An Overview of Divalent Cation and Citrate Handling by the Kidney

Unwin, RJ; Capasso, Giovambattista; Shirley, David G.

doi:10.1159/000080259

Cited by 57 publications

(45 citation statements)

References 30 publications

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“…Systemic acidosis has an important effect on citrate excretion by conversion of citrate 3j into citrate 2j and thereby increasing the availability of transportable divalent citrate, resulting in a decrease of citrate excretion [25]. In our study we only found a higher pH at day 14 in the treated group.…”

Section: Discussioncontrasting

confidence: 57%

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Does citrate prevent nephrocalcinosis in preterm neonates?

et al. 2006

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Nephrocalcinosis (NC) occurs frequently in preterm neonates. A high U-calcium/citrate is one of the contributing factors to the development of NC. In stone-forming children and adults citrate supplementation is a successful preventive therapy. In this randomized controlled trial the effect of citrate therapy was studied on the development of NC in preterm neonates with a gestational age <32 weeks. Thirty-eight preterm neonates (mean gestational age 29.8 weeks (SD 1.6), mean birth weight 1,300 g (SD 351) were treated with sodium citrate (0.52 mmol/kg/day in four doses) from day 8 of life until at term and 36 preterm neonates (mean gestational age 29.6 weeks (SD 1.6), mean birth weight 1,282 g (SD 256) were not treated. U-calcium, U-creatinine, U-citrate and U-pH were measured at day 7, 14, 21, 28 of life and at term. Renal ultrasonography (US) was performed at term. U-citrate/creatinine and U-pH were significantly higher and U-calcium/citrate was significantly lower in the citrate group at day 14, 21 and 28 compared with the control group (P<0.05). Complications of citrate administration were not encountered, however the incidence of NC was not significantly different in the treated (34%) compared with the control group (44%), P=0.37. Preterm neonates treated with citrate in the first months of life have higher U-citrate/creatinine and lower U-calcium/citrate compared with controls. Sodium citrate therapy in a dosage of 0.52 mmol/kg/day is safe but does not prevent NC. Whether a higher dose or potassium citrate decreases the incidence of NC should be evaluated in further studies.

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Section: Discussioncontrasting

confidence: 57%

“…In order to keep the sodium level intracellular low, sodium is transported to the peritubular space by Na + /K + -ATPase. [25]. Therefore, less citrate will be excreted when citrate supplementation is combined with sodium in stead of potassium.…”

Section: Discussionmentioning

confidence: 99%

Does citrate prevent nephrocalcinosis in preterm neonates?

et al. 2006

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“…Several families have felt that acetazolamide has been helpful. This is interesting in light of its ability to alter urinary citrate excretion, possibly as a consequence of changes in urinary or renal cell pH (28,29). However, it is also possible that the effects of acetazolamide are related to changes in pH or metabolism in the CNS (27).…”

Section: Discussionmentioning

confidence: 99%

Mutations in the Na+/Citrate Cotransporter NaCT (SLC13A5) in Pediatric Patients with Epilepsy and Developmental Delay

Klotz

Porter

Colas

et al. 2016

Mol Med

125

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Mutations in the SLC13A5 gene that codes for the Na + /citrate cotransporter, NaCT, are associated with early onset epilepsy, developmental delay and tooth dysplasia in children. In this study, we identify additional SLC13A5 mutations in nine epilepsy patients from six families. To better characterize the syndrome, families with affected children answered questions about the scope of illness and the treatment strategies. Currently, there are no effective treatments, but some antiepileptic drugs targeting the γ-aminobutyric acid system reduce seizure frequency. Acetazolamide, a carbonic anhydrase inhibitor and atypical antiseizure medication, decreases seizures in four patients. In contrast to previous reports, the ketogenic diet and fasting resulted in worsening of symptoms. The effects of the mutations on NaCT transport function and protein expression were examined by transient transfections of COS-7 cells. There was no transport activity from any of the mutant transporters, although some of the mutant transporter proteins were present on the plasma membrane. The structural model of NaCT suggests that these mutations can affect helix packing or substrate binding. We tested various treatments, including chemical chaperones and low temperatures, but none improved transport function in the NaCT mutants. Interestingly, coexpression of NaCT and the mutants results in decreased protein expression and activity of the wild-type transporter, indicating functional interaction. In conclusion, this study has identified additional SLC13A5 mutations in patients with chronic epilepsy starting in the neonatal period, with the mutations producing inactive Na + /citrate transporters.online address: http://www.molmed.org

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“…The mechanism of calcium handling in the kidneys has been investigated by many researchers (Seldin 1999;Unwin et al 2004). The renal tubules such as the proximal tubules (PTs), the thick ascending limbs (TALs) of Henle's loop, and the distal tubules (DTs) are mainly involved in reabsorbing the filtered calcium, and their functions are mainly controlled by PTH and vitamin D (Unwin et al 2004). Parathyroid hormone is known to control renal tubular functions such as phosphate reabsorption in the proximal tubules and cyclic adenosine monophosphate (AMP) production in the TALs.…”

Section: Methodsmentioning

confidence: 99%

Chloride-Dependent Intracellular pH Regulation via Extracellular Calcium-Sensing Receptor in the Medullary Thick Ascending Limb of the Mouse Kidney

Aslanova

Morimoto

Farajov

et al. 2006

Tohoku J. Exp. Med.

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The extracellular calcium-sensing receptor (CaSR) located in either luminal or basolateral cell membranes of various types of renal tubules including proximal tubules, Henle's loop and collecting ducts has been thought to play a fundamental role in electrolyte metabolism. To further identify the physiological roles of the CaSR, we examined the effects of Ca 2+ and calcimimetics neomycin (Neo), gentamicin and gadolinium chloride (Gd 3+ ) on the intracellular pH (pHi) of in vitro microperfused mouse medullary thick ascending limb (mTAL) cells of Henle's loop, by loading the cells with fluorescent pH indicator 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein and measuring the ratio of fluorescence emission at 530 nm after exciting the dye at 490 and 440 nm. In a steady-state condition in Hepes-buffered solution, the pHi in the mTALs was 7.29 ± 0.04 (n = 9). A concentration of 200 μ mol/l Neo in the basolateral side decreased the pHi after 1 min by −0.13 ± 0.02 (n = 34, p < 0.0001). The other calcimimetics showed similar effects on pHi, whereas none of these calcimimetics in the lumen affected pHi. Na + removal or the inhibition of Na + and proton transport with amiloride, bumetanide, or bafilomycin did not eliminate the effect of Neo on pHi. On the other hand, Cl − removal clearly eliminated the Neo-induced pHi decrease (−0.06 ± 0.01 vs −0.00 ± 0.05 in Cl − removal, n = 4, p < 0.003). Thus, we have demonstrated for the first time that the CaSR is involved in the regulation of the pHi in the mTAL and requires Cl − to exert its effect. intracellular pH; renal medulla; chloride; amiloride; BCECF

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An Overview of Divalent Cation and Citrate Handling by the Kidney

Cited by 57 publications

References 30 publications

Does citrate prevent nephrocalcinosis in preterm neonates?

Does citrate prevent nephrocalcinosis in preterm neonates?

Mutations in the Na+/Citrate Cotransporter NaCT (SLC13A5) in Pediatric Patients with Epilepsy and Developmental Delay

Chloride-Dependent Intracellular pH Regulation via Extracellular Calcium-Sensing Receptor in the Medullary Thick Ascending Limb of the Mouse Kidney

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