Evidence for Secondary Hyperparathyroidism in Idiopathic Hypercalciuria

Coe, Fredric L.; Canterbury, Janet M.; Firpo, John J.; Reiss, Eric

doi:10.1172/jci107156

Cited by 338 publications

(119 citation statements)

References 15 publications

(21 reference statements)

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“…In one study, no change was found in PTH in IH patients during TZ treatment compared with baseline (37). However, in accordance with two other studies, we found a small, but significant, decrease in PTH related to TZ treatment (8,9). In our study, PTH was measured at multiple time points throughout the day, which may facilitate the detection of small, but potentially significant, changes in PTH related to TZ treatment.…”

Section: F595 Thiazide Increases Proximal Tubule Calcium Reabsorptionsupporting

confidence: 90%

Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

Bergsland

Worcester

Coe

2013

American Journal of Physiology-Renal Physiology

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Bergsland KJ, Worcester EM, Coe FL. Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria. Am J Physiol Renal Physiol 305: F592-F599, 2013. First published May 29, 2013 doi:10.1152/ajprenal.00116.2013The most common metabolic abnormality found in calcium (Ca) kidney stone formers is idiopathic hypercalciuria (IH). Using endogenous lithium (Li) clearance, we previously showed that in IH, there is decreased proximal tubule sodium absorption, and increased delivery of Ca into the distal nephron. Distal Ca reabsorption may facilitate the formation of Randall's plaque (RP) by washdown of excess Ca through the vasa recta toward the papillary tip. Elevated Ca excretion leads to increased urinary supersaturation (SS) with respect to calcium oxalate (CaOx) and calcium phosphate (CaP), providing the driving force for stone growth on RP. Thiazide (TZ) diuretics reduce Ca excretion and prevent stone recurrence, but the mechanism in humans is unknown. We studied the effect of chronic TZ administration on renal mineral handling in four male IH patients using a fixed three meal day in the General Clinical Research Center. Each subject was studied twice: once before treatment and once after 4 -7 mo of daily chlorthalidone treatment. As expected, urine Ca fell with TZ, along with fraction of filtered Ca excreted. Fraction of filtered Li excreted also fell sharply with TZ, as did distal delivery of Ca. Unexpectedly, TZ lowered urine pH. Together with reduced urine Ca, this led to a marked fall in CaP SS, but not CaOx SS. Since CaOx stone formation begins with an initial CaP overlay on RP, by lowering urine pH and decreasing distal nephron Ca delivery, TZ might diminish stone risk both by reducing CaP SS, as well as slowing progression of RP. calcium oxalate; calcium phosphate; idiopathic hypercalciuria; kidney calculi; thiazide THE MOST COMMON METABOLIC abnormality found in calcium (Ca) stone formers is so-called idiopathic hypercalciuria (IH) (40). Patients with IH absorb more Ca from a given meal than normal people (N), but also have abnormally decreased renal tubule Ca reabsorption, so that they often excrete more Ca than they have absorbed, exhibit decreased bone density, and have a propensity for increased fractures (22,42). Elevated urine Ca excretion leads to increased urinary supersaturation (SS) with respect to both calcium oxalate (CaOx) and calcium phosphate (CaP), providing the driving force for kidney stone formation (36). In addition, urine Ca excretion is correlated with the amount of interstitial apatite deposits (called Randall's plaque) found on the surface of the renal papillae (19). These deposits are the attachment sites for most CaOx stones and appear to be critical for stone formation (14). A plausible mechanism by which increased Ca reaches the deep papillae is via washdown from reabsorption in the thick ascending limb; an increase in delivery of Ca to this site would tend to increase reabsorption and washdown into the papilla and potentially increase...

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Section: F595 Thiazide Increases Proximal Tubule Calcium Reabsorptionsupporting

confidence: 90%

Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

Bergsland

Worcester

Coe

2013

American Journal of Physiology-Renal Physiology

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“…Although the results are not conclusive, these patients probably suffered from secondary hyperparathyroidism, as in the cases of renal hypercalciuria reported by Coe, Canterbury, Firpo, and Reiss (6). However, the features presented by these patients were the same as those found in patients with "normocalcemic" primary hyperparathyroidism (30).…”

Section: Discussionmentioning

confidence: 54%

“…There are two major proposed causes for the hypercalciuria in idiopathic hypercalciuria. The first is an enhanced intestinal absorption of calcium (absorptive hypercalciuria) (3)(4)(5) and the second is a primary defect in the renal tubular reabsorption of calcium ("renal leak" or renal hypercalciuria) (5,6). However, these pathogenetic mechanisms have not been fully documented or characterized and.…”

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confidence: 99%

“…In contrast, the therapy for absorptive hypercalciuriashould ideally be directed at reducing intestinal absorption of calcium (7). In renal hypercalciuria, the thiazide diuretics have been shown to "correct" both the hypercalciuria and the secondary hyperparathyroidism (6). Unfortunately, it has been often difficult to differentiate the three forms of hypercalciuria, because of the lack of clear-cut diagnostic criteria.…”

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confidence: 99%

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The Hypercalciurias CAUSES, PARATHYROID FUNCTIONS, AND DIAGNOSTIC CRITERIA

Pak¹,

Oata²,

Lawrence³

et al. 1974

J. Clin. Invest.

496

137

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A B S T R A C T The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58+3.63 SD gmol/g creatinine; normal, 4.02±0.70 umol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (CaA), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by 'I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their CaA exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion.of Ca and a suppression of cAMP excretion. The urinary Ca of 453±+154 SD mg/day was significantly higher than the control group's 211+42 mg/ day. The urinary cAMP of 2.26±0.56 umol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hvpercalciuria was kc'ceiz(l for plblicatifn 9 July 1073 and in rezxsed form 11 September 1973. corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since CaA was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their CaA exceeded urinal Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.

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“…This observation suggested that excessive urinary calcium losses in CKD patients, who are prone to tenuous calcium balance because of relative calcitriol deficiency, may promote intermittent reductions in serum calcium with resulting spikes in PTH, which eventually manifest clinically as secondary hyperparathyroidism. This hypothesis is supported by studies in the general population and CKD that showed that excessive calciuria driven by loop diuretics was associated with elevated PTH (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 69%

Daily Variability in Mineral Metabolites in CKD and Effects of Dietary Calcium and Calcitriol

Isakova

Xie

Barchi-Chung

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Primary prevention of disordered mineral metabolism in CKD necessitates knowledge of its early pathophysiology. This study evaluated daily fluctuations in mineral metabolites in patients with CKD stages 3 and 4 before and after short-term calcitriol treatment and tested the effects of dietary calcium and calcitriol supplementation on these parameters in the dynamic postprandial setting.Design, setting, participants, & measurements Twelve CKD patients received calcitriol (0.25 mg daily for 1 week) with hourly assessments of mineral metabolites made throughout the day and in the context of standardized meals before and after treatment. Calcium content (250 versus 500 mg) in the breakfasts constituted the dietary calcium intervention. Twelve healthy volunteers were used as controls.Results At baseline, compared with controls, fasting CKD subjects had higher parathyroid hormone and fibroblast growth factor 23 levels and greater fractional excretion of phosphate. After breakfast, urinary calcium excretion increased and parathyroid hormone levels dipped transiently in both groups, but they rose soon thereafter, reaching higher peaks in CKD. Calcitriol decreased fasting parathyroid hormone levels, and when combined with dietary calcium load, it normalized the postprandial parathyroid and calcemic responses. Daily variability in mineral metabolites was preserved in CKD before and after calcitriol. Fibroblast growth factor 23 levels increased after calcitriol, although the response was heterogeneous.Conclusions Short-term treatment with calcitriol and dietary calcium supplementation normalizes the parathyroid and calcemic postprandial responses in patients with CKD, in whom the diurnal rhythms of mineral metabolites are preserved. Future studies should investigate the variable fibroblast growth factor 23 response to calcitriol in CKD.

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Evidence for Secondary Hyperparathyroidism in Idiopathic Hypercalciuria

Abstract: A B S T R A C T Circulating levels of immunoreactive

Cited by 338 publications

References 15 publications

Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria

The Hypercalciurias CAUSES, PARATHYROID FUNCTIONS, AND DIAGNOSTIC CRITERIA

Daily Variability in Mineral Metabolites in CKD and Effects of Dietary Calcium and Calcitriol

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