Sodium-Glucose Cotransporter-2 Inhibitors—Miracle Drugs for the Treatment of Chronic Kidney Disease Irrespective of the Diabetes Status: Lessons from the Dedicated Kidney Disease-Focused CREDENCE and DAPA-CKD Trials
Abstract
:1. Introduction
2. Importance of Early Diagnosis and Therapeutic Intervention in Patients with DKD
3. Prognostic Biomarkers of eGFR Decline: Circulating Tumor Necrosis Factor (TNF) Receptors (TNFRs)
4. Effects of the SGLT2 Inhibitors on Kidney Outcomes in Patients with Nondiabetic CKD or Diabetes
5. Renoprotective Effects of the SGLT2 Inhibitors beyond Reductions in Albuminuria
6. Initial eGFR Declines and Volume Depletion: Concerning Side-Effects of the SGLT2 Inhibitors
7. Hyperkalemia
8. Effects of the SGLT2 Inhibitors in Patients with CKD and Normoalbuinuria
9. Effects of the SGLT2 Inhibitors on Atherosclerotic CVD (ASCVD) and HF in Patients with CKD
10. Promising Therapeutic Strategy
11. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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CREDENCE [15] (Canagliflozin) | DAPA-CKD [16] (Dapagliflozin) | DAPA-CKD (with T2D) | DAPA-CKD (without T2D) | |
---|---|---|---|---|
n | 4401 | 4304 | 2906 | 1398 |
Age (year) | 63 | 62 | 64 | 56 |
Male sex (%) | 66 | 67 | 67 | 67 |
Body mass index | 31.3 | 29.5 | 30.3 | 27.9 |
T2D (%) | 100 | 68 | 100 | 0 |
HbA1c (%) | 8.3 | 7.1 | 7.8 | 5.6 |
LSM change in HbA1c: % (95% CI) | −0.3 (−0.2 to −0.3) | −0.1 (−0.1 to 0.0) | −0.1 (−0.2 to 0.0) | 0.0 (−0.2 to 0.2) |
ACR (mg/g) | 927 | 949 | 1017 | 861 |
Geometric mean ACR change: % (95% CI) | −31 (−35 to −26) | −29 (−33 to −25) | −35 (−39 to −31) | −15 (−23 to −6) |
Stage 4 CKD (%) | 4 | 14 | 14 | 16 |
eGFR (mL/min/1.73 m2) | 56 | 43 | 44 | 42 |
LSM change in the eGFR slope (mL/min/1.73 m2/year) | 1.52 (1.11 to 1.93) | 0.93 (0.61 to 1.25) | 1.18 (0.79 to 1.56) | 0.46 (−0.10 to 1.03) |
Initial decline in eGFR * (SGLT2i vs. PBO) (mL/min/1.73 m2) | −3.7 vs. −0.6 | −4.0 vs. −0.8 | −3.2 vs. −0.6 | −2.8 vs. −0.8 |
Decline in eGFR after initial phase (SGLT2i vs. PBO) (mL/min/1.73 m2/year) | −1.9 vs. −4.6 | −1.7 vs. −3.6 | −1.6 vs. −3.8 | −1.9 vs. −3.2 |
Prior CV disease (%) | 50 | 37 | 44 | 24 |
Primary endpoint **: HR (95% CI) | 0.70 (0.59 to 0.82) | 0.61 (0.51 to 0.72) | 0.64 (0.52 to 0.79) | 0.50 (0.35 to 0.72) |
CV death or HHF ***: HR (95% CI) | 0.69 (0.57 to 0.83) | 0.71 (0.55 to 0.92) | 0.70 (0.53 to 0.92) | 0.79 (0.40 to 1.55) |
All cause mortality ***: HR (95% CI) | 0.83 (0.68 to 1.02) | 0.69 (0.53 to 0.88) | 0.74 (0.56 to 0.98) | 0.52 (0.29 to 0.93) |
DECLARE-TIMI58 | CANVAS | EMPA-REG OUTCOME | CREDENCE | DAPA-CKD | |
---|---|---|---|---|---|
Prior CVD (%) | 40.6 | 65.6 | 99.2 | 50.4 | 37.4 |
Baseline eGFR (mL/min/1.73 m2) | 85 | 77 | 74 | 56 | 43 |
Composite kidney outcomes *: HR (95% CI) | 0.53 (0.43 to 0.66) | 0.60 (0.47 to 0.77) | 0.54 (0.40 to 0.75) | 0.70 (0.59 to 0.82) | 0.61 (0.51 to 0.72) |
3P-MACE: HR (95% CI) | 0.93 (0.84 to 1.03) | 0.86 (0.75 to 0.97) | 0.86 (0.74 to 0.99) | 0.80 (0.67 to 0.95) | 0.92 (0.72 to 1.16) |
HHF: HR (95% CI) | 0.73 (0.61 to 0.88) | 0.67 (0.52 to 0.87) | 0.65 (0.50 to 0.85) | 0.61 (0.47 to 0.80) | 0.51 (0.34 to 0.76) |
HHF and CV death: HR (95% CI) | 0.85 (0.73 to 0.95) | 0.78 (0.67 to 0.91) | 0.66 (0.55 to 0.79) | 0.69 (0.57 to 0.83) | 0.71 (0.55 to 0.92) |
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Gohda, T.; Murakoshi, M. Sodium-Glucose Cotransporter-2 Inhibitors—Miracle Drugs for the Treatment of Chronic Kidney Disease Irrespective of the Diabetes Status: Lessons from the Dedicated Kidney Disease-Focused CREDENCE and DAPA-CKD Trials. Int. J. Mol. Sci. 2022, 23, 13749. https://doi.org/10.3390/ijms232213749
Gohda T, Murakoshi M. Sodium-Glucose Cotransporter-2 Inhibitors—Miracle Drugs for the Treatment of Chronic Kidney Disease Irrespective of the Diabetes Status: Lessons from the Dedicated Kidney Disease-Focused CREDENCE and DAPA-CKD Trials. International Journal of Molecular Sciences. 2022; 23(22):13749. https://doi.org/10.3390/ijms232213749
Chicago/Turabian StyleGohda, Tomohito, and Maki Murakoshi. 2022. "Sodium-Glucose Cotransporter-2 Inhibitors—Miracle Drugs for the Treatment of Chronic Kidney Disease Irrespective of the Diabetes Status: Lessons from the Dedicated Kidney Disease-Focused CREDENCE and DAPA-CKD Trials" International Journal of Molecular Sciences 23, no. 22: 13749. https://doi.org/10.3390/ijms232213749