Kidney-pancreas Recipients Research Articles

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.

High Intrapatient Tacrolimus Variability and Increased Cell-Free DNA in Kidney Transplant Recipients.

Introduction: An inverse relationship has been identified between tacrolimus serum concentrations and donor-derived cell-free DNA (dd-cfDNA) levels after lung transplant, but limited data exists on this relationship in the kidney transplant population. Project Aim: The purpose of this evaluation was to examine the relationship between high tacrolimus variability and elevated dd-cfDNA levels in kidney and simultaneous pancreas-kidney transplant recipients at a single center. Design: Single-center, retrospective, descriptive comparative evaluation of kidney and pancreas-kidney transplant recipients who received longitudinal ddcfDNA surveillance. Intrapatient tacrolimus variability was assessed using the coefficient of variation (%CV) measured between 1 and 12 months posttransplant. Pediatrics, retransplant or multiorgan transplant recipients, and pregnant recipients were excluded. Results: One hundred fifteen recipients with 518 dd-cfDNA levels and 3028 tacrolimus troughs were assessed. Pancreas-kidney recipients had significantly higher median dd-cfDNA (0.29% vs. 0.18%, P = .034) and were excluded from analysis. Ninety-nine kidney transplant recipients were included for analysis. Recipients with tacrolimus %CV ≥30 (N = 66) had significantly higher median dd-cfDNA than %CV <30 (0.22% vs. 0.17%, P = .031). Tacrolimus %CV ≥30 demonstrated higher median peak dd-cfDNA than %CV <30, though this was not statistically significant (0.36% vs. 0.28%, P = .058). Conclusion: These data demonstrated that high intrapatient tacrolimus variability may be associated with elevated dd-cfDNA in the first year after kidney 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.

The Impact of Kidney/Pancreas Transplantation on Peripheral Arterial Disease.

It is unclear whether kidney/pancreas (KP) transplantation will prevent the progression of peripheral arterial disease (PAD) in patients with insulin dependent diabetes (IDDM) and end-stage renal disease. We sought to determine the pre- and posttransplant prevalence of symptomatic PAD and changes in carotid artery intima-media thickness (IMT) in KP recipients. In this single center study, outcomes were compared between KP recipients with and without a history of PAD. A subset of recipients underwent pre- and posttransplant IMT measurements. Among the study group (N = 107), 18 (17%) recipients admitted to a pretransplant history of symptomatic PAD, comprised 11 foot infections and 7 amputations (5 minor and 2 major). Baseline characteristics of age, gender, race, years of diabetes, dialysis history, smoking history, years of hypertension, and history of coronary artery disease (CAD) were equivalent between PAD and non-PAD cohorts. At a median follow-up of 60 months (IQR: 28, 110), 16 (15%) KP recipients had suffered a PAD event. In multivariate analysis, a pretransplant history of PAD (hazard ratio [HR] 9.66, p < 0.001) and CAD (HR 3.33, p = 0.04) were independent predictors of posttransplant PAD events. Among a subset of 20 recipients (3 with PAD), mean IMT measurements pretransplant and at a median of 24 (range 18-24) months posttransplant, showed no evidence of disease progression. Based on IMT measurements and clinical results, KP transplantation stabilized PAD in most patients, but did not alter outcomes of symptomatic PAD recipients. A pretransplant history of PAD and CAD was an independent predictor of posttransplant PAD events.

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.

BK polyomavirus DNAemia in pancreas transplant recipients compared to pancreas-kidney recipients.

BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited regarding its epidemiology and outcomes in pancreas transplant recipients. We conducted a retrospective cohort study of adults who underwent pancreas transplantation from 2010-2020. The primary outcome was BKV DNAemia. Secondary outcomes were estimated glomerular filtration rate (eGFR) reduction by 30%, eGFR<30mL/min/1.73m2 , endstage kidney disease, and pancreas allograft failure. Cox regression with time-dependent variables was utilized. Four hundred and sixty-six patients were analyzed, including 74, 46, and 346 with pancreas transplant alone (PTA), pancreas-after-kidney, or simultaneous pancreas-kidney transplants, respectively. PTA recipients experienced a lower incidence of BKV DNAemia (8.8% vs. 32.9%; p<.001) and shorter duration of DNAemia (median 28.0 vs. 84.5 days). No PTA recipients with BKV DNAemia underwent kidney biopsy or developed endstage kidney disease. Lymphopenia, non-PTA transplantation, and older age were associated with BKV DNAemia, which itself was associated with pancreas allograft failure (adjusted hazard ratio 2.14, 95% confidence interval 1.27-3.60; p=.004). Among PTA recipients, BKV DNAemia was not associated with eGFR reduction or eGFR<30mL/min/1.73m2 . BKV DNAemia was common among PTA recipients, though lower than a comparable group of pancreas-kidney recipients. However, BKV DNAemia was not associated with adverse native kidney outcomes and no PTA recipients developed endstage kidney disease. Conversely, BKV DNAemia was associated with pancreas allograft failure. Further studies are needed to estimate the rate of BKV nephropathy in this population, and further evaluate long-term kidney outcomes.

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.

215.12: Renal Handling of Phosphorus Very Early After Kidney Transplantation in Adults

Introduction: To our knowledge there are no studies that describe phosphorus behavior in the early days of post kidney and simultaneous kidney-pancreas transplant. We aim to describe the urinary handling of phosphorus as well as the bone and mineral metabolism immediately before and during the first 8 days of post transplantation. Methods: Observational descriptive longitudinal study including 61 renal and simultaneous kidney-pancreas transplant adult recipients (either living or deceased donors) at Hospital CEMIC Buenos Aires. Baseline blood samples were drawn pre transplant and then after surgery along with urine samples at days 1,3,5, and 7 to measure serum phosphorus, calcium, creatinine, pre-transplant intact parathormone (iPTH), urinary phosphorus and creatinine excretion, glomerular filtration rate (by urinary creatinine clearance), and fractional excretion of phosphorus. Results: Mean age was 49 ± 13, 54% were male, 90% were kidney transplants, 75% received organs from deceased donors, average serum vitamin D was 22.1 ng/mL, 37% had hyperparathyroidism (iPTH>580 pg/mL) and 13% had hypoparathyroidism (iPTH<120 pg/mL) before transplant. We observed that creatininemia decreased (5.9 mg/dL at day 1 and 2.0 mg/dL at day 7 p 0.0001) and also serum phosphorus decreased (6.2 ± 1.9 mg/dL at day 1 and 4.2 ± 2.8 mg/dL at day 7 p 0.0001), while serum calcium and phosphaturia increased [0.5 g/day (0.1-1.3) at day 1 vs 0.63 g/day (0.4-0.88) at day 7 p 0,015] during the follow up. Interestingly, there were no changes in phosphorus fractional excretion (PEF) (table 1). In subgroup analysis recipients of living donors showed lower phosphatemia (4.8 mg/dL vs 6.7 mg/dL at day 1, p 0.000, and 2,2 mg/dL vs 4.8 mg/dL at day 7, p 0.000) probably related to the greater GFR and substantially higher phosphaturia [1.44 g/day (0.81-1.69) vs 0.29 (0.8-0.76) at day 1, p 0.000], on the other hand, PEF was lower when compared to deceased donors recipients (DDR). Among DDR (n:46), those without delayed graft function (n:29) (DGF) had higher GFR and phosphaturia during the whole study, [a greater phosphorus excretion was statistically significant at day 1 and 3: 0.54 g/day vs 0.10 g/day p 0.000 at day 1, 0.85 g/day vs 0.10 g/day at day 3, 0.77 g/day vs 0.47 g/day p 0.09 at day 5, 0.71 g/day vs 0.42 g/day p 0.07 at day 7 (table 2)], and there was no difference regarding PEF compared to those with DGF. Patients were divided by tertiles of iPTH, and there were no differences in any measured aspect and also no correlation between iPTH and phosphaturia. Conclusion: In this study we observed how phosphaturia improves with the recovery of GFR while PEF remains unchanged. This finding suggests that the tubules and interstitium, together with the hormonal context might not play a significant role in phosphorus handling at this point when the organ is still regaining function.

Patient and kidney transplant survival in type 1 diabetics after kidney transplant alone compared to simultaneous pancreas-kidney transplant.

BackgroundDonor and other differences mean understanding drivers of transplant survival for type 1 diabetics is challenging. We aimed to compare outcomes of simultaneous pancreas‐kidney transplant over kidney transplant alone for people with end‐stage kidney disease (ESKD) and type 1 diabetes.MethodsWe performed a population‐based cohort study comparing outcomes from kidney alone and kidney‐pancreas transplants using registry data. Our study population was people in Australia and New Zealand with type 1 diabetes and ESKD who received a kidney transplant in 1984–2016. Primary outcomes were time to kidney transplant failure and all‐cause death. Secondary outcomes were time to cardiovascular and non‐cardiovascular death. We compared adjusted survival using Cox regression (hazard ratio HR and 95% confidence intervals CI).ResultsOf 1295 type 1 diabetics receiving a transplant, 430 (33%) received deceased donor kidney, 172 (13%) received living donor kidney, and 693 (54%) received pancreas‐kidney transplant. Compared to deceased donor kidney, pancreas‐kidney recipients had 40% lower rate of kidney transplant failure (adjusted HR 0.60; 95% CI 0.45–0.81; p = 0.001) and 34% lower mortality (adjusted HR 0.66; 95% CI 0.53–0.83; p < 0.001), driven by 49% reduction in cardiovascular mortality (adjusted HR 0.51; 95% CI 0.36–0.72; p < 0.001). Pancreas‐kidney recipients had similar reductions in transplant failure and mortality compared to living kidney recipients, after adjusting for transplant timing.ConclusionsFor people with type 1 diabetes, pancreas‐kidney transplant provides improved transplant and overall survival compared to deceased donor kidney alone. Living donor kidneys may perform just as well as pancreas‐kidney transplant if waiting times are short.

Impact of Late and Recurrent Acute Graft Pyelonephritis on Long-Term Kidney Graft Outcomes.

BackgroundWhile Urinary tract infections are the most common infections in kidney transplant recipients, the impact of late acute graft pyelonephritis (AGPN) on graft outcomes remains unknown. Our study was performed to more precisely evaluate the long-term impact of AGPN.MethodsWe included 9052 kidney and combined kidney-pancreas recipients who underwent transplantation between 2008 and 2018 from a French multicenter cohort. The relationships between AGPN and patient and graft survival were analyzed with a time-dependent multivariate Cox model.ResultsThe cumulative incidence of AGPN was 20.9%. A first episode of early AGPN is associated with a non-significant increase in the risk of graft failure (hazard ratio [HR], 1.27; 95% confidence interval [95% CI], 0.90 to 1.79). Though, cumulative number of AGPN episodes (HR = 1.51; 95% CI, 0.89 to 2.57 for two episodes and HR = 2.08; 95% CI, 1.17 to 3.69 for three or more episodes) is associated with an increased risk of graft failure. In contrast, when the first episode of AGPN occurred late (i.e., 6 months post transplantation), the risk of graft failure is significantly increased (HR = 2.25; 95% CI, 1.65 to 3.07), and this risk remains relatively stable with the recurrence of late AGPN episodes. The onset of late AGPN were also associated with a higher risk of patient death. ConclusionThis analysis shows that late AGPN and recurrent AGPN are both risk factors for a poor long-term graft outcome and mortality. Late AGPN should not be considered benign infections in post-transplantation follow-up.

Six-month Antibody Kinetics and Durability After 3 Doses of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.

Six-month Antibody Kinetics and Durability After 3 Doses of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.

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.

Graft Loss due to Chronic Rejection in Pancreas Transplantation: Impact of HLA Matching

Chronic rejection has remained the Achilles heel in improving the long-term graft survival in pancreas transplants. A single center retrospective analysis of outcomes was performed to determine if HLA mismatches were associated with graft loss due to chronic rejection. In this study, we analyzed all simultaneous kidney-pancreas transplants performed at our center between January 2000 to January 2011. Patients with functioning grafts (FG) were compared to those with grafts lost due to chronic rejection (CRG) with respect to their HLA A, B and DR matches and mismatches. Of the 112 kidney pancreas recipients, 72 recipients (64%) had functioning graft at more than 10 year follow up. 28 patients (25%) lost their graft to chronic rejection. Twelve recipients (11%) with failed grafts due to surgical or infectious complications were excluded from the study. The recipients with graft loss due to chronic rejection (CRG) were slightly younger (mean age 37 in comparison to 42) than recipients with functioning grafts (FG). Both groups had similar mean BMI of 25. Mean pancreas preservation time in FG and CRG groups were 12.5 and 12 hours respectively. The mean HLA A, B and DR mismatches in FG group (1.43,1.58,1.34) was comparable to those in CRG group (1.46,1.5,1.53). The mean total HLA mismatches in the FG and CRG groups were 4.36 and 4.5 respectively. Our data does not support the use of HLA matching to predict pancreas graft loss due to chronic rejection in simultaneous kidney pancreas transplant recipients.

934. Epidemiology and Outcomes of Epstein-Barr Virus DNAemia in Adult Solid Organ Transplant Recipients

BackgroundImmunosuppression in solid organ transplantation (SOT) increases the risk of Epstein-Barr virus (EBV) DNAemia, which may herald development of post-transplant lymphoproliferative disease (PTLD). The objective of this study was to characterize the epidemiology and risk factors for EBV DNAemia and to describe the impact of these factors on development of PTLD in a cohort of SOT recipients.MethodsWe retrospectively examined adult (≥18 years) SOT recipients between 1/1/2015 to 12/31/2019. Demographics, immunosuppression, and clinical outcomes were examined. Subjects were stratified as having a positive (EBV viral load > 200 copies/mL) or negative viral load. Sustained EBV DNAemia was defined as EBV DNA detection ( > 200 copies/mL) on at least 3 consecutive samples. Categorical variables were analyzed using chi-square or Fishers exact test. Mann-U Whitney test was used for continuous variables. Results442 SOT recipients (258 kidney, 141 liver, 22 kidney-pancreas (KP), 15 kidney-liver, 6 pancreas) were examined. Most subjects (430, 97%) were EBV intermediate risk (recipient (R)+). 8 subjects (2%) were EBV high risk (donor (D)+, R-) and 4 (1%) were EBV low risk (D-/R-). EBV viral loads were obtained in 177/442 (40.0%) recipients. DNAemia was detected in 18/442 subjects (4.1%). It was most common in pancreas recipients(1/6; 16.7%) compared with kidney (10/258; 3.9%), liver (5/141; 3.5%), and KP recipients (1/22; 4.5%). DNAemia was most frequently observed in the D+/R- (3/8; 37.5%) group compared to intermediate risk (R+) (15/430; 3.5%) and D-/R- (0%) groups. Median time to EBV viral load detection was 14 months (range 3-60). In univariate analysis, EBV high-risk serostatus was the factor most strongly associated with development of EBV DNAemia (p< 0.001). Sustained DNAemia (median viral load 1829 copies/mL; peak viral load 1.9 million copies/mL) was observed in 8 subjects (1.8%). PTLD developed in 6 subjects (1.4%); 50% had sustained DNAemia prior to diagnosis.ConclusionWhile uncommon, development of sustained EBV DNAemia was associated with subsequent development of PTLD in our cohort of adult SOT recipients. These data provide guidance for identifying subjects at risk for PTLD above and beyond baseline EBV high-risk serostatus. Disclosures All Authors: No reported disclosures

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.

The addition of adjunctive letermovir to valganciclovir for refractory cytomegalovirus viremia in kidney transplant recipients.

Persistent viral replication resulting in ongoing cytomegalovirus (CMV) viremia despite adequate therapy is difficult to manage and associated with negative outcomes. We report a case series of kidney transplant recipients receiving adjunctive letermovir in combination with valganciclovir for refractory CMV. Adult patients receiving a kidney or kidney-pancreas transplant were included if they developed CMV viremia and initiated letermovir 480mg daily as part of a dual therapy regimen with valganciclovir 900mg twice daily between 1/9/2020 and 31/12/2020. Included patients received ≥90 days of valganciclovir and had a detectable viral load less than 1000 Iu/ml (log10 <3) at the time of letermovir initiation. The primary objective was to evaluate the impact of adjunctive letermovir on viral clearance to negativity. We also evaluated effect of letermovir on tacrolimus levels. Eight patients were included. Letermovir was added 223 ± 105 days after initiation of CMV treatment with ganciclovir derivatives. Median viral load at initiation was 139.7 (range: 73-355) IU/ml and did not clear or change significantly after 2, 4 and 12weeks of adjunctive letermovir (132.5 [range: 34.5-513] IU/ml vs. 68.7 [range: 34.5-574] IU/ml vs. 78.3 [range: 34.5-347] IU/ml, p>0.05). Tacrolimus was reduced by ∼30% in anticipation of a letermovir-tacrolimus drug interaction. Despite this reduction, mean tacrolimus serum levels two weeks after adjunctive letermovir increased by 43% (5.6 ± 1.6ng/ml vs 8.0 ± 4.6ng/ml). In kidney and kidney-pancreas recipients with refractory CMV, the use of adjunctive letermovir did not result in viral clearance. Additionally, despite a mean tacrolimus dose reduction of 30% at letermovir initiation, serum concentrations increased by over 40%. Further investigation into the optimal approach to refractory CMV is needed.

Six-month risk of Pneumocystis pneumonia following acute cellular rejection: A case-control study in solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at risk of Pneumocystis pneumonia (PCP). PCP is associated with significant morbidity and mortality. The effect of acute T cell-mediated rejection (TCMR) on post-transplant PCP has not been determined yet. In this case-control study, we estimated the risk of PCP following acute TCMR during a lookback period of 180days. We also determined the effects of contributing factors such as CMV infection. We compared 15 SOT (8 kidney, 4 heart, 2 liver, and 1 kidney-pancreas) recipients with PCP with 60 matched recipients who did not develop PCP (control group) during the study period (December 2013 to February 2016). PCP occurred after a complete course of prophylaxis (ie, late-onset PCP) in 60% of patients. Patients with PCP frequently required intensive care unit (ICU) admission (73.3%). Post-transplant PCP was associated with considerable allograft loss (53.4%) and mortality (26.7%). In the 6-month lookback period, acute TCMR (OR: 13.1, 95% CI: 3.2, 53.2), and CMV infection (OR: 15.1,95% CI: 4.0, 53.2.1) were significantly associated with post-transplant PCP. Post-transplant PCP is associated with substantial risk of ICU admission, allograft failure, and mortality. Anti-Pneumocystis prophylaxis for at least 6months following acute TCMR may reduce the risk.

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.