Oxalate: From the Environment to Kidney Stones

Abstract Oxalate urolithiasis (nephrolithiasis) is the most frequent type of kidney stone disease. Epidemiological research has shown that urolithiasis is approximately twice as common in men as in women, but the underlying mechanism of this sex-related prevalence is unclear. Oxalate in the organism partially originate from food (exogenous oxalate) and largely as a metabolic end-product from numerous precursors generated mainly in the liver (endogenous oxalate). Oxalate concentrations in plasma and urine can be modified by various foodstuffs, which can interact in positively or negatively by affecting oxalate absorption, excretion, and/or its metabolic pathways. Oxalate is mostly removed from blood by kidneys and partially via bile and intestinal excretion. In the kidneys, after reaching certain conditions, such as high tubular concentration and damaged integrity of the tubule epithelium, oxalate can precipitate and initiate the formation of stones. Recent studies have indicated the importance of the SoLute Carrier 26 (SLC26) family of membrane transporters for handling oxalate. Two members of this family [Sulfate Anion Transporter 1 (SAT-1; SLC26A1) and Chloride/Formate EXchanger (CFEX; SLC26A6)] may contribute to oxalate transport in the intestine, liver, and kidneys. Malfunction or absence of SAT-1 or CFEX has been associated with hyperoxaluria and urolithiasis. However, numerous questions regarding their roles in oxalate transport in the respective organs and male-prevalent urolithiasis, as well as the role of sex hormones in the expression of these transporters at the level of mRNA and protein, still remain to be answered. Sažetak Oksalatna urolitijaza (nefrolitijaza) najučestaliji je tip bolesti bubrežnih kamenaca. Rezultati epidemioloških istraživanja pokazali su da je urolitijaza približno dvostruko učestalija u muškaraca nego u žena, ali osnovni mehanizam nastanka ove spolno-ovisne prevalencije nije razjašnjen. Oksalat u organizmu dijelom potječe iz hrane (egzogeni oksalat), a glavninom nastaje kao konačni produkt metabolizma raznih preteča u jetrima (endogeni oksalat). Na koncentraciju oksalata u plazmi i urinu utječu razne tvari iz hrane, koje mogu pozitivno ili negativno djelovati na apsorpciju, metaboličke puteve i/ili izlučivanje oksalata. Oksalat se iz organizma izlučuje u manjem obimu putem žuči u crijevo, a glavninom bubrezima. U bubrezima, pri odgovarajućim uvjetima kao što su visoka koncentracija oksalata i oštećenje epitela bubrežnih kanalića, oksalat može precipitirati i time potaknuti stvaranje kamenaca. Rezultati novih istraživanja upućuju na važnost membranskih prijenosnika otopljenih tvari (SoLute Carriers) iz obitelji 26 (SLC26) za prijenos oksalata u specifičnim organima. Smatra se da dva člana ove obitelji: prijenosnik sulfatnog aniona (Sulfate Anion Transporter 1; SAT-1; SLC26A1) i izmjenjivač klora i mravlje kiseline (Chloride/Formate EXchanger; CFEX; SLC26A6), imaju značajnu ulogu u prijenosu oksalata u crijevima, jetrima i bubrezima; hiperoksalurija i nefrolitijaza utvrđeni su pri slaboj aktivnosti ili nedostatku SAT-1 i CFEX proteina. Međutim, još uvijek postoje brojne nejasnoće glede prijenosa oksalata u navedenim organima, mehanizma nastanka spolnih razlika u nefrolitijazi i utjecaja spolnih hormona na ekspresiju proteina i mRNA za navedene prijenosnike.