Diabetic Kidney Disease Phenotype and Other Determinants of Cardiovascular and Renal Outcomes in Type 2 Diabetes

Background and Hypothesis: Diabetic kidney disease (DKD) is one of the major risk factors for all-cause mortality and cardiovascular disease in patients with diabetes mellitus. Different phenotypes have been described. In view of their different pathophysiology, these subtypes may behave differently. Methods: In this retrospective study, patients with type 2 diabetes mellitus (T2DM) were followed up for a maximum of 10 years or until death, whichever came first. Subjects were categorized into four DKD phenotypes: no DKD (no albuminuria or decreased estimated glomerular filtration rate (eGFR)), albuminuria without decreased eGFR (DKD 1), decreased eGFR without albuminuria (DKD 2 or non-albuminuric DKD), and decreased eGFR with albuminuria (DKD 3). Data on laboratory results, hospitalization, and mortality were obtained through electronic patient records. Univariate analyses were performed and the variables that were significant were entered as covariates in multivariate logistic regression models to estimate the risks of death, hospitalization for CAD, HF, and CrVD, and CKD progression. Results: Among 778 patients, 53.3% had no DKD, 31.2% had DKD 1, 5.4% had DKD 2, and 10% had DKD 3. Patients with DKD 2 exhibited the highest odds of mortality compared to those with no DKD (odds ratio (OR) of 6.7 [95% CI 2.8–16.0], p < 0.001). Pairwise comparisons using the log-rank test showed a significant difference in mortality between DKD 1 and DKD 2 (p < 0.001) and DKD 1 and DKD 3 (p < 0.001). However, no statistically significant difference in mortality was found between DKD 2 and DKD 3. Additionally, the greater variability in HbA1c and higher neutrophil–lymphocyte ratio (NLR) independently predicted all-cause mortality as well as hospitalization for heart failure. Conclusions: This contemporary T2DM cohort demonstrated that the DKD phenotype, HbA1c variability, and elevated NLR are linked to increased mortality. These factors may improve existing risk stratification models by enabling better identification of high-risk DKD patients and guide more personalized management.