Pancreas‐After‐Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for Restoring Durable Insulin Independence

Islet transplantation offers a minimally invasive approach for β cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. We describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure with long‐term follow‐up of pancreatic graft survival and renal function. Despite highly variable panel reactive antibody levels prior to pancreas transplant (mean 27 ± 35%), all seven patients achieved stable and durable insulin independence with a mean follow‐up of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet, prepancreas levels (mean 8.1 ± 1.5%) to postpancreas levels (mean 5.3 ± 0.1%; p = 0.0022). Three patients experienced acute rejection episodes that were successfully managed with thymoglobulin and methylprednisolone, and none of these preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas‐after‐islet transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure.     

Higher rates of rejection in HIV‐infected kidney transplant recipients on ritonavir‐boosted protease inhibitors: 3‐year follow‐up study

Rejection rates in HIV‐infected kidney transplant (KTx) recipients are higher than HIV‐negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug‐drug interactions, likely influencing outcomes. This is an IRB‐approved, single‐center, retrospective study of adult HIV‐infected KTx patients between 5/2009 and 12/2014 with 3‐year follow‐up, excluding antibody‐depleting induction. A total of 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre‐transplant dialysis. All patients received IL‐2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir‐boosted PI‐based HAART (rtv+) regimen. Patient and graft survival at 3 years were 93% and 90%. At 1‐, 2‐, and 3‐year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy‐proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P = 0.029), 59% vs 24% (P = 0.029), and 68% vs 24% (P = 0.01). Despite higher rejection rates, HIV‐infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.     

Parainfluenza 3 Infections Early After Kidney or Simultaneous Pancreas–Kidney Transplantation

Parainfluenza virus (PIV) can cause serious infections after hematopoietic stem cell or lung transplantation. Limited data exist about PIV infections after kidney transplantation. We describe an outbreak of PIV‐3 in a transplant unit. During the outbreak, 45 patients were treated on the ward for postoperative care after kidney or simultaneous pancreas–kidney (SPK) transplantation. Overall, 29 patients were tested for respiratory viruses (12 patients with respiratory symptoms, 17 asymptomatic exposed patients) from nasopharyngeal swabs using polymerase chain reaction. PIV‐3 infection was confirmed in 12 patients. One patient remained asymptomatic. In others, symptoms were mostly mild upper respiratory tract symptoms and subsided within a few days with symptomatic treatment. Two patients suffered from lower respiratory tract symptoms (dyspnea, hypoxemia, pulmonary infiltrates in chest computed tomography) and required supplemental oxygen. Four of six SPK patients and eight of 39 of kidney transplant patients were infected with PIV (p = 0.04). In patients with follow‐up tests, PIV‐3 shedding was still detected 11–16 days after diagnosis. Despite rapid isolation of symptomatic patients, PIV‐3 findings were diagnosed within 24 days, and the outbreak ceased only after closing the transplant ward temporarily. In conclusion, PIV‐3 infections early after kidney or SPK transplantation were mostly mild. PIV‐3 easily infected immunosuppressed transplant recipients, with prolonged viral shedding.     

Identification of Optimal Donor–Recipient Combinations Among Human Immunodeficiency Virus (HIV)–Positive Kidney Transplant Recipients

For some patient subgroups, human immunodeficiency virus (HIV) infection has been associated with worse outcomes after kidney transplantation (KT); potentially modifiable factors may be responsible. The study goal was to identify factors that predict a higher risk of graft loss among HIV‐positive KT recipients compared with a similar transplant among HIV‐negative recipients. In this study, 82 762 deceased donor KT recipients (HIV positive: 526; HIV negative: 82 236) reported to the Scientific Registry of Transplant Recipients (SRTR) (2001–2013) were studied by interaction term analysis. Compared to HIV‐negative recipients, the hepatitis C virus (HCV) amplified risk 2.72‐fold among HIV‐positive KT recipients (adjusted hazard ratio [aHR]: 2.72, 95% confidence interval [CI]: 1.75–4.22, p < 0.001). Forty‐three percent of the excess risk was attributable to the interaction between HIV and HCV (attributable proportion of risk due to the interaction [AP]: 0.43, 95% CI: 0.23–0.63, p = 0.02). Among HIV‐positive recipients with more than three HLA mismatches (MMs), risk was amplified 1.80‐fold compared to HIV‐negative (aHR: 1.80, 95% CI: 1.31–2.47, p < 0.001); 42% of the excess risk was attributable to the interaction between HIV and more than three HLA MMs (AP: 0.42, 95% CI: 0.24–0.60, p = 0.01). High‐HIV‐risk (HIV‐positive/HCV‐positive HLAwith more than three MMs) recipients had a 3.86‐fold increased risk compared to low‐HIV‐risk (HIV‐positive/HCV‐negative HLA with three or fewer MMs)) recipients (aHR: 3.86, 95% CI: 2.37–6.30, p < 0.001). Avoidance of more than three HLA MMs in HIV‐positive KT recipients, particularly among coinfected patients, may mitigate the increased risk of graft loss associated with HIV infection.     

The Outcomes of Kidney Transplantation in Hepatitis B Surface Antigen (HBsAg)–Negative Recipients Receiving Graft From HBsAg‐Positive Donors: A Retrospective,Propensity Score‐Matched Study

The outcomes of kidney transplantation (KT) from hepatitis B surface antigen–positive [HBsAg(+)] donors to HBsAg(?) recipients remain inconclusive, possibly due to substantial differences in methodological and statistical models, number of patients, follow‐up duration, hepatitis B virus (HBV) prophylactic regimens and hepatitis B surface antibody (anti‐HBs) levels. The present retrospective, longitudinal study ( clinicaltrial.gov NCT02044588) using propensity score matching technique was conducted to compare outcomes of KT between HBsAg(?) recipients with anti‐HBs titer above 100 mIU/mL undergoing KT from HBsAg(+) donors (n = 43) and HBsAg(?) donors (n = 86). During the median follow‐up duration of 58.2 months (range 16.7–158.3 months), there were no significant differences in graft and patient survivals. No HBV‐infective markers, including HBsAg, hepatitis B core antibody, hepatitis B extracellular antigen and HBV DNA quantitative test were detected in HBsAg(+) donor group. Renal pathology outcomes revealed comparable incidences of kidney allograft rejection while there were no incidences of HBV‐associated glomerulonephritis and viral antigen staining. Recipients undergoing KT from HBsAg(+) donors with no HBV prophylaxis (n = 20) provided comparable outcomes with those treated with lamivudine alone (n = 21) or lamivudine in combination with HBV immunoglobulin (n = 2). In conclusion, KT without HBV prophylaxis from HBsAg(+) donors without hepatitis B viremia to HBsAg(?) recipients with anti‐HBs titer above 100 mIU/mL provides excellent graft and patient survivals without evidence of HBV transmission.

     

Optimal timing of hepatitis C treatment among HIV/HCV coinfected ESRD patients: Pre‐ vs posttransplant

Patients with end‐stage renal disease (ESRD) who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have access to effective treatment options for HCV infection. However, they also have access to HCV‐infected kidneys, which historically afford shorter times to transplantation. Given the high waitlist mortality and rapid progression of liver fibrosis among coinfected kidney‐only transplant candidates, identification of the optimal treatment strategy is paramount. Two strategies, treatment pre‐ and posttransplant, were compared using Monte Carlo microsimulation of 1 000 000 candidates. The microsimulation was stratified by liver fibrosis stage at waitlist addition and wait‐time over a lifetime time horizon. Treatment posttransplant was consistently cost‐saving as compared to treatment pretransplant due to the high cost of dialysis. Among patients with low fibrosis disease (F0‐F1), treatment posttransplant also yielded higher life months (LM) and quality‐adjusted life months (QALM), except among F1 candidates with wait times ≥ 18 months. For candidates with advanced liver disease (F2‐F4), treatment pretransplant afforded more LM and QALM unless wait time was <18 months. Moreover, treatment pretransplant was cost‐effective for F2 candidates with wait times >71 months and F3 candidates with wait times >18 months. Thus, optimal timing of HCV treatment differs based on liver disease severity and wait time, favoring pretransplant treatment when cirrhosis development prior to transplant seems likely.     

Incidence and outcomes of cytomegalovirus in pancreas transplantation with steroid‐free immunosuppression

Cytomegalovirus (CMV) is a common opportunistic infection encountered after pancreas transplantation. The records of 407 pancreas transplant recipients (226 simultaneous pancreas and kidney transplant (SPK), 101 pancreas transplant after kidney (PAK), and 97 pancreas transplants alone [PTA]) performed at a single center with at least 1‐yr follow‐up were reviewed. Immunosuppression included rabbit antithymocyte globulin induction, steroid withdrawal, and maintenance therapy of tacrolimus and sirolimus (± mycophenolate). In addition, PTA recipients received a single dose of rituximab. All recipients received valganciclovir prophylaxis. Donor (D)+/recipient (R)− recipients received 6 months of prophylaxis; all others received 3 months. The overall CMV infection rate was 12%. The cumulative incidences of CMV infection at 3, 6, 9, and 12 months after transplant were 0.25%, 3%, 7%, and 8%, respectively. CMV infection rates were 20.2% in the D+/R− group, 16.5% in the D+/R+ group, 5.0% in the D−/R+ group, and 2.8% in the D−/R− group. Infections were less common in SPK recipients. Most infections developed at least 3 months post‐transplant, and 24% demonstrated tissue‐invasive disease. Immunosuppression was NOT reduced in 72% of patients with infections. Ganciclovir‐resistant CMV occurred in four patients. No patients died or lost their allografts due to CMV‐related infection; one graft was lost due to chronic rejection associated with a reduction in immunosuppression. In many cases, CMV infections may be treated in pancreas transplant recipients without necessarily reducing immunosuppression.     

Pancreas After Islet Transplantation: A First Report of the International Pancreas Transplant Registry

Pancreas after islet (PAI) transplantation is a treatment option for patients seeking insulin independence through a whole‐organ transplant after a failed cellular transplant. This report from the International Pancreas Transplant Registry (IPTR) and the United Network for Organ Sharing (UNOS) studied PAI transplant outcomes over a 10‐year time period. Forty recipients of a failed alloislet transplant subsequently underwent pancreas transplant alone (50%), pancreas after previous kidney transplant (22.5%), or simultaneous pancreas and kidney (SPK) transplant (27.5%). Graft and patient survival rates were not statistically significantly different compared with matched primary pancreas transplants. Regardless of the recipient category, overall 1‐ and 5‐year PAI patient survival rates for all 40 cases were 97% and 83%, respectively; graft survival rates were 84% and 65%, respectively. A failed previous islet transplant had no negative impact on kidney graft survival in the SPK category: It was the same as for primary SPK transplants. According to this IPTR/UNOS analysis, a PAI transplant is a safe procedure with low recipient mortality, high graft‐function rates in both the short and long term and excellent kidney graft outcomes. Patients with a failed islet transplant should know about this alternative in their quest for insulin independence through transplantation.     

Outcomes after simultaneous kidney‐pancreas versus pancreas after kidney transplantation in the current era

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1‐year graft survival for both organs was not different. At last follow‐up, uncensored and death‐censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times.     

Outcomes of Lung Transplantation in Recipients With Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV‐positive, compared to 443 HCV‐negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1‐, 3‐, and 5‐year survival were similar in HCV RNA–positive versus ‐negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long‐term follow‐up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon‐free HCV therapies this should not be a barrier to LuTx.     

Ciprofloxacin for BK viremia prophylaxis in kidney transplant recipients: Results of a prospective,double‐blind,randomized, placebo‐controlled trial

In kidney transplantation, BK virus infection has historically resulted in high rates of graft dysfunction and graft loss. Unlike other opportunistic infections, no therapies have been shown to prevent BK. The purpose of the current study was to evaluate the safety and efficacy of ciprofloxacin for the prevention of BK viremia in kidney transplant recipients. Two hundred kidney transplant recipients were enrolled in a prospective, randomized, double‐blind, placebo‐controlled trial comparing a 3‐month course of ciprofloxacin (n = 133) vs placebo (n = 67) for the prevention of BK viremia. The primary endpoint of BK viremia at month 6 posttransplant occurred in 25 (18.8%) patients in the ciprofloxacin group and 5 (7.5%) in the placebo group (P = .03). Higher rates of BK viremia (23.3% vs 11.9%; P = .06) and BK nephropathy (5.8% vs 1.5%; P = .26) remained at 12 months in the ciprofloxacin group. Ciprofloxacin use was associated with a significantly higher rate of fluoroquinolone‐resistant gram‐negative infections (83.3% vs 50%; P = .04). A 3‐month course of ciprofloxacin was ineffective at preventing BK viremia in kidney transplant recipients and was associated with an increased risk of fluoroquinolone‐resistant infections. Clinical trial registration number: NCT01789203.     

First experience of SARS‐CoV‐2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, comprehensive data of SARS‐CoV‐2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS‐CoV‐2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%), and diarrhea (33%). Ninety‐five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS‐CoV‐2 infection in middle‐aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.     

Preventive Strategies Against Cytomegalovirus and Incidence of α‐Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella‐zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person‐years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5–5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7–14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2–4] versus 9.8% [95% CI 8.4–11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus‐positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.     

Genetic Variation in Caveolin‐1 Correlates With Long‐Term Pancreas Transplant Function

Pancreas transplantation is a successful treatment for a selected group of people with type 1 diabetes. Continued insulin production can decrease over time and identifying predictors of long‐term graft function is key to improving survival. The aim of this study was to screen subjects for variation in the Caveolin‐1 gene (Cav1), previously shown to correlate with long‐term kidney transplant function. We genotyped 435 pancreas transplant donors and 431 recipients who had undergone pancreas transplantation at the Oxford Transplant Centre, UK, for all known common variation in Cav1. Death‐censored cumulative events were analyzed using Kaplan–Meier and Cox regression. Unlike kidney transplantation, the rs4730751 variant in our pancreas donors or transplant recipients did not correlate with long‐term graft function (p = 0.331–0.905). Presence of rs3801995 TT genotype (p = 0.009) and rs9920 CC/CT genotype (p = 0.010) in our donors did however correlate with reduced long‐term graft survival. Multivariate Cox regression (adjusted for donor and recipient transplant factors) confirmed the association of rs3801995 (p = 0.009, HR = 1.83;[95% CI = 1.16–2.89]) and rs9920 (p = 0.037, HR = 1.63; [95% CI = 1.03–2.73]) with long‐term graft function. This is the first study to provide evidence that donor Cav1 genotype correlates with long‐term pancreas graft function. Screening Cav1 in other datasets is required to confirm these pilot results.     

Donor evaluation in the era of HIV‐positive organ transplantation: The importance of the infectious diseases specialist

A 61‐year‐old female with well‐controlled human immunodeficiency virus (HIV) and end‐stage renal disease was on the kidney transplant waitlist awaiting an organ offer, including from HIV‐positive donors through the HIV Organ Policy Equity (HOPE) Act. We present three different scenarios where HIV‐positive donor offers were evaluated for this one recipient, discuss the donor evaluation process, explain where the infectious diseases provider fits in this scheme, and describe the challenges encountered by organ procurement organizations. This is the first case under the HOPE Act at our center where discovery of an HIV‐specific issue led to a turndown of an organ offer.     

Belatacept Conversion in an HIV‐Positive Kidney Transplant Recipient With Prolonged Delayed Graft Function

We report an HIV‐positive renal transplant recipient with delayed graft function who was converted from tacrolimus to belatacept in an attempt to improve renal function. The patient had kidney biopsies at 4 and 8 weeks posttransplant that revealed acute tubular necrosis and mild fibrosis. After 14 weeks of delayed function, belatacept was initiated and tacrolimus was weaned off. Shortly after discontinuing tacrolimus, renal function began to improve. The patient was able to discontinue dialysis 21 weeks posttransplant. HIV viral load was undetectable at last follow‐up. To our knowledge, this is the first report of belatacept use in a patient with HIV.     

Challenges and Clinical Decision‐Making in HIV‐to‐HIV Transplantation: Insights From the HIV Literature

Life expectancy among HIV‐infected (HIV+) individuals has improved dramatically with effective antiretroviral therapy. Consequently, chronic diseases such as end‐stage liver and kidney disease are growing causes of morbidity and mortality. HIV+ individuals can have excellent outcomes after solid organ transplantation, and the need for transplantation in this population is increasing. However, there is a significant organ shortage, and HIV+ individuals experience higher mortality rates on transplant waitlists. In South Africa, the use of organs from HIV+ deceased donors (HIVDD) has been successful, but until recently federal law prohibited this practice in the United States. With the recognition that organs from HIVDD could fill a critical need, the HIV Organ Policy Equity (HOPE) Act was passed in November 2013, reversing the federal ban on the use of HIV+ donors for HIV+ recipients. In translating this policy into practice, the biologic risks of using HIV+ donors need to be carefully considered. In this mini‐review, we explore relevant aspects of HIV virology, antiretroviral treatment, drug resistance, opportunistic infections and HIV‐related organ dysfunction that are critical to a transplant team considering HIV‐to‐HIV transplantation.     

Everolimus with low‐dose tacrolimus in simultaneous pancreas and kidney transplantation

The efficacy and safety of everolimus (EVR) in simultaneous pancreas and kidney transplantation (SPKT) is unclear. We retrospectively evaluated 25 consecutive SPKT recipients at our center from November 2011 to March 2013. All patients received dual induction (Thymoglobulin/basiliximab) and low‐dose tacrolimus plus corticosteroids. Nine patients who received EVR were compared with 14 patients who received enteric‐coated mycophenolate sodium (EC‐MPS); two patients who received sirolimus were excluded from the analysis. With a median follow‐up of 14 months, the pancreas graft survival rate was 100% in both groups, and the kidney graft survival rate was 100% and 93% in EVR and EC‐MPS patients, respectively. One EC‐MPS patient lost her kidney graft from proteinuric kidney disease. Another EC‐MPS patient received treatment for clinically diagnosed pancreas and kidney graft rejection. No rejection was observed in EVR patients. Serum creatinine and HbA1c levels were similar between the groups. There was no significant difference of surgical or medical complications. In conclusion, EVR seems to provide comparable short‐term outcome to EC‐MPS when combined with low‐dose tacrolimus/steroids and dual induction therapy. A larger study with a longer follow‐up is required to further assess this combination.     

A prospective multicenter observational study of cell‐mediated immunity as a predictor for cytomegalovirus infection in kidney transplant recipients

T cell immunity is essential for the control of cytomegalovirus (CMV) infection after transplantation. We evaluated a CMV‐specific peptide‐based enzyme‐linked immunosorbent spot (ELISPOT) assay to determine whether assay results could predict subsequent CMV events. Adult kidney transplant recipients at 43 centers underwent ELISPOT testing to enumerate interferon gamma (IFN‐γ) binding spot‐forming units (sfu) after stimulation of cells with an overlapping peptide pool of CMV phosphoprotein 65 (pp65) and immediate early‐1 (IE‐1) protein at the end of antiviral prophylaxis (EOP) and various time points thereafter. The primary outcome was a CMV event in the first posttransplant year. In 583 kidney transplant recipients (260 seropositive donor [D+]/seronegative recipient [R?] and 277 R+), CMV events occurred in 44 of 368 eligible patients (11.8%) at a median of 227 days (range 92‐360) posttransplant. A cutoff value of >40 sfu/2.5 × 10⁵ cells for either IE‐1 or pp65 was derived as a threshold for positivity, with a negative predictive value of >97% for CMV events. CMV events were significantly lower in assay positive vs assay negative patients (3.0% vs 19.5%, P < .0001 for pp65). Time to CMV event post‐EOP was significantly greater in those with sfu >40 at EOP (P < .0001). In this large, multicenter trial of kidney transplant recipients, we show that an assessment of CMV‐specific immunity using a novel ELISPOT assay is able to predict protection from CMV infection.     

Tacrolimus‐ versus sirolimus‐based immunosuppression after simultaneous pancreas and kidney transplantation: 5‐year results of a randomized trial

Tacrolimus, the cornerstone immunosuppression after simultaneous pancreas and ‐kidney (SPK) transplantation, may exert nephrotoxic and diabetogenic effects. We therefore prospectively compared in an open‐label, randomized, monocentric, 5‐year follow‐up study, a tacrolimus‐ and a sirolimus‐based immunosuppressive regimen. Randomization using the block method allowing a blind allocation was done at the time of surgery. All patients received anti‐thymocyte globulin and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids. At month 3, tacrolimus was continued or replaced by sirolimus. The primary endpoint was kidney and pancreas graft survival at 1 and 5 years. Fifty patients were included in the final analysis in each group. At 1 year, differences for kidney and pancreas graft survival between sirolimus and tacrolimus were 0% (90% confidence interval ?4.61% to 4.61%) and 6% (90% confidence interval ?6.32% to 18.32%), respectively. There was no difference in renal and pancreas graft survival at 5 years. Thirty‐four patients (68%) in the sirolimus group vs three (6%) in the tacrolimus group needed definitive withdrawal of the study drug. Despite noninferiority of sirolimus compared to tacrolimus for kidney and pancreas graft survival, the high rate of sirolimus discontinuation does not favor its use as cornerstone therapy after SPK transplantation (NCT00693446).