Emerging Role of Sodium-Glucose Co-Transporter 2 Inhibitors for the Treatment of Chronic Kidney Disease.

Chronic kidney disease is one of the leading causes of morbidity and mortality in the Philippines. It is associated with a growing health burden as many patients progress to end-stage renal disease. Until recently, therapeutic options for the management of chronic kidney disease were limited. Sodium-glucose co-transporter 2 inhibitors offer an alternative therapeutic approach for patients with chronic kidney disease. Several trials have shown renal benefits with sodium-glucose co-transporter 2 inhibitors in patients with cardiovascular disease with and without type 2 diabetes and across a range of estimated glomerular filtration rate levels. In the Philippines, the sodium-glucose co-transporter 2 inhibitors dapagliflozin and canagliflozin are approved for the prevention of new and worsening nephropathy in type 2 diabetes. With emerging treatment options, an urgent need exists for guidance on the management of chronic kidney disease within the Philippines. In this review, we focus on the putative renal-protective mechanisms of sodium-glucose co-transporter 2 inhibitors, including effects on tubuloglomerular feedback, albuminuria, endothelial function, erythropoiesis, uric acid levels, renal oxygen demand, and hypoxia. Furthermore, we discuss the findings of recent large clinical trials using sodium-glucose co-transporter 2 inhibitors in patients with chronic kidney disease and diabetic kidney disease, summarize safety aspects, and outline the practical management of patients with chronic kidney disease in the Philippines.

Dapagliflozin and Anemia in Patients with Chronic Kidney Disease.

DAPA and Anemia in Patients with CKDThis post hoc analysis of the DAPA-CKD (Dapagliflozin in Patients with Chronic Kidney Disease) trial assessed the impact of dapagliflozin treatment on the correction and prevention of anemia. Results over a 2.4-year median follow-up show that dapagliflozin is associated with increase in hematocrit, correction of anemia, and reduced risk of incident anemia in patients with CKD with or without type 2 diabetes.

Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions.

Introduction: This study aimed to examine the efficacy and safety of dapagliflozin in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (NCT03036150) by geographic region. Methods: Adults with chronic kidney disease (CKD) with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25 to 75 ml/min per 1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were randomized to dapagliflozin (10 mg once daily) or placebo. The primary end point was a composite of a sustained decline in eGFR of ≥50%, end-stage kidney disease or death from kidney or cardiovascular causes. We categorized recruiting countries into 4 broad global regions: Asia, Europe, Latin America, and North America. Of 4304 randomized patients, 1346 (31.3%) were from Asia, 1233 (28.6%) from Europe, 912 (21.2%) from Latin America, and 813 (18.9%) from North America. Results: The relative risk of the primary composite end point was lower in patients randomized to dapagliflozin (relative to placebo) in all regions, with hazard ratios (95% CI) of 0.70 (0.48-1.00), 0.60 (0.43-0.85), 0.61 (0.43-0.86), and 0.51 (0.34-0.76) among patients from Asia, Europe, Latin America, and North America, respectively. There was no effect modification by region (interaction P = 0.77). Occurrence of serious adverse events (SAEs) was lower among patients randomized to dapagliflozin versus placebo (21.9% vs. 26.8%, 34.1% vs. 38.6%, 29.8% vs. 31.5%, and 34.9% vs. 41.0% in Asia, Europe, Latin America, and North America, respectively). Conclusion: Dapagliflozin reduced kidney and cardiovascular events and prolonged survival in patients with CKD, with and without type 2 diabetes, with no apparent effect modification by geographic region.

The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics.

BACKGROUND: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. METHODS: In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). RESULTS: Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). CONCLUSIONS: Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2-4 and increased albuminuria, with and without T2D.