Renal tubular cell damage and oxidative stress in renal stone patients and the effect of potassium citrate treatment

Abstract

Our objective was to evaluate the oxidative stress and renal tubular cell damage in patients who have renal stones compared to normal subjects. The patients were re-evaluated after 1-months supplementation with potassium citrate. We recruited 30 patients (11 males and 19 females) diagnosed with kidney stones and scheduled for surgical stone removal the following month, and 30 healthy non-stone formers (14 males and 16 females). Two 24-h urine samples and one heparinized blood sample were collected from each subject. Plasma was separated from the erythrocytes and assayed for creatinine, potassium, sodium, calcium, magnesium, phosphate, malondialdehyde (MDA, a lipid peroxidation product) (P-MDA), protein thiol as an indicator of protein oxidation, and vitamin E. Erythrocytes were analysed for MDA (E-MDA), reduced glutathione (GSH) and cellular glutathione peroxidase (cGPx) activity. The urine was analyzed for pH, creatinine, potassium, sodium, calcium, magnesium, phosphate, oxalate, citrate, MDA (U-MDA), total protein (U-protein) and N-acetyl-beta-glucosaminidase (NAG) activity. For the stone patients, urine and blood samples were re-evaluated after supplementation with potassium citrate (60 mEq/day) for 1 month. Renal stone patients had higher plasma creatinine and lower plasma potassium, urinary pH, potassium, magnesium, phosphate and citrate than the controls. The patients had higher P-MDA, E-MDA, U-MDA, U-protein and NAG activity, but lower GSH, cGPx activity, protein thiol and vitamin E, when compared with controls. After potassium citrate supplementation, P-MDA and E-MDA decreased while plasma vitamin E, urinary NAG activity and citrate increased. Renal stone disease is associated with high oxidative stress and damage to renal tubular cells. These abnormalities are coincident with an increase in blood lipid peroxidation products and a decrease in antioxidant status. Although supplementation with potassium citrate improved urinary citrate levels and oxidative stress, it neither reduced urinary lipid peroxidation products nor remedied the damage to renal tubular cells, probably due to the existence of kidney stones.

Interaction between submicron COD crystals and renal epithelial cells

“…Elevated MDA content is an obvious sign of cell oxidative damage. 22,23 This result was consistent with that of cell viability determination ( Figure 4A) demonstrated via the evident injury effect of hydrogen peroxide on Vero cells.…”

Messenger RNA expression of monocyte chemoattractant protein‐1 and interleukin‐6 in stone‐containing kidneys

“…A high urinary level of oxidatively modified substances has been documented in patients with nephrolithiasis, and the severity of oxidative stress was correlated with renal tubular damage [2,21,22]. Urinary NAG activity has been widely used as a sensitive marker of renal tubular function in kidney diseases, including nephrolithiasis [2,21,22].…”

“…It is known that crystal formation, which takes place in chronically supersaturated urine, and crystal deposition in the renal interstitium, are prerequisite events in lithogenesis. Oxidative stress, renal tubular injury and inflammation are well recognized as being involved in the pathogenesis of kidney stones [1,2].…”

A Meta-Analysis of Coffee Intake and Risk of Urolithiasis

“…Given that nephrolithiasis has been associated with high oxidative stress and damage to renal tubular cells in humans [35], it is postulated that antioxidants may play a role in the prevention of urolithiasis. Some researches have previously evaluated the possible role of oxidative stress in animal models by demonstrating increased markers of lipid peroxidation and oxygen free radicals in in vivo models of nephrolithiasis in porcine [36], canine and rat models [37].…”