Antibody-induced albuminuria and accelerated focal glomerulosclerosis in the Thy-1.1 transgenic mouse.

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 Int

journal_title

Kidney international

authors

Assmann KJ,van Son JP,Dïjkman HB,Mentzel S,Wetzels JF

doi

10.1046/j.1523-1755.2002.00428.x

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

116-26

issue

1

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)48528-X

journal_volume

62

pub_type

杂志文章
  • Antiphospholipid syndrome and kidney disease.

    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

    authors: Bienaimé F,Legendre C,Terzi F,Canaud G

    更新日期:2017-01-01 00:00:00

  • Influence of continuous ambulatory peritoneal dialysis on the anemia of endstage renal disease.

    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

    authors: De Paepe MB,Schelstraete KH,Ringoir SM,Lameire NH

    更新日期:1983-05-01 00:00:00

  • CD154-CD40 T-cell co-stimulation pathway is a key mechanism in kidney ischemia-reperfusion injury.

    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

    authors: de Ramon L,Ripoll E,Merino A,Lúcia M,Aran JM,Pérez-Rentero S,Lloberas N,Cruzado JM,Grinyó JM,Torras J

    更新日期:2015-09-01 00:00:00

  • Renal anaphylaxis. I. Antigen-initiated responses from isolated perfused rat kidney.

    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

    authors: Pirotzky E,Pintos-Morell G,Burtin C,Boudet J,Bidault J,Benveniste J

    更新日期:1987-08-01 00:00:00

  • Cimetidine improves the reliability of creatinine as a marker of glomerular filtration.

    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

    authors: Hilbrands LB,Artz MA,Wetzels JF,Koene RA

    更新日期:1991-12-01 00:00:00

  • Cellular and molecular pathways of renal repair after acute kidney injury.

    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

    authors: Kumar S

    更新日期:2018-01-01 00:00:00

  • Sirtuin 6 and renal injury: another link in the β-catenin chain?

    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

    authors: Gewin LS

    更新日期:2020-01-01 00:00:00

  • Long-term caffeine consumption exacerbates renal failure in obese, diabetic, ZSF1 (fa-fa(cp)) rats.

    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

    authors: Tofovic SP,Kost CK Jr,Jackson EK,Bastacky SI

    更新日期:2002-04-01 00:00:00

  • Endotoxin provocation of experimental renal cystic disease.

    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

    authors: Gardner KD Jr,Reed WP,Evan AP,Zedalis J,Hylarides MD,Leon AA

    更新日期:1987-09-01 00:00:00

  • Imaging renal structures by X-ray phase-contrast microtomography.

    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

    authors: Wu J,Takeda T,Lwin TT,Momose A,Sunaguchi N,Fukami T,Yuasa T,Akatsuka T

    更新日期:2009-05-01 00:00:00

  • Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients.

    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

    authors: Kutsogiannis DJ,Gibney RT,Stollery D,Gao J

    更新日期:2005-06-01 00:00:00

  • Canonical Wnt/β-catenin signaling mediates transforming growth factor-β1-driven podocyte injury and proteinuria.

    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

    authors: Wang D,Dai C,Li Y,Liu Y

    更新日期:2011-12-01 00:00:00

  • Fructokinase activity mediates dehydration-induced renal injury.

    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

    authors: Roncal Jimenez CA,Ishimoto T,Lanaspa MA,Rivard CJ,Nakagawa T,Ejaz AA,Cicerchi C,Inaba S,Le M,Miyazaki M,Glaser J,Correa-Rotter R,González MA,Aragón A,Wesseling C,Sánchez-Lozada LG,Johnson RJ

    更新日期:2014-08-01 00:00:00

  • Augmented arginine uptake, through modulation of cationic amino acid transporter-1, increases GFR in diabetic rats.

    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

    authors: Schwartz IF,Iaina A,Benedict Y,Wollman Y,Chernichovski T,Brasowski E,Misonzhnik F,Ben-Dor A,Blum M,Levo Y,Schwartz D

    更新日期:2004-04-01 00:00:00

  • High dose-B-vitamin treatment of hyperhomocysteinemia in dialysis patients.

    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

    authors: Bostom AG,Shemin D,Lapane KL,Hume AL,Yoburn D,Nadeau MR,Bendich A,Selhub J,Rosenberg IH

    更新日期:1996-01-01 00:00:00

  • Angiotensin II does not acutely reverse the reduction of proteinuria by long-term ACE inhibition.

    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

    authors: Heeg JE,de Jong PE,van der Hem GK,de Zeeuw D

    更新日期:1991-10-01 00:00:00

  • Lipopolysaccharide-induced MCP-1 gene expression in rat tubular epithelial cells is nuclear factor-kappaB dependent.

    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

    authors: Wang Y,Rangan GK,Goodwin B,Tay YC,Harris DC

    更新日期:2000-05-01 00:00:00

  • Prevention of obesity-linked renal disease: age-dependent effects of dietary food restriction.

    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

    authors: Maddox DA,Alavi FK,Santella RN,Zawada ET Jr

    更新日期:2002-07-01 00:00:00

  • Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study.

    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

    authors: Kopple JD,Levey AS,Greene T,Chumlea WC,Gassman JJ,Hollinger DL,Maroni BJ,Merrill D,Scherch LK,Schulman G,Wang SR,Zimmer GS

    更新日期:1997-09-01 00:00:00

  • Dialysate calcium profiling during hemodialysis: use and clinical implications.

    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

    authors: Kyriazis J,Glotsos J,Bilirakis L,Smirnioudis N,Tripolitou M,Georgiakodis F,Grimani I

    更新日期:2002-01-01 00:00:00

  • Cell surface aminopeptidase A and N activities in human glomerular epithelial cells.

    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

    authors: Stefanovic V,Vlahovic P,Ardaillou N,Ronco P,Ardaillou R

    更新日期:1992-06-01 00:00:00

  • Substrate oxidation by isolated single nephron segments of the rat.

    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

    authors: Klein KL,Wang MS,Torikai S,Davidson WD,Kurokawa K

    更新日期:1981-07-01 00:00:00

  • Renal involvement in von Hippel-Lindau disease.

    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

    authors: Chauveau D,Duvic C,Chrétien Y,Paraf F,Droz D,Melki P,Hélénon O,Richard S,Grünfeld JP

    更新日期:1996-09-01 00:00:00

  • Expression of type 1 plasminogen activator inhibitor in renal tissue in murine lupus nephritis.

    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

    authors: Keeton M,Ahn C,Eguchi Y,Burlingame R,Loskutoff DJ

    更新日期:1995-01-01 00:00:00

  • Pharmacokinetics and pharmacodynamics of oral tolvaptan in patients with varying degrees of renal function.

    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

    authors: Shoaf SE,Bricmont P,Mallikaarjun S

    更新日期:2014-04-01 00:00:00

  • Bioflavonoids attenuate renal proximal tubular cell injury during cold preservation in Euro-Collins and University of Wisconsin solutions.

    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

    authors: Ahlenstiel T,Burkhardt G,Köhler H,Kuhlmann MK

    更新日期:2003-02-01 00:00:00

  • Glutathione S-transferase polymorphisms and skin cancer after renal transplantation.

    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

    authors: Marshall SE,Bordea C,Haldar NA,Mullighan CG,Wojnarowska F,Morris PJ,Welsh KI

    更新日期:2000-11-01 00:00:00

  • A clinical study of anti-NDP in the sera of patients in a large repetitive hemodialysis program.

    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

    authors: Crosson JT,Moulds J,Comty CM,Polesky HF

    更新日期:1976-12-01 00:00:00

  • Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease.

    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

    authors: Fujita T,Ando K,Nishimura H,Ideura T,Yasuda G,Isshiki M,Takahashi K,Cilnidipine versus Amlodipine Randomised Trial for Evaluation in Renal Desease(CARTER) Study Investigators.

    更新日期:2007-12-01 00:00:00

  • Protein synthesis and degradation in skeletal muscle of chronically uremic rats.

    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

    authors: Li JB,Wassner SJ

    更新日期:1986-06-01 00:00:00