Abstract:
INTRODUCTION:Thiazide diuretics have the unique characteristic of increasing renal Na+ excretion, while decreasing Ca2+ excretion. However, the molecular mechanism responsible for this thiazide-induced hypocalciuria remains unclear. The present study investigates the effect of thiazides on the expression of the proteins involved in active Ca2+ transport as well as the role of extracellular volume (ECV) status. METHODS:Hydrochlorothiazide (HCTZ), 12 mg/24 hours, was administered during 7 days to Wistar rats by osmotic minipumps. In addition, ECV contraction was either prevented by Na+ repletion or induced by a low-salt diet. Expression levels of the proteins involved in active Ca2+ transport [i.e., epithelial Ca2+ channel (TRPV5/ECaC1), calbindin-D28K, Na+/Ca2+ exchanger (NCX1)], as well as the thiazide-sensitive Na+ Cl- cotransporter (NCC) were determined by real-time quantitative polymerase chain reaction (PCR) and semiquantitative immunohistochemistry. RESULTS:HCTZ significantly reduced urinary Ca2+ excretion (22%+/- 5% relative to controls). Hematocrit was significantly increased, confirming ECV contraction. In addition, Na+ depletion virtually abolished Ca2+ excretion (8%+/- 1%), while Na+ repletion during HCTZ treatment prevented both ECV contraction and hypocalciuria. HCTZ significantly decreased mRNA expression of TRPV5 (71%+/- 6%), calbindin-D28K (53%+/- 6%), NCX1 (51%+/- 8%) and NCC (50%+/- 11%), regardless of ECV status or calciuresis. Immunohistochemistry revealed reduced TRPV5 (43%+/- 2%), calbindin-D28K (59%+/- 1%) and NCC (56%+/- 4%) abundance. Furthermore, during HCTZ treatment, the subset of tubules coexpressing NCC and calbindin-D28K was significantly reduced (43%+/- 5%) and a disturbed cellular localization of NCC was observed. CONCLUSION:These data suggest that ECV contraction is a critical determinant of the thiazide-induced hypocalciuria, which is accompanied by a decreased expression of Ca2+ transport proteins.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Nijenhuis T,Hoenderop JG,Loffing J,van der Kemp AW,van Os CH,Bindels RJdoi
10.1046/j.1523-1755.2003.00128.xsubject
Has Abstractpub_date
2003-08-01 00:00:00pages
555-64issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49361-5journal_volume
64pub_type
杂志文章abstract::Eight patients with chronic renal failure (GFR 18.8 +/- 2.7 ml/min) were randomized to a crossover comparison of a very low protein diet (VLPD) containing 0.28 g protein and 35 kcal per kg per day, plus an isosmolar mixture of either ketoacids (KA) or essential amino acids (EAA). Subjects initiated the diets 14 days b...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1994.157
更新日期:1994-04-01 00:00:00
abstract:BACKGROUND:The pathophysiology of hypertension in patients with chronic kidney disease (CKD) is largely attributed to positive sodium balance. It is unclear how loop diuretics affect fluid volume compartments, especially with respect to their antihypertensive effect. METHODS:Subjects with CKD were administered a singl...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2003.00273.x
更新日期:2003-11-01 00:00:00
abstract::A novel variant of the LLC-PK1 cell line was used to examine directly the mechanism whereby PGF2 alpha and TPA inhibit renal ammoniagenesis. The variant cells, which exhibit a growth pattern and morphology similar to the parent cell line, were isolated by a self selection process utilizing long-term cultures of parent...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.368
更新日期:1994-10-01 00:00:00
abstract::Uracil ribonucleotide-sugars and aminosugars are required for glomerular basement membrane (GBM) biosynthesis. Since these nucleotides are metabolic derivatives of uridine 5'-triphosphate (UTP), we have studied the cellular pools of uridine 5'-diphosphoglucose (UDPG), uridine 5'-diphosphoglucuronic acid (UDPGA), uridi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.146
更新日期:1986-07-01 00:00:00
abstract::The role of endogenous atrial natriuretic peptide (ANP) in the immediate response of sodium excretion to unilateral nephrectomy (UNX) was investigated in anesthetized euvolemic rats through measurement of UNX-induced change in plasma ANP concentration and the response of the remaining kidney to UNX following administr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.178
更新日期:1993-06-01 00:00:00
abstract::The microvillus brush border on the renal proximal tubule epithelium allows the controlled reabsorption of solutes that are filtered through the glomerulus and thus participates in general body homeostasis. Here, using the lipid 5-phosphatase Ship2 global knockout mice, proximal tubule-specific Ship2 knockout mice, an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.01.008
更新日期:2017-07-01 00:00:00
abstract::The present study examined the effect of sodium transport inhibition by amiloride, ouabain, and luminal sodium removal on potassium secretion in isolated cortical collecting tubules from adrenalectomized and DOCA-stimulated rabbits. Collecting tubules from adrenalectomized rabbits had a mean potassium secretion of 3.6...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.96
更新日期:1985-06-01 00:00:00
abstract::Although the pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) remains elusive, multiple epidemiologic, clinical, and experimental studies converge on the common theme of immune dysregulation. Initially, T-cell adaptive immunity was solely emphasized; however, the role of humoral immunity in nephrotic syndro...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.05.031
更新日期:2019-10-01 00:00:00
abstract::The development of donor-specific anti-human leukocyte antigen antibodies (DSAs) following renal transplantation significantly reduces long-term renal graft function and survival. The traditional therapies for antibody-mediated rejection (AMR) have provided inconsistent results and transient effects that may be due to...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2011.502
更新日期:2012-06-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) are key mediators of adverse peritoneal membrane remodeling in peritoneal dialysis eventually leading to ultrafiltration failure. Both are pleiotropic growth factors with cell type-dependent regulation of expression and biological eff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.217
更新日期:2013-12-01 00:00:00
abstract::In uremic patients resistance to the action of insulin has been documented, but it is not known at what stage of renal disease it appears. We therefore examined 29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult polycystic kidney disease (ADPKD) in different stages of renal failure, and in addi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00898.x
更新日期:1998-05-01 00:00:00
abstract::The widths of slit diaphragms in rat glomeruli were quantitatively measured on electron micrographs obtained by the rapid-freezing and freeze-substitution (FS) fixation method and compared to those prepared by conventional chemical fixation procedures, such as tannic acid, glutaraldehyde and osmium tetroxide (TGO) or ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.253
更新日期:1991-10-01 00:00:00
abstract::In six healthy males on a fixed sodium/potassium (Na/K) intake, we studied the relation between plasma K and urine K and Na excretion after an oral K load. Studies were repeated during fludrocortisone (0.5 mg bid) or spironolactone (50 mg qid), that is, after escape from the Na-retaining and Na-excreting effects of th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.235
更新日期:1988-11-01 00:00:00
abstract:BACKGROUND:Atherogenic lipoproteins cause injury to the vascular wall in the early phase of atherogenesis. We assessed the effects of native (nLDL) and oxidized (oxLDL) low-density lipoprotein (LDL) and lipoprotein (a) [Lp(a)] on O2- formation and cell death in cultured human umbilical vein endothelial cells (HUVECs) a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00351.x
更新日期:1999-04-01 00:00:00
abstract::The essential role of the glycoprotein hormone erythropoietin (Epo) in the control of red blood cell production is well established. Synthesis of Epo is induced in response to low oxygen (hypoxia). In response to stimulation, increases in serum Epo levels are paralleled by changes in the abundance of Epo mRNA. These c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.70
更新日期:1997-02-01 00:00:00
abstract::Obesity could affect associations between creatinine generation, estimated body surface area, and excretory burden, with effects on chronic kidney disease assessment. We therefore examined the impact of obesity on the performances of estimated glomerular filtration rate (eGFR), the urine albumin:creatinine ratio (ACR)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.112
更新日期:2014-12-01 00:00:00
abstract:INTRODUCTION:Transforming growth factor-beta (TGF-beta) is known to play a pivotal role in the regulation of extracellular matrix (ECM) accumulation. Since diabetic nephropathy (DMN) is characterized by basement membrane thickening and mesangial expansion, control of ECM deposition is believed to be important in the pa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00919.x
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Immune response to oxidized low-density lipoprotein (oxLDL) may modulate the process of atherogenesis and cardiovascular disease. METHODS:We performed a prospective, observational cohort study in 249 patients with end-stage renal disease (ESRD) to examine whether the serum titer of anti-oxLDL antibody can p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00692.x
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND:We have recently found evidence for increased reactive oxygen species (ROS) in rats with lead-induced hypertension. We hypothesized that increased ROS activity may contribute to hypertension by enhancing inactivation of nitric oxide (NO) in this model. METHODS:Rats were treated for 12 weeks with either lead...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00670.x
更新日期:1999-10-01 00:00:00
abstract::Chronic kidney disease (CKD) has received increased attention as a leading public health problem worldwide. Globally surveillance systems for kidney disease are still lacking, especially in developing countries like China, which constitutes an obstacle to develop effective preventive strategies. China Kidney Disease N...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.11.011
更新日期:2019-03-01 00:00:00
abstract::Albuminuria and a reduced glomerular filtration rate are conventional predictors of a future decline in kidney function in patients with type 2 diabetes mellitus. Using a nested case-control study we assessed whether circulating transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) levels mor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.383
更新日期:2013-02-01 00:00:00
abstract::IgA nephropathy (IgAN) often shows lesions morphologically identical with those of focal segmental glomerulosclerosis (FSGS). In order to determine the possible role of FSGS in IgAN lesions, we measured glomerular capsular adhesions, often the first step toward FSGS, in biopsies from 127 patients with IgAN, 100 with l...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.466
更新日期:2011-03-01 00:00:00
abstract::Aminopeptidase A is one of the most potent enzymes within the renin-angiotensin system in terms of angiotensin II degradation. Here, we examined whether there is a kidney phenotype and any compensatory changes in other renin angiotensin system enzymes involved in the metabolism of angiotensin II associated with aminop...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.11.012
更新日期:2020-12-11 00:00:00
abstract::Kidney cancer, although relatively rare when compared to other malignancies, occurs not uncommonly in patients with renal disease and is often discovered incidentally during the initial nephrologic work-up, or by the savvy clinician who is familiar with the paraneoplastic signs. While surgical approaches are generally...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000065
更新日期:2006-01-01 00:00:00
abstract::Aboriginal dialysis patients have reduced access to kidney transplantation. The reasons for this disparity are unknown. Tonelli et al. show that in Canada, residence location does not significantly impact on an Aboriginal dialysis patient's likelihood of receiving kidney transplantation. This Commentary explores the i...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5001762
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:The cyclopentenone prostaglandin 15-deoxy-delta12,14-prostaglandin J2 (15dPGJ2) affects mesangial proliferation, survival and production of proinflammatory proteins. During a survey of the mesangial cell proteome after treatment with 15dPGJ2, heat shock protein 70 (HSP70) was found to be the most conspicuous...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00454.x
更新日期:2004-03-01 00:00:00
abstract::The effect of the tricarboxylic acid (TCA) cycle precursor, pyruvate, on glutamine metabolism by isolated renal cortical mitochondria was assessed by quantitating its key nitrogen and carbon metabolites. When mitochondria from normal rats were incubated at pH 7.4, pyruvate (2 mM) inhibited ammonia production by almost...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.166
更新日期:1982-09-01 00:00:00
abstract::Severe segmental glomerulonephritis (Seg GN) (greater than or equal to 50% involvement) in systemic lupus erythematosus (SLE) is classified as diffuse GN (DPGN) in the WHO classification. We tested the validity of the assumption that severe Seg GN and DPGN have the same prognosis by determining the proportion of glome...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.203
更新日期:1987-08-01 00:00:00
abstract::Nephropathic cystinosis is a multisystem autosomal recessive disease caused by cystine accumulation, which is usually treated by oral cysteamine. In order to determine long-term effects of this therapy, we enrolled 86 adult patients (mean age 26.7 years) diagnosed with nephropathic cystinosis, 75 of whom received cyst...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.277
更新日期:2012-01-01 00:00:00
abstract::Unidirectional 32P-phosphate and 3H-mannitol fluxes were simultaneously measured, at two minutes intervals, in frog urinary bladders. The spontaneous or externally imposed transepithelial potential (PD) and short circuit current (SCC) were also recorded in most experiments. It was observed that: (1) Phosphate transfer...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.9
更新日期:1988-01-01 00:00:00