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Observational Study
. 2020 Feb 7;15(2):247-256.
doi: 10.2215/CJN.08970719. Epub 2020 Jan 23.

Recurrence of FSGS after Kidney Transplantation in Adults

Audrey Uffing  1   2 , Maria José Pérez-Sáez  1   3 , Marilda Mazzali  4 , Roberto C Manfro  5 , Andrea Carla Bauer  5 , Frederico de Sottomaior Drumond  5 , Michelle M O'Shaughnessy  6 , Xingxing S Cheng  6 , Kuo-Kai Chin  6 , Carlucci G Ventura  7 , Fabiana Agena  7 , Elias David-Neto  7 , Juliana B Mansur  8 , Gianna Mastroianni Kirsztajn  8 , Helio Tedesco-Silva Jr  8 , Gilberto M V Neto  8 , Carlos Arias-Cabrales  3 , Anna Buxeda  3 , Mathilde Bugnazet  9 , Thomas Jouve  9 , Paolo Malvezzi  9 , Enver Akalin  10 , Omar Alani  10 , Nikhil Agrawal  11 , Gaetano La Manna  12 , Giorgia Comai  12 , Claudia Bini  12 , Saif A Muhsin  13 , Miguel Carlos Riella  14 , Silvia R Hokazono  14 , Samira S Farouk  15 , Meredith Haverly  15 , Suraj Sarvode Mothi  1 , Stefan P Berger  2 , Paolo Cravedi  15 , Leonardo V Riella  1
Affiliations
Observational Study

Recurrence of FSGS after Kidney Transplantation in Adults

Audrey Uffing et al. Clin J Am Soc Nephrol. .

Abstract

Background and objectives: FSGS 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, & measurements: The 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.

Results: Among 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.

Conclusions: Idiopathic 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.

Keywords: Nephrectomy; adult; body mass index; cohort studies; focal segmental glomerulosclerosis; graft survival; humans; incidence; kidney; kidney diseases; kidney transplantation; plasmapheresis; recurrence; registries; renal transplantation; risk factors; rituximab; sample size; transplant outcomes; transplant recipients; treatment outcome.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
FSGS recurs in one third of kidney transplant recipients. (A) Cumulative incidence curve of FSGS recurrence in kidney transplant recipients with biopsy-proven idiopathic FSGS. Overall recurrence of FSGS was 32%, with median time to recurrence of 1.5 months. Shaded area around the curve represents the 95% confidence interval. (B) Recurrence rates per geographical location of the centers.
Figure 2.
Figure 2.
Recurrence of FSGS is associated with reduced graft survival, especially in patients with no response to treatment. (A) Kaplan–Meier graft survival curve comparing patients with and without recurrent FSGS after kidney transplantation. (B) Kaplan–Meier graft survival curve comparing only patients with recurrent FSGS stratified by their treatment response. Areas around the curve represent the 95% confidence intervals.
Figure 3.
Figure 3.
Treatment of recurrent FSGS with plasmapheresis with or without rituximab leads to complete remission in only a minority of patients. (A) Overall effect of treatment in patients treated with plasmapheresis and/or rituximab. (B) Flow chart of treatment outcome per treatment modality. One patient treated with plasmapheresis was also treated with cyclophosphamide, without remission.
Figure 4.
Figure 4.
Clinical outcomes of patients who achieve complete remission of rFSGS are comparable with patients who did not experience recurrence. Comparison of levels of (A) proteinuria and (B) eGFR calculated by Modification of Diet in Renal Disease Study (MDRD) in patients without recurrence with patients with recurrent FSGS (rFSGS) stratified by their response to treatment. eGFR after graft loss was imputed with a value of 5 ml/min per 1.73 m2. Error bars represent SEMs.
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