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Background It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. Methods To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). Results Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). Conclusions This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.

The aim was to evaluate feasibility and safety of calcineurin inhibitor-free immunosuppression in high-risk donor kidney transplantation with sequential sirolimus introduction. Kidney transplant patients (n=76) with a donor aged >60 years, donor with acute renal failure, or a nonheartbeating donor were included. Immunosuppression consisted of antithymocyte globulin or basiliximab, mycophenolate mofetil, prednisone, and sequential introduction of sirolimus. One-year patient survival was 96.2% and 95.8%; graft survival was 94.2% and 91.7%; acute rejection rates were 21.2% and 12.4%; delayed graft function was 21.2% and 66.7%; and creatinine clearance was 58+/-20 mL/min and 56+/-21 mL/min for the brain-dead donor group and the nonheartbeating donor group, respectively. Most adverse events were infections, but also three lymphoceles, three urinary fistulas, three wound seromas. Sequential sirolimus introduction in high-risk donor kidney transplantation was found to lead to good patient and graft survival and incidence of acute rejection and delayed graft function.

Background Levels of fibroblast growth factor (FGF)-23, a phosphaturic hormone, increase from the early stages of CKD and are dramatically elevated in dialysis patients. Excessive FGF-23 may be involved in the hypophosphatemia and inappropriately low calcitriol levels observed after kidney transplantation (KT).This prospective observational cohort study was carried out to determine whether there are any differences in the changes in FGF-23 levels after surgery in KT recipients according to whether they were or not on dialysis before transplantation and to assess the influence of FGF-23 in the development of posttransplantation hypophosphatemia. Methods Consecutive KT recipients at the Hospital Clinic of Barcelona were recruited. Patients developing delayed graft function were excluded. Mineral metabolism parameters, including C-terminal fragment of FGF-23, intact parathyroid hormone, and 1,25(OH)(2)D(3), were measured in 72 KT recipients (58 on dialysis before transplantation and 14 preemptive transplant recipients) at baseline, on day 15, and at 1, 3, and 6 months after transplantation. No patients received treatment with calcimimetics, bisphosphonates, vitamin D, or phosphate supplementation during the follow-up. Results FGF-23 decreased significantly in the first month after transplantation. Baseline and FGF-23 levels within the first posttransplantation month were lower in preemptive transplant recipients than in patients on dialysis at transplantation. Serum phosphate levels were lower in dialysis patients until the third month after transplantation. Pretransplantation FGF-23 was the main predictor of posttransplantation phosphate blood levels. Conclusions FGF-23 levels and the risk of developing posttransplantation hypophosphatemia were lower in preemptive kidney transplant recipients than in patients on dialysis before transplantation.

Background. Treatment with oral risedronate to prevent bone mineral density (BMD) loss in renal transplant recipients has been shown to be effective. There is no agreement on the optimum moment of introduction or how long it should be continued. The aim was to evaluate the effectiveness of risedronate at doses of 35 mg/week in renal transplant recipients who underwent treatment immediately after transplant. Methods. A randomized clinical trial was performed on 101 renal transplant patients. The study group (52 patients) received 35 mg risedronate weekly, vitamin D, and calcium, whereas the control group (49 patients) received only vitamin D and calcium. At baseline, 3, 6, and 12 months, basic biochemistry and mineral bone metabolic parameters were determined. Vertebra and hip fracture assessment was performed by means of x-ray and DEXA; an intention-to-treat analysis was performed. Results. Patients in control group showed a significant worsening of BMD (P

BACKGROUND Persistent secondary hyperparathyroidism (SHP) is the most frequent cause of hypercalcemia observed in approximately 10% of renal transplanted (RT) patients 1 year after surgery. Persistent SHP with hypercalcemia is an important factor of bone loss after renal transplantation. This study prospectively evaluates the effects of cinacalcet therapy on serum calcium (SCa) and parathyroid hormone (PTH) blood levels, and basically on bone mineral density (BMD) in RT patients with persistent hyperparathyroidism. METHODS Nine RT patients (eight women, one man) with allograft function more than 6 months were included based on total SCa more than 10.5 mg/dL and intact parathyroid hormone (iPTH) concentration more than 65 pg/mL. After inclusion, patients started on a single daily oral dose of 30 mg of cinacalcet. At inclusion and every study visit blood levels of creatinine, Ca, P, alkaline phosphatase, iPTH 1,25- dihydroxyvitamin D3, and 25-hydroxyvitamin D3 were assessed. Baseline and at the end of study radial BMD were measured. Study follow-up was 12 months. RESULTS During the study period, SCa decreased from 11.72+/-0.39 to 10.03+/-0.54 mg/dL (P

Chronic allograft nephropathy (CAN), cardiovascular mortality, and posttransplant malignancy are complications of conventional immunosuppression after kidney transplantation. The aim was to study feasibility of sirolimus (SRL) maintenance monotherapy in a pilot experience. All patients with SRL monotherapy of at least 6 months follow-up were included. In 19 patients, age 58 (34-74) years, SRL monotherapy was introduced 98.1 (49-193) months after transplantation by withdrawing concomitant immunosuppressants from protocols already including SRL or introducing SRL and withdrawing other immunosuppressants. Follow-up is 20.0 (6-41) months. One patient died from hepatocellular carcinoma, diagnosed before SRL monotherapy, with functioning graft. No rejections occurred. SRL trough concentration was 10.7 (4.6-16.1) microg/L. Creatinine (1.77 [1.0-2.9] mg/dL vs. 1.68 [0.8-3.3] mg/dL after 6 months, 1.97 [0.8-4.6] mg/dL at last follow-up; P=NS). Proteinuria increased tendentially (333 [67-893] vs. 890 [46-4011] mg/day). No significant changes of hemoglobin, triglycerides, or cholesterol occurred. SRL monotherapy late after kidney transplantation is feasible in selected patients.