Dapagliflozin in Patients With COVID-19: Mind The Kidneys

Contact: Audrey Hu audrey.hu@wecistanche.com

We read the DARE-19 trial by Mikhail Kosiborod and colleagues,1 published in The Lancet Diabetes and Endocrinology with interest. The DARE-19 trial was a randomized, double-blind, placebo-controlled trial of patients hospitalized with COVID-19. Key inclusion criteria were hospitalization with laboratory-confirmed or clinically suspected SARS-CoV-2 infection no more than 4 days before screening, the requirement of oxygen supplementation of 5 L/min or less to achieve an oxygen saturation of at least 94%, and one or more cardiometabolic risk factors including chronic kidney disease (estimated glomerular filtration rate [eGFR] between 25–60 mL/min per 1·73 m²). Praiseworthy logistics were applied resulting in the recruitment of 1250 patients from 95 sites in seven countries, with 60% of participants from Brazil.

Adding dapagliflozin 10 mg versus placebo to usual care did not affect the two primary outcomes: reduction in organ dysfunction or death and improvement in clinical recovery. The development of acute kidney injury was hierarchically the most important secondary outcome. The authors concluded that dapagliflozin did not increase the risk of acute kidney injury because there was no difference in the proportion of patients with serum creatinine concentrations two times that reported at baseline. However, doubling of serum creatinine represents acute kidney injury stage 2 according to current Kidney Disease: Improving Global Outcomes (KDIGO) criteria2 and does not exclude stage 1 acute kidney injury or worse stages that manifest only as oliguria. A retrospective cohort study of patients hospitalized with COVID-19 confirmed that acute kidney injury occurred in 1835 (46%) of 3993 individuals.3 Morality was significantly worse in those with acute kidney injury. Of note, 716 (39%) of 1835 patients with acute kidney injury cohort in the retrospective study would not have met the acute kidney injury criteria used in DARE-19 and would have been missed. In DARE-19, acute kidney injury occurred in only 62 (5%) of 1250 patients, but the true incidence was likely much higher.

Cistanche can treat chronic kidney disease

Dapagliflozin is an SGLT2 inhibitor-associated with a hemodynamically driven reduction in eGFR.4 Patients hospitalized with COVID-19 are at high risk of developing kidney injury for various reasons, such as dehydration and hypotension (70%), and viral sepsis (22%).3,5 In this context, starting a drug that might reduce glomerular perfusion could have a detrimental effect. In our opinion, it is premature to claim that dapagliflozin is safe with respect to kidney function in patients who are acutely ill. To avoid potentially misleading conclusions and to prevent iatrogenic acute kidney injury in high-risk patients, we strongly recommend that appropriate criteria be applied in future clinical trials. Furthermore, studying the effect of dapagliflozin using biomarkers of glomerular and tubular injury would add granularity to the functional criteria (serum creatinine elevation or urine output decline).6 We strongly suggest that full KDIGO criteria be used (possibly with the inclusion of biomarkers of kidney damage) in upcoming investigations.

Cistanche boosts immunity and treating kidney disease

TR received consulting fees from Baxter and Contatti Medical (CytoSorbents) and payment or honoraria from AstraZeneca, Baxter, Contatti Medical (CytoSorbents), B Braun, Jafron, and Eurofarma. MO received lecture fees to their institution from bioMérieux, Fresenius Medical, and Baxter, and payment to their institution for participation on the advisory board for NxStage. AZ received grants from Baxter, bioMérieux, consulting fees from Guard Therapeutics, AM-Pharma, and Piano, payment or honoraria from Fresenius, Baxter, and bioMérieux, payment for participation in advisory boards for Guard Therapeutics, AM-Pharma, and Fresenius, and payment for leadership on boards for ESAIC, A&A, and Anästhesist. JAK received grants or contracts, consulting fees, and payment or honoraria from Astute Medical/bioMérieux. CR received consulting fees and payment or honoraria from ASAHI, Baxter, bioMérieux, B. Braun, CytoSorbents, ESTOR, Fresenius Medical Care, General Electric, Medtronic, and Toray.

Thiago Reis, Marlies Ostermann, Alexander Zarbock, John A Kellum, *Claudio Ronco

Laboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Brasília, Asa Norte, Brasília, Brazil (TR); Department of Kidney Transplantation, Clínica de Doenças Renais de Brasília—DF STAR Hospital, Brasília, Brazil (TR); Department of Critical Care and Nephrology, King’s College London, Guy’s and St Thomas’ Hospital, London UK (MO); Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Münster, Germany (AZ); Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburg, Pittsburg, PA, USA (JAK); Department of Medicine, Università Degli Studi di Padova, 35128 Padua, Italy (CR); Department of Nephrology, Dialysis and Kidney Transplantation, San Bortolo Hospital, International Renal Research Institute of Vicenza, Vicenza, Italy (CR)

Cistanche can tonifying kidney

REFERENCE

1 Kosiborod MN, Esterline R, Furtado RHM, et al. Dapagliflozin in patients with cardiometabolic risk factors hospitalized with COVID-19 (DARE-19): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 2021; 9: 586–94.

2 Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet 2019; 394: 1949–64.

3 Chan L, Chaudhary K, Saha A, et al. AKI in hospitalized patients with COVID-19. J Am Soc Nephrol 2021; 32: 151–60.

4 Heerspink HJL, Karasik A, Thuresson M, et al. Kidney outcomes associated with the use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study. Lancet Diabetes Endocrinol 2020; 8: 27–35.

5 Procaccini FL, Alcázar Arroyo R, Albalate Ramón M, et al. Acute kidney injury in 3182 patients admitted with COVID-19: a single-center, retrospective, case-control study. Clin Kidney J 2021; 14: 1557–69.

6 Ostermann M, Zarbock A, Goldstein S, et al. Recommendations on acute kidney injury biomarkers from the acute disease quality initiative consensus conference: a consensus statement. JAMA Netw Open 2020; 3: e2019209.

Improve kidney function cistanche