Calcium transport in the pars recta and thin descending limb of Henle of the rabbit, perfused in vitro.

Rouse, D.; Ng, Roland C.K.; Suki, Wadi N.

doi:10.1172/jci109657

Cited by 71 publications

(31 citation statements)

References 18 publications

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“…Whether or not this relationship is disrupted, in part, by active calcium transport in the S3 segment (31), as has been demonstrated in perfused rabbit S3 segments, cannot be determined in humans at the present time. Likewise, under conditions of diuretic-induced volume contraction, lithium reabsorption in the distal nephron via ENaC-mediated transport may render interpretation of lithium clearance less certain as a marker of proximal tubule reabsorption (18,35).…”

Section: F595 Thiazide Increases Proximal Tubule Calcium Reabsorptionmentioning

confidence: 74%

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 Reabsorptionmentioning

confidence: 74%

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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“…It should be immediately emphasized that this approach did not entirely exclude rats with AH or resorptive hypercalciuria. Calculations indicate that even on a 0.03% Ca diet, the amount of Ca ingested per rat (average of [15][16][17][18][19][20] g of food) ranged between 4 and 6 mg/d, whereas the amount of Ca excreted varied from 0.6 to 2.0 mg/d. Accordingly, on this diet urine Ca accounts for only 10-50% of the diet Ca, values that are more in the same order of magnitude as for the adult man.…”

Section: Discussionmentioning

confidence: 99%

“…Several attempts were made (either between the same pair of breeders or between breeders within the same categories) to yield a total of [15][16][17][18][19][20][21][22][23][24][25] offspring of a given sex within a given group.…”

Section: Methodsmentioning

confidence: 99%

Tubular Mechanism for the Spontaneous Hypercalciuria in Laboratory Rat

Lau¹,

Eby²

1982

J. Clin. Invest.

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A B S T R A C T Recently it has been observed that Ca excretion in laboratory rats does not follow a Gaussian distribution, with -10% of them excreting Ca at a rate of 2 SD above the group mean. This phenomenon has been described as spontaneous hypercalciuria (SH). Our studies were designed to define its mechanism. 48 Wistar rats were subjected to metabolic studies to identify SH, prospectively defined as Ca excretion 2 SD above the group mean during 7 d of dietary Ca deprivation (<0.03% by analysis), in the absence of hypercalcemia, P04 depletion, or exaggerated natriuresis.Progenies from SH rats were found to have significantly higher urine Ca/creatinine (micrograms per milligram) (male = 38 vs. 23, P < 0.05; female = 79 vs. 60, P < 0.005) with 7/20 males and 9/26 females having values 2 SD above the means of normal. After a 12-h fast and during 10% volume expansion with saline, clearance and micropuncture studies were performed on three groups of acutely parathyroidectomized female rats; (a) normocalciuric (N) progenies from the normal, (b) normocalciuric (NC) progenies from SH, and (c) hypercalciuric (HC) progenies from SH rats. Among these groups, there was no significant difference in body weights, glomerular filtration rate, plasma ultrafiltrable Ca (4.5, 4.6 vs. 4.7 mg/100 g), P04, and the fractional excretion (FE) late distal tubule (6.9 vs. 6.9 and 7.6%, P = NS). Although FECa exceeded late distal FDCa in all three groups, the increment was significantly greater in HC rats (7.02%) than both N (3.4, P < 0.05) and NC rats (3.05, P < 0.02).The effects of chlorothiazide (27.5 mg/kg/d, i.p. X 7 d) were evaluated in the female offsprings of the SH rats. Before chlorothiazide, average urine Ca/creatinine (253 vs. 77.2) and cyclic AMP (26.6 vs. 13.4 jAmol/mg creatinine, P < 0.001) on days 7 and 8 of the Ca-deprived diet were higher than the normal. On days 6 and 7 of chlorothiazide, average cyclic AMP (cAMP) excretion fell to normal range (11.7 vs. 12.7 ,umol/mg creatinine) as Ca excretion was reduced to normal (62 vs. 59.4 tsg Ca/mg creatinine).We conclude: (a) SH, as defined in this study, is an inheritable biochemical marker and renal in origin. (b) The hypercalciuria is independent of parathyroid hormone, changes in plasma Ca and tubular handling of Na. (c) As studied in the PTX and volume expanded conditions of our experiments, decreased Ca reabsorption in superficial proximal convoluted tubule is demonstrable, but the hypercalciuria is probably mediated by diminished Ca transport by the deep nephron. The unlikely possibility of increased secretion by the terminal nephron, however, remains to be excluded. (d) In normal rats, there is internephron heterogeneity in regard to Ca transport during saline loading.

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“…These segments were almost impermeable to Ca2+, as shown by the isolated tubule microperfusion technique [22,24]. Type(2) distribution occurred in the proximal tubules, segments 2 and 3.…”

Section: Localization Of Ca2+in Nephronsmentioning

confidence: 90%

Ultracytochemical Study of the Pathway of Ca2+ Transportation across the Epithelial Cell Layer of a Nephron.

Fujioka

Sasaki

1997

Acta Histochem. Cytochem

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Calcium transport in the pars recta and thin descending limb of Henle of the rabbit, perfused in vitro.

Cited by 71 publications

References 18 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

Tubular Mechanism for the Spontaneous Hypercalciuria in Laboratory Rat

Ultracytochemical Study of the Pathway of Ca2+ Transportation across the Epithelial Cell Layer of a Nephron.

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