A large, international study on post-transplant glomerular diseases: the TANGO project

Abstract

BackgroundLong-term outcomes in kidney transplantation (KT) have not significantly improved during the past twenty years. Despite being a leading cause of graft failure, glomerular disease (GD) recurrence remains poorly understood, due to heterogeneity in disease pathogenesis and clinical presentation, reliance on histopathology to confirm disease recurrence, and the low incidence of individual GD subtypes. Large, international cohorts of patients with GD are urgently needed to better understand the disease pathophysiology, predictors of recurrence, and response to therapy.MethodsThe Post-TrANsplant GlOmerular Disease (TANGO) study is an observational, multicenter cohort study initiated in January 2017 that aims to: 1) characterize the natural history of GD after KT, 2) create a biorepository of saliva, blood, urine, stools and kidney tissue samples, and 3) establish a network of patients and centers to support novel therapeutic trials. The study includes 15 centers in America and Europe. Enrollment is open to patients with biopsy-proven GD prior to transplantation, including IgA nephropathy, membranous nephropathy, focal and segmental glomerulosclerosis, atypical hemolytic uremic syndrome, dense-deposit disease, C3 glomerulopathy, complement- and IgG-positive membranoproliferative glomerulonephritis or membranoproliferative glomerulonephritis type I-III (old classification). During phase 1, patient data will be collected in an online database. The biorepository (phase 2) will involve collection of samples from patients for identification of predictors of recurrence, biomarkers of disease activity or response to therapy, and novel pathogenic mechanisms. Finally, through phase 3, we will use our multicenter network of patients and centers to launch interventional studies.DiscussionMost prior studies of post-transplant GD recurrence are single-center and retrospective, or rely upon registry data that frequently misclassify the cause of kidney disease. Systematically determining GD recurrence rates and predictors of clinical outcomes is essential to improving post-transplant outcomes. Furthermore, accurate molecular phenotyping and biomarker development will allow better understanding of individual GD pathogenesis, and potentially identify novel drug targets for GD in both native and transplanted kidneys. The TANGO study has the potential to tackle GD recurrence through a multicenter design and a comprehensive biorepository.

Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem

“…From literature data, it has been hypothesized that the permeability factor may lead to the loss of nephrin and to the reduction of the expression of podocin [ 74 ]. Indeed, mutation of the gene NPHS2 which encodes for podocin, is associated with familiar and sporadic FSGS and the rate risk of recurrence in patients with this mutation is around 8%, contrary to the belief that familiar forms of FSGS do not recur [ 75 ]. In particular, suPAR seems to alter podocyte cytoskeleton and podocyte attachment with activation of beta 3-integrin and STAT1 in vascular smooth muscle cells through a PDGF receptor [ 76 ].…”

“…Furthermore, the duration of dialysis and the type of post-transplant immunosuppression seem to be risk factors of recurrence [ 110 ]. A recent study by TANGO project group demonstrated that idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss; moreover, the authors demonstrated that a response to treatment was associated with significantly better outcomes achieved in only half of the cases analyzed [ 75 ].…”

Familial Focal Segmental Glomerulosclerosis With Late-Onset Presentation and R229Q/R291W Podocin Mutations

“…Renal transplantation is a matter of concern in patients with FSGS as the general rate of recurrence is high (Uffing et al, 2018). Although three women of the 2nd generation were submitted to renal transplantation, none of them presented recurrent FSGS.…”

A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease

“…However, the heterogeneous treatment response suggests the opportunity to design a larger multicenter study in C3 GP patients after kidney transplantation. For this reason in 2017, a group of researchers across Europe and North and South America initiated the post-TrANsplant GlOmerular (TANGO) disease study, an observational multicenter cohort study with the aim to enroll patients who arrived to ESKD for different forms of glomerulonephritis, mainly C3 GP [64].…”