Finally, Some Reason for Hope in Proteinuric Kidney Disease
- 1 Lankenau Medical Center, Wynnewood, USA
- 2 Lankenau Medical Center, Wynnewood, USA
- 3 Lankenau Medical Center, Wynnewood, USA
Abstract
Background: After years of predictable outcomes with limited tools to combat the ravages of proteinuric chronic kidney disease (CKD) associated with or without diabetes, exciting new options are available to slow the progression of CKD. Purpose: Focusing on sodium-glucose co-transporter 2 inhibitors (SGLT2), angiotensin receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACE I), and new mineralocorticoid antagonists (MRA), this review examines how these agents compliment the standard of care in an attempt to educate and stimulate broader use of these agents. Methods: Using the search terms “mineralocorticoid antagonist, sodium glucose co-transporter 2 inhibitors, proteinuria, albuminuria, and diabetic kidney disease,” five randomized controlled clinical trials were identified and then analyzed in the context of the results found from the Irbesartan Diabetic Nephropathy Trial (IDNT). Two trials using SGLT2 and 2 using MRA were reviewed. Results: In the 2 SGLT2 trials renal outcomes were reduced by 30% - 39% among patients with estimated GFR ranging from roughly 25 - 90 mL/min. In the 2 MRA trials, renal outcomes fell by 13% - 18% among patients with estimated GFR ranging from 25 - 90 mL/min. In the IDNT, renal outcomes fell by 19%. Trial duration ranged from 28 - 41 months, and in all trials, the IDNT, Ace inhibitors (ACE I) and ARBs use was uniform. There is small overlap in the 5 trials in which both MRA and SGLT2 agents were used. Conclusions: Over a wide range of renal function, both MRA and SGLT2 inhibitors demonstrate outstanding efficacy in diabetic and non-diabetic (SGLT2) proteinuric kidney disease. Compared to the prior standard of care, these agents dramatically improve outcomes.
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (2018) United States Renal Data System. Annual Data Report. https://adr.usrds.org/2020/end-stage-renal-disease/1-incidence-prevalence-patient-characteristics-and-treatment-modalities
- The Kidney Project. Statistics, 2018. https://pharm.ucsf.edu/kidney/need/statistics
- Lewis, E.J., Hunsicker, L.G., Clarke, W.R., et al. (2001) Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes. The New England Journal of Medicine, 345, 851-860. https://doi.org/10.1056/NEJMoa011303
- Syed, S.H., Gosavi, S., Shami, W., et al. (2015) A Review of Sodium Glucose Co-Transporter 2 Inhibitors Canagliflozin, Dapagliflozin and Empagliflozin. Cardiovascular & Hematological Agents in Medicinal Chemistry, 13, 105-112. https://doi.org/10.2174/1871525714666151106121215
- Pitt, B., Filippatos, R., Agarwal, S.D., et al. (2021) Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. The New England Journal of Medicine, 385, 2252-2263. https://doi.org/10.1056/NEJMoa2110956
- Chin, M.P., Bakris, G.L., Block, G.A., et al. (2018) Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study. American Journal of Nephrology, 47, 40-47. https://doi.org/10.1159/000486398
- Maqsood, K., Siddiqui, A. and Teehan, G. (2013) Antihypertensive Therapy in Non-Diabetic Chronic Kidney Disease Associated with Proteinuria in Adults. Open Journal of Nephrology, 3, 128-134. https://doi.org/10.4236/ojneph.2013.33024
- Mann, J.F., Schmieder, R.E., McQueen, M., et al. (2008) Renal Outcomes with Telmisartan, Ramipril, or Both, in People at High Vascular Risk (the ONTARGET Study): A Multicentre, Randomised, Double-Blind, Controlled Trial. The Lancet, 372, 547-553. https://doi.org/10.1016/S0140-6736(08)61236-2
- Cowart, S.L. and Stachura, M.E. (1990) Chapter 139. Glucosuria. In: Walker, H.K., Hall, W.D. and Hurst, J.W., Eds., Clinical Methods: The History, Physical, and Laboratory Examinations, 3rd Edition, Butterworths, Boston. https://www.ncbi.nlm.nih.gov/books/NBK245
- Vallon, V. (2020) Glucose Transporters in the Kidney in Health and Disease. Pflügers Archiv, 472, 1345-1370. https://doi.org/10.1007/s00424-020-02361-w