15 d after the second dose). All patients were diagnosed with COVID-19 through a nasopharyngeal swab after a mean time of 84.71 ± 27.43 d from the second vaccine dose (52% with pneumonia). SARS-CoV-2 variants could be determined in 5 patients: 2 patients were infected with the Alpha variant and 3 with the Delta one. Table 1 summarizes demographic, transplantation immunosuppression, and COVID-19 characteristics of the analyzed patients. Two patients (9%) were asymptomatic. TABLE 1. - Demographic, transplantation, and COVID-19 characteristics of the analyzed patients Kidney transplant recipients (n = 21) Gender, male 9 (43) Age at COVID-19 diagnosis, y 57.61 ± 11.96 Transplant type Kidney transplant 20 (95) Simultaneous pancreas-kidney transplant 1 (5) Time from transplant to COVID-19 diagnosis, y 3.79 (1.83–13.12) Induction immunosuppression No induction 6 (29) Basiliximab 6 (29) Thymoglobulin 9 (42) Maintenance immunosuppression Tacrolimus 21 (100) Mycophenolate 15 (71) Everolimus 6 (29) Prednisone 21 (100) SARS-CoV-2 vaccine BNT162b2, Pfizer/BioNTech 2 (9) mRNA-1273, Moderna 19 (91) SARS-CoV-2 IgG antibodies after vaccination, yes 1 (5) Time from second vaccine dose to COVID-19 diagnosis, d 84.71 ± 27.43 SARS-CoV-2 variant Alpha 2 (9) Delta 3 (14) Symptoms at COVID-19 diagnosis Asymptomatic 2 (9) Fever 16 (76) Cough 11 (52) Dyspnea 8 (38) Diarrhea 4 (19) Patient hospital admission, yes 11 (52) ICU admission with MV, yes 6 (29) COVID-19 treatment Dexamethasone 6 (29) Remdesivir 5 (24) Remdesivir plus baricitinib 1 (5) Remdesivir plus anakinra 1 (5) Tocilizumab 3 (14) ≥1 immunosuppressant withdrawn, yes 16 (76) Patient outcomes Discharged 13 (62) Dead 1 (5) Hospital stay, d 11 (7–20) Data are presented as mean ± SD, median (IQR), or n (%), unless otherwise specified.COVID-19, coronavirus disease 2019; ICU, intensive care unit; IgG, immunoglobulin G; IQR, interquartile range; MV, mechanical ventilation; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Regarding patient management, 11 patients (52%) required hospital admission, and 7 (33%) required intensive care unit (ICU) admission with the need for mechanical ventilation in 6. Ten (48%) were managed as outpatients (Table 1). Of the 21 patients, 1 (5%) died, 7 (33%) are still admitted (5 of them in the ICU), and 13 (62%) have been already discharged. Current median hospital stay is 11 (7–20) d. With this letter, we would like to provide preliminary information about a single-center kidney transplant population in Spain after a full COVID-19 vaccination regimen and reinforce the apparently less efficient immunization effect that COVID-19 vaccines provide in KTRs and the need to vaccinate their close relatives, as well as to still maintain precautions against COVID-19 in this population (especially against the Delta variant), even after full vaccination course. Nevertheless, actual hospital and ICU admission rates are lower compared with a nonvaccinated cohort of KTRs (79% and 52% for hospital and ICU admission, respectively) from our center. Larger studies are needed to provide robust information on the prognosis and management of KTRs with COVID-19 after vaccination, as well as the potential need for a third dose to increase the immunization rate.

Metastatic Donor-derived Malignancies Following Simultaneous Pancreas-kidney Transplant: Three Case Reports and Management Strategies.

Background.Stopping immunosuppression in a transplant patient with donor-derived malignancy offers the theoretical benefit that reconstitution of the patient’s immune system will allow “rejection” of the malignancy, as the malignancy also originates from allogeneic tissue. However, this option exists with the caveat that the patient’s allograft(s) will likely be rejected too. In simultaneous pancreas-kidney (SPK) recipients, the normal continued functioning and possible absence of malignancy in either the unaffected kidney or pancreas further complicate this decision.Methods.The charts of 3 patients with donor-derived metastatic malignancies after SPK were retrospectively reviewed in detail. We provide treatment and management recommendations based on successful outcomes and a review of the existing literature.Results.Consistent with a broad review of the literature, in all 3 cases, complete immunosuppression cessation, removal of both grafts, and in 1 case treatment with an immune checkpoint inhibitor to augment the immune response was successful. One patient is doing well 1 year after successfully undergoing kidney retransplantation, while a second patient is active on the waitlist for SPK retransplantation after no evidence of metastatic disease for 2 years.Conclusion.The successful management of metastatic donor-derived malignancies requires allograft removal, immunosuppression cessation, and adjuvant therapy that includes occasional use of checkpoint inhibitors to augment the immune response.

Early technical pancreas failure in Simultaneous Pancreas-Kidney Recipients does not impact renal allograft outcomes.

Early pancreas loss in simultaneous pancreas-kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients (n=218). Early pancreas allograft loss occurred in 12.8% (n=28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p=0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p=0.22), surgical wound complications (p=0.12), or rejection episodes occurring in the first year (p=0.87). Despite differences in DGF, both groups had excellent renal function at 1year post-transplant (eGFR 64.1±20.8 vs. 65.8±22.9, p=0.75). There were no differences in patient (HR 0.58, 95% CI 0.18-1.87, p=0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23-3.06, p=0.77). One- and 2-year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2years (p=0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.

Daily use of a muscle pump activator device reduces duration of hospitalization and improves early graft outcomes post-kidney transplantation: A randomized controlled trial.

Kidney and simultaneous pancreas-kidney (SPK) transplant recipients can have prolonged postoperative hospitalization due to edema. Thrombo-embolic-deterrent (TED) stockings with intermittent pneumatic compression devices (TED+IPC) have been used to improve venous return during the perioperative period. The objective of this trial was to evaluate the effects of TED+IPC vs. muscle pump activator (MPA) devices on factors that could reduce postoperative complications and duration of hospitalization. In this single-center, prospective, randomized, controlled trial, 221 kidney and SPK transplant recipients were randomized to either wearing TED+IPC or MPA for six days postoperatively. Groups were compared with respect to postoperative urine output, lower limb edema, weight, days in hospital, mobility, serum creatinine, delayed graft function, need for dialysis, and lower extremity blood flow. Patients in the MPA group had significantly higher urine output and less increase in mid-calf leg circumference and weight gain compared to the TED+IPC group (p=0.003, p=0.001, and p=0.003, respectively). The MPA group also experienced shorter hospitalization (p=0.038), higher femoral vein velocity (p=0.001), and took more steps (p=0.009). Incidence of delayed graft function (p=0.72) and number of dialysis runs (p=0.39) was not different between study groups. Subgroup analysis of primary endpoints in donation after cardiac death recipients and SPK recipients did not yield any significance between the study arms. Postoperative use of the MPA device increases urine output, decreases leg edema, minimizes weight gain, and decreases duration of hospitalization after kidney transplantation. A larger and longer-term trial is needed to evaluate the impact on graft function.