Risk factors associated with allograft failure in pediatric kidney transplant recipients with focal segmental glomerulosclerosis

Abstract

Background With improved outcomes for children transplanted with FSGS since previous NAPRTCS registry reports, this study re‐evaluates the association of living donation, immunosuppression, and DGF on graft survival. Setting Patients transplanted between 2002 and 2016, comparing FSGS diagnosis vs other glomerular diseases. Methods Primary outcomes were allograft survival and FSGS recurrent‐free graft survival. Potential risk factors were obtained at the time of transplant and up to 30 days post‐transplantation. Analysis considered a priori that DGF may be a proxy for severe FSGS recurrence. Multivariable survival models for outcome were tested for sensitivity without/with DGF to determine features independent of recurrence. Results From the larger cohort of 3010 patients, 5‐year graft survival in children with FSGS (n = 455) was worse (74.3%) compared with other glomerular diseases (87.1%, n = 690) (HR 1.45, P = 0.033). Modeling all glomerular diseases, survival risk was associated with deceased donor (HR 1.83, P = 0.002), re‐transplantation (HR 1.58, P = 0.013), and recipient age (HR 1.06/y, P = 0.002). The living donor advantage was not confirmed in a FSGS model (HR 1.51 for deceased, P = 0.12). DGF was highly associated with graft failure (HR 4.39, P < 0.001) and independent of re‐transplant history but not FSGS diagnosis. Induction agents or primary immunosuppression choices were not associated with survival. Conclusion Graft survival rates have improved since the previous report. Living donor did not predict graft failure, but there remains no survival advantage. DGF was the primary independent predictor for graft loss secondary to FSGS recurrence, consistent with DGF being a proxy for severe recurrent disease.

Clinical practice recommendations for recurrence of focal and segmental glomerulosclerosis/steroid‐resistant nephrotic syndrome

“…Living donation was not advantageous. The renal allograft survival risk was associated with re‐transplantation and recipient age 20 PICO question 2 : What is the optimal immunosuppressive regimen in patients with FSGS and/or SRNS? …”

Multicenter data to improve health for pediatric renal transplant recipients in North America: Complementary approaches of NAPRTCS and IROC

“…In attempts to address the limited pool of donor kidneys, Moudgil et al reported that pediatric renal transplant recipients from young donors (age <5 years) as compared to ideal donors (age 6‐35 years) had comparable patient and graft survival 20 . In regard to FSGS and disease recurrence, a recent NAPRTCS study demonstrated that while graft survival rates have improved in the more recent years, the 5‐year graft survival in children with FSGS (74.3%) was worse as compared with other glomerular diseases (87.1%), demonstrating the need for new therapeutic approaches in the prevention and management of FSGS recurrence 21 . As noted previously, revised data elements will collect more granular data in regard to recurrent glomerular disease, laboratory manifestations of recurrence, and management.…”

“…First rejection rates, for (A) living donor and (B) deceased donor kidney transplant recipients and era, demonstrating a steady decline in early acute rejection rates in more recent eras. In the most recent era, however, late first acute rejection is noted to be increasing, particularly in the living donor recipients (red dotted line = 2012-2017 cohort)In regard to FSGS and disease recurrence, a recent NAPRTCS study demonstrated that while graft survival rates have improved in the more recent years, the 5-year graft survival in children with FSGS (74.3%) was worse as compared with other glomerular diseases (87.1%), demonstrating the need for new therapeutic approaches in the prevention and management of FSGS recurrence 21. As noted previously, revised data elements will collect more granular data in regard to recurrent glomerular disease, laboratory manifestations of recurrence, and management.In addition to studies performed using the existing data, leveraging collaboration of the NAPRTCS network of centers has facilitated additional studies in special study populations.This includes a study by Dharnidarka et al, to determine prognostic factors and outcomes after PTLD, using a supplementary questionnaire to the NAPRTCS centers.…”

Therapeutic Options for Recurrence of Primary Focal Segmental Glomerulonephritis (FSGS) in the Renal Allograft: Single-Center Experience

“…Focal segmental glomerulosclerosis (FSGS) accounts for 2-4.6% of the primary diseases found in adults and 11-12.9% found in children receiving a kidneyallograft [2,3]. Focal segmental glomerulosclerosis recurrence in the graft remains a major challenge, as it occurs early with the reported incidence accounting for 30-50% in adults [3][4][5][6][7] and 60% in children [6][7][8]. It often responds poorly to treatment, with a substantial proportion, 30-50% of these patients losing their graft within 5 to 7 years [3,5,7,[9][10][11][12].…”

“…The latter is the strongest predictor of recurrence, with a risk of 65-85% in the second transplant [9][10][11]. Others report factors such as non-black race, graft from a living donor, and native kidney nephrectomy, but evidence is controversial [4,6,7]. Duration of renal replacement therapy and choice of immunosuppression do not seem to affect risk of recurrence [4,6,12].…”