Pretreatment GFR Slopes Predict Dapagliflozin Response in IgA Nephropathy

Introduction: Dapagliflozin exerts renoprotective effects in patients with IgA nephropathy (IgAN). However, the association between the pretreatment estimated glomerular filtration rate (eGFR) slope and posttreatment outcomes in patients with slowly progressing IgAN with optimal standard care is unc...

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Main Authors: Hiroyuki Ueda, Nobuo Tsuboi, Kei Matsumoto, Shohei Fukunaga, Akihiro Shimizu, Masahiro Okabe, Shinya Yokote, Takaya Sasaki, Takashi Yokoo
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024925002670
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author Hiroyuki Ueda
Nobuo Tsuboi
Kei Matsumoto
Shohei Fukunaga
Akihiro Shimizu
Masahiro Okabe
Shinya Yokote
Takaya Sasaki
Takashi Yokoo
author_facet Hiroyuki Ueda
Nobuo Tsuboi
Kei Matsumoto
Shohei Fukunaga
Akihiro Shimizu
Masahiro Okabe
Shinya Yokote
Takaya Sasaki
Takashi Yokoo
author_sort Hiroyuki Ueda
collection DOAJ
description Introduction: Dapagliflozin exerts renoprotective effects in patients with IgA nephropathy (IgAN). However, the association between the pretreatment estimated glomerular filtration rate (eGFR) slope and posttreatment outcomes in patients with slowly progressing IgAN with optimal standard care is unclear. Methods: This study included patients with biopsy-confirmed IgAN who were prescribed dapagliflozin during outpatient visits (August 2021–March 2022). Longitudinal eGFR and proteinuria data were analyzed 2 to 3 years before and after treatment. The eGFR slope and time-averaged urinary protein-to-creatinine ratio (UPCR) were compared between the pretreatment period and the posttreatment chronic phase (≥ 90 days). Multivariable regression analysis was performed to examine the association between the pretreatment eGFR slope and posttreatment changes in the slope. Results: A total of 84 patients (median age: 55.5 years; 38% female; median eGFR: 40.0 ml/min per 1.73 m2; median follow-up: 10.4 years at dapagliflozin initiation) were analyzed. The eGFR slope improved significantly from −1.92 to −0.69 ml/min per 1.73 m2/yr, whereas time-averaged UPCR remained unchanged during observation periods of 1161 and 1050 days pretreatment and posttreatment, respectively. Patients with a steeper pretreatment eGFR decline tended to show greater posttreatment improvement. Multivariable analysis showed that the pretreatment eGFR slope was independently associated with the posttreatment eGFR slope after adjusting for confounders, including pretreatment UPCR. Conclusion: Dapagliflozin was associated with a slower eGFR decline in patients with IgAN, particularly those with a steeper pretreatment eGFR slope, suggesting that pretreatment eGFR slope may help guide individualized therapy.
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spelling doaj-art-4999a1406cf54604b5e02c766d4602b02025-08-20T03:24:16ZengElsevierKidney International Reports2468-02492025-07-011072405241310.1016/j.ekir.2025.04.042Pretreatment GFR Slopes Predict Dapagliflozin Response in IgA NephropathyHiroyuki Ueda0Nobuo Tsuboi1Kei Matsumoto2Shohei Fukunaga3Akihiro Shimizu4Masahiro Okabe5Shinya Yokote6Takaya Sasaki7Takashi Yokoo8Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan; Correspondence: Hiroyuki Ueda, Division of Nephrology and Hypertension, The Jikei University School of Medicine, 3-19-18, Nishi-shinbashi, Minato-ku, Tokyo 105-8471, Japan.Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanDivision of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, JapanIntroduction: Dapagliflozin exerts renoprotective effects in patients with IgA nephropathy (IgAN). However, the association between the pretreatment estimated glomerular filtration rate (eGFR) slope and posttreatment outcomes in patients with slowly progressing IgAN with optimal standard care is unclear. Methods: This study included patients with biopsy-confirmed IgAN who were prescribed dapagliflozin during outpatient visits (August 2021–March 2022). Longitudinal eGFR and proteinuria data were analyzed 2 to 3 years before and after treatment. The eGFR slope and time-averaged urinary protein-to-creatinine ratio (UPCR) were compared between the pretreatment period and the posttreatment chronic phase (≥ 90 days). Multivariable regression analysis was performed to examine the association between the pretreatment eGFR slope and posttreatment changes in the slope. Results: A total of 84 patients (median age: 55.5 years; 38% female; median eGFR: 40.0 ml/min per 1.73 m2; median follow-up: 10.4 years at dapagliflozin initiation) were analyzed. The eGFR slope improved significantly from −1.92 to −0.69 ml/min per 1.73 m2/yr, whereas time-averaged UPCR remained unchanged during observation periods of 1161 and 1050 days pretreatment and posttreatment, respectively. Patients with a steeper pretreatment eGFR decline tended to show greater posttreatment improvement. Multivariable analysis showed that the pretreatment eGFR slope was independently associated with the posttreatment eGFR slope after adjusting for confounders, including pretreatment UPCR. Conclusion: Dapagliflozin was associated with a slower eGFR decline in patients with IgAN, particularly those with a steeper pretreatment eGFR slope, suggesting that pretreatment eGFR slope may help guide individualized therapy.http://www.sciencedirect.com/science/article/pii/S2468024925002670dapagliflozineGFR slopeIgA nephropathyproteinuria
spellingShingle Hiroyuki Ueda
Nobuo Tsuboi
Kei Matsumoto
Shohei Fukunaga
Akihiro Shimizu
Masahiro Okabe
Shinya Yokote
Takaya Sasaki
Takashi Yokoo
Pretreatment GFR Slopes Predict Dapagliflozin Response in IgA Nephropathy
Kidney International Reports
dapagliflozin
eGFR slope
IgA nephropathy
proteinuria
title Pretreatment GFR Slopes Predict Dapagliflozin Response in IgA Nephropathy
title_full Pretreatment GFR Slopes Predict Dapagliflozin Response in IgA Nephropathy
title_fullStr Pretreatment GFR Slopes Predict Dapagliflozin Response in IgA Nephropathy
title_full_unstemmed Pretreatment GFR Slopes Predict Dapagliflozin Response in IgA Nephropathy
title_short Pretreatment GFR Slopes Predict Dapagliflozin Response in IgA Nephropathy
title_sort pretreatment gfr slopes predict dapagliflozin response in iga nephropathy
topic dapagliflozin
eGFR slope
IgA nephropathy
proteinuria
url http://www.sciencedirect.com/science/article/pii/S2468024925002670
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