Recurrent focal glomerulosclerosis: natural history and response to therapy.
OBJECTIVE
Recurrent focal glomerulosclerosis (FGS) has been well documented since it was first reported in 1972. However, the course of the disease after transplantation and the optimal treatment regimen have not been well defined since the introduction of newer treatment modalities.


METHODS
We reviewed all the charts of patients with biospy-proven FGS who received renal transplants at our institution from January 1980 through December 1990. Case histories consistent with diagnoses other than primary FGS (such as reflux nephropathy or intravenous drug use) were eliminated from the study. During this time period, 78 allografts were received by 71 patients with FGS. Independent variables that were analyzed included sex, race, time in months between the diagnosis of FGS and end-stage disease (dialysis or transplantation), age at time of transplantation, type of dialysis, source of allograft (cadaveric or living related), haplotype matching, donor-specific transfusions, age and sex of the donor, post-transplantation acute tubular necrosis, rejection episodes, immunosuppression regimen, use of plasmapheresis and angiotensin converting enzyme (ACE) inhibitors, and outcome.


RESULTS
FGS recurred in 25 allografts (32%) of 21 patients. Biopsy-proven diagnosis of recurrence was made a mean of 7.5 months (range: 0.5 to 44 months) after transplantation. Patients who had rapid progression to end-stage disease tended to experience more frequent recurrences. Of seven patients who received a second transplant, five patients lost the first graft to recurrent FGS, and four of those patients (80%) had a recurrence in the second allograft. Recurrent disease developed in 34% of patients concurrently treated with cyclosporine and in 28% of those treated with prednisone and azathioprine alone (NS). Patients with recurrent FGS who were treated with ACE inhibitors benefited from a significant reduction of proteinuria. Six patients underwent plasmapheresis after diagnosis of the recurrence. Three of five patients in whom the diagnosis was made early in the course of the disease and in whom plasmapheresis was initiated immediately had reversal of epithelial foot process effacement and remission of proteinuria. End-stage disease eventually developed in 14 allografts (56%) an average of 23.7 months (range: 1 to 65 months) after diagnosis of recurrent disease. The cause of failure was chronic rejection in four allografts and recurrent disease in the remaining 10 allografts.


CONCLUSIONS
FGS recurs in approximately 30% of allografts and causes graft loss in half of these. Patients who have lost a first allograft to recurrent FGS are at high risk for developing recurrent disease in a second allograft. Prolonged allograft survival is possible in patients with recurrent FGS and may best be obtained with a combination of treatment modalities including cyclosporine (perhaps in higher dosages than are routinely used in clinical renal transplantation), ACE inhibitors, and early use of plasmapheresis. The efficacy of these modalities supports the notion that recurrent FGS is caused by a circulating humoral mediator.
Artero
M
M
Transplant Service, University of California, San Francisco 94143.
Biava
C
C
Amend
W
W
Tomlanovich
S
S
Vincenti
F
F
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000503:physiopathology* / Q000601:surgery*; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D011507:Proteinuria / Q000188:drug therapy / Q000628:therapy; D012008:Recurrence; D006435:Renal Dialysis; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D016572:Cyclosporine