Abstract:
BACKGROUND:Podocytes play an important role in the development of proteinuria and focal glomerulosclerosis. Previously we have demonstrated that a combination of two monoclonal antibodies (mAb) against aminopeptidase A (APA), an enzyme present on podocytes, induces a massive acute albuminuria in mice. The present study examined the relationship between the acute antibody-induced albuminuria and the development of focal glomerulosclerosis in the Thy-1.1 transgenic mouse. This mouse expresses a hybrid human-mouse Thy-1.1 antigen on the podocytes, and slowly but spontaneously develops albuminuria and focal glomerulosclerosis. METHODS:Five-week-old non-albuminuric Thy-1.1 transgenic and non-transgenic control mice were injected with anti-APA and anti-Thy-1.1 mAb or saline. Albuminuria was measured at days 1, 7, 14 and 21. At day 21 kidneys were processed for light microscopy, immunofluorescence, and electron microscopy. RESULTS:Injection of anti-APA and anti-Thy1.1 mAb in Thy-1.1 transgenic mice induced an albuminuria at day 1 that persisted at day 21. The acute albuminuria after injection of anti-APA mAb was more prominent but transient in non-transgenic mice. In non-trangenic mice no albuminuria could be induced with anti-Thy 1.1 mAb. Light microscopy revealed normal glomeruli at day 1 in all transgenic mice, however, at day 21 advanced glomerulosclerotic lesions were seen in mice injected with either anti-APA mAb (37+/-19% of glomeruli affected) or anti-Thy-1.1 mAb (71+/-5%). Non-transgenic mice did not reveal sclerotic lesions at any time investigated. In the transgenic mice the percentage of focal glomerulosclerosis at day 21 did not correlate with albuminuria at day 21. However, we found a highly significant correlation between percentage of focal glomerulosclerosis and the time-averaged albuminuria over the three-week study period (P < 0.001). CONCLUSION:Injection of a combination of anti-APA or anti-Thy-1.1 mAb into one mo old, non-albuminuric Thy-1.1 transgenic mice induces an acute albuminuria at day 1 that is accompanied by an accelerated focal glomerulosclerosis at day 21. We suggest that the Thy-1.1 transgenic mouse is an excellent model to study specifically the relation between podocytic injury, albuminuria and the development of focal glomerulosclerosis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Assmann KJ,van Son JP,Dïjkman HB,Mentzel S,Wetzels JFdoi
10.1046/j.1523-1755.2002.00428.xsubject
Has Abstractpub_date
2002-07-01 00:00:00pages
116-26issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)48528-Xjournal_volume
62pub_type
杂志文章abstract::The antiphospholipid syndrome is a common autoimmune disease caused by pathogenic antiphospholipid antibodies, leading to recurrent thrombosis and/or obstetrical complications. Importantly for nephrologists, antiphospholipid antibodies are associated with various renal manifestations including large renal vessel throm...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2016.06.026
更新日期:2017-01-01 00:00:00
abstract::To evaluate the effect of continuous ambulatory peritoneal dialysis (CAPD) on the anemia of endstage renal disease, serial measurements of red cell mass and other hematological parameters were performed in 34 patients. Twenty-five patients were measured at the start and at 6 months (group 1), 13 at the start, at 6 and...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.88
更新日期:1983-05-01 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::Isolated perfused rat kidneys were passively sensitized by addition of either mouse ascitic fluid containing monoclonal IgE against dinitrophenol (DNP) or DNP-specific purified IgE. After washing the organ, defined doses of DNP-bovine serum albumin were given as bolus injection via the kidney artery. Antigen challenge...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.197
更新日期:1987-08-01 00:00:00
abstract::To investigate whether the administration of cimetidine can improve the reliability of creatinine as a marker of GFR, we compared the creatinine clearance (CCr) to the clearance of the true filtration markers 51Cr-EDTA (CEDTA) and inulin (CIn), after oral ingestion of cimetidine in 10 healthy men and 29 patients with ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.331
更新日期:1991-12-01 00:00:00
abstract::The acutely injured mammalian kidney mounts a cellular and molecular response to repair itself. However, in patchy regions such intrinsic processes are impaired and dysregulated leading to chronic kidney disease. Currently, no therapy exists to treat established acute kidney injury per se. Strategies to augment human ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2017.07.030
更新日期:2018-01-01 00:00:00
abstract::A protective role for sirtuin 6 (Sirt6) in the context of chronic renal injury is reported by Cai et al. in this issue of Kidney International. The mechanism is thought to be mediated by Sirt6's deacetylase activity, specifically on β-catenin target genes. This commentary discusses these results and the interaction be...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.09.022
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Our preliminary studies indicate that chronic caffeine consumption has adverse renal effects in nephropathy associated with high blood pressure and insulin resistance. The purpose of this study was to investigate the effects of early (beginning at 8 weeks of age) and long-term (30 weeks) caffeine treatment (...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00278.x
更新日期:2002-04-01 00:00:00
abstract::Germ free rats provide a unique model in which to assess biological response to environment. In 48 germ-free male, Sprague-Dawley rats we examined the consequences of oral exposure to nordihydroguaiaretic acid (NDGA), a nephrotoxin; to Staphylococcus epidermidis and bacillus species, non-endotoxin-containing bacteria;...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.213
更新日期:1987-09-01 00:00:00
abstract::X-ray crystal interferometer-based X-ray phase-contrast microtomography (phase-contrast microtomography) is able to image microstructures within soft tissue without the use of a contrast agent. Here we determined the feasibility of using this technique in the non-destructive inspection of formalin-fixed kidney tissue ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.42
更新日期:2009-05-01 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::Transforming growth factor-β1 (TGF-β1) upregulation occurs in virtually all chronic kidney diseases and is associated with podocyte injury and proteinuria; however, the mechanisms contributing to this in vivo are ambiguous. In vitro, incubation of podocytes with TGF-β1 induced Wnt1 expression, β-catenin activation, an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.255
更新日期:2011-12-01 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:BACKGROUND:It is suggested that either arginine or its metabolites, nitric oxide and polyamines play a role in the renal hemodynamic alterations observed in the early stages of diabetes. Yet, the regulation of arginine transport in diabetic kidneys has never been studied. METHODS:Arginine uptake was determined in glom...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00508.x
更新日期:2004-04-01 00:00:00
abstract::Hyperhomocysteinemia, an arteriosclerotic risk factor, persists in 75% of dialysis patients despite routine low dose supplementation with the B-vitamin co-factors/substrates for homocysteine (Hcy) metabolism, and normal or supernormal plasma status of these vitamins (Atherosclerosis 114:93, 1995). We conducted a place...
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:10.1038/ki.1996.19
更新日期:1996-01-01 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:BACKGROUND:Endotoxin is an important factor in the development of acute renal failure related to infection and in acceleration of chronic nephritis. Lipopolysaccharide (LPS; the major component of endotoxin) is one of the most potent triggers for renal cells to produce monocyte chemoattractant protein-1 (MCP-1), a key ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00051.x
更新日期:2000-05-01 00:00:00
abstract:BACKGROUND:Hyperphagic obese Zucker rats develop glomerular injury and die of renal disease, an outcome prevented by food restriction at an early age. We examined the effects of food restriction imposed at different ages on systemic, renal hemodynamic, and hormonal changes to gain insight into the mechanisms of obesity...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00412.x
更新日期:2002-07-01 00:00:00
abstract::The safety of dietary protein and phosphorous restriction was evaluated in the Modification of Diet in Renal Disease (MDRD) Study. In Study A, 585 patients with a glomerular filtration rate (GFR) of 25 to 55 ml/min/1.73 m2 were randomly assigned to a usual-protein diet (1.3 g/kg/day) or a low-protein diet (0.58 g/kg/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.1997.395
更新日期:1997-09-01 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::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::Substrate oxidation was assessed by measuring 14CO2 production from 14C-labeled substrates in proximal convoluted tubules (PCT), medullary (MTAL), and cortical (CTAL) thick ascending limb of Henle, nephron segments rich in mitochondria and characterized by active solute transport. PCT, MTAL, and CTAL were dissected fr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.100
更新日期:1981-07-01 00:00:00
abstract::Renal involvement in von Hippel-Lindau (VHL) disease has emerged as the most prevalent cause of death in this hereditary disorder. In a group of 43 VHL patients (23 unrelated families) with renal lesions we examined whether severity of renal disease is affected by parental inheritance and VHL subtype (1, without pheoc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.395
更新日期:1996-09-01 00:00:00
abstract::Many renal diseases are associated with fibrin deposition in the glomeruli, a situation that reflects an abnormality in the balance between the coagulation and fibrinolytic systems. We recently demonstrated that normal mouse kidney contains very low levels of type 1 plasminogen activator inhibitor (PAI-1), a potent an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.17
更新日期:1995-01-01 00:00:00
abstract::The selective vasopressin V2-receptor antagonist tolvaptan is eliminated almost exclusively by non-renal mechanisms. As renal impairment can influence the pharmacokinetics of drugs even when eliminated by non-renal mechanisms, we evaluated the effect of renal insufficiency on the pharmacokinetics/pharmacodynamics of t...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.2013.350
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Cold ischemia and reperfusion during kidney transplantation are associated with release of free oxygen radicals and damage of renal tubular cells. Bioflavonoids may diminish cold storage-induced injury due to antioxidant and iron chelating activities. This study was designed to delineate the renoprotective m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00774.x
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND:Susceptibility to skin cancer after transplantation is multifactorial, and risk factors include skin type, sun exposure, and level of immunosuppression. A major mechanism of carcinogenesis is ultraviolet radiation-induced free radical damage, and genetically determined ability to metabolize free radicals may...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00392.x
更新日期:2000-11-01 00:00:00
abstract::Anti-NDP has been detected in the sera of 38 of 430 patients on regular hemodialysis at the Regional Kidney Disease Program in Minneapolis. It developed in these patients from 7 to 58 months after commencement of dialysis. Bacterial infection appeared temporally related to the development of anti-NDP in 12 patients. H...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1976.133
更新日期:1976-12-01 00:00:00
abstract::Cilnidipine, a dual L-/N-type calcium channel blocker, dilates both efferent and afferent arterioles and is renoprotective. Our multi-center, open-labeled, and randomized trial compared the antiproteinuric effect of cilnidipine with that of amlodipine in hypertensive patients with kidney disease. A group of 339 patien...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/sj.ki.5002623
更新日期:2007-12-01 00:00:00
abstract::We used the perfused hemicorpus preparation to measure individual rates of protein synthesis and degradation. Using fed animals, perfused either with or without insulin, muscle protein synthesis and hemicorpus protein degradation rates were similar, but myofibrillar protein degradation was clearly increased in the ure...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.119
更新日期:1986-06-01 00:00:00