Characterizing the Association Between Toll-like Receptor Subtypes and Nephrolithiasis With Renal Inflammation in an Animal Model.

ABSTRACT

OBJECTIVE: To show experimentally induced renal stone disease and to evaluate secondary inflammatory responses in vivo, and to characterize changes in the expression of Toll-like receptor (TLR) subtypes in this model. METHODS: Twenty 5- to 6-week-old male Wistar rats were divided into control and hyperoxaluria groups (n = 10 per group) and were supplied with normal water or 1% ethylene glycol, respectively, for 16 weeks. The animals were then placed in metabolic cages, and urine was collected for a 24-hour urine oxalate level evaluation. Following sacrifice, rats were subjected to bilateral nephrectomy and both kidneys were histopathologically evaluated. A 1-mm3 biopsy section from the right kidney of each rat was subjected to real-time polymerase chain reaction of the TLR expression. RESULTS: At the end of week 16, the hyperoxaluria group had a higher mean 24-hour urine oxalate level (1.91) than the control group (0.29) (P <.05) and a remarkably increased deposition of renal CaOx crystals (15/20) than the control group (0/20) (P <.05), which was universally accompanied by inflammation (15/15). Twelve and no rats in the hyperoxaluria and control groups, respectively, had macroscopically visible renal pelvic stones (P <.05). Quantitative real-time polymerase chain reaction revealed significant decreases in the expression of several TLRs, particularly TLR11 and TLR7. Decreases in TLR1, TLR3, and TLR6 expressions and an increase in the TLR2 expression did not differ significantly between the groups. CONCLUSION: We believe that is the first evaluation of TLR expression associated with renal stone formation in an animal model of inflammation. These results might lead to novel TLR-based treatments for nephrolithiasis and related inflammatory renal damage.