Dapagliflozin Delays the Loss of Renal Function in Peritoneal Dialysis Patients

Official title

Dapagliflozin Delays the Loss of Residual Renal Function in Patients Undergoing Peritoneal Dialysis: A Single-Center Randomized Open-Label Study

Overview

This study aims to explore the role of dagliflozin in preserving the residual renal function(RRF) in peritoneal dialysis (PD) patients.

Detailed description

Residual renal function (RRF) plays the role of removing water and body metabolic wastes, as well as secretion of erythropoietin and promotion of vitamin D absorption, which can maintain the stability of the internal environment. Several studies have demonstrated that preservation of RRF in PD patients reduces complications, increases dialysis adequacy and decreases mortality. In addition, residual renal function is an important factor in the technique survival. Methods to protect residual renal function in peritoneal dialysis patients include controlling blood pressure, controlling blood glucose, adjusting dialysis prescription, and using renin-angiotensin inhibitors. However, the above methods currently play only a limited role.

Sodium-dependent glucose transporters 2 (SGLT2) inhibitors are drugs used in the treatment of type 2 diabetes mellitus that inhibit the reabsorption of glucose by the kidneys, causing glucose to be excreted in the urine and lowering blood glucose. Studies have demonstrated that SGLT2 inhibitors also attenuate renal tubular injury, reduce the excretion of proteinuria, and have a protective effect on RRF in non-dialysis patients with chronic kidney disease. However, there are no clinical studies demonstrating whether the use of SGLT2 inhibitors in peritoneal dialysis patients is renal protective.

In light of this, this study introduces dagliflozin orally to PD patients over a 24-week period to explore its protective effects on RRF and cardiac health, with participants being randomly divided into a dagliflozin group and a control group. The results of this study will be beneficial in informing the clinical practice of SGLT2 inhibitors and improving dialysis outcomes in PD patients.

Interventions

• Drug Dapagliflozin
  Dapagliflozin10MG, PO once daily

Primary outcome measures

• Change in 24 urine volume [Time frame: Baseline, 2,12 and 24 weeks.]

Secondary outcome measures (12)

• Change in renal Kt/Vurea [Time frame: Baseline, 2, 12 and 24 weeks.]
• Change in BNP（Brain natriuretic peptide） [Time frame: Baseline, 2, 12 and 24 weeks.]
• Change in EF% [Time frame: Baseline and 24 weeks.]
• Change in ultrafiltration [Time frame: Baseline, 2, 12 and 24 weeks.]
• Change in HbA1C （Hemoglobin A1C) rate [Time frame: Baseline, 12 and 24 weeks.]
• Change in serum sodium concentration [Time frame: Baseline, 2, 12 and 24 weeks.]
• Change in urinary sodium concentration [Time frame: Baseline, 2, 12 and 24 weeks.]
• Change in dialysate sodium concentration [Time frame: Baseline, 2, 12 and 24 weeks.]
• Change in urinary glucose concentration [Time frame: Baseline, 2, 12 and 24 weeks.]
• Change in blood pressure [Time frame: Baseline, 2, 12 and 24 weeks.]
• Change in body weight [Time frame: Baseline, 2, 12 and 24 weeks.]
• Episodes of peritonitis [Time frame: 24 weeks.]

Eligibility criteria

Inclusion criteria

• Patients with PD duration between 1 month and 3 months.
• Patients aged between 18 and 75 years.
• Voluntary signing of informed consent.
• Stable use of a maximum tolerated dose of RAAS inhibitors for one month if hypertension is present.
• Daily urine output ≥ 400ml/day.
• Stable PD prescription for one month.

Exclusion criteria

• Pregnant and lactating women.
• Patients with type 1 diabetes mellitus.
• Patients with type 2 diabetes mellitus who have experienced diabetic ketoacidosis in the past.
• Patients with chronic liver disease, including non-alcoholic fatty liver disease, cirrhosis, ALT > 120 IU/L, and other clinically confirmed severe liver diseases.
• Patients with more than 2 episodes of urinary tract infection in the past six months.
• Patients with severe allergic reactions (rash or angioedema) to Dapagliflozin.
• Patients using the following medications: rifampicin, phenytoin.
• Patients with malignant tumors.
• Patients who developed peritonitis within one month.
• Patients undergoing combined hemodialysis treatment.
• Patients with a willingness for kidney transplantation within six months.
• Patients with a history of pancreatitis or pancreatic transplantation.
• Patients who experienced acute coronary syndrome or cerebrovascular events within one month.
• Hemoglobin level less than 90g/L.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospita — Chengdu

Publications

• van der Wal WM, Noordzij M, Dekker FW, Boeschoten EW, Krediet RT, Korevaar JC, Geskus RB; Netherlands Cooperative Study on the Adequacy of Dialysis Study Group (NECOSAD). Full loss of residual renal function causes higher mortality in dialysis patients; findings from a marginal structural model. Nephrol Dial Transplant. 2011 Sep;26(9):2978-83. doi: 10.1093/ndt/gfq856. Epub 2011 Feb 11. PMID 21317411
• Bargman JM, Thorpe KE, Churchill DN. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol. 2001 Oct;12(10):2158-2162. doi: 10.1681/ASN.V12102158. PMID 11562415
• Bello AK, Okpechi IG, Osman MA, Cho Y, Cullis B, Htay H, Jha V, Makusidi MA, McCulloch M, Shah N, Wainstein M, Johnson DW. Epidemiology of peritoneal dialysis outcomes. Nat Rev Nephrol. 2022 Dec;18(12):779-793. doi: 10.1038/s41581-022-00623-7. Epub 2022 Sep 16. PMID 36114414
• Parving H-H, Lambers-Heerspink H, de Zeeuw D. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Nov 3;375(18):1800-1. doi: 10.1056/NEJMc1611290. No abstract available. PMID 28106974
• Persson F, Rossing P, Vart P, Chertow GM, Hou FF, Jongs N, McMurray JJV, Correa-Rotter R, Bajaj HS, Stefansson BV, Toto RD, Langkilde AM, Wheeler DC, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial. Diabetes Care. 2021 Aug;44(8):1894-1897. doi: 10.2337/dc21-0300. Epub 2021 PMID 34183431
• Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Furtado RHM, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Sabatine MS. Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus. Circulation. 2019 Apr 23;13 PMID 30786725
• Birkeland KI, Jorgensen ME, Carstensen B, Persson F, Gulseth HL, Thuresson M, Fenici P, Nathanson D, Nystrom T, Eriksson JW, Bodegard J, Norhammar A. Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis. Lancet Diabetes PMID 28781064
• Persson F, Nystrom T, Jorgensen ME, Carstensen B, Gulseth HL, Thuresson M, Fenici P, Nathanson D, Eriksson JW, Norhammar A, Bodegard J, Birkeland KI. Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: A multinational observational study. Diabetes O PMID 28771923

Identifiers

NCT: NCT06398977 · DDLR-PD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗