α-lipoic acid in patients with autosomal dominant polycystic kidney disease

Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.6 g alpha-lipoic acid (ALA) daily for 3 and 6 on the main markers of systemic inflammation, endothelial dysfunction, and atherosclerosis, as well as on nutritional, cardiovascular, and psychocognitive parameters, in ADPKD patients with CKD stage G2/G3 Kidney Disease Improving Global Outcomes chronic kidney disease (KDIGO) compared to controls. Methods: This was a controlled, longitudinal, prospective, interventional study with 59 patients with ADPKD. Of the patients, 33 were treated with ALA (1.6 g/d) for 6 mo and 26 were controls. Clinical, laboratory (inflammation and metabolic indexes), instrumental parameters (intima media thickness (IMT), renal resistive index (RRI), flow-mediated dilation (FMD), ankle-brachial index (ABI), and psycho-cognitive tests (Mini-Mental State Examination [MMSE], Hamilton Depression Rating Scale [HAM-D], Beck Depression Inventory-II [BDI-II]) were evaluated at baseline (T0), 3 mo (T1), and 6 mo (T2). Results: Patients treated with ALA at T1 and T2 showed a significant reduction in serum glucose, insulin, homeostatic model assessment-insulin resistance, and serum uric acid (P = 0.013, P = 0.002, P = 0.002, P<0.001; respectively) and significantly higher values of base excess (P<0.001), compared with the control group. Moreover, the results showed a significant increase in bicarbonates (P = 0.009) and FMD (P < 0.001), and a significant reduction of C-reactive protein (P<0.001) and RRI (P = 0.013). On the other hand, we did not assess a significant difference in IMT and ABI at T1 and T2. Psychocognitive tests (BDI-II, HAM-D, and MMSE) were significantly improved (P = 0.007, P < 0.001, P < 0.001; respectively) in patients treated with ALA for 6 mo compared with the control group. A significant difference in nicotinamide adenine dinucleotide phosphate oxidase 2 concentrations was observed between T0 and T2 only in ADPKD patients treated with ALA (P=0.039, P=0.039; respectively), although we did not find a significant difference in interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha concentrations in either group. Conclusions: We suggest an early and careful monitoring of traditional and non-traditional cardiovascular risk factors in patients with ADPKD. Moreover, we suggest the use of ALA, an anti-inflammatory and antioxidant nutraceutical with few side effects. Additionally, it is important to evaluate the cognitive abilities, psychological health, and quality of life of patients with ADPKD, especially at the early stage of disease. (C) 2019 Elsevier Inc. All rights reserved.