High Sodium-Induced Oxidative Stress and Poor Anticrystallization Defense Aggravate Calcium Oxalate Crystal Formation in Rat Hyperoxaluric Kidneys

Abstract

Enhanced sodium excretion is associated with intrarenal oxidative stress. The present study evaluated whether oxidative stress caused by high sodium (HS) may be involved in calcium oxalate crystal formation. Male rats were fed a sodium-depleted diet. Normal-sodium and HS diets were achieved by providing drinking water containing 0.3% and 3% NaCl, respectively. Rats were fed a sodium-depleted diet with 5% hydroxyl-L-proline (HP) for 7 and 42 days to induce hyperoxaluria and/or calcium oxalate deposition. Compared to normal sodium, HS slightly increased calcium excretion despite diuresis; however, the result did not reach statistical significance. HS did not affect the hyperoxaluria, hypocalciuria or supersaturation caused by HP; however, it increased calcium oxalate crystal deposition soon after 7 days of co-treatment. Massive calcium oxalate formation and calcium crystal excretion in HS+HP rats were seen after 42 days of treatment. HP-mediated hypocitraturia was further exacerbated by HS. Moreover, HS aggravated HP-induced renal injury and tubular damage via increased apoptosis and oxidative stress. Increased urinary malondialdehyde excretion, in situ superoxide production, NAD(P)H oxidase and xanthine oxidase expression and activity, and decreased antioxidant enzyme expression or activity in the HS+HP kidney indicated exaggerated oxidative stress. Interestingly, this redox imbalance was associated with reduced renal osteopontin and Tamm-Horsfall protein expression (via increased excretion) and sodium-dependent dicarboxylate cotransporter NaDC-1 upregulation. Collectively, our results demonstrate that a HS diet induces massive crystal formation in the hyperoxaluric kidney; this is not due to increased urinary calcium excretion but is related to oxidative injury and loss of anticrystallization defense.

Experimental rat model for acute tubular injury induced by high water hardness and high water fluoride: efficacy of primary preventive intervention by distilled water administration

“…Further, some studies have shown that high sodium intake induces intra-renal oxidative stress via increased NAD(P)H oxidase (NOX) activity and decreased expression of superoxide dismutase (SOD) [62]. And also increases the urinary elimination of calcium in proportion to sodium and water via reduced passive reabsorption of calcium [63]. As calcium transport is closely linked to sodium transport in renal tubules, high dietary sodium tends to decrease calcium reabsorption and increase calcium excretion via urine leading to a temporary decrease in serum calcium.…”

High‐salt diet promotes crystal deposition through hypertension in Dahl salt‐sensitive rat model

“…Reportedly, the HS diet induces intrarenal oxidative stress by elevating the NADPH oxidase activity . The HS diet enhances crystal deposition because of the elevation of AP (CaOx) and oxidative stress . In rats, chronic treatment with aldosterone and a HS diet caused severe proteinuria and renal tissue injury characterized by glomerulosclerosis and tubulointerstitial fibrosis.…”

Calcium Kidney Stones are Associated with Increased Risk of Carotid Atherosclerosis: The Link between Urinary Stone Risks, Carotid Intima-Media Thickness, and Oxidative Stress Markers

“…Both animal [22,23] and clinical studies [3] have demonstrated that increases in oxidative stress in the kidneys of stone-forming patients and animals is indicated by the urinary excretion of ROS, the production of lipid peroxidation, and renal tubular enzymuria. An in vitro cell culture study showed that exposure to crystals, CaOx, and CaP leads to the development of oxidative stress [24].…”