Prediction and Treatment of Recurrent Focal Segmental Glomerulosclerosis After Renal Transplantation in Children Roberto Dall’Amico, MD, GianMarco Ghiggeri, MD, Michele Carraro, MD, Mary Artero, MD, Luciana Ghio, MD, Edgarda Zamorani, MD, Cristina Zennaro, PhD, Giancarlo Basile, MD, Giovanni Montini, MD, Lucia Rivabella, MD, Massimo Cardillo, MD, Mario Scalamogna, MD, and Fabrizio Ginevri, MD ● The recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation has a potentially detrimental course toward the loss of renal function. To identify prognostic markers for recurrence and efficacy of treatment, we evaluated the outcome of 32 renal allografts in 29 pediatric patients with FSGS who underwent transplantation from 1987 to 1998 in the North Italy Transplant program. Recurrence was observed in 15 of 29 patients (52%) after the first transplant and in 3 of 3 patients (100%) after the second graft. No significant differences in sex, age at FSGS onset, age at transplantation, or length of dialysis were noted between patients with recurrent and nonrecurrent FSGS. Those with recurrence originally developed end-stage renal failure faster (3.9 years) than those without recurrence (6.2 years). Pretransplantation serum samples from 25 patients were tested in an in vitro assay that evaluates glomerular permeability to albumin. FSGS recurred in 11 of 13 children who tested positive for the permeability factor and in 4 of 12 patients with a negative test result; the odds ratio for developing recurrence was 10.99 (95% confidence limit, 1.6 to 75.47) in the former group. The immediate onset of proteinuria after transplantation was a negative prognostic factor for the outcome; 6 of 9 patients in whom proteinuria appeared within 2 days of transplantation returned to dialysis in less than 24 months. In 9 of 11 patients who were treated with plasmapheresis plus cyclophosphamide after recurrence, proteinuria was successfully reversed and persistent remission was obtained in 7 patients. These data show that the glomerular permeability test has a significant predictive value for the recurrence of proteinuria in children with FSGS who have received a renal allograft. Of the clinical parameters considered, only the duration of disease was significantly different in patients with recurrent versus nonrecurrent FSGS. Treatment with plasmapheresis plus cyclophosphamide can be effective in the control of FSGS relapse after renal transplantation.  1999 by the National Kidney Foundation, Inc. INDEX WORDS: Focal segmental glomerulosclerosis (FSGS); renal allograft; recurrence; permeability factors. F OCAL SEGMENTAL glomerulosclerosis (FSGS) represents approximately 10% of the idiopathic nephrotic syndromes in chil- dren. 1,2 In 40% to 75% of the cases, FSGS responds poorly to steroids, and despite the use of such drugs as cytotoxic agents, cyclosporine (CsA), and tacrolimus (FK506), the disease progresses to renal failure in 30% of the patients within 5 years. 3-7 Moreover, the disease recurs in 30% to 50% of the patients after renal transplantation, and subse- quent renal grafts carry a high risk for graft loss (up to 85%). The recurrence of FSGS usually starts within the first month and is characterized by massive proteinuria and rapid deterioration of renal function, usually leading to end-stage renal failure in less than 2 years. However, a substan- tial proportion of patients have mild proteinuria and maintain normal renal function for years. 8 Because the risk for recurrence poses serious threats, the current view is that children with FSGS should not be regarded as candidates for a living donor transplant. 9 Prediction of recurrence could therefore be of considerable importance in deciding the clinical strategies after transplanta- tion in these patients. Several variables, such as age of onset of the original disease, rapid evolu- tion to renal failure, mesangial prominence, length of dialysis therapy, and HLA matching with the graft donor, have been investigated; however, the predictive value of these variables is still de- bated. 3,10,11 A large body of evidence indicates that circu- lating humoral factors that alter the integrity of From the Department of Pediatrics, University of Padua; Nephrology Unit and Blood Transfusion Center, G. Gaslini Children’s Hospital, Genoa; Department of Internal Medi- cine, University of Trieste; Nephrology Unit, Hospital of Cividale; Department of Pediatrics, University of Milan; North Italy Transplant Program, Transplant Immunology and Blood Transfusion Center, and the Maggiore Hospital, Milan, Italy. Received February 15, 1999; accepted in revised form June 25, 1999. Address reprint requests to Fabrizio Ginevri, MD, Nephrol- ogy Unit, G. Gaslini Hospital, Largo Gaslini 5, 16148 Genoa, Italy. E-mail: labnefro@tin.it  1999 by the National Kidney Foundation, Inc. 0272-6386/99/3406-0009$3.00/0 1048 American Journal of Kidney Diseases, Vol 34, No 6 (December), 1999: pp 1048-1055