Urinary macromolecules and renal tubular cell protection from oxalate injury: Comparison of normal subjects and recurrent stone formers

Abstract

Aim:To determine whether urinary macromolecules (UMM), which are the high molecular weight substances in urine, can provide protection against the oxalate-associated injury to the renal tubular cells. Methods: UMM were extracted from 24-h urine of 12 healthy adult male volunteers and 13 recurrent-stone-former male patients. Urine parameters in relation to urolithiasis were measured, including the level of glycosaminoglycans (GAG) in the UMM. MadinDarby canine kidney (MDCK) cells were used to evaluate the protective activity of UMM from oxalate-induced cytotoxicity by LDH release measurement and methyl-thiazolyl tertrazolium (MTT) assay. Results: Considering urinary parameters, citrate was significantly higher in urine from normal subjects than stone-former subjects; the other parameters show no differences between the groups. Total UMM and the level of GAG in the UMM were also significantly higher in the normal subject group. Compared with normal subject and stone-former subject UMM, after cells were treated with the UMM and then exposed to oxalate solution, LDH release was significantly higher in stone-former group. In the MTT assay, we found that more viable cells were observed after treatment with UMM compared to control in both groups. Moreover, UMM from the normal subjects showed higher protective activity against oxalate-related cytotoxicity than UMM from the stone-former subjects. Conclusion: UMM protected renal epithelial cells from oxalate-related injury. This protective activity was found to be higher in normal subject UMM than stone-former UMM. Among other factors, a higher concentration of GAG and citrate in normal subject UMM might affect some parts in this finding.

Expression of heterologous oxalate decarboxylase in HEK293 cells confers protection against oxalate induced oxidative stress as a therapeutic approach for calcium oxalate stone disease

“…Earlier studies have elucidated the abrasive effects of both oxalate and CaOx crystals in renal epithelial cell injury through free radicals 22 , 23 . ROS generation increases in response to renin angiotensin system activation and eventually causes mitochondrial damage 24 .…”

Mechanism of calcium oxalate renal stone formation and renal tubular cell injury

“…Urinary macromolecules (UMM) might protect renal tubular cells from oxalate‐related injury, and UMM from normal subjects might have a stronger protective effect than UMM from stone‐forming subjects 76 …”

“…75 Urinary macromolecules (UMM) might protect renal tubular cells from oxalate-related injury, and UMM from normal subjects might have a stronger protective effect than UMM from stone-forming subjects. 76 Fibronectin is one of the macromolecules oversecreted from renal tubular cells as a result of stimulation by COM crystals. 20 It has also been reported that FN protected against renal tubular cell injury caused by oxalate and COM crystals, as shown by MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide] assay and morphological examination.…”

Urine and serum glycosaminoglycan levels in the diagnosis of urological diseases and conditions: A narrative review of the literature

“…may predispose individuals to stone formation. 35 GAGs have been shown to be present on all surfaces of the urinary tract and to directly inhibit stone formation. [36][37][38] The amount of GAGs excreted in urine and the integrity of the GAG layer in various parts of the urinary tract may be involved in the adhesion, formation, and growth of urine crystals.…”

“…42 Although various inhibitory effects of GAGs on stone formation were identified in several in vitro studies, the results of studies comparing urinary GAG levels in patients and control groups are contradictory. 13,35,39,[43][44][45] Many reports showed low urinary GAGs in adult nephrolithiasis patients. 38,39,43,[45][46][47][48] Ombra et al 48 separated the patients into subgroups and found a significant difference in the urinary GAG/creatinine ratio between the recurrent stone disease patients and the first-time stone disease patients.…”