Abstract:
:Mutations in the NPHS2 gene, encoding podocin, are responsible for familial autosomal recessive and sporadic cases of steroid-resistant nephrotic syndrome. We have successfully generated a mouse model in which the common p.R138Q mutation found in nephrotic patients is expressed in the kidney. Homozygous mice express the mutant protein, which is mislocated to the cytoplasm, along with a portion of the nephrin pool. These mice die within the first month of life, but their survival depends on the genetic background. Albuminuria manifests early and leads to progressive renal insufficiency, characterized histologically by diffuse mesangiolysis and mesangial sclerosis, endothelial lesions along with podocyte abnormalities such as widespread foot process effacement. Gene expression profiling revealed marked differences between these and the podocin-null mice, including significant perturbations of podocyte-expressed genes such as Cd2ap, Vegfa and the transcription factors Lmx1b and Zhx2. Upregulation of Serpine1 and Tgfb1 implicates these as potential mediators of disease progression in these mice. This mouse model of nephrotic syndrome may serve as a valuable tool in studies of in vivo intracellular protein trafficking of podocyte proteins, as well as testing therapeutic modalities aimed at correcting the targeting of mutant proteins.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Philippe A,Weber S,Esquivel EL,Houbron C,Hamard G,Ratelade J,Kriz W,Schaefer F,Gubler MC,Antignac Cdoi
10.1038/ki.2008.27subject
Has Abstractpub_date
2008-05-01 00:00:00pages
1038-47issue
9eissn
0085-2538issn
1523-1755pii
S0085-2538(15)53133-5journal_volume
73pub_type
杂志文章abstract::Because of high risk of cardiovascular disease, patients with chronic kidney disease may benefit from cholesterol-lowering therapy beyond statins. A cost-effectiveness analysis of adding ezetimibe to high-dose statins for primary cardiovascular disease prevention in patients with non-dialysis-dependent chronic kidney ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.02.029
更新日期:2019-07-01 00:00:00
abstract::The relationship between body mass index (BMI) and end-stage renal disease (ESRD) is confounded by co-morbidities associated with both conditions. Furthermore, the association at low range BMI is controversial. We studied this association in the Singapore Chinese Health Study, a population-based prospective cohort tha...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.03.019
更新日期:2017-10-01 00:00:00
abstract::Angiotensin converting enzyme (ACE) inhibitors are known to lower urinary protein excretion in human renal disease. This proteinuria lowering effect of ACE inhibition has been hypothesized to be a result of renal hemodynamic changes due to the inhibition of angiotensin II (Ang II) production. To test this hypothesis w...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1991.268
更新日期:1991-10-01 00:00:00
abstract::We studied binding and degradation of vasoactive intestinal peptide (VIP) by highly purified brush border and basolateral membranes from rabbit kidney cortex. Brush border and basolateral membranes were capable of 73 and 49% degradation of VIP after 20 minutes, and the degradation was totally prevented by bacitracin. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.32
更新日期:1991-02-01 00:00:00
abstract:BACKGROUND:A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Co...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.1523-1755.2003.00720.x
更新日期:2003-01-01 00:00:00
abstract::The main distal nephron segment sodium transporters are the distal tubule chlorothiazide-sensitive sodium chloride cotransporter (NCC) and the collecting duct amiloride-sensitive epithelial sodium channel (ENaC). The infusion of ghrelin into the renal interstitium stimulates distal nephron-dependent sodium reabsorptio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.187
更新日期:2013-09-01 00:00:00
abstract::Renal cell carcinoma (RCC) is the most common kidney malignancy and has a poor prognosis owing to its resistance to chemotherapy. RCC cells overexpress the transcription factor, PAX2, normally expressed in fetal kidney but downregulated at birth. Since Pax2 suppresses apoptosis during renal development, we reasoned th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000136
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:There is accumulating evidence that adult bone marrow (BM) cells show unexpected plasticity, and can differentiate into a wide range of specialized cells. In the case of intrinsic renal glomerular cells, BM-derived cells have been reported to differentiate into both mesangial cells and podocytes. However, th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00291.x
更新日期:2005-05-01 00:00:00
abstract:BACKGROUND:The National Kidney Foundation Dialysis Outcomes Quality Initiative (DOQI) clinical practice guidelines have suggested minimal weekly Kt/V urea and creatinine clearance goals for peritoneal dialysis patients maintained on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2000.00120.x
更新日期:2000-06-01 00:00:00
abstract::Cell surface aminopeptidases N (APN) and A (APA) have been characterized on cultured human glomerular epithelial cells and a SV40-transformed cell line derived from them. APN had a wide substrate specificity whereas APA only attacked peptides with an acidic N terminal amino acid. Both enzymes also differed by their se...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.227
更新日期:1992-06-01 00:00:00
abstract::Apoptosis mediated by verotoxins (VTs) has been identified in a renal carcinoma cell line, ACHN cells, which are an in vitro model of renal tubular epithelial cells. ACHN cells express the renal tubular marker CD24 as well as globotriaosyl ceramide/CD77, the receptor for VTs. VT binding to the ACHN cell surface was co...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00939.x
更新日期:1998-06-01 00:00:00
abstract::We described the characteristics in a referred cohort of type II diabetic patients in the Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes study evaluating the global prevalence and determinants of microalbuminuria (MA). A cross-sectional study evaluating 32,208 type ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000377
更新日期:2006-06-01 00:00:00
abstract::Accumulation of extracellular matrix within the mesangium is an important event in the development of glomerular disease. In this report we have used indirect immunofluorescence to positively identify a number of constituents of the mesangial matrix synthesized by rat mesangial cells (RMC) in vitro including laminin, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.412
更新日期:1995-10-01 00:00:00
abstract::Cardiac surgery associated-acute kidney injury (CS-AKI) occurs in 30-50% of patients undergoing surgery for congenital heart disease. Here we determine if CS-AKI is associated with chronic kidney disease (CKD) in patients with congenital heart disease. Using Danish regional population-based registries, our cohort stud...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.02.021
更新日期:2017-09-01 00:00:00
abstract::Fibroblasts in parenchymal organs potentially contribute extracellular matrix to local fibrogenic processes. This contribution, in some circumstances, may be initiated by cytokines disseminated from inflammatory lesions. Different populations of fibroblasts, however, might respond distinctively to this cytokine bath d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.3
更新日期:1992-01-01 00:00:00
abstract::Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by dysregulated complement activation. Clinically, aHUS is effectively treated by an anti-C5 monoclonal antibody (mAb) but whether the disease is mediated by the C5a receptor (C5aR) or C5b-9 pathway, or both, is unknown. Her...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.01.009
更新日期:2019-07-01 00:00:00
abstract::One reason for the inadequacy of current renoprotective therapy and the persistent poor renal prognosis in diabetic nephropathy is the large interindividual variation in response to treatment. Genetic as well as non-genetic factors are known to influence treatment efficacy. This Commentary summarizes the impact of the...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5000283
更新日期:2006-04-01 00:00:00
abstract::From August 1987 through February 1995 we performed 42 surgical procedures in 29 patients with occluded or stenotic radiocephalic arteriovenous fistulae. Operations were designed to preserve native veins for cannulation (Group I) or to preserve access in the same forearm, bypassing the failed fistula (Group II). For 2...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00769.x
更新日期:1998-02-01 00:00:00
abstract::Leukocytes play a major role in the development and progression of autoimmune diseases. We measured gene expression differences in leukocytes from patients that were antineutrophil cytoplasmic autoantibody (ANCA) positive, patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), and healthy donor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002371
更新日期:2007-10-01 00:00:00
abstract::Spontaneous and aspirated blood samples were collected from the welling points of surface efferent arterioles in the rat kidney. The amount of tubular reabsorbate in each sample was calculated from measurements of the inulin concentration in the sample and systemic arterial plasma. Both spontaneous and aspirated sampl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.44
更新日期:1984-03-01 00:00:00
abstract::US adults with metabolic syndrome, as defined by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, have been shown to be at increased risk of chronic kidney disease (CKD), but there is limited information in other populations. The relationship between metabolic syndrome and CKD ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002128
更新日期:2007-04-01 00:00:00
abstract::Lipid abnormalities have been suggested as a major cause of the accelerated atherosclerosis and the high incidence of coronary heart disease in chronic renal failure patients. In the present work the postprandial lipoprotein metabolism was studied in chronic dialysis patients with or without fasting hypertriglyceridem...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.411
更新日期:1992-11-01 00:00:00
abstract::In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.242
更新日期:1991-09-01 00:00:00
abstract:BACKGROUND:Elimination of residual proteinuria is the novel target in renoprotection; nevertheless, whether a greater suppression of renin-angiotensin system (RAS) effectively improves the antiproteinuric response in patients with moderate proteinuria remains ill-defined. METHODS:We evaluated the effects of maximizing...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2003.00015.x
更新日期:2003-06-01 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:BACKGROUND:Bone marrow reconstitution using genetically-modified hematopoietic stem cells has been reported to confer resistance to inflammation and prevent renal injury in glomerulonephritis. Although this strategy has potentials for clinical use, taking hematopoietic stem cells from bone marrow is highly stressful fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00046.x
更新日期:2003-07-01 00:00:00
abstract::The ankyrin repeat and sterile α motif (SAM) domain-containing six gene (Anks6) is a candidate for polycystic kidney disease (PKD). Originally identified in the PKD/Mhm(cy/+) rat model of PKD, the disease is caused by a mutation (R823W) in the SAM domain of the encoded protein. Recent studies support the etiological r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.122
更新日期:2015-08-01 00:00:00
abstract::The study by Rieg et al. is the first to examine potassium handling in BK(-/-) mice, thereby addressing many unanswered questions regarding the separate roles of BK and ROMK channels in renal potassium secretion. This Commentary is an interpretation and opinion of their results, by two researchers who have been studyi...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002438
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Both high glucose (HG) and angiotensin II (Ang II) causes glomerular mesangial cell (GMC) growth and increased synthesis of matrix proteins like collagen IV contributing to diabetic nephropathy. We have recently found that exposure of vascular smooth muscle cells to HG augments the Ang II activation of the g...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00311.x
更新日期:2002-05-01 00:00:00
abstract::We have previously identified the engulfment and cell motility 1 (ELMO1) as a susceptibility gene for diabetic nephropathy. To elucidate the role of ELMO1 in the pathogenesis of chronic renal injury, we examined the expression of Elmo1 in the kidney of a rat model for chronic glomerulonephritis (uninephrectomy plus an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001939
更新日期:2006-11-01 00:00:00