Abstract:
BACKGROUND:Podocytes are highly differentiated glomerular epithelial cells with limited potential to divide. They are responsible for maintaining and supporting the glomerular basement membrane so as to facilitate efficient filtration. The hypothesis tested was whether the development of glomerulosclerosis in the puromycin aminonucleoside (PAN)-treated rat could be attributed to podocyte depletion. METHODS:PAN was injected in Sprague-Dawley rats once, twice, or three times at 30-day intervals. Podocytes were counted in glomeruli using immunoperoxidase histochemistry and antibodies to both GLEPP1 (PTPRO) and WT-1. Podocytes were assayed in urine using reverse transcription-quantitative polymerase chain reaction (RT-QPCR). Glomerular areas were measured by computerized morphometry. RESULTS:In a preliminary experiment, a single injection of PAN caused a reduction in the glomerular podocyte count by 25%. Additional independent confirmation that podocytes were lost from glomeruli after PAN injection was obtained identifying detached podocytes in Bowman's space, measurement of nephrin and GLEPP1 mRNAs in urine, ultrastructural analysis of glomeruli, and identification of TUNEL-positive apoptotic podocytes in glomeruli. In a second experiment, sequential podocyte depletion by 15, 31, and 53% was achieved by the administration of one, two, or three injections of PAN at 30-day intervals. The region of the glomerulus devoid of podocytes developed glomerulosclerosis, and this area progressively increased as podocytes were progressively depleted. The correlation coefficient (r(2)) value for the relationship between percent podocyte depletion and glomerulosclerotic area was 0.99. The Y intercept of this plot showed that glomerulosclerosis was initiated when only 10 to 20% of podocytes were lost. CONCLUSION:This report supports the growing body of data linking glomerulosclerosis directly to a reduction in relative podocyte number [increased glomerular area per podocyte (GAPP)]. It raises important questions related to the mechanisms of podocyte loss, strategies for prevention of podocyte depletion, and the prevention of progression of glomerular diseases.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Kim YH,Goyal M,Kurnit D,Wharram B,Wiggins J,Holzman L,Kershaw D,Wiggins Rdoi
10.1046/j.1523-1755.2001.060003957.xsubject
Has Abstractpub_date
2001-09-01 00:00:00pages
957-68issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(15)47950-5journal_volume
60pub_type
杂志文章abstract:BACKGROUND:Fistula failure has been classified as early and late. Early failure refers to those cases in which the arteriovenous (AV) fistula never develops to the point that it can be used or fails within the first 3 months of usage. It has been common practice to abandon these early failures; however, aggressive eval...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00210.x
更新日期:2003-10-01 00:00:00
abstract::Migration of monocytes into the vessel wall contributes to the onset and progression of atherosclerosis. Because monocytes are a heterogeneous population, we determined potential associations between monocyte subsets and cardiovascular events in a prospective cohort of 94 dialysis patients followed for 35 months. The ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002744
更新日期:2008-03-01 00:00:00
abstract::Prostaglandin E2 (PGE2) may be an important negative feedback modulator of endothelin-1 (ET-1)-stimulated mesangial cell proliferation and contraction. Recent studies suggest that ET-1 may induce prolonged mesangial cell PGE2 production, however the mechanism of this effect is unknown. The current study was undertaken...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.6
更新日期:1995-01-01 00:00:00
abstract::One hundred six patients with terminal renal insufficiency and 29 medical personnel were given three doses of hepatitis B vaccine at an interval of 0, 1, and 6 months (Merck, Sharp and Dohme, West Point, Pennsylvania, part of a joint study no. 649). Chronic hemodialysis patients (N = 99) received 40 micrograms vaccine...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.18
更新日期:1984-01-01 00:00:00
abstract::The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a s...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2011.118
更新日期:2011-08-01 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::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:BACKGROUND:The purpose of this study was to evaluate the renoprotective effect as reflected by short-term changes in albuminuria of ultrahigh doses of irbesartan in type 2 diabetic patients with microalbuminuria. METHODS:This double-masked randomized crossover trial included 52 (41 males) hypertensive type 2 diabetic ...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00511.x
更新日期:2005-09-01 00:00:00
abstract::Hypocalcemia, hyperphosphatemia, and resistance to the action of PTH are well characterized features in the setting of advanced chronic renal failure (CRF). Although the underlying mechanisms are ill-understood, clinical and experimental evidence points to both PTH receptor down-regulation and post-receptor abnormalit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.79
更新日期:1994-02-01 00:00:00
abstract::In the epidemiologic study of end-stage renal disease (ESRD), accurate adjustment for comorbidity is essential to controlling bias in the comparison of outcomes across groups of patients or dialysis facilities. Liu et al. derive and validate a novel comorbidity index using data from the United States Renal Data System...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.431
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:The podocyte is the focus of much research into the mechanisms of renal disease progression, and the number of podocytes per glomerulus has thus become a parameter of much interest. When counting podocytes, the actual particle counted is the cell nucleus. The majority of published studies estimating podocyte...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1111/j.1523-1755.2004.00787.x
更新日期:2004-08-01 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:BACKGROUND:Adiponectin is an adipocyte-derived cytokine that has anti-inflammatory properties. A preliminary proteomic evaluation of urine for biomarkers of systemic lupus erythematosus (SLE) nephritis demonstrated high levels of adiponectin in SLE urine. This prompted investigation of adiponectin expression in human S...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00601.x
更新日期:2005-10-01 00:00:00
abstract::Diabetes is a major cause of chronic kidney disease, and oral antidiabetic drugs are the mainstay of therapy for most patients with Type 2 diabetes. Here we evaluated their role on renal outcomes by using a national Veterans Administration database to assemble a retrospective cohort of 93,577 diabetic patients who fil...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.444
更新日期:2012-04-01 00:00:00
abstract::Isotomic fluid reabsorption (JV) of rat renal proximal tubules was examined by the shrinking droplet method in combination with simulatneous perfusion of blood capillaries. Sensitivity of JV measurement was improved by using each punctured tubule for control measurements: 1) Parathyroid hormoen (PTH) on the contralumi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.12
更新日期:1977-02-01 00:00:00
abstract::Ambient glucose concentrations alter type 1 angiotensin II receptor (AT1R) expression in renal tissues. The direction of change in AT1R density may depend on the specific cell type and the capacity for that cell type to use glucose as an energy substrate. Given the effects of angiotensin II (Ang II) in proximal tubule...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.307
更新日期:1997-07-01 00:00:00
abstract::Previously, uremic toxins were sometimes regarded as a large, mysterious, but also anonymous group of factors potentially contributing to morbidity and mortality in end-stage renal disease. By identifying the protein-bound solute p-cresol as a risk factor for mortality in dialysis patients, Bammens and colleagues for ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5000236
更新日期:2006-03-01 00:00:00
abstract::Intercellular adhesion molecule-1 (ICAM-1) and MHC class II (Ia) antigens are increased on proximal tubular epithelial cells (TEC) in autoimmune nephritis and transplant rejection. ICAM-1 is a member of the immunoglobulin gene superfamily that increases the avidity of T cell interactions with antigen-presenting cells ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.221
更新日期:1990-09-01 00:00:00
abstract::International clinical practice guidelines for the management of anemia in chronic kidney disease suggest target hemoglobin levels ≤ 11.5 g/dl (115 g/l), with individualized consideration of slightly higher hemoglobin targets to improve quality of life. An updated meta-analysis of randomized trials demonstrates no sig...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.03.001
更新日期:2016-05-01 00:00:00
abstract::Human mesangial cells (MC) in culture, when stimulated by interleukin 1 alpha(IL-1 alpha) or tumour necrosis factor (TNF alpha), but not with lipopolysaccharide (LPS), express interleukin 8 (IL-8) mRNA, and both cell associated and extracellular IL-8. Dexamethasone treatment of mesangial cells induced partial inhibiti...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.184
更新日期:1991-07-01 00:00:00
abstract::The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.01.027
更新日期:2020-05-01 00:00:00
abstract::Multiphoton excitation fluorescence microscopy is a state-of-the-art confocal imaging technique ideal for deep optical sectioning of living tissues. It is capable of performing ultrasensitive, quantitative imaging of organ functions in health and disease with high spatial and temporal resolution which other imaging mo...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002461
更新日期:2007-11-01 00:00:00
abstract::Amyloidosis results from protein misfolding, and ongoing amyloid deposition can ultimately lead to organ failure and death. Historically, this is a group of diseases with limited treatment options and frequently poor prognosis. However, there are now 'targeted' therapeutics emerging in the form of stabilizers of the p...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2014.368
更新日期:2015-03-01 00:00:00
abstract::Clinical and experimental studies have shown that serum aluminum (Al) is bound to transferrin and that cellular uptake of Al appears to be mediated by transferrin receptors. Based on these findings it is widely believed that intestinal Al absorption occurs via iron-specific, transferrin-dependent pathways and that iro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.509
更新日期:1996-12-01 00:00:00
abstract::Current characterization of the immune risk in renal transplant patients is only focused on the assessment of preformed circulating alloantibodies; however, alloreactive memory T cells are key players in mediating allograft rejection. Immune monitoring of antidonor alloreactive memory/effector T cells using an IFN-γ E...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.236
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Gentamicin is commonly used in hemodialysis patients. Gentamicin pharmacokinetics during traditional hemodialysis have been described. Slow daily home (SDH) hemodialysis (7 to 9 hours a day/6 days a week) use is increasing due to benefits observed with increased hemodialysis. We determined gentamicin pharmac...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2003.00819.x
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:Cisplatin (CP) induced polyuria in rats is associated with a reduction in medullary hypertonicity, normally generated by the thick ascending limb (TAL) salt transporters, and the collecting duct urea transporters (UT). To investigate the molecular basis of this abnormality, we determined the protein abundanc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00048.x
更新日期:2001-12-01 00:00:00
abstract:BACKGROUND:The tissue renin-angiotensin system (RAS) may modulate the structural and functional changes that occur in the diabetic kidney. METHODS:Hypertensive transgenic (mREN-2)27 rat (TGR) that exhibit increased tissue renin expression were administered streptozotocin (STZ, diabetic) or citrate buffer (non-diabetic...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00019.x
更新日期:1998-08-01 00:00:00
abstract::We report the first case of a mitochondrial DNA (mtDNA) deletion diagnosed by renal biopsy. An eight-year-old girl with megaloblastic anemia and severe growth retardation developed progressive renal insufficiency accompanied by partial Fanconi syndrome. Histologic examination of the renal biopsy disclosed nonspecific ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.181
更新日期:1994-05-01 00:00:00
abstract::IgM in the blood of normal individuals consists mainly of 'natural' polyreactive antibodies. Natural IgM is thought to provide an initial defense against infection and to promote the healing of wounded cells. Yet, as Panzer and colleagues show, these benefits can be eclipsed when the IgM binds to damaged cells of the ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2015.153
更新日期:2015-09-01 00:00:00