Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial.
DAPA-CKD
dapagliflozin
eGFR slope
focal segmental glomerulosclerosis
Journal
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402
Informations de publication
Date de publication:
22 08 2022
22 08 2022
Historique:
received:
27
05
2021
pubmed:
2
12
2021
medline:
25
8
2022
entrez:
1
12
2021
Statut:
ppublish
Résumé
Despite renin-angiotensin-aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy. In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment). Of 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m2 and median (interquartile range) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (-4.5, 95% CI -5.9 to -3.1 versus -0.9, -2.1 to 0.4 mL/min/1.73 m2/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were -1.9 (-3.0, -0.9) and -4.0 (-4.9, -3.0) mL/min/1.73 m2/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin. Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared with placebo, although this difference was not statistically significant.
Sections du résumé
BACKGROUND
Despite renin-angiotensin-aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy.
METHODS
In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment).
RESULTS
Of 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m2 and median (interquartile range) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (-4.5, 95% CI -5.9 to -3.1 versus -0.9, -2.1 to 0.4 mL/min/1.73 m2/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were -1.9 (-3.0, -0.9) and -4.0 (-4.9, -3.0) mL/min/1.73 m2/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin.
CONCLUSIONS
Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared with placebo, although this difference was not statistically significant.
Identifiants
pubmed: 34850160
pii: 6440167
doi: 10.1093/ndt/gfab335
pmc: PMC9395378
doi:
Substances chimiques
Benzhydryl Compounds
0
Glucosides
0
Sodium-Glucose Transporter 2 Inhibitors
0
dapagliflozin
1ULL0QJ8UC
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1647-1656Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.
Références
Nephrol Dial Transplant. 2011 Feb;26(2):414-30
pubmed: 21068142
N Engl J Med. 2011 Dec 22;365(25):2398-411
pubmed: 22187987
Am J Kidney Dis. 2021 Feb;77(2):216-225
pubmed: 32791086
Am J Kidney Dis. 2020 Jan;75(1):84-104
pubmed: 31473020
Circulation. 2016 Sep 6;134(10):752-72
pubmed: 27470878
Circulation. 2021 Feb 2;143(5):438-448
pubmed: 33186054
Kidney Int. 2021 Jul;100(1):215-224
pubmed: 33878338
Am J Kidney Dis. 2014 Feb;63(2):244-50
pubmed: 24210590
Lancet Diabetes Endocrinol. 2019 Jun;7(6):415-417
pubmed: 31047903
Lancet Diabetes Endocrinol. 2021 Jan;9(1):22-31
pubmed: 33338413
Clin J Am Soc Nephrol. 2018 Mar 7;13(3):414-421
pubmed: 29167190
Clin J Am Soc Nephrol. 2017 Mar 7;12(3):502-517
pubmed: 28242845
Nephrology (Carlton). 2018 Oct;23 Suppl 4:57-61
pubmed: 30298667
Kidney Int. 2019 Feb;95(2):281-295
pubmed: 30665569
N Engl J Med. 2016 Jul 28;375(4):323-34
pubmed: 27299675
N Engl J Med. 2020 Oct 8;383(15):1436-1446
pubmed: 32970396
N Engl J Med. 2017 Aug 17;377(7):644-657
pubmed: 28605608
Lancet Diabetes Endocrinol. 2020 Jul;8(7):582-593
pubmed: 32559474
Lancet Diabetes Endocrinol. 2019 Aug;7(8):606-617
pubmed: 31196815
Am J Kidney Dis. 2014 Jul;64(1):74-85
pubmed: 24787763
Am J Kidney Dis. 2021 Feb;77(2):280-286
pubmed: 32711072
Kidney Int. 2011 Oct;80(8):868-78
pubmed: 21734640
Nephrol Dial Transplant. 2020 Feb 1;35(2):274-282
pubmed: 32030417
Lancet Diabetes Endocrinol. 2019 Jun;7(6):429-441
pubmed: 30992195
Kidney Int Rep. 2020 Jan 08;5(4):494-502
pubmed: 32274453
Clin J Am Soc Nephrol. 2007 May;2(3):529-42
pubmed: 17699461
Annu Rev Med. 2015;66:255-70
pubmed: 25341005
Am J Nephrol. 2019;49(4):331-342
pubmed: 30921791
Diabetologia. 2021 Jun;64(6):1256-1267
pubmed: 33665685
Kidney Int. 2021 Oct;100(4S):S1-S276
pubmed: 34556256
Nephrol Dial Transplant. 2020 Oct 1;35(10):1700-1711
pubmed: 32862232
Circulation. 2014 Feb 4;129(5):587-97
pubmed: 24334175