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 the basolateral membrane of proximal tubular cells and disruption of Kcnj15 caused a hyperchloremic metabolic acidosis associated with a reduced threshold for bicarbonate in the absence of a generalized proximal tubule dysfunction. Urinary ammonium excretion rates in Kcnj15- deleted mice were inappropriate to acidosis under basal and acid-loading conditions, and not related to a failure to acidify urine or a reduced expression of ammonia transporters in the collecting duct. In contrast, the expression of key proteins involved in ammonia metabolism and secretion by proximal cells, namely the glutamine transporter SNAT3, the phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase enzymes, and the sodium-proton exchanger NHE-3 was inappropriate in Kcnj15-deleted mice. Additionally, Kcnj15 deletion depolarized the proximal cell membrane by decreasing the barium-sensitive component of the potassium conductance and caused an intracellular alkalinization. Thus, the Kir4.2 potassium channel subunit is a newly recognized regulator of proximal ammonia metabolism. The kidney consequences of its loss of function in mice support the proposal for KCNJ15 as a molecular basis for human isolated proximal renal tubular acidosis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Bignon Y,Pinelli L,Frachon N,Lahuna O,Figueres L,Houillier P,Lourdel S,Teulon J,Paulais Mdoi
10.1016/j.kint.2019.09.028subject
Has Abstractpub_date
2020-02-01 00:00:00pages
304-315issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(19)31032-4journal_volume
97pub_type
杂志文章abstract::Our genetic hypercalciuric (GH) rats have been selected and inbred for 29 generations to maximize urine calcium (UCa) excretion compared to identical gender controls (Ctl). To determine the effect of the increased UCa on urinary supersaturation and stone formation, we pair fed 15 GH and 15 Ctl rats a standard 1.2% cal...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.468
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND:Elevated glucose levels and glomerular hypertension (Pgc) are considered to contribute to the elaboration of matrix protein by mesangial cells (MCs) in diabetic glomeruli. MCs grown in 30 mM of glucose produce excessive matrix protein, as do MCs exposed to cyclic strain, and the combination of the two exacer...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00743.x
更新日期:1999-11-01 00:00:00
abstract::The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.492
更新日期:2014-08-01 00:00:00
abstract::Chemotherapy-induced nephrotoxicity limits the success of cancer therapy. Landau et al. now describe a mechanism by which a first dose of cisplatin renders the kidney sensitive to necroptosis mediated by a second dose. Unresolved injury and sustained necrosis, therefore, may represent a pathophysiological means of tra...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.12.004
更新日期:2019-04-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of kidney cysts leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Identification of an early biomarker that can predict progression of CKD is urgently needed. In an earlier Consortium for Radiolog...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.09.027
更新日期:2018-03-01 00:00:00
abstract::Indomethacin antagonizes the natriuretic and chloruretic response to hydrochlorothiazide in most studies. Neither the mechanism nor nephron site of this antagonism has been determined. To identify sites and potential mechanisms, cortical micropuncture was performed during hydrochlorothiazide treatment in control and i...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.114
更新日期:1987-05-01 00:00:00
abstract:BACKGROUND:We determined the effect of regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill subjects suffering from acute renal failure who were not at high risk for hemorrhagic complications. METHODS:Between April 1999 and June 2002, 30 critically ill sub...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00342.x
更新日期:2005-06-01 00:00:00
abstract::Serum fibroblast growth factor 23 (FGF23) is a novel phosphaturic factor and important for the regulation of inorganic phosphate (Pi) homeostasis. In this study, we examined an acute effect of oral Pi loading on serum FGF23 levels to clarify the role in rapid adjustment of serum Pi level. We performed a randomized, do...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5002000
更新日期:2006-12-01 00:00:00
abstract::[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels and involved in vascular contraction. Recently, we generated V1a receptor-deficient (V1aR(-/-)) mice and found that they were hypotensive. In addition, ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.319
更新日期:2009-11-01 00:00:00
abstract::We studied renal autoregulation in pancreatectomized Munich-Wistar diabetic rats and in their sham-operated controls. In a second experiment we studied renal autoregulation in untreated and insulin treated streptozotocin diabetic Munich-Wistar rats and their nondiabetic controls. In the first experiment the diabetic r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.65
更新日期:1990-03-01 00:00:00
abstract::The application of our evolving knowledge of adhesion receptors to experimental models of immune complex glomerulonephritis has led to substantial advances in our understanding of how leukocytes emigrate from the vasculature into glomeruli and produce glomerular dysfunction. With respect to neutrophil (PMN) migration ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1997.201
更新日期:1997-05-01 00:00:00
abstract::Ischemia-reperfusion injury is an important cause of graft failure. Because carnitine regulates substrate flux and energy balance across membranes which may be deranged in ischemia we determined whether its use was effective in preventing kidney injury in an allogeneic transplant model. Brown Norway rats received a Le...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.399
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Bioimpedance, a noninvasive technique to analyze body composition, has attracted interest in determining body hydration in hemodialysis patients. However, the so-called whole-body (wrist-to-ankle) bioimpedance analysis (WBIA) is sensitive to changes in regional fluid distribution and tends to underestimate f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00588.x
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND:The hypothesis that angiotensin-converting enzyme (ACE) inhibitors interfere with the treatment of anemia with recombinant human erythropoietin (rHuEPO) remains controversial. To test this hypothesis, a retrospective analysis was conducted in a large group of hemodialysis patients with renal anemia. METHODS...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00028.x
更新日期:2001-11-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase. Its activation results in beneficial or detrimental consequences, depending on the particular setting. Earlier studies in the animal model of acute kidney injury showed that EGFR activation promotes renal tubular cell proliferation. Activation of E...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2012.435
更新日期:2013-05-01 00:00:00
abstract::The kidney is influenced by circadian rhythms and is entrained to the sleep-wake cycle allowing anticipation of the metabolic and physiological demands of the kidney throughout a 24-hour cycle. Although sleep disruption has been studied extensively in cardiovascular and metabolic disease, its association with chronic ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2015.12.048
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:The "intact" parathyroid hormone (PTH) assay recognizes PTH-(1-84) as well as amino terminally truncated PTH fragments, that is, large carboxyterminal PTH fragments (C-PTH fragments). The present study investigated whether the use of the plasma PTH-(1-84)/C-PTH fragment ratio enhances the noninvasive assessm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00949.x
更新日期:2001-10-01 00:00:00
abstract:BACKGROUND:Alterations of large artery function and structure are frequently observed in renal allograft recipients. However, endothelial function has not yet been assessed in this population. METHODS:Flow-mediated vasodilation is a useful index of endothelial function. We measured the diameter and distensibility of t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.0550031104.x
更新日期:1999-03-01 00:00:00
abstract::Undecalcified sections of doubly tetracycline-labeled transiliac bone biopsy specimens obtained from ten hemodialyzed patients before and 10 to 16 months after parathyroidectomy (PTX) were analyzed. Before parathyroidectomy (total PTX with autotransplant in six patients and subtotal PTX in four patients), all the pati...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1985.27
更新日期:1985-02-01 00:00:00
abstract::Adhesion of calcium oxalate (CaOx) crystals to kidney cells may be a key event in the pathogenesis of kidney stones associated with marked hyperoxaluria. Previously, we found that 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), isolated from a traditional medicinal herb, reduced CaOx crystal adhesion to renal epithelial ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.458
更新日期:2011-03-01 00:00:00
abstract::Using a combination of intra-operative digital photography and micro-biopsy we measured renal cortical and papillary changes in five patients with primary hyperparathyroidism and abundant calcium phosphate kidney stones. Major tissue changes were variable papillary flattening and retraction, dilation of the ducts of B...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.161
更新日期:2008-07-01 00:00:00
abstract::As the worldwide prevalence of end-stage renal disease increases it is important to evaluate the rate of living kidney donation in various countries; however there is no comprehensive global assessment of these rates. To measure this, we compiled data from representatives, renal registries, transplant networks, publis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.20
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Somatic cells in vitro have a finite life expectancy before entering a state of senescence, but it is unclear whether this state occurs in vivo in kidney development, growth, and aging. We previously showed that human kidney cortex displays telomere shortening with age. In this study, we compared the structu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00032.x
更新日期:2003-06-01 00:00:00
abstract::Accurate measurement of glomerular filtration rate (GFR) is complicated and costly; therefore, GFR is commonly estimated by assessing creatinine or cystatin C concentrations. Because estimates based on cystatin C predict cardiovascular disease better than creatinine, these estimates have been hypothesized to be superi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.321
更新日期:2010-12-01 00:00:00
abstract::Chronic kidney disease (CKD) is usually associated with interstitial leukocytic cell infiltrates, which may contribute to disease progression by production of proinflammatory, proapoptotic, and profibrotic mediators. Recruiting leukocytes into the kidney involves local expression of chemotactic cytokines, that is, che...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000053
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Recently, we observed that the severity of glomerulonephritis in an experimental model of immunoglobulin A nephropathy (IgAN) induced by Sendai virus differs between C57BL/6 and BALB/c mouse strains. The determinants of differing renal insufficiency are not understood. In the present study, we examine the ca...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00258.x
更新日期:2003-11-01 00:00:00
abstract::The proximal tubule uses a complex process of apical acid secretion and basolateral bicarbonate absorption to regulate both luminal acidification and fluid absorption. One of the primary regulators of apical acid secretion is the luminal sodium-hydrogen exchanger expressed along the apical membrane of the proximal tub...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.137
更新日期:2013-08-01 00:00:00
abstract::Long-term complications of continuous immunosuppression still remain a serious threat and are currently drawing the attention of transplant physicians. Wimmer et al. show that malignancy occurs approximately fourfold more frequently in renal-transplant recipients than in a normal control population. Besides immunosupp...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002306
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND:Mesangial immunoglobulin A (IgA) deposition is incidentally encountered in asymptomatic individuals, but its precise frequency and significance had not been clarified. The background of the latent IgA deposition is related to the epidemiology and pathogenesis of IgA nephropathy. METHODS:Zero-hour allograft ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.63.6s.2.x
更新日期:2003-06-01 00:00:00
abstract::Thrombomodulin (TM), an endothelial receptor for thrombin, endowed with a powerful anticoagulant activity, plays an important role in the antithrombogenicity of the vascular endothelium. Its presence within the human renal glomerulus is already known but was thought to be only endothelial. We looked for TM expression ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.99
更新日期:1997-03-01 00:00:00