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Query: UMLS:C0020438 (
hypercalciuria
)
2,502
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hypercalciuria
is the most common metabolic abnormality that causes urolithiasis. The pathogenetic mechanisms responsible for
hypercalciuria
include enhanced gastrointestinal absorption of calcium, increased bone resorption and/or decreased renal reabsorption of calcium; the main dietary factors promoting
hypercalciuria
are high dietary sodium intake and protein-rich diet. The authors discuss pathophysiology of
hypercalciuria
and genetic factors behind 'idiopathic
hypercalciuria
'. The simplified diagnostic approach to
hypercalciuria
is outlined herein, and available therapeutic interventions of proven efficacy in idiopathic
hypercalciuria
are presented as well. Dietary intervention for
hypercalciuria
should include reduced sodium, protein and oxalate intake.
Thiazide
diuretics, in conjunction with a low-sodium diet, tend to reduce urinary calcium excretion and ameliorate idiopathic
hypercalciuria
. Potassium citrate acts as an inhibitor of calcium stone formation in the urinary tract. A low-calcium diet should generally be avoided, as it may increase urinary oxalate excretion and actually promote stone formation. In addition, a low-calcium diet may lead to negative calcium balance in subjects with
hypercalciuria
, and therefore increases the risk of osteopenia.
...
PMID:[Hypercalciuria]. 2175 20
The 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.
...
PMID:Role of proximal tubule in the hypocalciuric response to thiazide of patients with idiopathic hypercalciuria. 2372 Mar 47
There is a growing recognition that children with Lowe syndrome are at risk of nephrocalcinosis and nephrolithiasis from
hypercalciuria
. Increased fluid intake and correction of metabolic acidosis have remained the focus for intervention but are not always successful.
Thiazide
diuretics, which reduce urinary calcium excretion, have not been used in these children, due to concerns that (i) they may not work as a result of the underlying tubular abnormalities and (ii) their risk may outweigh the potential benefits they have to offer. Herein we report a child with Lowe syndrome who was successfully treated with thiazides in managing his
hypercalciuria
.
...
PMID:Hydrochlorothiazide reduces urinary calcium excretion in a child with Lowe syndrome. 2625 18
Background
Hypercalciuria
can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle's loop controls Ca
2+
excretion and NaCl reabsorption in response to extracellular Ca
2+
However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss.
Methods
We used a combination of
in vitro
and
in vivo
models to examine the effects of CaSR on NCC activity. Because the KLHL3-WNK4-SPAK pathway is involved in regulating NaCl reabsorption in the DCT, we assessed the involvement of this pathway as well.
Results
Thiazide
-sensitive
22
Na
+
uptake assays in
Xenopus laevis
oocytes revealed that NCC activity increased in a WNK4-dependent manner upon activation of CaSR with Gd
3+
In HEK293 cells, treatment with the calcimimetic R-568 stimulated SPAK phosphorylation only in the presence of WNK4. The WNK4 inhibitor WNK463 also prevented this effect. Furthermore, CaSR activation in HEK293 cells led to phosphorylation of KLHL3 and WNK4 and increased WNK4 abundance and activity. Finally, acute oral administration of R-568 in mice led to the phosphorylation of NCC.
Conclusions
Activation of CaSR can increase NCC activity
via
the WNK4-SPAK pathway. It is possible that activation of CaSR by Ca
2+
in the apical membrane of the DCT increases NaCl reabsorption by NCC, with the consequent, well known decrease of Ca
2+
reabsorption, further promoting
hypercalciuria
.
...
PMID:The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway. 2984 7
Thiazide
and thiazide-like diuretics are widely used for the management of
hypercalciuria
among stone-forming patients. Although the effects of different thiazides should be relatively similar in terms of prevention of stone recurrence, their potency and side effects may differ. However, there is scarce data concerning the metabolic and bone effects of these agents among recurrent nephrolithiasis patients with
hypercalciuria
. The aim of this update article was to compare our experience in the use of thiazide and thiazide- like diuretics with that of the current literature, concerning their anticalciuric properties and consequent reduction of recurrent stone formation. Their impact on bone mass and potential side effects were also discussed.
...
PMID:Thiazide and thiazide-like diuretics in nephrolithiasis. 3317 17
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