Synergistic renoprotection and renal targeting of radiolabeled finerenone combined with compound α-Ketoacid tablets in type 2 diabetic nephropathy

Effective therapies to halt diabetic nephropathy (DN) progression are needed. Finerenone mitigates renal inflammation and fibrosis, while Compound α-Ketoacid Tablets reduce renal metabolic load. This study evaluated the synergistic renoprotective effect of their combination and assessed renal drug targeting using radionuclide imaging in type 2 DN. In this study with a hybrid design (n = 220), patients received Finerenone monotherapy or combination therapy with Compound α-Ketoacid Tablets for 3 months. All participants prospectively underwent dynamic renal SPECT/CT with 99 ᵐTc-Finerenone as per a pre-specified protocol. Metabolic parameters, urinary biomarkers, renal function, and safety were assessed. Renal cortical tracer uptake and retention were quantified. Statistical analyses included sample size calculation, handling of missing data, and correction for multiple comparisons. The combination therapy group demonstrated superior improvements in lipid profiles, a significantly higher overall response rate in urinary albumin-to-creatinine ratio (UACR) (68.3% vs. 25.0%, P < 0.001), and better preservation of estimated glomerular filtration rate (eGFR) compared to the monotherapy group (all P < 0.05). Modest but statistically significant improvements in glycemic control were also observed. SPECT/CT revealed 32.7% higher renal cortical uptake and prolonged tracer retention in the combination group, which strongly correlated with the improvements in UACR and eGFR (r = 0.82, P < 0.01). Both regimens were well-tolerated with a similar safety profile. The combination of Finerenone and Compound α-Ketoacid Tablets confers synergistic renoprotection in type 2 DN. The enhanced renal targeting and prolonged retention of radiolabeled Finerenone suggest modulated intrarenal drug distribution. This approach highlights the utility of nuclear imaging in visualizing and evaluating targeted therapies for DN.