Recent advances on the mechanisms of kidney stone formation (Review)

Abstract

Kidney stone disease is one of the oldest diseases known to medicine; however, the mechanisms of stone formation and development remain largely unclear. Over the past decades, a variety of theories and strategies have been developed and utilized in the surgical management of kidney stones, as a result of recent technological advances. Observations from the authors and other research groups suggest that there are five entirely different main mechanisms for kidney stone formation. Urinary supersaturation and crystallization are the driving force for intrarenal crystal precipitation. Randall's plaques are recognized as the origin of calcium oxalate stone formation. Sex hormones may be key players in the development of nephrolithiasis and may thus be potential targets for new drugs to suppress kidney stone formation. The microbiome, including urease-producing bacteria, nanobacteria and intestinal microbiota, is likely to have a profound effect on urological health, both positive and negative, owing to its metabolic output and other contributions. Lastly, the immune response, and particularly macrophage differentiation, play crucial roles in renal calcium oxalate crystal formation. In the present study, the current knowledge for each of these five aspects of kidney stone formation is reviewed. This knowledge may be used to explore novel research opportunities and improve the understanding of the initiation and development of kidney stones for urologists, nephrologists and primary care.

Plants Used in Mexican Traditional Medicine for the Management of Urolithiasis: A Review of Preclinical Evidence, Bioactive Compounds, and Molecular Mechanisms

“…The formation of urinary stones is a result of the supersaturation of urine and the subsequent formation of crystalline materials. The formation of urinary stones involves a sequence of events, including saturation, supersaturation, nucleation, crystal growth, crystal aggregation, crystal retention, and, finally, stone formation [ 3 , 4 ]. During urinary supersaturation and crystallization, there is intrarenal crystal precipitation, which is mainly caused by inherited or acquired diseases associated with renal function impairment [ 4 , 5 ].…”

“…The formation of urinary stones involves a sequence of events, including saturation, supersaturation, nucleation, crystal growth, crystal aggregation, crystal retention, and, finally, stone formation [ 3 , 4 ]. During urinary supersaturation and crystallization, there is intrarenal crystal precipitation, which is mainly caused by inherited or acquired diseases associated with renal function impairment [ 4 , 5 ]. During UL, many factors contribute to urinary stone formation, including alteration in urinary pH and metabolic alterations such as hypercalciuria, hyperuricosuria, hyperoxaluria, hypocitraturia, hypomagnesuria, and hypercystinuria [ 2 , 3 ].…”

“…During UL, many factors contribute to urinary stone formation, including alteration in urinary pH and metabolic alterations such as hypercalciuria, hyperuricosuria, hyperoxaluria, hypocitraturia, hypomagnesuria, and hypercystinuria [ 2 , 3 ]. These factors are related because the urinary pH promotes excessive concentrations of many compounds such as calcium, oxalates, phosphates, uric acids, urates, struvite, amino acids, and purines, which, subsequently, results in supersaturation and crystallization [ 4 ]. The chemical composition of urinary stones depends on the biochemical abnormalities in urine composition.…”

“…Calcium oxalate (CaOx) is the most common component of urinary stones; it represents up to 80% of analyzed stones [ 2 ]. Other types of stones that are less frequent are calcium phosphate, struvite (5–15%), uric acid (5–10%), and cystine stones that correspond to 1–3% of stone types [ 4 ].…”

On the protein content of kidney stones: an explorative study

“…Modern literature no longer regards urinary proteins as an innocent bystander in urolithiasis, but more and more highlights their role [5,6]. Crystal nucleation, growth, aggregation in urine and crystal attachment to renal epithelial cells depend upon the modulatory compounds in renal environment [3].…”