Kidney Week

Abstract: TH-PO443

Design and Patient Characteristics of a Study to Assess the Renoprotective Effects of the SGLT2 Inhibitor Dapagliflozin in Non-Diabetic Proteinuric Kidney Disease (DIAMOND)

Session Information

• CKD: Clinical, Outcomes, Trials - I
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Dekkers, Claire, University Medical Center Groningen, Groningen, Netherlands

Claire Dekkers,

• Cherney, David, University Health Network, Toronto, Ontario, Canada

David Cherney,

• Reich, Heather N., Toronto General Hospital, Toronto, Ontario, Canada

Heather N. Reich,

• Barbour, Sean, University of British Columbia, Vancouver, British Columbia, Canada

Sean Barbour,

• Abdul gafor, Abdul halim, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia

Abdul halim Abdul gafor,

• Lim, Soo Kun, Univeristy Malaya Medical Centre, Kuala Lumpur, Malaysia

Soo Kun Lim,

• Wong, Muh Geot, The George Institute for Global Health, Sydney, New South Wales, Australia

Muh Geot Wong,

• Laverman, Gozewijn Dirk, ZGT Almelo, Almelo, OVERIJSSEL, Netherlands

Gozewijn Dirk Laverman,

• Vervloet, Marc G., Amsterdam University Medical Center, Overveen, Netherlands

Marc G. Vervloet,

• Gansevoort, Ron T., University Medical Center Groningen, Groningen, Netherlands

Ron T. Gansevoort,

• L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink,

Background

Sodium glucose co-transporter 2 (SGLT2) inhibition decreases albuminuria and reduces the risk of kidney disease progression in patients with type 2 diabetes. These beneficial effects are likely mediated by activation of tubuloglomerular feedback by natriuresis, leading to decreased intraglomerular hypertension. Since non-diabetic kidney diseases are also characterized by glomerular hypertension, we tested the hypothesis that in patients with non-diabetic proteinuric kidney disease, SGLT2 inhibition with dapagliflozin reduces proteinuria and acutely and reversibly reduces glomerular filtration rate (GFR).

Methods

We designed a multicenter double-blind randomized placebo controlled 6-week cross-over study to assess the change from baseline in 24-hour proteinuria with dapagliflozin 10 mg/day in patients with proteinuric kidney disease without diabetes (ClinicalTrials.gov identifier: NCT03190694). The secondary endpoint was the change in iohexol-derived GFR. The main inclusion criteria were: urinary protein excretion >500 mg/24hr and ≤3500 mg/24hour, eGFR ≥25 mL/min/1.73m²; stable dose of RAAS inhibitors.

Results

Patients with non-diabetic kidney disease were enrolled between November 2017 and April 2019. A total of 58 patients were screened of whom 53 patients were randomized in this ongoing study. The mean age at screening was 51 (SD 13) years and 32% were female. Mean screening eGFR was 59 (29) ml/min/1.73m² and median proteinuria 1074 (25^th to 75^th Percentile 810 -1400) mg/24hr. Overall, blood pressure was well controlled (SBP/DBP 128 (15) /78 (8) mmHg) and mean body weight was 83.0 (20) kg. Mean HbA_1c was 5.6 (0.4) % and mean hemoglobin level 138 (20) g/L. All patients were using a RAAS inhibitor.

Conclusion

This is the first placebo controlled clinical trial to examine the effects of an SGLT2 inhibitor in a non-diabetic population at risk for progressive kidney function loss. Final study results are expected in December 2019.

Funding

• Commercial Support – AstraZeneca