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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gitelman's syndrome is an autosomal recessive disorder characterized by sodium wasting and hypotension. A middle-aged woman was diagnosed with Gitelman's syndrome because of typical clinical manifestations in the youth and homozygous mutations of 18-base-pair insertion in exon 6 of thiazide-sensitive NaCl-cotransporter gene. It was unusual that she showed hypertension with advancing age. Her serum potassium levels remained low at around 3.5 mEq/l despite potassium supplementation. This case demonstrates that hypertension could result in spite of the extremely decreased sodium reabsorption in Gitelman's syndrome and that essential hypertension is genetically heterogeneous, and abnormality of all genes may not be necessarily required to cause blood pressure rise.
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PMID:Hypertension in a patient with Gitelman's syndrome. 1500 4

TWO FORMS: Pseudohypoaldosteronisms (PHA) are characterized by end-organ resistance to aldosterone inducing hyperkalemia and hyperaldosteronism. There are two forms of PHA classified according to the level of blood pressure with either hypotension (Type 1 PHA or PHA 1) or hypertension (Type 2 PHA or PHA 2). PHA 1: The association with hypotension and high renin level (PHA 1) is responsible for type 4 tubular acidosis and should suggest congenital or acquired excessive salt loss. Acquired forms are associated with salt wasting of urinary (nephropathy) or digestive (colon resection + ileostomy) origin. Congenital neonatal forms are either sporadic or autosomal dominant or recessive. Sporadic or autosomal dominant forms are caused by mutations in the mineralocorticoid receptor gene and generally remit with age. Autosomal recessive forms are caused by mutations in the gene encoding the amiloride-sensitive sodium channel and are clinically more severe with pulmonary symptoms. PHA 2: The association of hyperkalemia/hyperaldosteronism with high blood pressure should suggest PHA 2 or Gordon's syndrome, still called familial hyperkalemic hypertension. This form of low-renin hypertension is caused by mutations in the WNK genes (WNK 1 for PHA 2C and WNK 4 for PHA 2B), but other genes located on different loci are also involved. These WNK kinases constitute a new signalisation pathway that would regulate blood pressure and homeostasy of Na+, K+, H+ and Cl- ions.
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PMID:[Pseudo-hypoaldosteronisms]. 1502 8

The chloride channel ClC-Kb is expressed in the basolateral cell membrane of the distal nephron and participates in renal NaCl reabsorption. Loss-of-function mutations of ClC-Kb lead to classic Bartter syndrome, a rare salt-wasting disorder. Recently, we identified the ClC-Kb(T481S) polymorphism, which confers a strong gain-of-function effect on the ClC-Kb chloride channel. The present study has been performed to explore the prevalence of the mutation and its functional significance in renal salt handling and blood pressure regulation. As evident from electrophysiological analysis with the 2-electrode voltage-clamp technique, heterologous expression of ClC-Kb(T481S) in Xenopus oocytes gave rise to a current that was 7-fold larger than the current produced by wild-type ClC-Kb. The prevalence of the mutant allele was significantly higher in an African population from Ghana (22%) than in whites (12%). As tested in 1 white population, carriers of ClC-Kb(T481S) were associated with significantly higher systolic (by approximately 6.0 mm Hg) and diastolic (by approximately 4.2 mm Hg) blood pressures and significantly higher prevalence (45% versus 25%) of hypertensive (> or =140/90 mm Hg) blood pressure levels. Individuals carrying ClC-Kb(T481S) had significantly higher plasma Na+ concentrations and significantly decreased glomerular filtration rate. In conclusion, the mutation ClC-Kb(T481S) of the renal epithelial Cl- channel ClC-Kb strongly activates ClC-Kb chloride channel function in vitro and may predispose to the development of essential hypertension in vivo.
Hypertension 2004 Jun
PMID:Activating mutation of the renal epithelial chloride channel ClC-Kb predisposing to hypertension. 1644 91

Hypokalemic paralysis is a medical emergency due to the risks of cardiac arrhythmia, respiratory failure, and rhabdomyolysis. Besides supplementing patients with KCl to hasten recovery, the astute physician must search for the underlying cause to avoid missing a treatable and curable disorder. We report on an elderly Korean man who presented with marked limb paralysis, myalgias, and mild hypertension. He had prostate cancer treated with orchiectomy and hormone therapy 2 years previously. The major biochemical abnormalities were hypokalemia (K+: 1.7 mmol/l) associated with high renal K+ wasting and metabolic alkalosis (HCO3-: 42.6 mmol/l). Low plasma renin activity, low aldosterone concentration, and normal cortisol concentration pointed to a state of pseudohyperaldosteronism. While reviewing his drug history, the patient revealed he had been consuming eight packs (100 ml/pack) of a Korean herbal tonic daily to treat his prostate cancer for the past 2 months. A significant amount of glycyrrhizic acid (0.23 mg/ml), an active ingredient of licorice, was detected in the tonic. Discontinuation of the herbal tonic along with KCl supplementation achieved recovery in 2 weeks. As many complementary/alternative medicines for cancer contain licorice, this must be kept in mind as a cause of hypokalemia in cancer patients.
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PMID:A hidden cause of hypokalemic paralysis in a patient with prostate cancer. 1535 80

Primary hyperaldosteronism or Conn's syndrome is rare after renal transplantation. We present a case of a 34-year-old woman with end-stage renal disease, who had received a living renal transplant and showed persistent hypertension and hypokalemia. The common causes of hypertension after kidney transplantation were excluded and hypokalemia persisted despite potassium supplementation and angiotensin converting enzyme inhibitors. Biochemical findings revealed extremely elevated plasma aldosteron levels, suppressed plasma renin activity, and massive urinary potassium wasting. Abdominal computerized tomography scan showed a left 25-mm adrenal nodule. Her hypertension and hypokalemia was cured by the removal of the adenoma.
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PMID:Renal transplantation unveils Conn's syndrome: a case report. 1562 Nov 24

We present a successful pregnancy in a 37-year-old women with severe renal impairment due to medullary cystic disease. She presented five years earlier with hypertension and chronic renal failure with creatinine was 2.1 mg/dl (Ccr 35 ml/min). She had had two successful pregnancies in the past, nine and seven years earlier. Diagnosis of medullary cystic disease (MCD) was made based on typical ultrasound appearance, sodium wasting and acidosis out of the proportion to the degree of renal failure. Over the next 5 years, a slow progression of chronic renal failure was observed with creatinine reaching 5.1 mg/dl (Ccr 15,4 ml/min), shortly before she became pregnant in December 2001. Her hypertension remained well-controlled and serum creatinine decreased at the beginning of the second trimester to 3.7 mg/dl with subsequent increase toward the end of the pregnancy. She required increasing doses of erythropoietin and intravenous iron supplementation to maintain hemoglobin levels. The polyhydramnios developed necessitating five procedures of amnio reduction. She was not treated by dialysis. A boy weighing 1,600 g was delivered by cesarean section in the 35th week of gestation. The mother's creatinine rose to 5.2 mg/dl (Ccr 15 ml/min) post partum and her renal function declined only slightly over the next 20 months. Our report illustrates that successful fetal and maternal outcome can be achieved even in cases of advanced renal failure preceding gestation. It appears that the type of renal disease influences the pregnancy course and outcome and thus should be considered in patient counseling and therapeutic decisions.
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PMID:Successful pregnancy in a patient with medullary cystic disease and severe renal impairment. 1567 98

Glucocorticoid-remediable aldosteronism (GRA) is a monogenic form of human hypertension that predisposes to cerebral hemorrhage. As a result of a chimeric gene duplication, aldosterone is ectopically synthesized in the cortisol-secreting zona fasciculata of the adrenal gland under the control of adrenocorticotropin (ACTH). Hypertension frequently has its onset during childhood and is usually refractory to standard anti-hypertensives such as ACE inhibitors and beta-blockers. Hypokalemia can develop in those treated with a potassium-wasting diuretic, but random potassium levels are usually normal. Diagnosis has been facilitated by the availability of a genetic test. Suppression of ACTH release with exogenous dexamethasone is a useful diagnostic and therapeutic strategy. Treatment with the mineralocorticoid receptor antagonists spironolactone and epleronone is also efficacious. The diagnosis of GRA facilitates directed therapies and screening of at-risk individuals and kindreds.
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PMID:Glucocorticoid-remediable aldosteronism. 1576 39

A simulation of the rat distal convoluted tubule (DCT) is completed with a model of the late portion, or connecting tubule (CNT). This CNT model is developed by relying on a prior cortical collecting duct (CCD) model (Weinstein AM. Am J Physiol Renal Physiol 280: F1072-F1092, 2001), and scaling up transport activity of the three cell types to a level appropriate for DCT. The major difference between the two tubule segments is the lower CNT water permeability. In early CNT the luminal solution is hypotonic, with a K(+) concentration less than that of plasma, and it is predicted that osmotic equilibration requires the whole length of CNT, to end with a nearly isotonic fluid, whose K(+) concentration is severalfold greater than plasma. With respect to potassium secretion, early CNT conditions are conducive to maximal fluxes, whereas late conditions require the capacity to transport against a steep electrochemical gradient. The parameter dependence for K(+) secretion under each condition is different: maximal secretion depends on luminal membrane K(+) permeability, but the limiting luminal K(+) concentration does not. However, maximal secretion and the limiting gradient are both enhanced by greater Na(+) reabsorption. While higher CNT water permeability depresses K(+) secretion, it favors Na(+) reabsorption. Thus in antidiuresis there is a trade-off between enhanced Na(+)-dependent K(+) secretion and the attenuation of K(+) secretion by slow flow. When the CNT model is configured in series with the early DCT, thiazide diuretics promote renal K(+) wasting by shifting Na(+) reabsorption from early DCT to CNT; they promote alkalosis by shifting the remaining early DCT Na(+) reabsorption to Na(+)/H(+) exchange. This full DCT is suitable for simulating the defects of hyperkalemic hypertension, but the model offers no suggestion of a tight junction abnormality that might contribute to the phenotype.
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PMID:A mathematical model of rat distal convoluted tubule. II. Potassium secretion along the connecting segment. 1585 58

Several monogenic hypertensive disorders are caused by genetic mutations leading to the deranged function and/or regulation of renal tubular NaCl transport, such as mutations of the renal epithelial Na+ channel (ENaC) in Liddle syndrome, of the kinase WNK1 (with no K) in Gordon syndrome, and of the mineralocorticoid receptor, or of 11beta-hydroxysteroid dehydrogenase. Moreover, excessive formation of aldosterone in glucocorticoid-remediable hypertension leads to severe hypertension. Conversely, impaired function of the Na+,K+,2Cl- cotransporter (NKCC2), the renal outer medullary K+ channel (ROMK1), and the renal epithelial Cl- channel ClCKb/Barttin causes Bartter syndrome and defective Na+,Cl+ cotransporter (NCCT) Gitelman syndrome, salt-wasting disorders with hypotension. These monogenic disorders are rare, but illustrate the significance of renal tubular transport in blood pressure regulation. There is little doubt, however, that deranged renal salt reabsorption significantly contributes to essential hypertension polymorphisms of several genes participating in the regulation of renal Na+ transport have been shown to be associated with blood pressure and prevalence of hypertension. Two common genes will be discussed in more detail. The first encodes the renal Cl- channel ClCKb. A gain-of-function mutation of ClCKb, increasing channel activity by 7- to 20-fold is found in approximately 20% of unselected Caucasians and 40% of an unselected African population. The second common gene variant (prevalence, 3%-5% in unselected Caucasians), to be discussed in more detail, affects the serum and glucocorticoid inducible kinase SGK1, a kinase upregulated by mineralocorticoids and enhancing the activity of ENaC, ROMK, and Na+/K+ATPase. Both gene variants are associated with slightly increased blood pressure. SGK1 further stimulates the glucose transporter SGLT1, and the SGK1 gene variant correlates, in addition, with increased body mass index.
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PMID:Renal tubular transport and the genetic basis of hypertensive disease. 1598 Sep 41

The objective of this article is to relate the diagnostic and clinical evolution of a 15 year old patient with a congenital adrenal steroidogenesis dysfunction that can present as hypertension diagnosed later in life (adolescence), virilization or salt wasting (birth and childhood).
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PMID:[Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency]. 1642 3


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