Nephrolithiasis: Molecular Mechanism of Renal Stone Formation and the Critical Role Played by Modulators

Abstract

Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person's ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation.

Evaluation of antiurolithiatic effects of Parmelia perlata against calcium oxalate calculi in hyperoxaluric rats

“…Effects of PPE on other stone promoting and inhibiting factors Formation of urinary stone is considered to be affected by various stone promoting and inhibiting factors. The calcium and phosphorus are considered as the stone promoting inorganic factors while the magnesium is stone inhibiting (Basavaraj et al, 2007). In the present study, EG + AC treatment significantly elevated the calcium and phosphorus level in urine, serum, and kidney tissue homogenates of hyperoxaluric rats as shown in Table 3.…”

“…After staining with hematoxylin and eosin, the kidney sections were examined (at 400x), under a light microscope equipped with a digital camera, for the presence of crystals of CaOx and various renal pathological changes like tubular necrosis, glomerular and tubular architecture etc. (Atmani et al, 2009;Goyal et al, 2017;Pareta et al, 2011).…”

“…Crystal deposition is usually associated with cellular injury and caused a variety of changes in renal architecture that facilitate crystal retention. The interactions between injured tubular epithelial cells and oxalate crystals are considered to have a significant role in the development of urinary stones (Aggarwal et al, 2010;Bijarnia et al, 2008;Grover et al, 1990;Khan, 2004;Khan et al, 2000). PPE (100, 300 and 500 mg/kg), when compared with urolithiatic group, significantly restored the normal renal architecture as shown in Figure 1 D, E, and F respectively.…”

“…More than 80% of renal stones are composed of calcium oxalate (CaOx) and occurs in two forms i.e. mono and di-hydrates of CaOx (Aggarwal et al, 2013;Goyal et al, 2017;Khan, 1997). Urinary stone formation occurs as a result of cascade of physiochemical events started with supersaturation of urine and followed by nucleation, growth, aggregation and retention of crystals (Li et al, 2017;Moe, 2006).…”

Antiurolithiatic Activity of Daucus carota: An In vitro Study

“…13 Present study was designed to address these key events involved in CaOx stone formation as a means to investigate the efficacy of D. carota roots as an antiurolithiatic. Nucleation is a prerequisite in the pathogenesis of CaOx urolithiasis.…”