Human umbilical vein endothelial cells accelerate oxalate-induced apoptosis of human renal proximal tubule epithelial cells in co-culture system which is prevented by pyrrolidine dithiocarbamate

Sarıca, K. | Aydin, H. | Yencilek, F. | Telci, D. | Yılmaz, B.

Article | 2012 | Urological Research40 ( 5 ) , pp.461 - 466

Oxalate is the most common component of kidney stones and elevated urinary levels induce renal tubular cell toxicity and death which is essential for crystal attachment. Endothelial cells, in some studies have been shown to regulate certain functions of renal proximal tubule cells. The aim of this study was to evaluate the effect of endothelial cells on tubular cell apoptosis in a coculture system mimicking the in vivo renal physiological settings. The human umbilical vein endothelial cells (HUVEC) and human renal proximal tubule epithelial cells (RPTEC) were exposed to increasing concentrations (0-1.0 mM) of oxalate with or without . . . 10 µM PDTC pretreatment for 24 h. In HUVEC, RPTEC and HUVEC-RPTEC co-cultures, the cell viability was measured using the WST-1 assay and cell death with the TUNEL analysis using the flow cytometry. The treatment of RPTECs with oxalate lead to 8.9-26.2% cell death which was reduced to 0-1.6% with the PDTC pretreatment. The death rate of RPTECs was significantly increased by 15-19% at different oxalate concentrations when co-cultured with HUVECs. In contrast, cell viability was not substantially altered in PDTC pretreated RPTECs that were co-cultured with HUVECs. Apoptosis was the way of cell death as similar rate of apoptosis was observed in cell culture systems. Although cell viability of RPTECs was further reduced when co-cultured with HUVECs, it was restored with the pretreatment of PDTC. This is the first study focusing on the role of endothelial cells on RPTEC apoptosis following hyperoxaluria. © Springer-Verlag 2012 Daha fazlası Daha az

Increased 10-year cardiovascular disease and mortality risk scores in asymptomatic patients with calcium oxalate urolithiasis

Aydin, H. | Yencilek, F. | Erihan, I.B. | Okan, B. | Sarica, K.

Article | 2011 | Urological Research39 ( 6 ) , pp.451 - 458

Both the prevalence of cardiovascular risk factors and event rate are increased in patients with urolithiasis. Screening is recommended to all patients who have high cardiovascular risk. The aim of this study was to document 10-year risk of cardiovascular disease and mortality in asymptomatic patients with urolithiasis. Consecutive 200 patients with calcium oxalate urolithiasis were compared with 200 age- and sex-matched healthy controls. Ten-year cardiovascular disease risk was calculated with the Framingham Risk Score and mortality risk with SCORE risk score. Calcium, oxalate, and citrate excretion were studied as urinary stone ri . . .sk factors. The results indicate that patients with urolithiasis had higher total cholesterol (p < 0.0001), lower HDL-cholesterol (p < 0.0001), and higher systolic blood pressure (p < 0.0001) and hsCRP (p < 0.0001) compared with controls. Patients with urolithiasis had a higher Framingham Risk Scores [OR 8.36 (95% CI 3.81-18.65), p = 0.0001] and SCORE risk score [OR 3.02 (95% CI 1.30-7.02), p = 0.0006] compared with controls. The Framingham and SCORE risk score were significantly correlated with urinary calcium (p = 0.0001, r = 0.460, and p = 0.005, r = 0.223, respectively) and oxalate excretion (p = 0.0001, r = 0.516, p = 0.001, r = 0.290, respectively). In multiple linear regression analysis, urinary calcium and oxalate excretion, age, sex, total cholesterol, HDL-cholesterol, hsCRP and smoking were the independent predictors of 10-year cardiovascular disease risk and urinary calcium and oxalate excretion, age, sex, total cholesterol, fasting blood glucose for 10-year cardiovascular mortality. In conclusion, patients with calcium oxalate urolithiasis carry high risk of cardiovascular disease and mortality. All patients should be screened at the initial diagnosis of urolithiasis for the risk factors. © 2011 Springer-Verlag Daha fazlası Daha az

Ethylene Glycol Induced Hyperoxaluria Increases Plasma and Renal Tissue Asymmetrical Dimethylarginine in Rats: A New Pathogenetic Link in Hyperoxaluria Induced Disorders

Aydin, H. | Yencilek, F. | Mutlu, N. | Çomunoglu, N. | Koyuncu, H.H. | Sarica, K.

Article | 2010 | Journal of Urology183 ( 2 ) , pp.759 - 764

Purpose: The pathogenesis of kidney stones remains elusive. There is some evidence that hyperoxaluria may effect vascular endothelium and many studies link renal stones to atherosclerosis. Also, renal vascular endothelial cells regulate proximal tubular epithelial cell function. We determined the effect of hyperoxaluria on plasma and tissue levels of asymmetrical dimethylarginine. The secondary aim was to determine the effect of verapamil on asymmetrical dimethylarginine. Materials and Methods: A total of 42 Sprague-Dawley rats were included in the study. In groups 1A, 1B and 1C hyperoxaluria was induced with ethylene glycol for 2 w . . .eeks. Groups 2A, 2B and 2C received ethylene glycol for 14 days and verapamil for 28 days. Control group 3 received no specific medication but distilled water. Blood samples were obtained at 24 hours and at study end, and kidney samples were obtained at 24 hours, and 7 and 28 days for histopathological evaluation. Results: Plasma asymmetrical dimethylarginine increased early in the hyperoxaluric group (p = 0.0002). The effect was retained at the end of the study period (p = 0.01). There was no increase in asymmetrical dimethylarginine in the verapamil group on short-term and long-term followup. Hyperoxaluria induced a significantly dense staining pattern in renal tissue asymmetrical dimethylarginine vs controls (p = 0.01). Asymmetrical dimethylarginine staining did not differ in the control and verapamil groups. Conclusions: Increased systemic and local tissue asymmetrical dimethylarginine may help explain the pathogenetic mechanisms of hyperoxaluria induced disorders such as nephrolithiasis and atherosclerosis. © 2010 American Urological Association Daha fazlası Daha az

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