Immunosuppressive Treatment of Idiopathic Focal Segmental Glomerulosclerosis: A Five-Year Follow-Up Study

Abstract

Background/Aims: Focal segmental glomerulosclerosis (FSGS) is a common type of glomerular disease that can lead to chronic renal failure. Various therapeutic regimens have been used in nephrotic FSGS patients. The effect of treatment with prednisolone alone or its combination with azathioprine and cyclosporin and parameters related to a poor outcome are studied. Methods: Fifty-one patients with idiopathic FSGS and a follow-up period of 5 years were included. Twenty-five were treated with prednisolone alone (1 mg/kg BW/day) or combination of prednisolone (0.5 mg/kg BW/day) with azathioprine (2 mg/kg BW/day) or cyclosporine (3 mg/kg BW/day) in gradually reduced doses whereas 26 patients received no immunosuppressive drugs. Lower prednisolone dose regimens were used as initial treatment in obese, borderline diabetics or patients with bone disease. The clinical course was estimated using the end-points of 50% or doubling of baseline serum creatinine and/or end-stage renal failure. The contribution of clinical and histological parameters in the clinical outcome was estimated by univariate and multivariate analyses. Results: Increase of baseline serum creatinine by 50% during the follow-up period was observed in 2 treated and 9 untreated patients (8% vs. 35%, p = 0.03) whereas doubling of serum creatinine in 2 and 5 patients respectively (8% vs. 19%, p = NS). End-stage renal failure developed in 4 of 51 patients (8%), 2 treated and 2 untreated (p = NS). Parameters related to a poor outcome were baseline serum creatinine and severity of glomerulosclerosis (multivariate analysis OR = 1.08, p = 0.01). Most of patients (68%) who reached end-points had persistent nephrotic syndrome during the follow-up. Remission of nephrotic syndrome was observed more frequently among treated (75 vs. 30.7%, p = 0.05). Prednisolone alone was followed by remission of nephrotic syndrome in 62.5% whereas combination of lower prednisolone dose with azathioprine and cyclosporin in 80 and 85.7% of patients. No serious side-effects were observed. Conclusion: This and previous studies suggest that steroid and/or immunosuppressive therapy have a role in amelioration of the clinical course and remission of nephrotic syndrome in patients with FSGS A combination of low predisolone dose with cyclosporine could be used as initial treatment in patients with higher risk for side-effects from the usual prednisolone dose.

Primary FSGS in Nephrotic Adults: Clinical Profile, Response to Immunosuppression and Outcome

“…In our cohort, 63.2% patients had an initial response to steroids, which is similar to the response observed in other studies [4,6,9,10,17]. About 63.9% of our steroid responsive patients had sustained remission (no relapse) similar to that found in other cohorts [4,5].…”

“…Our patients were younger than other populations [5,6,10,15], though similar to Indian studies [9,12,16]. Only 2 patients in our cohort had spontaneous remission, which is known to be uncommon in primary FSGS with NS [5,9,15,16].…”

“…It is characterized by an aggressive clinical course. If not treated adequately, >50% patients may progress to end-stage renal disease (ESRD) in 5-10 years [4,5,6,7]. Oral steroid is the first line of treatment [8], but only about 50-60% patients show complete remission (CR) [9,10].…”

Optimal management of primary focal segmental glomerulosclerosis in adults

“…36 Tacrolimus (trough level of ~5.5 ng/mL) has also been used as a firstline therapy. 37 Another strategy to reduce patients' exposure to steroids is using mycophenolate mofetil (MMF).…”

Rethinking First-Line Immunosuppression for Idiopathic FSGS

“…These recommendations are primarily on the basis of small retrospective case series (4,(9)(10)(11)(12)(13)(14)(15), the largest of which comprised 53 patients (10). Although randomized, controlled trials have compared the effectiveness of therapies for steroid-resistant FSGS, data comparing first-line glucocorticoids with other potential first-line therapies are extremely limited (16)(17)(18).…”