Background and objectivesFSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients.Design, setting, participants, & measurementsThe Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors.ResultsAmong 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0–8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival.ConclusionsIdiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

Background. Tacrolimus trough concentrations (mean/variability), as well as concentration-to-dose ratio (C/D ratio), affect kidney allograft outcomes. We investigated the link between the C/D ratio and death-censored kidney graft survival (DCGS). Methods. We performed a retrospective study on 1029 kidney transplant patients (2004–2016) with the following criteria: tacrolimus-based immunosuppression, >1-year graft survival, no initial use of everolimus, and available anti–human leukocyte antigen antibody data. We analyzed the impact of the time-varying C/D ratio on DCGS. Fast metabolizers were defined by a C/D ratio < 1.05. We also investigated the effect of an early (mo 3 to mo 6 post transplantation) C/D ratio below 1.05. Cox survival analyses were performed, adjusting for potential confounders (tacrolimus trough, variability of tacrolimus trough, de novo donor-specific antibody development, cytochrome P450 3A5 genotype, pregraft sensitization, mo 3 glomerular filtration rate). Results. Time-varying C/D ratio was significantly associated with DCGS (hazard ratio [HR], 2.35; P < 0.001) in a univariate model, on the full analysis set comprising 1029 patients. In the multivariate time-varying model, based on 666 patients with available cytochrome P450 3A5 genotypes, the effect of the C/D ratio remained significant (HR, 2.26; P = 0.015); even when glomerular filtration rate at month 3 < 30 mL/min/1.73 m2 (HR, 2.61; P = 0.011), de novo donor-specific antibody development (HR, 4.09; P < 0.001) and continued steroid prescription (HR=2.08, P = 0.014) were taken into account (other covariates, including tacrolimus trough concentrations, were nonsignificant). In the same multivariate model, the effect of early C/D ratio (median at mo 3 and mo 6) remained significantly associated with DCGS (HR, 2.25; P = 0.041). Conclusions. C/D ratio is an independent and early predictor of DCGS. Identification of fast metabolizers could be a strategy to improve graft survival, for example, by optimizing tacrolimus formulation. Mechanistic studies to understand the C/D ratio effect are required.

Background and objectivesIn patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small.Design, setting, participants, & measurementsWe performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 “The Post-Transplant Glomerular Disease” study centers in Europe, North America, and South America.ResultsOut of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence.ConclusionsIn our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.