Most calcineurin inhibitor (CNI) based protocols reduce blood trough goals approximately 2–3 months post-transplant in clinically stable kidney transplant recipients. The CNI target trough level to prevent rejection, after reduction, is unknown. Using a multivariate Cox proportional hazards model we determined the association of time-varying tacrolimus (TAC) trough levels with acute rejection (AR) occurring in the first 6 months post-transplant, but specifically we assessed this association after 3 months. 1,930 patients received TAC based immunosuppression prior to AR in a prospective study. Of the 151 (7.8%) who developed AR, 47 developed AR after 3 months post-transplant. In an adjusted time varying multivariate model, each 1 ng/mL decrease in TAC trough levels was associated with a 7.2% increased risk of AR [HR=1.07, 95% CI (1.01, 1.14) P=0.03] in the first 6 months. There was an additional 23% increased risk of AR with each 1 ng/mL decrease in the TAC trough levels in months 3–6 [HR=1.23, 95% CI (1.06, 1.43) P=0.008]. In conclusion, lower TAC trough levels were significantly associated with increased risk of AR in the first 6 months post-transplant with additional risk of AR between months 3–6 post-transplant. The timing and practice of TAC dose reduction should be personalized based on the individual’s risk factors.
eGFR(CKD-EPI-Creat+CysC) equation provides comparable accuracy to the eGFR(MDRD) in overall estimation of mGFR, but with higher precision. However, eGFR(CKD-EPI-Creat+CysC) clearly misses many of those with a post-donation GFR less than 60 mL/min/1.73 m and therefore eGFR(MDRD) is preferable in detecting donors with GFR less than 60 mL/min/1.73 m.
In the general population, obesity is associated with an increased risk of developing hypertension (HTN), type 2 diabetes mellitus (DM), and end-stage renal disease (ESRD). Therefore, most transplant centers have a body mass index (BMI) threshold for accepting living kidney donors. But there have been no studies of postdonation weight gain trends and any associated risks. We tracked serial BMIs in 940 donors for a median (IQ range) follow-up of 22.3 (15.4-35.8) years. We studied the impact of postdonation weight gain in a model adjusted for family history of HTN or DM. Donor characteristics included age, sex, smoking, fasting blood glucose, eGFR, systolic and diastolic BP, and BMI at time of donation and time postdonation. Postdonation weight gain was associated with a significant increase in the relative risk of developing HTN RR 1.93 (95% CI 1.51-2.46) (P < 0.001) and/or DM RR 4.18 (95% CI 2.05-8.5) (P < 0.0001), but not (to date) cardiovascular disease (CVD), reduced eGFR or death. Like the general population, donors gained weight as they aged; a higher BMI was associated with higher incidence of DM and HTN. Postdonation care should include ongoing counseling on the risks of substantial weight gain.
Objective: We examined the association between induction type and outcomes of live-donor pediatric kidney recipients on tacrolimus and mycophenolate maintenance. Material and Methods:We analyzed the SRTR standard analysis file to evaluate primary live-donor pediatric kidney recipients between 2000 and 2018. Recipients were grouped by induction type into three groups: alemtuzumab n = 289, anti-thymocyte n = 1197, and IL-2RA n = 1625. Kaplan-Meier curves were generated for recipient and death-censored graft survival. Predictors of recipient and allograft survival were examined using Cox proportional hazards models. Models were adjusted for age, sex, ethnicity, renal failure etiology, HLA-mismatches, transplant year, steroid maintenance, preemptive transplantation, payor type, and donor factors such as age, sex, and donor-recipient relationship. The transplant center was included as a random effect to account for inter-center variability. Results: Rejection rates at 6 months (Alemtuzumab 9.5% vs. r-ATG 5.7% vs. IL2-RA 5.3%; P: .023) and 12 months (Alemtuzumab 14.5% vs. r-ATG 10.8% vs. IL2-RA 9%; P: .028) were significantly higher in the alemtuzumab group. PTLD rate (Alemtuzumab 0.8% vs. r-ATG 2.2% vs. IL2-RA 1%; P: .028) was significantly higher in the anti-thymocyte group. In the multivariable models, induction type did not influence patient or death-censored graft survival within ten years post-transplant. Conclusion:In this large cohort of standard immunological risk primary pediatric livedonor kidney recipients, as compared to IL-2RA, neither alemtuzumab nor anti-thymocyte globulin was associated with improved long-term graft or recipient survival.In the first year post-transplant, recipients of alemtuzumab induction had a higher rejection rate, while PTLD was more frequently observed in the anti-thymocyte recipients.
Background:We studied the association of induction immunosuppression and pediatric deceased-donor kidney recipient and graft survival. Methods:We utilized the SRTR to evaluate all primary pediatric deceased-donor kidney transplants from January 1st, 2000, through December 2018. We included only recipients who were maintained on tacrolimus and mycophenolate. Recipients were grouped by induction type: alemtuzumab n = 320, r-ATG n = 2091 and IL-2RA n = 2165. Recipient and allograft survival, and their predictors, were examined.Models were adjusted for age, sex, ethnicity, HLA-antigen mismatches, transplant year, steroid maintenance, pre-emptive transplantation and payor type, with the transplant center included as a random effect. Results: Rejection rates at 6 months (alemtuzumab 8.6% vs r-ATG 7.8% vs IL2-RA 9.2%; P = .30) and 12 months (alemtuzumab 17.2% vs r-ATG 15.7% vs IL2-RA 16.5%; P = .70) were not significantly different between induction groups.
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