Empagliflozin on Residual Kidney Function in Incident Peritoneal Dialysis Patients

Diabetes is the leading cause of end stage kidney disease in developed countries. Peritoneal dialysis (PD) is a home-based and cost-effective modality of kidney placement therapy. Maintenance of residual kidney function (RKF) is one of the most crucial objectives to improve outcomes of PD patients. Observational studies showed that residual urine volume or residual glomerular filtration rate (GFR), but not peritoneal creatinine clearance, independently predicted patient survival. This benefit is likely attributed to better volume control, improved nutritional status, preserved endocrine function and enhanced clearance of uremic toxins in the presence of RKF. However, current therapeutic strategies to preserve RKF were most limited to the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and biocompatible PD solutions.

Hong Kong adopted the 'PD-first' policy since 1985, and has the highest proportion of PD patients in the world. Inadequate dialysis, which is directly related to the loss of RKF, is the second most common reason for a permanent transfer to hemodialysis among PD patients. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce albuminuria and delay progression of chronic kidney disease even in patients with advanced stages of kidney disease. It is postulated that the renoprotective effect of SGLT-2 inhibitors may be extended to dialysis population since a considerable proportion of patients still have urine output. SGLT2 inhibitors may potentially attenuate GFR decline in PD patients because heavy proteinuria independently predicted decline in residual GFR and onset of anuria. Moreover, preclinical studies suggested that empagliflozin reduced inflammation and oxidative stress by decreasing proinflammatory cytokines, inducing expression of anti-inflammatory M2 phenotype of macrophages, and antagonizing the effect of advanced glycation products. This beneficial effect may be particularly relevant to PD patients, where subclinical inflammation is common and inversely correlated with RKF.

Despite the potential promising effect of SGLT2-inhibitors in RKF in PD patients, dialysis patients were excluded in previous randomized controlled trials. In the present study, the investigators hypothesize that oral empagliflozin in addition to RAAS inhibitor, compared to RAAS inhibitor alone, better preserves RKF in patients newly started on PD. After a run-in period of 6 to 8 weeks where the dose of RAAS inhibitors are uptitrated to maximally tolerated dose, 48 incident PD patients will be randomized to empagliflozin or control (no empagliflozin) for a total of 6 months. This study aims to explore the feasibility of conducting a full-scale, adequately powered randomized controlled trial that investigates the effect of empagliflozin on RKF in incident PD patients.

• Slope of residual GFR [Срок оценки: 6 months]
• Time to anuria [Срок оценки: 6 months]
• Difference in residual urine volume [Срок оценки: Month 0, 2, 4, 6]
• Difference in volume of overhydration [Срок оценки: Month 0, 2, 4, 6]
• Difference in plasma N-terminal pro-brain type natriuretic peptide [Срок оценки: Month 0, 2, 4, 6]
• Difference in systolic blood pressure [Срок оценки: Month 0, 2, 4, 6]
• Difference in volume of ultrafiltration per day [Срок оценки: Month 0, 1, 2, 4, 6]
• Incidence of urinary tract infection [Срок оценки: 6 months]
• Incidence of genital tract infection [Срок оценки: 6 months]
• Incidence of ketoacidosis [Срок оценки: 6 months]
• Incidence of lower limb amputation [Срок оценки: 6 months]
• Incidence of severe hypoglycemia [Срок оценки: 6 months]