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.

Results: In 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).

Conclusions: The 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.

Keywords: ESRD; calcineurin inhibitors; focal segmental glomerulosclerosis; glomerular disease; glucocorticoids; humans; immunosuppression; immunosuppressive agents; nephrotic syndrome.

Figure 1.

Study flow diagram. CNI, calcineurin inhibitor.

Figure 2.

Probability density function of time length between renal biopsy and immunosuppression therapy. CNI, calcineurin inhibitor.

Figure 3.

Kaplan–Meier (K-M) curves of time to ESRD by immunosuppression status. (A) For all patients; (B) for adults only.

Figure 4.

Predicted ESRD–free Nelson–Aalen curves: these curves are predicted for the adjusted Cox time–dependent model. Outcomes for the glucocorticoids alone and calcineurin inhibitors (CNIs) with or without glucocorticoids groups are computed at the mean (age, men, not otherwise specified variant, baseline serum albumin, and eGFR).