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Citrate therapy for calcium phosphate stones

Rimer, Jeffrey D.a; Sakhaee, Khashayarb; Maalouf, Naim M.b

Current Opinion in Nephrology and Hypertension: March 2019 - Volume 28 - Issue 2 - p 130–139
doi: 10.1097/MNH.0000000000000474
CLINICAL NEPHROLOGY: Edited by David S. Goldfarb
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Purpose of review Calcium phosphate (CaP) stones represent an increasingly encountered form of recurrent nephrolithiasis, but current prophylactic medical regimens are suboptimal. Although hypocitraturia is a well-described risk factor for CaP stones, strategies that enhance citrate excretion have not consistently been effective at reducing CaP saturation and stone recurrence. This review summarizes the role of citrate therapy in CaP nephrolithiasis.

Recent findings Citrate in urine inhibits CaP stone formation through multiple mechanisms, including the formation of soluble citrate–calcium complexes, and inhibition of CaP nucleation, crystal growth and crystal aggregation. Recent in-vitro studies demonstrate that citrate delays CaP crystal growth through distinct inhibitory mechanisms that depend on supersaturation and citrate concentration. The impact of pharmacological provision of citrate on CaP saturation depends on the accompanying cation: Potassium citrate imparts a significant alkali load that enhances citraturia and reduces calciuria, but could worsen urine pH elevation. Conversely, citric acid administration results in minimal citraturia and alteration in CaP saturation.

Summary Citrate, starting at very low urinary concentrations, can significantly retard CaP crystal growth in vitro through diverse mechanisms. Clinically, the net impact on CaP stone formation of providing an alkali load during pharmacological delivery of citrate into the urinary environment remains to be determined.

aDepartment of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas

bDepartment of Internal Medicine, and Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Correspondence to Naim M. Maalouf, MD, Department of Internal Medicine, and Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8885, USA. E-mail: naim.maalouf@utsouthwestern.edu

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