The incidence of kidney stones in women is lower than in men throughout adult life. However, stone incidence has been reported to increase in women during the 6th decade of life, while for men it begins to decrease. A retrospective analysis of patient data obtained during previous funding cycles of this P01 has disclosed a significant increase in urinary calcium excretion during the 6th decade in women stone-formers. This time corresponds to the onset of menopause in many women. Moreover, udnary calcium excretion was substantially lower in postmenopausal women treated with estrogen than in those who were not, commensurate with a similar decline in urinary saturation of calcium oxalate. These findings are consistent with the possibility that estrogen deficiency increases the risk of stone formation. Our central hypothesis to be tested in this proposal is that the apparent increase in stone formation rate following menopause is in part due to pdmary impairment of renal tubular calcium reabsorption from estrogen lack. This hypothesis will be tested through four specific aims representing a translational approach to uncover the mechanism(s) of renal calcium leak.
The specific aims are: (1) evaluate the effects of short-term estrogen treatment on the renal handling of calcium and the propensity for stone formation in normal postmenopausal women as well as postmenopausal women with kidney stones: (2) quantitate the effect of estrogen replacement on calcium transport via clearance studies as well as in vivo microperfusion of the proximal tubule, loop of Henle and distal convoluted tubule in the ovariectomized (OVX) rat; (3) characterize estrogen-dependent regulation of calbindin-D28K gene expression in renal tubular cells; and (4) examine the mechanism for calbindin-D28K regulation of calcium entry via epithelial calcium channel (ECaC). These proposed studies represent a translational approach that will characterize the effect of estrogen on renal calcium handling using clinical, whole animal, and molecular models. It is anticipated that the findings will expand our understanding of hormonal regulation of renal calcium transport, offer a mechanism for increased stone propensity in postmenopausal women, and open new avenues for investigation of potential countermeasures to stone formation not only for this select group of patients but for the stone-forming population in general.
| Xu, Li Hao Richie; Maalouf, Naim M (2017) Effect of acute hyperinsulinemia on magnesium homeostasis in humans. Diabetes Metab Res Rev 33: |
| Xu, Li Hao Richie; Adams-Huet, Beverley; Poindexter, John R et al. (2017) Temporal Changes in Kidney Stone Composition and in Risk Factors Predisposing to Stone Formation. J Urol 197:1465-1471 |
| Sakhaee, Khashayar; Poindexter, John; Aguirre, Crystal (2016) The effects of bariatric surgery on bone and nephrolithiasis. Bone 84:1-8 |
| Hu, Ming Chang; Shi, Mingjun; Cho, Han Jun et al. (2015) Klotho and phosphate are modulators of pathologic uremic cardiac remodeling. J Am Soc Nephrol 26:1290-302 |
| Hajibeigi, Asghar; Dioum, Elhadji M; Guo, Jianfei et al. (2015) Identification of novel regulatory NFAT and TFII-I binding elements in the calbindin-D28k promoter in response to serum deprivation. Biochem Biophys Res Commun 465:414-420 |
| Yoon, Vivienne; Adams-Huet, Beverley; Sakhaee, Khashayar et al. (2013) Hyperinsulinemia and urinary calcium excretion in calcium stone formers with idiopathic hypercalciuria. J Clin Endocrinol Metab 98:2589-94 |
| Capolongo, Giovanna; Abul-Ezz, Sameh; Moe, Orson W et al. (2012) Subclinical celiac disease and crystal-induced kidney disease following kidney transplant. Am J Kidney Dis 60:662-7 |
| Cameron, MaryAnn; Maalouf, Naim M; Poindexter, John et al. (2012) The diurnal variation in urine acidification differs between normal individuals and uric acid stone formers. Kidney Int 81:1123-30 |
| Sakhaee, Khashayar; Capolongo, Giovanna; Maalouf, Naim M et al. (2012) Metabolic syndrome and the risk of calcium stones. Nephrol Dial Transplant 27:3201-9 |
| Nguyen, Trang Q; Maalouf, Naim M; Sakhaee, Khashayar et al. (2011) Comparison of insulin action on glucose versus potassium uptake in humans. Clin J Am Soc Nephrol 6:1533-9 |
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