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.

BACKGROUND: Unknown cell-culture contaminants were described by Kajander and Ciftçioğlu in 1998. These contaminants were called nanobacteria initially and later calcifying nanoparticles (CNPs). Their exact nature is unclear and controversial. CNPs have unique and unusual characteristics, which preclude placing them into any established evolutionary branch of life.
OBJECTIVE: The aim of this systematic review was to assess published data concerning CNPs since 1998 in general and in relation to dental diseases in particular.
METHODS: The National Library of Medicine (PubMed) and Society of Photographic Instrumentation Engineers (SPIE) electronic and manual searches were conducted. Nanobacteria and calcifying nanoparticles were used as keywords. The search yielded 135 full-length papers. Further screening of the titles and abstracts that followed the review criteria resulted in 43 papers that met the study aim.
CONCLUSIONS: The review showed that the existence of nanobacteria is still controversial. Some investigators have described a possible involvement of CNPs in pulpal and salivary gland calcifications, as well as the possible therapeutic use of CNPs in the treatment of cracked and/or eroded teeth.