TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus‐based regiMen) was a 24‐month, prospective, open‐label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced‐exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard‐exposure CNI. Consistent with previously reported 12‐month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy‐proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m² was achieved at month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval = −0.3, 8.7; P = .006). Mean eGFR was stable up to month 24 (52.6 vs 54.9 mL/min per 1.73 m²) in both arms. The incidence of de novo donor‐specific antibodies (dnDSA) was lower in the EVR + rCNI arm (12.3% vs 17.6%) among on‐treatment patients. Although discontinuation rates due to adverse events were higher with EVR + rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR + rCNI even in the D+/R− high‐risk group (P < .0001). In conclusion, the EVR + rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard‐of‐care up to 24 months. Clinicaltrials.gov number: NCT01950819.

This study compared the incidence of CMV infection/disease in de novo kidney transplant recipients receiving everolimus or mycophenolate and no CMV pharmacological prophylaxis. We randomized 288 patients to receive a single 3 mg/kg dose of antithymocyte globulin, tacrolimus, everolimus, and prednisone (r‐ATG/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (BAS/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (BAS/MPS, n = 101). The primary end‐point was the incidence of first CMV infection/disease in the intention‐to‐treat population at 12 months. Patients treated with r‐ATG/EVR showed a 90% proportional reduction (4.7% vs. 37.6%, HR 0.10, 95% CI 0.037–0.29; p < 0.001), while those treated with BAS/EVR showed a 75% proportional reduction (10.8% vs. 37.6%, HR 0.25, 95% CI 0.13–0.48; p < 0.001) in the incidence of CMV infection/disease compared to BAS/MPS. There were no differences in the incidence of acute rejection (9.4 vs. 18.6 vs. 15.8%, p = 0.403), wound‐healing complications, delayed graft function, and proteinuria. Mean estimated glomerular filtration rate was lower in BAS/EVR (65.7 ± 21.8 vs. 60.6 ± 20.9 vs. 69.5 ± 21.5 ml/min, p = 0.021). In de novo kidney transplant recipients receiving no pharmacological CMV prophylaxis, reduced‐dose tacrolimus and everolimus was associated with a significant reduction in the incidence of CMV infection/disease compared to standard tacrolimus dose and mycophenolate (ClinicalTrials.gov NCT01354301).

Background: This study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF). Methods: In this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals. Results: Mean cold ischemia time was high but not different between the 2 groups (25.6 ± 6.6 hours vs 25.05 ± 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 ± 19.9 mL/min per 1.73 m² vs 49.0 ± 26.9 mL/min per 1.73 m²; P = 0.262) and 1 year (48.3 ± 19.8 mL/min per 1.73 m² vs 54.4 ± 28.6 mL/min per 1.73 m²; P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed. Conclusions: In this cohort of recipients of deceased donor kidneys with high mean cold ischemia time and high incidence of DGF, the use of continuous machine perfusion was associated with a reduced risk of DGF compared with the traditional cold storage preservation method.

This retrospective multicenter (n=18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1‐year kidney transplant (KT) outcomes. Of 3,992 deceased donor KT performed in 2014‐2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (_{lower‐bound‐95%CI} OR _{upper‐bound‐95%CI}) were male gender (_1.0661.249_1.463), diabetic kidney disease (_1.0531.296_1.595), time on dialysis (_1.0051.007_1.009), retransplantation (_1.0351.397_1.885), preformed anti‐HLA antibodies (_1.0111.383_1.892), HLA mismatches (_1.0061.066_1.130), donor age (_1.0111.017_1.023), donor final serum creatinine (sCr) (_1.2391.317_1.399), cold ischemia time (CIT) (_1.0311.043_1.056), machine perfusion (_0.4010.542_0.733), and induction therapy with rabbit antithymocyte globulin (rATG) (_0.6580.800_0.973). Duration of DGF> 4 days was associated with inferior renal function and DGF> 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance accounts for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.

Kidney transplant recipients are a subset of patients with chronic kidney disease (CKD) that remain at high risk for progression to dialysis and mortality. Recent advances in immunosuppression have only partially improved long‐term graft and patient survival. Discovery of new immunosuppressive regimens is a slow and resource‐intensive process. Hence, recognition and management of modifiable allogeneic and non‐allogeneic risk factors for progression to CKD among kidney transplant recipients is of major interest for improving long‐term outcomes. Graft survival is mainly determined by the quality of the allograft and by the patient’s alloimmune response, which is influenced by human leukocyte antigen matching and the presence of donor‐specific antibodies. Alloimmune responses manifest as acute and chronic forms of cell‐ and antibody‐mediated rejection, which can be worsened by patient non‐adherence or under‐immunosuppression. However, donor and patient ages, glomerular disease recurrence, time on dialysis, pre‐existing cardiovascular burden, medication side‐effects and traditional risk factors, such as hypertension, proteinuria, anaemia, dyslipidaemia, diabetes and bone mineral disorder, which can ultimately lead to severe endothelial derangement, also contribute to graft loss and mortality. These traditional risk factors, common to pre‐dialysis patients, often are considered of secondary importance when compared to alloimmunity and immunosuppression concerns. In this review article, we focus on the epidemiological, pathophysiological and therapeutic features of non‐allogeneic traditional risk factors for CKD. We also discuss the benefit of adopting a multidisciplinary approach to pursue the same therapeutic targets recommended for pre‐dialysis patients.

This analysis, using data from the Brazilian kidney transplant (KT) COVID-19 study, seeks to develop a prediction score to assist in COVID-19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28-day fatality after the COVID-19 diagnosis, assessed by the area under the ROC curve (AUC-ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28-day fatality rate was 17% (n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID-19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC-ROC of 0.767 (95% CI 0.698–0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non-hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776.