Louis-Philippe Laurin1, Adil M Gasim2, Caroline J Poulton3, Susan L Hogan3, J Charles Jennette2, Ronald J Falk3, Bethany J Foster4, Patrick H Nachman3. 1. Division 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. 2. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina; 3. Division of Nephrology and Hypertension, University of North Carolina Kidney Center and. 4. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Division of Nephrology, Montreal Children's Hospital, Montreal, Quebec, Canada; and Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
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.
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.
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Authors: Laura H Mariani; Andrew S Bomback; Pietro A Canetta; Michael F Flessner; Margaret Helmuth; Michelle A Hladunewich; Jonathan J Hogan; Krzysztof Kiryluk; Patrick H Nachman; Cynthia C Nast; Michelle N Rheault; Dana V Rizk; Howard Trachtman; Scott E Wenderfer; Corinna Bowers; Peg Hill-Callahan; Maddalena Marasa; Caroline J Poulton; Adelaide Revell; Suzanne Vento; Laura Barisoni; Dan Cattran; Vivette D'Agati; J Charles Jennette; Jon B Klein; Louis-Philippe Laurin; Katherine Twombley; Ronald J Falk; Ali G Gharavi; Brenda W Gillespie; Debbie S Gipson; Larry A Greenbaum; Lawrence B Holzman; Matthias Kretzler; Bruce Robinson; William E Smoyer; Lisa M Guay-Woodford Journal: Am J Kidney Dis Date: 2018-11-09 Impact factor: 11.072