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

<i>Background and Objectives:</i> The combination of resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) accelerates the 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 the progressive decline in kidney function in patients with RHTN and T2DM. <i>Materials and Methods:</i> The prospective interventional study (REFRAIN, NCT04948918) included men and women > 20 y.o. with true RHTN. Eligible patients underwent dRDN. The primary endpoint was a change in eGFR from baseline to 12 months. 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. <i>Results:</i> 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/1.73 m², 23 (79%) patients with CKD, and 2 patients with albuminuria only. There were no perioperative complications. Twenty-seven (93%) participants completed 12 month 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 24 h pulse pressure (<i>p</i> = 0.030) and HbA1c (<i>p</i> = 0.010). <i>Conclusions:</i> Distal RDN demonstrates a substantial nephroprotective effect in patients with RHTN and T2DM, which may be partly mediated by a reduction in arterial stiffness and is negatively dependent on baseline hyperglycemia.