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Published on: February 8, 2019
Treatment with Glucocorticoids or Calcineurin Inhibitors in Primary FSGS
Louis-Philippe Laurin1, Adil M Gasim2, Caroline J Poulton3
1Division of Nephrology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada; Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Division of Nephrology and Hypertension, University of North Carolina Kidney Center and louis-philippe.laurin@umontreal.ca.
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.
Insights
Early immunosuppressive therapy, including calcineurin inhibitors and glucocorticoids, improved kidney survival in primary focal segmental glomerulosclerosis (FSGS). However, calcineurin inhibitors did not prove superior to glucocorticoids alone for preventing end-stage renal disease (ESRD).
Area of Science:
- Nephrology
- Immunosuppressive therapy
- Glomerular diseases
Background:
- Primary focal segmental glomerulosclerosis (FSGS) treatment often involves glucocorticoids, with calcineurin inhibitors typically reserved for resistant cases.
- Limited data exist on the early use of calcineurin inhibitors in primary FSGS management.
- This study investigates the association between early therapeutic choices and end-stage renal disease (ESRD) risk in primary FSGS.
Purpose of the Study:
- To estimate the association between different early therapeutic strategies and the risk of ESRD in patients with primary FSGS.
- To compare the effectiveness of glucocorticoids versus calcineurin inhibitors in the early treatment of primary FSGS.
- To identify factors influencing the choice of immunosuppressive therapy in primary FSGS.
Main Methods:
- An inception cohort of 458 patients diagnosed with primary FSGS via kidney biopsy (1980-2012) was analyzed.
- Logistic regression identified factors associated with therapy initiation.
- Time-dependent Cox models were used to compare time-to-ESRD across different treatment groups.
Main Results:
- Immunosuppressive therapy (glucocorticoids and/or calcineurin inhibitors) was associated with significantly better renal survival compared to no immunosuppression (HR, 0.49).
- Calcineurin inhibitors, with or without glucocorticoids, did not show a statistically significant advantage over glucocorticoids alone in reducing ESRD risk (HR, 0.42).
- Factors like tip lesion variant, preserved eGFR, and hypoalbuminemia predicted higher likelihood of receiving immunosuppressive therapy.
Conclusions:
- Early immunosuppressive therapy, encompassing calcineurin inhibitors and/or glucocorticoids, is linked to improved renal outcomes in primary FSGS.
- The study did not provide definitive evidence for the superiority of calcineurin inhibitors over glucocorticoids alone in early FSGS treatment.
- Further research is needed to clarify optimal early immunosuppressive strategies for primary FSGS.
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