Diabetes Metab J.  2023 Jul;47(4):523-534. 10.4093/dmj.2022.0096.

Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea

• Lee SE
• Yoo J
• Choi HS
• Han K
• Kim KA

• KMID: 2544731
• DOI: http://doi.org/10.4093/dmj.2022.0096

Abstract

Background
Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments.
Methods
The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories.
Results
During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFR^lowPU– phenotype, followed by eGFR^norPU⁺ and eGFR^norPU^–. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFR^norPU^– category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFR^norPU⁺ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFR^lowPU^–. Among altered phenotypes, the category converted to eGFR^lowPU⁺ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU^– to PU⁺ showed a higher risk of HHF than those who converted from PU⁺ to PU^–.
Conclusion
Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM.

Keyword

Diabetes mellitus; Diabetic nephropathies; Heart failure; Proteinuria

Figure

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  Fig. 1. Cumulative incidence of hospitalization for heart failure (HHF) according to changes in diabetic kidney disease phenotype. (A) Cumulative incidence of HHF according to the result of 1st examination. Black line, blue line, and red line indicate G1, G2, and G3 at 1st examination, respectively. (B-D) Cumulative incidence of HHF according to changes in diabetic kidney disease phenotype status: G1 (B), G2 (C), and G3 (D) at 1st examination. G1, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, proteinuria (PU)−; G2, eGFR ≥60 mL/min/1.73 m2, PU+; G3, eGFR <60 mL/min/1.73 m2, PU−; G4, eGFR <60 mL/min/1.73 m2, PU+. aIn case of group 3 and 4 at 2nd examination, only patients with eGFR 30 to 60 mL/min/1.73 m2 were included according to the study inclusion criteria.

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  Fig. 2. Incidence rates (IRs) and hazard ratios (HRs) of hospitalization for heart failure (HHF) according to changes in diabetic kidney disease phenotype. Bar graphs represent IR per 1,000 person-years with scales on the right. Line graphs with error bars represent the HR with 95% confidence interval (CI) for HHF with scales on the left. HRs were adjusted for age, sex, body mass index, smoking, drinking, physical activity, hypertension, dyslipidemia, atrial fibrillation, ischemic heart disease, fasting glucose, diabetes duration, hemoglobin level, and insulin usage. G1, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, proteinuria (PU)−; G2, eGFR ≥60 mL/min/1.73 m2, PU+; G3, eGFR <60 mL/min/1.73 m2, PU−; G4, eGFR <60 mL/min/1.73 m2, PU+. PY, person-year. aIn case of group 3 and 4 at 2nd examination, only patients with eGFR 30 to 60 mL/min/1.73 m2 were included according to the study inclusion criteria.

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  Fig. 3. Subgroup analyses according to age, body mass index (BMI), and heart failure (HF) subgroups. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of hospitalization for heart failure according to changes in diabetic kidney disease phenotype stratified by age group (A), BMI (B), and presence of HF (C). HRs were adjusted for age, sex, body mass index, smoking, drinking, physical activity, hypertension, dyslipidemia, atrial fibrillation, ischemic heart disease, fasting glucose, diabetes duration, hemoglobin level, and insulin usage. G1, eGFR ≥60 mL/min/1.73 m2, proteinuria (PU)−; G2, eGFR ≥60 mL/min/1.73 m2, PU+; G3, eGFR <60 mL/min/1.73 m2, PU−; G4, eGFR <60 mL/min/1.73 m2, PU+. aIn case of group 3 and 4 at 2nd examination, only patients with eGFR 30 to 60 mL/min/1.73 m2 were included according to the study inclusion criteria.

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