Diabetic Kidney Disease Update

The major determinants of the development of chronic kidney disease (CKD) in people with diabetes are hyperglycemia, hypertension, genetic susceptibility, dyslipidemia, and inflammation. By better understanding these factors, we can modify the risk of kidney damage and subsequent complications among people with diabetes. Elevation in glucose levels leads to both metabolic and hemodynamic changes, including glomerular hyperfiltration, podocyte injury, and progressive albuminuria, while hypertension accelerates glomerular damage 1. Genetic predisposition, along with lifestyle factors such as obesity and smoking, further increases the risk. Dyslipidemia and oxidative stress contribute to endothelial dysfunction and tubulointerstitial injury 2, and inflammation 3 and activation of fibrotic pathways play important roles in disease progression 4, 5. CKD is defined operationally by estimated glomerular filtrate rate (eGFR) 0.08 mM/L) over a 27-month period of observation. Finally, genetic variants associated with higher 3-hydroxybutyrate used in a Mendelian Randomization study suggested a significant inverse association of B-OHB with serum cystatin C and creatinine levels. It is noteworthy that a consistent action of SGLT2 inhibitors is to increase B-OHB, an effect which has been hypothesized to contribute to their protective benefit 18. What clinical message can one derive from the three discussed publications? The epidemiologic evidence of benefit of lifestyle intervention is in accord with the 2024 KDIGO CKD guidelines for slowing diabetic CKD in control of hypertension (BP 120 if tolerated), dyslipidemia (LDL < 70 mg/L), obesity (BMI ≤ 27) and hyperglycemia (HbAIC < 7%) 12. More attention is needed to dietary modification with protein restriction favoring plant proteins and lower salt intake, to encouraging regular exercise, to not smoking, and to increasing physical activity to at least 150 min/week. The effect of SGLT2 inhibitors in increasing ketone levels may be of greater importance than generally recognized, and appropriate dietary modification to safely accomplish this without causing ketoacidosis may be a goal of future studies. The findings of incremental improvement in favorable lifestyle being associated with reduction in diabetic CKD are impressive and enforce its importance. Finally, the role of genetic factors in diabetic CKD is beginning to be better understood, and studies of this aspect of CKD prevention should be encouraged. The authors declare no conflicts of interest.