step 1 – step 3 Extremely patients with hypercalciuria provides IH. The elevated removal of urinary calcium supplements raises the likelihood having nucleation and you will development of CaOx and you https://datingranking.net/es/citas-sobrias/ will/or Limit deposits towards the medically extreme renal rocks. 1
From inside the clients with IH, K-cit is frequently accustomed stop recurrent stone development. 8 – 13 But not, no possible managed degree when you look at the humans demonstrated the effectiveness of K-cit during the preventing recurrent Cover brick creation. 23 Citrate features a complicated impact on pee solute excretion, as well as effect on pee supersaturation in terms of Cover brick formation is difficult to assume. Specific research shows one to CaOx rocks get changes into the Cover rocks throughout the years, and use out of citrate treatment may determine this experience. 50 , 51 Although not, zero definitive studies have yet turned-out otherwise refused the brand new character out-of citrate within the sales out-of CaOx to help you Cover stone situation.
Within study having fun with GHS rats, the provision out-of K-cit resulted in an increase in pee citrate excretion and you will K-cit and additionally effortlessly reduced urinary calcium supplements. Brand new system for which K-cit decrease urinary calcium supplements is practically indeed multifactorial. When you are citrate is actually conveniently immersed on the bowels, 52 it minimizes calcium consumption and urinary calcium removal. 14 , 15 Improved urinary citrate could join urinary calcium, removing this new calcium throughout the pool available for joining that have phosphate otherwise oxalate. Concurrently, citrate kcalorie burning so you’re able to bicarbonate contributes to systemic alkalinization, and therefore privately reduces bones resorption 53 and you will expands kidney tubule calcium reabsorption, and so reducing the level of calcium during the pee. The latest reduced amount of urinary calcium by itself create absolutely beat urinary supersaturation with respect to calcium supplements-that has had kidney stones.
Although not, i in addition to discover a rise in urinary oxalate, sulfate, and you can phosphorus and you can a reduction in solution phosphorus into the GHS mice treated with citrate, modifications maybe not before stated in the humans given citrate. This new joining off abdominal calcium by the citrate you certainly will fall off intestinal binding regarding calcium supplements so you can oxalate, probably allowing better absorption regarding oxalate. In the renal, oxalate try transferred in the proximal tubule. 54 , 55 The newest murine anion transporter Slc26a6, included in kidney proximal tubule and you can bowels, possess specificity to have chloride/oxalate replace. 56 – 58 Knockout out-of Slc26a6 in rats causes hyperoxaluria, 59 , 60 hypocitraturia, 61 and CaOx brick formation. 59 Inside perfusion studies the existence of sulfate otherwise bicarbonate inhibited oxalate transportation, suggesting competitive suppression of the anions. 55 Co-phrase from Slc26a6 additionally the citrate transporter NaDC-1 demonstrates that this type of transporters come together. 61 NaDC-step one increased Slc26a6 transport hobby, whenever you are Slc26a6 inhibited NaDC-1. 61 Such data strongly recommend a virtually relationships between oxalate and you can citrate transport. Inside studies we found that government away from K-cit resulted in a serious escalation in pee oxalate excretion, and therefore improve would increase urinary supersaturation in terms of CaOx.
While the noticed in individuals, citrate treatment lower urine calcium supplements and you will elevated urinary citrate and you may pH regarding the GHS rat
The brand new binding of abdominal calcium from the citrate might make it deeper assimilation out-of phosphate. Kidney phosphate reabsorption is actually regulated because of the particular II Na + -paired phosphate cotransporter regarding proximal tubule, that’s suppressed from the extracellular acidification. 62 The general and urinary alkalinization induced by the K-cit perform boost renal tubular phosphate reabsorption; yet not, the rise inside PTH, not mathematically high, you’ll make up the increase during the pee phosphate and you can decrease in gel phosphate, which had been found in this study.
Urine sulfate improved inside the GHS mice provided K-cit. This new anion transporter Slc26a2, which shows substrate specificity having sulfate, oxalate, and you can chloride, is additionally within the new proximal tubule. 63 Mutation from SLC26A2 within the human beings can result in recessive chondrodysplasia, as a result of abnormal sulfate transport. 63 When indicated in the Xenopus oocytes, acid extracellular pH inhibited anion exchange, if you are acidic intracellular pH activated replace regarding extracellular chloride having intracellular sulfate but not chloride or oxalate. 64 Then studies might be must influence as to why urinary sulfate improved on GHS mice provided K-cit.