Treatment with Glucocorticoids or Calcineurin Inhibitors in Primary FSGS

Abstract

Background and objectives In primary FSGS, calcineurin inhibitors have primarily been studied in patients deemed resistant to glucocorticoid therapy. Few data are available about their use early in the treatment of FSGS. We sought to estimate the association between choice of therapy and ESRD in primary FSGS.Design, setting, participants, & measurements We used an inception cohort of patients diagnosed with primary FSGS by kidney biopsy between 1980 and 2012. Factors associated with initiation of therapy were identified using logistic regression. Time-dependent Cox models were performed to compare time to ESRD between different therapies. ResultsIn total, 458 patients were studied (173 treated with glucocorticoids alone, 90 treated with calcineurin inhibitors with or without glucocorticoids, 12 treated with other agents, and 183 not treated with immunosuppressives). Tip lesion variant, absence of severe renal dysfunction (eGFR$30 ml/min per 1.73 m 2 ), and hypoalbuminemia were associated with a higher likelihood of exposure to any immunosuppressive therapy. Only tip lesion was associated with initiation of glucocorticoids alone over calcineurin inhibitors. With adjusted Cox regression, immunosuppressive therapy with glucocorticoids and/or calcineurin inhibitors was associated with better renal survival than no immunosuppression (hazard ratio, 0.49; 95% confidence interval, 0.28 to 0.86). Calcineurin inhibitors with or without glucocorticoids were not significantly associated with a lower likelihood of ESRD compared with glucocorticoids alone (hazard ratio, 0.42; 95% confidence interval, 0.15 to 1.18). ConclusionsThe use of immunosuppressive therapy with calcineurin inhibitors and/or glucocorticoids as part of the early immunosuppressive regimen in primary FSGS was associated with improved renal outcome, but the superiority of calcineurin inhibitors over glucocorticoids alone remained unproven.

Open-Label Clinical Trials of Oral Pulse Dexamethasone for Adults with Idiopathic Nephrotic Syndrome

“…Such prolonged high-dose steroid course has substantial toxicity and significant morbidity. Nevertheless, a recent retrospective case series from the University of North Carolina suggested more favorable outcomes, with a hazard ratio for renal survival of 0.49 (95% CI 0.28-0.86) in subjects with FSGS who received high-dose glucocorticoid therapy for a median of 3.0 months (interquartile range [IQR] 1.5-5.9 months) [3].…”

Rethinking First-Line Immunosuppression for Idiopathic FSGS

“…In this issue of the Clinical Journal of the American Society of Nephrology, Laurin et al (19) present an analysis of the largest cohort of patients with idiopathic FSGS to date. Using the Glomerular Disease Collaborative Network (GDCN) Registry, Laurin et al (19) showed that early treatment with any immunosuppression was associated with significantly greater renal survival compared with no immunosuppression in 458 adults and children with FSGS (hazard ratio, 0.49 for ESRD; 95% confidence interval [95% CI], 0.28 to 0.86).…”

“…Using the Glomerular Disease Collaborative Network (GDCN) Registry, Laurin et al (19) showed that early treatment with any immunosuppression was associated with significantly greater renal survival compared with no immunosuppression in 458 adults and children with FSGS (hazard ratio, 0.49 for ESRD; 95% confidence interval [95% CI], 0.28 to 0.86). There was no significant difference in renal survival among patients treated with glucocorticoids alone compared with patients treated with CNIs, although there was a trend toward greater survival among patients treated with CNIs.…”

“…Laurin et al (19) also used a type of survival analysis that takes into account changes in medication exposure over time, allowing for patients to crossover between treatment groups. The methodology is a practical approach to address a common occurrence in clinical practice that has the potential to heavily bias the results of an observational study.…”

“…It is likely that multiple mechanisms are responsible for the development of proteinuria and the FSGS lesion. Although the study by Laurin et al (19) adds to the epidemiologic data on the management of idiopathic FSGS, the mechanistic role of immunosuppression in the management of idiopathic FSGS remains unclear. As a field, we hope that basic and clinical research in glomerular diseases, including large cohort studies, such as the Nephrotic Syndrome Study Network and Cure Glomerulonephropathy, will lead to the (re) grouping of patients with FSGS on the basis of mechanism and therapeutic implications.…”