Renal Tubular Alteration by Crystalluria in Stone Disease – An Experimental Study by Means of MDCK Cells

Abstract

Objectives: Physicochemical properties of urine do not explain the formation of urinary stones. Clinical findings and results of animal experiments suggest that alteration to the renal tubular cell plays a key role in the initiation of urinary stone formation. It is not clear whether this is a primarily intracellular alteration of metabolic origin which, after lysis of the renal tubular cell in the lumen, presents a nucleus for the formation of concretions, or whether in the lumen it is tubular cell damage induced by crystalluria that triggers the formation of urinary stones. Materials and Method: Using Madin-Darby canine kidney cells, the influence of crystalluria on the renal tubular cell was tested in cell cultures. The influence of parathyroid hormone, vitamin D₃, oxalate and calcium concentrations and the extent to which these processes can be inhibited by allopurinol and selenium were investigated. Results: Calcium oxalate monohydrate crystals produced reproducible damage to the renal tubular cell which was independent of parathyroid hormone and vitamin D₃. The crystalluria-induced effects were unrelated to the oxalate and calcium concentration or the pH. Allopurinol and selenium were able to inhibit the processes. Conclusion: The results indicate secondary involvement of the renal tubular cell in lithogenesis as a result of luminal alteration caused by calcium oxalate crystals. Mechanical damage and interaction between crystal and tubular cell lead to the apposition of crystals. The nephroprotective effect of allopurinol and selenium as antioxidants might explain the benefit of allopurinol found clinically in terms of stone metaphylaxis.

The elementome of calcium-based urinary stones and its role in urolithiasis

“…146 In canine renal tubular cells, selenium inhibited the development of calcium oxalate monohydrate crystals. 147 Although selenium supplementation in experimental models has proved therapeutic, the effects of selenium on calcium-based stone formation in humans have not been reported.…”

Renal Tubular Dysfunction in Pediatric Urolithiasis: Proteomic Evidence

“…This is followed by fibrosis and collagen deposition (5). Crystal-induced tubular injury leads to crystal attachment and further renal epithelial damage (6). Markers of inflammation and tubulointerstitial damage were found in adults with calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid stones (7).…”

Evaluation of Selenium and Chloride levels in both sera and saliva samples in renal stone former patients

“…Urinary stones are similar to arteriosclerosis, the calcification that occurs in arteriosclerosis is inhibited by antioxidants [4] Oxalate and calcium concentration can be reduced and the process of crystallation can be inhibited by selenium which acts as nephroprotective antioxidant [5] .…”