Background:The aim of the present study was to investigate the impact of time in therapeutic range TTR on long-term outcomes of living kidney transplants. Methods:We included 1,241 living kidney transplants and randomized them into development and validation cohorts with a ratio of 2:1. The tacrolimus TTR percentage was calculated by linear interpolation with a target range (5-10 ng/ml months 0-3, 4-8 ng/ml months 4-12). The optimal TTR cutoff was estimated by the receiver operating characteristic curve analysis on the basis of acute rejection (AR) within 12 months in the development cohort. Outcomes were analyzed between patients with high TTR and low TTR in the development and validation cohorts, respectively. The TTR was also compared with other tacrolimus measures.Results: The optimal TTR cutoff value was 78%. In the development cohort, patients with TTR > 78% had significantly higher rejection-and infection-free survival. TTR < 78% was an independent risk factor for AR (OR: 2.97, 95%CI: 1.82-4.84) and infection (OR: 1.55, 95%CI: 1.08-2.22). Patient and graft survival were significantly higher in those with TTR>78%, and TTR<78% was associated with graft loss (OR: 3.2, 95%CI: 1.38-7.42) and patient death (OR: 6.54, 95%CI: 1.34-31.77). These findings were confirmed in the validation cohort. Furthermore, we divided all included patients into a high and low TTR group. TTR was more strongly associated with patient and graft survival than mean level, standard deviation, and intrapatient variability (IPV). Conclusions:Increasing the TTR of tacrolimus in the first year was associated with improved long-term outcomes in living kidney transplants, and TTR may be a novel valuable strategy to monitor tacrolimus exposure.

Context The prevalence of vitamin D deficiency (VDD) and its impact on clinical outcomes after kidney transplant (KT) remain poorly defined. Objectives We conducted a meta-analysis to evaluate the impact of early VDD on clinical outcomes after KT. Data Sources Electronic databases (PubMed, Embase, Web of Science, and The Cochrane Library) were systematically searched for eligible publications up to April 30, 2020. Data Extraction Relative risk was presented as hazard ratios (HRs) or odds ratios (ORs) and 95%CIs for dichotomous outcomes. Mean difference (MD) and 95%CIs were presented for continuous outcomes. Results A total of 28 studies (13 prospective and 15 retrospective) were included. VDD was common early after KT, with a prevalence of 52% (95%CI: 41%–64%) at transplant, 34% (95%CI: 17%–51%) at 3 months, and 23% (95%CI: 10%–35%) at 6 months. Early VDD was associated with higher mortality rate after KT (HR, 1.56; 95%CI: 1.32–1.84; P &lt; 0.001). In addition, early VDD led to higher risk of bacterial infection (OR, 1.82; 95%CI: 1.40–2.36; P &lt; 0.001), BK polyomavirus infection (OR, 2.11, 95%CI: 1.23–3.61; P = 0.006), and cytomegalovirus infection (OR, 1.69; 95%CI: 1.24–2.31; P = 0.001). Early VDD increased the risk of acute rejection as well (HR, 2.28; 95%CI: 1.57–3.30; P &lt; 0.001). Recipients with early VDD had lower estimated glomerular filtration rates (mean difference: −5.06; 95%CI: −7.28 to 2.83 mL/min; P &lt; 0.001). Sensitivity analyses showed good stability of the pooled results. Conclusion VDD was common early after KT and associated with higher risk of death and adverse outcomes.

BackgroundA systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs).MethodsMEDLINE, EMBASE, PubMed, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that compared the continuation of CNI with conversion to mTORi therapy.ResultsTwenty-nine RCTs (5,747 KTRs) were included in our analysis. Meta-analysis of the glomerular filtration rate (SMD 0.20; 95%CI 0.10–0.31; P&lt;0.01) and malignancy (RR 0.74; 95%CI 0.55–0.99; P=0.04) demonstrated a significant advantage of mTORi conversion over CNI continuation. However, the risk of acute rejection (RR 1.58; 95%CI 1.22–2.04; P&lt;0.01), infection (RR 1.55; 95%CI 1.01–1.31; P=0.04), proteinuria (RR 1.87; 95%CI 1.34–2.59; P&lt;0.01), leukopenia (RR 1.56; 95%CI 1.27–1.91; P&lt;0.01), acne (RR 6.43; 95%CI 3.43–12.04; P&lt;0.01), and mouth ulcer (RR 11.70; 95%CI 6.18–22.17; P&lt;0.01) were higher in the mTORi group. More patients in the conversion group had to discontinue study medication (RR 2.52; 95%CI 1.75–3.63; P&lt;0.01). There was no significant difference between the two groups with regard to death, graft loss, diabetes, chronic allograft nephropathy, and interstitial fibrosis/tubular atrophy.ConclusionsPosttransplant patients have a better graft function and lower incidence of malignancy after conversion from CNI to mTORi therapy. However, this conversion strategy may be prevented by the higher drug discontinuation rate due to mTORi-associated adverse events, such as more acute rejection, infection, proteinuria, leukopenia, acne, and mouth ulcer, indicating that conversion therapy may only be a treatment option in selected patients.