Favorable Effect of Distal Renal Denervation on Kidney Function in Diabetic Patients with Resistant Hypertension

Background and Objectives: The combination of resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) accelerates development of chronic kidney disease (CKD), which may be largely associated with sympathetic hyperactivity. Distal renal denervation (dRDN) effectively reduces sympathetic flow to the kidneys, causing renal vasodilation and increased renal perfusion. However, this effect may be limited by nephrotoxicity due to the multiple increase in the number of contrast injections, as well as a significant blood pressure (BP) reduction, which naturally worsens renal perfusion. This study aimed to test the hypothesis that dRDN prevents progressive decline of kidney function in patients with RHTN and T2DM. Materials and Methods: The prospective interventional study (REFRAIN, NCT04948918) included men and women >20 y.o. with true RHTN. Eligible patients underwent dRDN. The primary endpoint was change in eGFR from baseline to 12 month. Secondary endpoints were changes in 24-h BP, serum lipocalin-2, cystatin C, 24-h urinary albumin excretion, renal blood flow, and kidney volumes (by MRI). Multiple regression analysis was used to find independent predictors of individual estimated glomerular filtration rate (eGFR) change. Results: A total of 29 patients with RHTN and T2DM were included in the study (61.6±7.2 y.o., 10 males, mean 24-h ambulatory BP: 158.1±21.4/81.8±12.4 mmHg (systolic/diastolic respectively), HbA1c: 7.8±1.4%, and eGFR 56.7±19.9 mL/min/1.73m², 23 (79%) patients with СKD, 2 patients with albuminuria only. There were no perioperative complications. Twenty seven (93%) participants completed 12 months follow-up. eGFR did not change from baseline: +1.3 mL/min/1.73 m² [95% CI: −9.6, 12.1], despite the expected decrease due to a significant decrease in 24-h systolic BP (−18.2 mmHg [95% CI: −28.6, −7.8]). No changes in other secondary endpoints were observed. Independent predictors of individual eGFR change were baseline 24h-pulse pressure (p=0.030) and HbA1c (p=0.010). Conclusions: Distal RDN demonstrates a substantial nephroprotective effect in patients with RHTN and T2DM, which, however, is negatively affected by vascular stiffness and hyperglycemia.