Abstract:
BACKGROUND:Disorders that manifest hypokalemic metabolic alkalosis, such as Bartter's syndrome and Gitelman's syndrome, are caused by the malfunction of renal tubular electrolyte transporters. Bartter's syndrome may be linked to dysfunction of Na-K-2Cl cotransporter (NKCC2), renal outer medullary K channel (ROMK), or Cl channel Kb (ClC-Kb), while Gitelman's syndrome may be linked to Na-Cl cotransporter (NCCT) dysfunction. However, previous genetic analyses in these syndromes have included many heterozygotes for each gene and there has been no further analysis of other genes. Thus, to clarify the interaction of these transporter genes, in the present study we investigated all 4 transporter genes in 7 patients with hypokalemic metabolic alkalosis. METHODS:Seven patients from 5 families (patients A-G) were collected, and a mutation analysis of the 4 renal electrolyte transporter genes was performed by direct sequencing. RESULTS:We identified 12 mutations in these 7 patients. Three mutations (del245Y in NKCC2, R1009X in NCCT, V524I in ClC-Kb) have not been reported previously. In NKCC2 gene screening, patient A was homozygous for del245Y. In ClC-Kb gene screening, L27R was detected in patients B, D, and E. V524I was detected in patient C. Both T562M and E578K were observed in patients B and E. In NCCT gene screening, patients B-G shared a common novel mutation, R1009X, and patients D, E, F, and G carried this mutation in both alleles. Patients B and C carried R1009X in one allele, and a 6-amino acid insertion in exon 6 and L849H in another allele, respectively. The 4 other mutations did not result in any amino acid exchange. Despite the NCCT gene mutation, patients C and E showed normomagnesemia. CONCLUSION:Our findings demonstrate that in Bartter's and Gitelman's syndromes, it may not be uncommon to see mutations in several causative transporter genes.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Fukuyama S,Okudaira S,Yamazato S,Yamazato M,Ohta Tdoi
10.1046/j.1523-1755.2003.00163.xsubject
Has Abstractpub_date
2003-09-01 00:00:00pages
808-16issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49401-3journal_volume
64pub_type
杂志文章abstract::Recent linkage analyses of nondiabetic African-American patients with focal segmental glomerulosclerosis (FSGS) have identified MYH9, encoding nonmuscle myosin heavy chain IIA (NMMHC-IIA), as a gene having a critical role in this disease. Abnormalities of the MYH9 locus also underlie rare autosomal dominant diseases s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.21
更新日期:2010-07-01 00:00:00
abstract::Ischemia-reperfusion occurs in a great many clinical settings and contributes to organ failure or dysfunction. CD154-CD40 signaling in leukocyte-endothelial cell interactions or T-cell activation facilitates tissue inflammation and injury. Here we tested a siRNA anti-CD40 in rodent warm and cold ischemia models to che...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.146
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:Proteinase 3 is the major autoantigen in Wegener's granulomatosis (WG). Membrane PR3 expression is bimodal; low expressing cells (mPR3(low)) can be distinguished from cells with high expression (mPR3(high)) within a given individual. High mPR3 expression is a WG risk factor and is associated with relapse. Ho...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00640.x
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND:Low dialysate calcium (LdCa) concentration is used to prevent or treat hemodialysis (HD)-induced hypercalcemia, but its use has been complicated by intradialytic hypotension in some patients. Our goal was to explore the possibility that dialysis calcium profiling (dCaP) can ameliorate intradialytic hypotensi...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2002.00100.x
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:It is known that inhibition of cyclooxygenase (COX) impairs the renal actions of loop diuretics. Recently, we found that cyclosporine A (CsA) inhibits renal COX-2 expression. Therefore, we examined the interferences of CsA with the renal actions of loop diuretics. METHOD:We investigated the renal effects of...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00627.x
更新日期:2004-06-01 00:00:00
abstract::Disasters result in a substantial number of renal challenges, either by the creation of crush injury in victims trapped in collapsed buildings or by the destruction of existing dialysis facilities, leaving chronic dialysis patients without access to their dialysis units, medications, or medical care. Over the past two...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2013.392
更新日期:2014-05-01 00:00:00
abstract::We have developed an immunological procedure for measuring advanced glycosylation end-products (AGEs) in serum. Using this method, we measured AGEs in healthy volunteers, patients with diabetes, renal failure without treatment and in patients with renal failure, treated with hemodialysis (HD) or continuous ambulatory ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.262
更新日期:1994-07-01 00:00:00
abstract::Insulin resistance from chronic kidney disease (CKD) stimulates muscle protein wasting but mechanisms causing this resistance are controversial. To help resolve this, we used microarray analyses to identify initiators of insulin resistance in the muscles of mice with CKD, glucose intolerance, and insulin resistance. C...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.97
更新日期:2013-08-01 00:00:00
abstract::In view of the increasing concern about methicillin-resistant Staphylococcus aureus (MRSA) infections, we studied the characteristics and outcome of MRSA nasal carriage and infections in our CAPD program. All patients entering into the CAPD program from January 1989 to December 1991 were enrolled into the study. The p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.191
更新日期:1993-06-01 00:00:00
abstract::The prevalence of raised Na+/Li+ countertransport (CT) activity (greater than 0.41 mmol/liter RBC/hr) was assessed in 185 consecutive insulin-dependent diabetic patients attending an outpatient diabetic clinic. Normoalbuminuria was defined as an overnight albumin excretion rate (AER) of less than 20 micrograms/min (N ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.134
更新日期:1992-04-01 00:00:00
abstract::The metabolism of phenylalanine and tyrosine was evaluated in six normal men, five chronically uremic men, and three men undergoing maintenance hemodialysis. Phenylalanine, tyrosine, and 13 acidic metabolites of those amino acids were measured in plasma postabsorptively and in plasma and urine after a phenylalanine lo...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1978.104
更新日期:1978-08-01 00:00:00
abstract::The following bone density measurements have limited utility in determining bone strength because they do not include bone quality: microarchitecture, mineralization, ability to repair damage, collagen structure, crystal size, or marrow composition. Patients with kidney disease have poor bone quality. Newman et al. no...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2015.11.004
更新日期:2016-01-01 00:00:00
abstract::Dihydrotestosterone (DHT) binding studies and the effects of DHT on the expression of beta-glucuronidase (Gus) and kidney androgen-regulated protein (KAP) genes and cell growth were investigated in immortalized early PKSV-PCT and late PKSV-PR proximal tubule cells, derived from transgenic mice carrying the L-pyruvate ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00721.x
更新日期:1998-01-01 00:00:00
abstract::The purpose of these studies was to clarify the basis of the relationship between the urine bicarbonate concentration and the urine minus blood PCO2 difference in alkaline urine (U-B PCO2) and hence shed light on factors that influence hydrogen ion secretion in the collecting duct in vivo. The U-B PCO2 was used to mon...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.187
更新日期:1981-11-01 00:00:00
abstract::Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outc...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2015.12.001
更新日期:2016-03-01 00:00:00
abstract::Electron microprobe analysis on freeze-dried cryosections was used to determine the effect of the loop diuretics torasemide and furosemide on intracellular electrolyte concentrations in individual cells of the outer and inner stripe of the outer medulla and on cell rubidium uptake, the latter a measure of basolateral ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.359
更新日期:1992-10-01 00:00:00
abstract::A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy (MGN) was carried out to determine whether cyclosporine (D) would be more effective than placebo (P) in reducing the rate of deterioration in renal function. Patients (N = 64) with MGN were placed on a restricted protein d...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1995.161
更新日期:1995-04-01 00:00:00
abstract::Organomercurial diuretics stimulate renin secretion although the underlying cellular mechanisms remain undefined. Since organomercurials are also known to react with sulfhydryl groups, the present studies determined the effects of sulfhydryl reagents on renin secretion. The effects of the non-diuretic mercurial agent,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.57
更新日期:1989-03-01 00:00:00
abstract::Serum calcitriol and the free calcitriol index together with factors considered to regulate calcitriol production were measured in eleven patients with moderate chronic renal failure (MCRF) and eleven age- and sex-matched normal subjects. Although the serum dialysable calcium levels were similar in the two groups, the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.58
更新日期:1988-03-01 00:00:00
abstract:BACKGROUND:Renal salt wasting and hypotension are some of the frequent complications in patients treated with cis-diamminedichloroplatinum (II) (cDDP), and it is suggested that cDDP produces an abnormality in the renin-angiotensin system. However, not only the underlying mechanism but also prophylactic treatment of thi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00307.x
更新日期:2000-10-01 00:00:00
abstract::Mutations in the complement regulatory proteins are associated with several different diseases. Although these mutations cause dysregulated alternative pathway activation throughout the body, the kidneys are the most common site of injury. The susceptibility of the kidney to alternative pathway-mediated injury may be ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.02.036
更新日期:2016-07-01 00:00:00
abstract::The early identification of renal transplant recipients at enhanced risk of developing acute and subclinical rejection would allow individualized adjustment of immunosuppression before functional graft injury occurs and would exclude these patients from drug-weaning studies. Protein and reverse transcriptase-polymeras...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000343
更新日期:2006-05-01 00:00:00
abstract::Mitochondrial diseases represent a significant clinical challenge. Substantial efforts have been devoted to identifying therapeutic strategies for mitochondrial disorders, but effective interventions have remained elusive. Recently, we reported attenuation of disease in a mouse model of the human mitochondrial disease...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.08.038
更新日期:2019-02-01 00:00:00
abstract::Recent advances have led to a greater appreciation of how mitochondrial dysfunction contributes to diverse acute and chronic pathologies. Indeed, mitochondria have received increasing attention as a therapeutic target in a variety of diseases because they serve as key regulatory hubs uniquely situated at crossroads be...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2017.05.034
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:It is currently impossible to reliably predict which diabetic patients will develop nephropathy and progress to kidney failure. Microalbuminuria, often regarded as a predictor of overt diabetic renal disease is, in fact, an indicator of established glomerular damage. We have shown that glomerular expression ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00130.x
更新日期:2003-08-01 00:00:00
abstract::The interaction of 15-hydroxyeicosatetraenoic acid (15-HETE) and cultured MDCK renal tubular epithelial cells was investigated to determine whether incorporation of this lipoxygenase product will affect polyphosphoinositide formation. MDCK cells were incubated with 1 microM [3H]-15-HETE for 15 to 120 minutes. Maximum ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.131
更新日期:1994-04-01 00:00:00
abstract::The kidneys excrete the daily acid load mainly by generating and excreting ammonia but the underlying molecular mechanisms are not fully understood. Here we evaluated the role of the inwardly rectifying potassium channel subunit Kir4.2 (Kcnj15 gene product) in this process. In mice, Kir4.2 was present exclusively at t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.09.028
更新日期:2020-02-01 00:00:00
abstract::The clinical utility of cisplatin is limited by nephrotoxicity. Oh et al. report that β-lapachone prevents this nephrotoxicity but not cisplatin's cytotoxicity for cancers. In addition to its potential clinical importance, the beneficial effect of β-lapachone on cisplatin acute kidney injury may illustrate fundamental...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.419
更新日期:2014-03-01 00:00:00
abstract::The effects of two models of chronic hypercalcemia on renal acid-base metabolism were studied in rats. In the first series of experiments, rats were rendered hyperparathyroid by the autologous grafting of 20 to 24 parathyroid glands into a single recipient. Hypercalcemia (5.48 +/- 0.03 mEq/liter in high PTH animals, 4...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.68
更新日期:1982-04-01 00:00:00
abstract::Proteinuric diabetic patients have an increased risk of cardiovascular disease and almost always have hypertension. In the early stages of diabetic renal disease (microalbuminuria) when renal function is well preserved, systemic arterial blood pressure is already elevated compared to insulin-dependent diabetic patient...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1994.56
更新日期:1994-02-01 00:00:00