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Query: UMLS:C0020438 (
hypercalciuria
)
2,502
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Pseudohypoaldosteronism (PHA) type II is an extremely rare disorder which presents with hypertension, hyperkalemia, and normal anion gap metabolic acidosis. PHA II is also known as familial hyperkalemic hypertension, Gordon syndrome, and chloride shunt syndrome. PHA II is an autosomal dominant disorder and is caused by mutation in WNK1, WNK4, CULLIN3,
KLHL3
, OSR, SPAK gene. The expression of these proteins is limited to the distal convoluted tube and collecting duct of the kidney. PHA II usually responds to salt restriction and thiazide diuretics. We are reporting here a case of 16-year girl who presented with generalised fatigue and shortness of breath, and blood pressure (BP) of 220/110 mmHg. Laboratory investigation showed hyperkalemia, normal anion gap metabolic acidosis, and
hypercalciuria
. Workup for secondary causes of hypertension was negative. She responded to thiazide diuretics and her BP is well controlled, and acidosis and hyperkalemia are corrected.
...
PMID:Pseudohypoaldosteronism Type II: A Young Girl Presented with Hypertension, Hyperkalemia and Metabolic Acidosis. 2948 94
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
