Comparative profile of commercially available urinary biomarkers in preclinical drug-induced kidney injury and recovery in rats.

Abstract:

:We designed a study to provide reversibility and comparative injury data for several candidate urinary biomarkers of kidney injury in the United States Food and Drug Administration biomarker qualification process. The nephrotoxin gentamicin was given to rats once on each of three days and the animals were killed during dosing or over the following 42 days. Between days one and three, all biomarkers except albumin were elevated, peaked at day 7, and returned to control levels by day 10 (μ- and α-glutathione S-transferases, and renal papillary antigen-1) or day 15 (kidney injury molecule-1, lipocalin-2, osteopontin, and clusterin). All biomarkers performed better during injury than during recovery except osteopontin, which performed equally well in both time periods. During the evolution of injury, kidney injury molecule-1, renal papillary antigen-1, and clusterin best mirrored the histopathologic lesions. During injury resolution, kidney injury molecule-1, osteopontin, and blood urea nitrogen best reflected recovery. Based on histopathology, necrosis, or apoptosis scoring, kidney injury molecule-1 was the best biomarker of overall renal injury. Evaluation by regeneration score showed that renal papillary antigen-1 best reflected tubular and/or collecting duct regeneration, especially during recovery. Thus, these biomarkers performed with different effectiveness when evaluated by individual pathological processes such as necrosis, apoptosis, and regeneration.

journal_name

Kidney Int

journal_title

Kidney international

authors

Rouse RL,Zhang J,Stewart SR,Rosenzweig BA,Espandiari P,Sadrieh NK

doi

10.1038/ki.2010.463

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

1186-97

issue

11

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)54718-2

journal_volume

79

pub_type

杂志文章
  • Intrarenal ghrelin receptors regulate ENaC-dependent sodium reabsorption by a cAMP-dependent pathway.

    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

    authors: Kemp BA,Howell NL,Gildea JJ,Keller SR,Padia SH

    更新日期:2013-09-01 00:00:00

  • Binding of factor H to tubular epithelial cells limits interstitial complement activation in ischemic injury.

    abstract::Factor H is a regulator of the alternative pathway of complement, and genetic studies have shown that patients with mutations in factor H are at increased risk for several types of renal disease. Pathogenic activation of the alternative pathway in acquired diseases, such as ischemic acute kidney injury, suggests that ...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1038/ki.2011.115

    authors: Renner B,Ferreira VP,Cortes C,Goldberg R,Ljubanovic D,Pangburn MK,Pickering MC,Tomlinson S,Holland-Neidermyer A,Strassheim D,Holers VM,Thurman JM

    更新日期:2011-07-01 00:00:00

  • Acidifying defect induced by amphotericin B: comparison of bicarbonate and hydrogen ion permeabilities.

    abstract::The defect in urinary acidification induced by amphotericin B (AMB) was further characterized in turtle bladder. Since AMB has been shown to increase the hydrogen ion (H+) permeability of this epithelium in the absence of exogenous bicarbonate ions (HCO3-), we explored the permeability characteristics in the presence ...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1038/ki.1977.39

    authors: Finn JT,Cohen LH,Steinmetz PR

    更新日期:1977-04-01 00:00:00

  • Regulated necrosis in kidney ischemia-reperfusion injury.

    abstract::Ischemia-reperfusion injury (IRI) is the outcome of an inflammatory process that is triggered when an organ undergoes a transient reduction or cessation of blood flow, followed by re-establishment of perfusion. In the clinical setting, IRI contributes to significant acute kidney injury, patient morbidity and mortality...

    journal_title:Kidney international

    pub_type: 杂志文章,评审

    doi:10.1016/j.kint.2019.02.009

    authors: Pefanis A,Ierino FL,Murphy JM,Cowan PJ

    更新日期:2019-08-01 00:00:00

  • Awakening the Bowman: inhibition of CXCL12 signaling activates parietal epithelial cells.

    abstract::Glomerular podocytes are terminally differentiated cells, and podocyte loss is a common feature of progressive renal pathologies. In this issue, Romoli et al. focus on podocyte progenitors that were proposed to reside in the Bowman's capsule. They demonstrate that suppression of CXCL12/CXCR4 signaling activates pariet...

    journal_title:Kidney international

    pub_type: 评论,杂志文章

    doi:10.1016/j.kint.2018.09.011

    authors: Massa F,Schedl A

    更新日期:2018-12-01 00:00:00

  • Glomerular angiotensinase A in the rat: increase of enzyme activity following renal ablation.

    abstract::Angiotensinase A (aminopeptidase A; ATA) is an angiotensin II splitting exopeptidase, which is localized in endothelial and epithelial cells of the glomerular tuft. In order to investigate the influence of a reduction in renal mass on enzyme activity, ATA activity was measured in isolated rat glomeruli five and 14 wee...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1038/ki.1990.283

    authors: Wolf G,Thaiss F,Scherberich JE,Schoeppe W,Stahl RA

    更新日期:1990-11-01 00:00:00

  • Urinary peptidomics provides a noninvasive humanized readout of diabetic nephropathy in mice.

    abstract::Nephropathy is among the most frequent complications of diabetes and the leading cause of end-stage renal disease. Despite the success of novel drugs in animal models, the majority of the subsequent clinical trials employing those drugs targeting diabetic nephropathy failed. This lack of translational value may in par...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1016/j.kint.2016.06.023

    authors: Klein J,Ramirez-Torres A,Ericsson A,Huang Y,Breuil B,Siwy J,Mischak H,Peng XR,Bascands JL,Schanstra JP

    更新日期:2016-11-01 00:00:00

  • Effect of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on isotonic fluid reabsorption: polarity of proximal tubular cells.

    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

    authors: Baumann K,Chan YL,Bode F,Papavassiliou F

    更新日期:1977-02-01 00:00:00

  • Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease.

    abstract::In uremic patients resistance to the action of insulin has been documented, but it is not known at what stage of renal disease it appears. We therefore examined 29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult polycystic kidney disease (ADPKD) in different stages of renal failure, and in addi...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1046/j.1523-1755.1998.00898.x

    authors: Fliser D,Pacini G,Engelleiter R,Kautzky-Willer A,Prager R,Franek E,Ritz E

    更新日期:1998-05-01 00:00:00

  • Amylin deposition in the kidney of patients with diabetic nephropathy.

    abstract::Amylin (islet amyloid peptide) plays a critical role in islet amyloidosis and in the development of beta-cell dysfunction in patients with diabetes; however, the involvement of amylin in renal amyloidosis has not been studied. For this reason, we surveyed 149 patients with biopsy-proven diabetic nephropathy (DN). The ...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1038/sj.ki.5002305

    authors: Gong W,Liu ZH,Zeng CH,Peng A,Chen HP,Zhou H,Li LS

    更新日期:2007-07-01 00:00:00

  • The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection.

    abstract:BACKGROUND:While an understanding of the epidemiology and clinical course of HIV-associated nephropathy (HIVAN) is growing, little is known about the risk factors and clinical course of the other renal diseases that may also occur as a complication of HIV infection. This study was undertaken to compare HIVAN to the spe...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1111/j.1523-1755.2004.00865.x

    authors: Szczech LA,Gupta SK,Habash R,Guasch A,Kalayjian R,Appel R,Fields TA,Svetkey LP,Flanagan KH,Klotman PE,Winston JA

    更新日期:2004-09-01 00:00:00

  • Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases.

    abstract::This study offers morphological evidence of the involvement of lipid abnormalities in human glomerular injury. Renal biopsy tissues from patients with several types of glomerular diseases were immunocytochemically examined using antibodies to apolipoproteins (apo) A-I, B-100, and E, and antibodies to low density lipop...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1038/ki.1993.129

    authors: Takemura T,Yoshioka K,Aya N,Murakami K,Matumoto A,Itakura H,Kodama T,Suzuki H,Maki S

    更新日期:1993-04-01 00:00:00

  • Detection of hepatitis B virus DNA and RNA in kidneys of HBV related glomerulonephritis.

    abstract::Glomerular deposition of hepatitis B virus (HBV) antigens are observed in chronic HBsAg carriers with different glomerulonephritides yet the etiologic role of HBV remains uncertain. We examined the paraffin section of kidney biopsies from 40 chronic HBsAg carriers with membranous nephropathy (MGN), mesangiocapillary g...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1038/ki.1996.519

    authors: Lai KN,Ho RT,Tam JS,Lai FM

    更新日期:1996-12-01 00:00:00

  • Regulatory interactions between inducible nitric oxide synthase and eicosanoids in glomerular immune injury.

    abstract::In a rat model of glomerular immune injury induced by administration of anti-glomerular basement membrane antibody and resembling human rapidly progressive glomerulonephritis, we explored whether activation of inducible nitric oxide synthase (iNOS) regulates synthesis of eicosanoids originating from cyclooxygenation o...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1046/j.1523-1755.1998.00791.x

    authors: Lianos EA,Guglielmi K,Sharma M

    更新日期:1998-03-01 00:00:00

  • Albumin interaction with the glomerular capillary wall in vitro.

    abstract::The binding of albumin to the glomerular capillary wall was studied using albumin-gold in perfused kidneys, the interaction of [3H]albumin with isolated glomeruli at 37 degrees C and 4 degrees C and the interaction at [3H]albumin with purified basement membrane. The albumin-gold was found to bind predominantly to the ...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1038/ki.1995.149

    authors: Adal Y,Smit MF,Osicka TM,Comper WD

    更新日期:1995-04-01 00:00:00

  • Beta blockers in the management of chronic kidney disease.

    abstract::The sympathetic nervous system modulates renal function through its receptors namely beta1 (cardiac output and renin release), alpha1 (systemic and renovascular constriction), and beta2 renovascular dilation. Sympathetic overactivity is commonly seen in chronic kidney disease (CKD) and is an important contributor to i...

    journal_title:Kidney international

    pub_type: 杂志文章,评审

    doi:10.1038/sj.ki.5001835

    authors: Bakris GL,Hart P,Ritz E

    更新日期:2006-12-01 00:00:00

  • PDGF regulates gap junction communication and connexin43 phosphorylation by PI 3-kinase in mesangial cells.

    abstract:BACKGROUND:Gap junctional intercellular communication (GJIC) plays an important role in the regulation of cell growth, migration, and differentiation. Ultrastructural and histochemical studies indicate the existence of a high density of gap junctions among mesangial cells (MCs), but little is known about their regulati...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1046/j.1523-1755.2000.00041.x

    authors: Yao J,Morioka T,Oite T

    更新日期:2000-05-01 00:00:00

  • Functional effects of renal artery stent placement on treated and contralateral kidneys.

    abstract:BACKGROUND:This study examined the effects of stent placement for renal artery stenosis on the function of treated and contralateral kidneys. METHODS:Eighteen patients who underwent stent placement for unilateral renal artery stenosis presenting with hypertension and/or renal failure were studied before angiography an...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1046/j.1523-1755.2002.00456.x

    authors: Leertouwer TC,Derkx FH,Pattynama PM,Deinum J,van Dijk LC,Schalekamp MA

    更新日期:2002-08-01 00:00:00

  • Transcription, not synthesis, of interleukin-1 and tumor necrosis factor by complement.

    abstract::Stimulation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) production was studied during in vitro hemodialysis (HD) of whole blood using cuprammonium (Cup) or polysulfone (PS) dialyzers. In the absence of LPS, circulation of whole blood for two hours through Cup or PS dialyzers was not suffici...

    journal_title:Kidney international

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1038/ki.1990.12

    authors: Schindler R,Lonnemann G,Shaldon S,Koch KM,Dinarello CA

    更新日期:1990-01-01 00:00:00

  • Regulation of mesangial cell proliferation.

    abstract::Regardless of the source of injury, an imbalance in the control of mesangial cell proliferation appears to play a direct role in the degree of progressive renal injury and glomerulosclerosis. Some of the regulatory mechanisms include specific soluble or non-soluble extracellular factors and a complex array of receptor...

    journal_title:Kidney international

    pub_type: 杂志文章,评审

    doi:10.1046/j.1523-1755.1999.00710.x

    authors: Schöcklmann HO,Lang S,Sterzel RB

    更新日期:1999-10-01 00:00:00

  • The zebrafish pronephros: a model to study nephron segmentation.

    abstract::Nephrons possess a segmental organization where each segment is specialized for the secretion and reabsorption of particular solutes. The developmental control of nephron segment patterning remains one of the enigmas within the field of renal biology. Achieving an understanding of the mechanisms that direct nephron se...

    journal_title:Kidney international

    pub_type: 杂志文章,评审

    doi:10.1038/ki.2008.37

    authors: Wingert RA,Davidson AJ

    更新日期:2008-05-01 00:00:00

  • Positive antineutrophil cytoplasmic antibody serology in patients with lupus nephritis is associated with distinct histopathologic features on renal biopsy.

    abstract::Class IV-S lupus nephritis is often associated with more necrosis and fewer subendothelial immune deposits compared to class IV-G lupus nephritis, suggestive of necrotising glomerular inflammation found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. ANCAs are present in a significant proportion o...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1016/j.kint.2017.04.029

    authors: Turner-Stokes T,Wilson HR,Morreale M,Nunes A,Cairns T,Cook HT,Pusey CD,Tarzi RM,Lightstone L

    更新日期:2017-11-01 00:00:00

  • Alterations of glomerular podocytic processes in immunologically mediated glomerular disorders.

    abstract::The importance of the relationship between the alteration of podocytic processes (PP) and proteinuria has been controversial for almost 30 years. In spite of several morphometric studies the range of PP alterations in different proteinuric conditions has gone unnoticed. Thus, we studied the distribution of abnormally ...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1038/ki.1987.269

    authors: Fries JW,Rumpelt HJ,Thoenes W

    更新日期:1987-11-01 00:00:00

  • Cystatin C is not a better estimator of GFR than plasma creatinine in the general population.

    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

    authors: Eriksen BO,Mathisen UD,Melsom T,Ingebretsen OC,Jenssen TG,Njølstad I,Solbu MD,Toft I

    更新日期:2010-12-01 00:00:00

  • Propionyl-L-carnitine prevents early graft dysfunction in allogeneic rat kidney transplantation.

    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

    authors: Azzollini N,Cugini D,Cassis P,Pezzotta A,Gagliardini E,Abbate M,Arduini A,Peschechera A,Remuzzi G,Noris M

    更新日期:2008-12-01 00:00:00

  • Heme oxygenase-1: a provenance for cytoprotective pathways in the kidney and other tissues.

    abstract::Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme, converting heme to biliverdin, during which iron is released and carbon monoxide (CO) is emitted; biliverdin is subsequently converted to bilirubin by biliverdin reductase. At least two isozymes possess HO activity: HO-1 represents the isozyme...

    journal_title:Kidney international

    pub_type: 杂志文章,评审

    doi:10.1038/sj.ki.5001565

    authors: Nath KA

    更新日期:2006-08-01 00:00:00

  • Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction.

    abstract:BACKGROUND:The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo. METHODS:Rat renal tubular epithelial cells (NRK-52E) ...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1046/j.1523-1755.2001.0590041290.x

    authors: Miyajima A,Chen J,Poppas DP,Vaughan ED Jr,Felsen D

    更新日期:2001-04-01 00:00:00

  • Chronic metabolic acidosis accelerates whole body proteolysis and oxidation in awake rats.

    abstract::Previous work has documented an acceleration of proteolysis and branched-chain amino acid oxidation when muscles from rats with chronic metabolic acidosis were incubated in vitro. The present study examines the impact of chronic metabolic acidosis on whole body amino acid turnover and oxidation in chronically catheter...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1038/ki.1992.223

    authors: May RC,Masud T,Logue B,Bailey J,England B

    更新日期:1992-06-01 00:00:00

  • Role of cyanate in the induction of vascular dysfunction during uremia: more than protein carbamylation?

    abstract::Cyanate is a uremic toxin responsible for the carbamylation of proteins, which has been implicated as playing a key role in accelerating the progression of atherosclerosis in patients with chronic kidney disease. El-Gamal et al. report that while cyanate promotes protein carbamylation in vivo, the resulting endothelia...

    journal_title:Kidney international

    pub_type: 评论,杂志文章

    doi:10.1038/ki.2014.256

    authors: Hawkins CL

    更新日期:2014-11-01 00:00:00

  • Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2.

    abstract::Nitric oxide is synthesized in experimental immune complex glomerulonephritis due to local induction of type 2 nitric oxide synthase (NOS2). To determine the role of NOS2, the course of accelerated anti-glomerular basement membrane glomerulonephritis (anti-GBM) was examined in mice homozygous for disruption of the NOS...

    journal_title:Kidney international

    pub_type: 杂志文章

    doi:10.1111/j.1523-1755.1998.00892.x

    authors: Cattell V,Cook HT,Ebrahim H,Waddington SN,Wei XQ,Assmann KJ,Liew FY

    更新日期:1998-04-01 00:00:00