Characterizing the Association between Toll-Like Receptor Subtypes and Nephrolithiasis with Renal Inflammation in an Animal Model

To show experimentally induced renal stone disease and evaluate secondary inflammatory responses in vivo, and to characterize changes in expression of Toll-like receptor (TLR) subtypes in this model. To evaluate the associations of hyperoxaluria-induced renal stone formation and Toll-like receptors (TLRs) expression in a rat inflammation model.

Twenty 5-6-week-old male Wistar rats were divided into control and hyperoxaluria groups (n=10/group) and 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-h urine oxalate level (24HUOL) evaluation. Following sacrifice, rats were subjected to bilateral nephrectomy and both kidneys were histopathologically evaluated. A 1-mm(3) biopsy section from the right kidney of each rat was subjected to real-time polymerase chain reaction (PCR) of TLR expression.

At the end of week 16, the hyperoxaluria group had a higher mean 24HUOL (1.91 vs. control, 0.29, p<0.05) and a remarkably increased deposition of renal CaOx crystals (15/20 vs. 0/20, p<0.05), 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<0.05). Quantitative real-time PCR revealed significant decreases in the expression of several TLRs, particularly TLR11 and TLR7. Decreases in TLR1, TLR3, and TLR6 expressions and increase in TLR2 expression did not differ significantly between the groups.

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.

Urology. 2017 Oct 17 [Epub ahead of print]

Mahmut Taha Olcucu, Kerem Teke, Serdar Yalcin, Erkan Olcucuoglu, Vildan Caner, Nilay Sen Turk, Omer Levent Tuncay

Agri State Hospital, Urology, Agri, Turkey. Electronic address: ., Agri State Hospital, Urology, Agri, Turkey., Turkey Yuksek Ihtisas Education and Research Hospital, Urology, Ankara, Turkey., Pamukkale University School of Medicine, Genetics, Denizli, Turkey., Pamukkale University School of Medicine, Pathology, Denizli, Turkey., Pamukkale University School of Medicine, Urology, Denizli, Turkey.