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Item Pathophysiology-based treatment of idiopathic calcium kidney stones(American Society of Nephrology, 2011-08) Coe, Fredric L.; Evan, Andrew; Worcester, Elaine; Anatomy and Cell Biology, School of MedicineIdiopathic calcium oxalate (CaOx) stone-formers (ICSFs) differ from patients who make idiopathic calcium phosphate (CaP) stones (IPSFs). ICSFs, but not IPSFs, form their stones as overgrowths on interstitial apatite plaque; the amount of plaque covering papillary surface is positively correlated with urine calcium excretion and inversely with urine volume. The amount of plaque predicts the number of recurrent stones. The initial crystal overgrowth on plaque is CaP, although the stone is mainly composed of CaOx, meaning that lowering supersaturation (SS) for CaOx and CaP is important for CaOx stone prevention. IPSFs, unlike ICSFs, have apatite crystal deposits in inner medullary collecting ducts, which are associated with interstitial scarring. ICSFs and IPSFs have idiopathic hypercalciuria, which is due to decreased tubule calcium reabsorption, but sites of abnormal reabsorption may differ. Decreased reabsorption in proximal tubules (PTs) delivers more calcium to the thick ascending limb (TAL), where increased calcium reabsorption can load the interstitium, leading to plaque formation. The site of abnormal reabsorption in IPSFs may be the TAL, where an associated defect in bicarbonate reabsorption could produce the higher urine pH characteristic of IPSFs. Preventive treatment with fluid intake, protein and sodium restriction, and thiazide will be effective in ICSFs and IPSFs by decreasing urine calcium concentration and CaOx and CaP SS and may also decrease plaque formation by increased PT calcium reabsorption. Citrate may be detrimental for IPSFs if urine pH rises greatly, increasing CaP SS. Future trials should examine the question of appropriate treatment for IPSFs.Item Presentation of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Third International Workshop(Endocrine Society, 2009-02) Silverberg, Shonni J.; Lewiecki, E. Michael; Mosekilde, Leif; Peacock, Munro; Rubin, Mishaela R.; Medicine, School of MedicineBACKGROUND: At the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (PHPT) in May 2008, recent data on the disease were reviewed. We present the results of a literature review on issues arising from the clinical presentation and natural history of PHPT. METHODS: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was reviewed, and the questions of the International Task Force were addressed by the Consensus Panel. CONCLUSIONS: 1) Data on the extent and nature of cardiovascular involvement in those with mild disease are too limited to provide a complete picture. 2) Patients with mild PHPT have neuropsychological complaints. Although some symptoms may improve with surgery, available data remain inconsistent on their precise nature and reversibility. 3) Surgery leads to long-term gains in spine, hip, and radius bone mineral density (BMD). Because some patients have early disease progression and others lose BMD after 8-10 yr, regular monitoring (serum calcium and three-site BMD) is essential in those followed without surgery. Patients may present with normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism). Data on the incidence and natural history of this phenotype are limited. 4) In the absence of kidney stones, data do not support the use of marked hypercalciuria (>10 mmol/d or 400 mg/d) as an indication for surgery for patients. 5) Patients with bone density T-score -2.5 or less at the lumbar spine, hip, or distal one third radius should have surgery.Item Sex differences in proximal and distal nephron function contribute to the mechanism of idiopathic hypercalcuria in calcium stone formers(American Physiological Society, 2015-07-01) Ko, Benjamin; Bergsland, Kristin; Gillen, Daniel L.; Evan, Andrew P.; Clark, Daniel L.; Baylock, Jaime; Coe, Fredric L.; Worcester, Elaine M.; Department of Anatomy & Cell Biology, IU School of MedicineIdiopathic hypercalciuria (IH) is a common familial trait among patients with calcium nephrolithiasis. Previously, we have demonstrated that hypercalciuria is primarily due to reduced renal proximal and distal tubule calcium reabsorption. Here, using measurements of the clearances of sodium, calcium, and endogenous lithium taken from the General Clinical Research Center, we test the hypothesis that patterns of segmental nephron tubule calcium reabsorption differ between the sexes in IH and normal subjects. When the sexes are compared, we reconfirm the reduced proximal and distal calcium reabsorption. In IH women, distal nephron calcium reabsorption is decreased compared to normal women. In IH men, proximal tubule calcium reabsorption falls significantly, with a more modest reduction in distal calcium reabsorption compared to normal men. Additionally, we demonstrate that male IH patients have lower systolic blood pressures than normal males. We conclude that women and men differ in the way they produce the hypercalciuria of IH, with females reducing distal reabsorption and males primarily reducing proximal tubule function.