No abstract

These preliminary data underline the importance of long-term surveillance of transplant recipients, choice of immunosuppressive treatment, and careful donor selection.

OBJECTIVE -Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients. RESEARCH DESIGN AND METHODS -We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twentyfive patients did not receive a functioning islet transplant (kidney-only group).RESULTS -GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 Ϯ 3.5% at baseline to 74.9 Ϯ 2.1% at 3 years posttransplantation, P Ͻ 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 Ϯ 0.25 to 4.20 Ϯ 0.37 EDV/s, P Ͻ 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P Ͻ 0.05). The kidneyislet group also showed a reduction of both QT dispersion (53.5 Ϯ 4.9 to 44.6 Ϯ 2.9 ms, P Ͻ 0.05) and corrected QT (QTc) dispersion (67.3 Ϯ 8.3 to 57.2 Ϯ 4.6 ms, P Ͻ 0.05) with higher erythrocytes Na ϩ -K ϩ -ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness.CONCLUSIONS -Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft. Diabetes Care 28:1358 -1365, 2005M ost cardiac disease and events in type 1 diabetic patients are due to 1) diabetic cardiomyopathy, with progressive deterioration of left ventricular function; 2) diabetic coronary angiopathy, with progression of coronary atherosclerosis; or 3) diabetic sudden death resulting from myocyte electrical failure (1-3).With diabetic cardiomyopathy, systolic dysfunction in normotensive diabetic patients has not been clearly shown (3). Abnormality in diastolic dysfunction has been uniformly observed in asymptomatic diabetic patients, but its relationship with metabolic control in type 1 diabetic patients is still a matter of debate (4 -6).With diabetic coronary angiopathy, progressive worsening of coronary artery atherosclerosis and macroangiopathy is evident in patients with diabetes, but pancreas and islet transplants reduce this risk (7-11). A noninvasive marker of atherosclerosis and coronary events is intimamedia thickness (IMT) (12), which is stabil...

BackgroundOperational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell—based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell—based therapy after kidney transplantation.MethodsUpon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell—enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion.ResultsWe developed a medicinal product that was enriched in Tr1 cells, anergic to donor-cell stimulation, able to suppress proliferation upon donor- but not third-party stimulation in vitro, and stable upon cryopreservation. The protocol was reproducible upon up scaling to leukapheresis from patients on dialysis and was effective in yielding the expected number of T10 cells necessary for the planned infusions. The tolerogenic gene signature of circulating Tr1 cells was minimally compromised in kidney transplant recipients under standard immunosuppression and it eventually started to recover 36 weeks post-transplantation, providing rationale for selecting the timings of the cell infusions.ConclusionsThese data provide solid ground for proceeding with the trial and establish robust rationale for defining the correct timing of cell infusion during concomitant immunosuppressive treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1133-8) contains supplementary material, which is available to authorized users.

Italy was the first Western country to face the COVID-19 pandemic. Here we report the results of a national survey on kidney transplantation activity in February and March 2020, and the results of a three-round Delphi consensus promoted by four scientific societies: the Italian Society of Organ Transplantation, the Italian Society of Nephrology, the Italian Society of Anesthesia and Intensive Care, and the Italian Group on Antimicrobial Stewardship. All 41 Italian transplant centers were invited to express their opinion in the Delphi rounds along with a group of seven experts. The survey revealed that, starting from March 2020, there was a decline in kidney transplantation activity in Italy, especially for living-related transplants. Overall, 60 recipients tested positive for SARS-CoV2 infection, 57 required hospitalization, 17 were admitted to the ICU, and 11 died. The online consensus had high response rates at each round (95.8%, 95.8%, and 89.5%, respectively). Eventually, 27 of 31 proposed statements were approved (87.1%), 12 at the first or second round (38.7%), and 3 at the third (9.7%). Based on the Italian experience, we discuss the reasons for the changes in kidney transplantation activity during the COVID-19 pandemic in Western countries. We also provide working recommendations for the organization and management of kidney transplantation under these conditions.