Prevalence of diabetic nephropathy and subsequent cardiovascular outcomes: a nationwide study of 74,014 patients with type 2 diabetes

Abstract Background Nonsteroidal, selective mineralocorticoid receptor antagonists (MRAs) have been shown to reduce cardiovascular events among patients with diabetic nephropathy, a clinical syndrome characterized by persistent albuminuria. However, prior reports have suggested a substantial underuse of MRAs among eligible patients. In real-life, it is unknown how many have urinary excretion of albumin measured, and the cardiovascular outcomes among type 2 diabetes (T2D) patients with versus without albuminuria is relatively unknown. Purpose To identify candidates eligible for treatment with MRAs and compare the risk of cardiovascular events in real-life T2D patients with albuminuria versus without albuminuria. Methods Using the Danish nationwide registers, we identified all patients ≥18 years old with prevalent T2D at index date 1st January 2015 with an albumin-creatinine ratio (ACR) and a creatinine level measured within 365 days prior to the index date. For each patient, the last ACR and estimated glomerular filtration rate (eGFR) registered prior to the index date were used. eGFR was calculated using the CKD-EPI formula. The patients were separated into two groups consisting of patients with T2D with ACR ≥30 mg/g (albuminuria) or ACR<30 mg/g (no albuminuria), respectively. Outcomes for both groups were analyzed as time-to-event as a composite cardiovascular outcome of heart failure (HF), myocardial infarction (MI), stroke, and all-cause death and each component of the composite endpoint was analyzed individually. In both groups, we estimated the 4-year absolute risk of the cardiovascular outcome and the risk of experiencing HF, MI, and stroke. Results A total of 158,904 patients with T2D were identified and of those 74,014 patients (47%) had urinary ACR analyzed within the last year. Of those who had ACR analyzed 29,581 (40%) patients had albuminuria. The absolute 4-year risk of the composite cardiovascular outcome in patients with albuminuria and no albuminuria was 28.6% (95% confidence interval (CI): 28.1–29.1) versus 18.7% (95% CI: 18.4–19.1), respectively. The absolute 4-year risk for the individual components were HF 7.0% (95% CI: 6.7–7.3), MI 4.4% (95% CI: 4.2–4.6), and stroke 7.6% (95% CI: 7.3–7.9) for patients with albuminuria, versus HF 4.0% (95% CI: 3.8–4.2), MI 3.2% (95% CI: 3.1–3.4), and stroke 5.5% (95% CI: 5.3–5.7) for patients with no albuminuria. Conclusion In Denmark, only 47% of patients with T2D had ACR analyzed within a year indicating lack of adherence to the national T2D guidelines. A total of 40% of those who had albuminuria analyzed were eligible for treatment with MRAs based on trial inclusion criteria, and the absolute 4-year risk of experiencing a cardiovascular event was significant. However, patients with no albuminuria still displayed a substantial risk of experiencing a composite event of HF, MI, stroke, and all-cause death. Our analyses may have implications for implementation of new MRAs in patients with T2D. Funding Acknowledgement Type of funding sources: None.