RENOPROTECTIVE EFFECT OF DIETARY SUPPLEMENTATION WITH COENZYME Q10 AT DIFFERENT STAGES OF RENAL DAMAGE: PREVENTION OF SALT-SENSITIVE HYPERTENSION DEVELOPMENT

JORGE HUMBERTO MUDSKI; DANIELA JOSEFINA PORTA; NÉSTOR HORACIO GARCÍA; MARÍA ANGÉLICA RIVOIRA; MARÍA EUGENIA PASQUALINI

Congreso; World Congress of Nephrology 2024; 2024

Introduction: The pressure-induced natriuresis (PN) refers to increasein urinary sodium excretion due to an elevation in renalperfusion pressure, thereby reducing blood pressure (BP). Impairmentof this mechanism leads to adaptation, requiring higher BP tomaintain natriuresis. Salt sensitivity is defined as an increase in BPfollowing salt intake, activating proinflammatory and prooxidantmetabolic cascades. In this context, coenzyme Q10 (CoQ10) is a lipidsolubleand biologically active quinone with a high antioxidantcapacity due to the coexistence of its redox forms. These forms allowit to control cellular redox status by regulating the generation ofreactive oxygen species (ROS), protecting the cell from free radical.Furthermore, CoQ10 exhibits anti-inflammatory action and theability to inhibit proinflammatory genes. We hypothesize that dietarysupplementation with CoQ10 has a cardio-renoprotective effectin rats with normal renal function (FRN) and moderate renalinsufficiency (UNX) after salt overload through antioxidant andanti-inflammatory mechanisms.Methods: Two groups of Wistar rats (150 g) were used (n¼20 each),subjected to surgeries: uninephrectomy (UNX) to generate renal damagemodels. Normal renal function (NRF) group did not undergo surgery.After adaptation period (0 days for NRF and 30 days for UNX), eachgroup was subdivided into 4: G1¼(NNaD) Normal sodium diet: NaCl0.2%, G2¼(HNaD): NaCl 4%, G3¼CoQ10 (200mg/kg/day) + NaCl 4%,and G4¼CoQ10. BP was recorded using tail cuff technique, and baselineweight was measured at 45-and 100-days post-treatment. At the ends,proteinuria and creatinine clearance were determined. We measuredROS in whole blood, while in renal mitochondria, total glutathionecontent (GSHMt), superoxide dismutase activity (SODMt), and mitochondrialcomplexes (I-III) activity. Additionally, glomerular fibrosisscore was determined. To salt sensitivity evaluation, animals from G1and G4 (both NRF and UNX) underwent a 7-day sodium balance study,with a diet switch incorporating 4% NaCl while maintaining CoQ10supplementation. Increases in BP induced by NaCl was thendetermined.Results: In both groups, there was an increase in blood pressure (BP) inanimals HNaD compared to HNaD+CoQ10. This was not associated withweight changes. This effect persisted until Day 100. The prevention ofBP increase was associated with an 89% proteinuria reduction in HNaD.In UNX, CoQ10-mediated effects were also observed in creatinineclearance. While all groups increased clearance G3 did not showhyperfiltration effects (Clearance mL/min in G3¼ 1.87-1.51 at baselineand Day 100, respectively). These pathophysiological changes observedin G3 were associated with a lower incidence of Bowman?s basementmembrane thickening, adhesions, and glomerular folding, implying lessrenal fibrosis in these animals.After sodium balance study, prevention PN deterioration mechanismwas observed during CoQ10 supplementation (Figure 1). In theevaluation of redox response, we observed that HNaD had elevated ROSformation, and CoQ10 treatment decreased it. We also observed that thedecrease in GSHMt in HNaD was prevented with CoQ10. In this regard,an improvement in mitochondrial activity complexes I-III was alsoobserved in NRF animals treated with CoQ10, and there was no differencein UNX (Table 1).Conclusions: Dietary supplementation with CoQ10 during high-sodiumdiet in chronic kidney disease (CKD) prevented the increase in systemicand renal oxidative stress, preserving the pressure-induced natriuresis mechanism, reducing blood pressure, proteinuria, and the impairmentof target organs, such as the kidney.