Kidney Week

Abstract: FR-PO313

Simulated Effect of Dapagliflozin on Reducing Incidence of Albuminuria and CKD Using the Urinary Proteomics Classifier CKD273 in Normoalbuminuric Type 2 Diabetes

Session Information

• Diabetic Kidney Disease: Clinical Modeling, Diagnosis, Education, and More
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Rotbain Curovic, Viktor, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Viktor Rotbain Curovic, MD

• Persson, Frederik, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Frederik Persson, MD, DrMed

• Hansen, Tine, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Tine Hansen, MD

• Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Denmark

Peter Rossing, MD, DrMed

Group or Team Name

• The PRIORITY Study Group.

Background

Higher urinary proteomic classifier CKD273 levels are associated with higher albuminuria and chronic kidney disease (CKD) grade 3 risk, in type 2 diabetes (T2D). Treatment with dapagliflozin have shown to significantly lower CKD273 levels. We have investigated if the magnitude of CKD273 reduction, seen after treatment with dapagliflozin, is associated with a lower risk of developing albuminuria and CKD grade 3 in normoalbuminuric T2D.

Methods

Post-hoc simulation of the observational PRIORITY (NCT02040441) study originally designed to assess CKD273 as a predictor of albuminuria.People with T2D and normal albuminuria and eGFR were included. CKD273 levels at baseline were releveled according to the CKD273 reduction seen after dapagliflozin treatment in the DapKid (NCT03509454) study (-0.221 arb. units). Endpoints were development of persistent urinary albumin creatinine ratio >30 mg/g and development of CKD grade 3 (eGFR <60 ml/min/1.73m²). Cox proportional hazard models were fitted per -0.221 difference in baseline CKD273 level. Models were adjusted for sex, baseline age, diabetes duration, HbA_1c, systolic blood pressure, and eGFR.

Results

In total, 1589 were included, 995 (63%) were men, and followed for a median (IQR) of 2.4 (2.0, 3.0) years. Baseline mean (SD) age was 61.9 (8.3) years, diabetes duration was 11.8 (7.8) years, HbA_1c was 7.4 (1.1) %, and eGFR was 87 (16) ml/min/1.73m². Crude Cox analyses showed a 24% lower risk of albuminuria per 0.221 lower CKD273 levels at baseline (HR (95% CI): 0.76 (0.70, 0.83), p<0.001) and remained significant after adjustment (0.87 (0.80, 0.95), p=0.002). Similar results were seen with development of CKD grade 3, with 27% lower risk in crude models (0.73 (0.70, 0.84), p<0.001), confirmed in adjusted (0.84 (0.76, 0.92), p<0.001).

Conclusion

Across 2.4 years, in a population with T2D and no albuminuria, a 0.221 lower level of CKD273 was associated with a 24% lower risk of developing albuminuria and 27% lower risk of developing CKD grade 3. Associations remained significant after adjustment for relevant risk factors. Our results suggest that a reduction in CKD273 on par with that seen after treatment with dapagliflozin may lower renal events already in normoalbuminuric type 2 diabetes.