title: Pathophysiology-based treatment of urolithiasis.
abstract: Urolithiasis, a complex multifactorial disease, results from interactions between environmental and genetic factors. Epidemiological studies have shown the association of urolithiasis with a number of lifestyle-related diseases, including cardiovascular diseases, hypertension, chronic kidney disease, diabetes and metabolic syndrome. Elucidation of the mechanisms underlying urinary stone formation will enable development of new preventive treatments. The present article reviews the epidemiology, pathophysiology and potential treatment of urolithiasis. Recent literature has shown that oxidative stress and reactive oxygen species could be one such mechanistic pathway. Calcium oxalate crystals adhering to renal tubular cells are incorporated into the cells through the involvement of osteopontin. Stimulation of crystal-cell adhesion impairs acceleration of the mitochondrial permeability transition pore in tubular cells, resulting in mitochondrial collapse, oxidative stress and activation of the apoptotic pathway in the initial steps of renal calcium crystallization. With regard to genetic factors, studies show that single nucleotide polymorphisms in genes encoding calcium-sensing receptor, vitamin D receptor and osteopontin are correlated with urolithiasis. Genome-wide association studies have shown that CLDN14 and NPT2 are associated with urolithiasis in Caucasian and Japanese populations, respectively. Thus, single nucleotide polymorphism analysis would aid in the prediction of urolithiasis risk and recurrence. New diagnostic methods and preventive approaches, along with complete removal of stones, will improve the management of urolithiasis.
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okada
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Hamamoto
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ando
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tozawa
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D050356:Lipid Metabolism / Q000235:genetics; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism; D008928:Mitochondria / Q000473:pathology*; D051336:Mitochondrial Membranes / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D000077205:Pioglitazone / Q000494:pharmacology / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species / Q000378:metabolism; D012008:Recurrence; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism; D012307:Risk Factors; D052878:Urolithiasis / Q000453:epidemiology / Q000209:etiology / Q000473:pathology / Q000628:therapy*
chemical_list: D002791:Cholesterol, Dietary; D017382:Reactive Oxygen Species; D000077205:Pioglitazone
keywords: calcium oxalate; kidney calculi; mitochondria; nephrolithiasis; oxidative stress; urolithiasis