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Citations to this article

Acute renal failure with selective medullary injury in the rat.
S N Heyman, … , F H Epstein, S Rosen
S N Heyman, … , F H Epstein, S Rosen
Published August 1, 1988
Citation Information: J Clin Invest. 1988;82(2):401-412. https://doi.org/10.1172/JCI113612.
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Acute renal failure with selective medullary injury in the rat.

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Abstract

Since human acute renal failure (ARF) is frequently the result of multiple rather than single insults, we used a combination of treatments to induce ARF in rats. Uninephrectomized, salt-depleted rats injected with indomethacin developed ARF after administration of radiocontrast. After 24 h, the plasma creatine rose from 103 +/- 3 to 211 +/- 22 mumol/liter (mean +/- SE) and the creatinine clearance dropped from 0.7 +/- 0.1 to 0.2 +/- 0.04 ml/min (P less than 0.001). Severe injury was confined to the outer medulla and comprised necrosis of medullary thick ascending limbs (mTALs), tubular collapse, and casts. Other nephron segments were free of damage except for the proximal convoluted tubules which showed vacuole formation originating from lateral limiting membranes that resembled changes reported in human contrast nephropathy. Cell damage to mTALs included mitochondrial swelling, nuclear pyknosis, and cytoplasmic disruption with superimposed calcification; these changes were most severe in the deepest areas of the outer medulla, away from vasa recta in zones remote from oxygen supply. The fraction of mTALs with severe damage was 30 +/- 7% (range 2-68) and the extent of injury was correlated with a rise in plasma creatinine (r = 0.8, P less than 0.001). Thus, the nature of mTAL injury was similar to the selective lesions observed in isolated kidneys perfused with cell-free medium and was shown to derive from an imbalance between high oxygen demand by actively transporting mTALs and the meager oxygen supply to the renal medulla. Combined multiple renal insults in the rat produce ARF that resembles the clinical syndrome of contrast nephropathy and is characterized by selective mTAL injury conditioned by medullary hypoxia.

Authors

S N Heyman, M Brezis, C A Reubinoff, Z Greenfeld, C Lechene, F H Epstein, S Rosen

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M Brezis, S Rosen
The American journal of physiology 1999
Nephrotoxicity of contrast media
G Deray
Nephrology Dialysis Transplantation 1999
Hypercholesterolemia aggravates radiocontrast nephrotoxicity: Protective role of L-arginine
L Andrade, SB Campos, AC Seguro
Kidney International 1998
Prevention of contrast-media-induced renal impairment by adenosine antagonists in humans
CM Erley, H Osswald
Drug Development Research 1998
Contrast media-induced nephrotoxicity--questions and answers
SK Morcos
British Journal of Radiology 1998
Acute Renal Failure in Experimental Envenomation with Africanized Bee Venom
MA Reis, RS Costa, TM Coimbra, VP Teixeira
Renal Failure 1998
Critical Care Nephrology
C Ronco, R Bellomo
1998
Renal microcirculation and tissue damage during acute ureteral obstruction in the rat: Effect of saline infusion, indomethacin and radiocontrast
SN Heyman, S Fuchs, R Jaffe, A Shina, L Ellezian, M Brezis, S Rosen
Kidney International 1997
The SHR as a Small Animal Model for Radiocontrast Renal Failure. Relation of Nephrotoxicity to Animal's Age, Gender, Strain, and Dose of Radiocontrast
CG Duarte, J Zhang, S Ellis
Renal Failure 1997
The role of endothelin in radiocontrast nephropathy
A Anarat, N Duman, A Noyan, M Kibar, R Anarat
International Urology and Nephrology 1997
MR assessment of iodinated contrast-medium-induced nephropathy in rats using ultrasmall particles of iron oxide
JP Laissy, S Benderbous, JM Idée, S Chillon, H Beaufils, E Schouman-Claeys
Journal of Magnetic Resonance Imaging 1997
Endothelin and atrial natriuretic peptide levels following radiocontrast exposure in humans
BA Clark, D Kim, FH Epstein
American Journal of Kidney Diseases 1997
Contrast media induced changes in tubular electrophysiology and glomerular filtration rate in the mouse kidney
NS Morgunov, GS Foster, DJ Hirsch
Canadian Journal of Physiology and Pharmacology 1997
Suki and Massry’s THERAPY OF RENAL DISEASES AND RELATED DISORDERS
WN Suki, SG Massry
1997
Nitric Oxide and the Kidney
MS Goligorsky, SS Gross
1997
Adenosine modulates vasomotor tone in outer medullary descending vasa recta of the rat
EP Silldorff, MS Kreisberg, TL Pallone
Journal of Clinical Investigation 1996
Reliability of Experimental Models of Iodinated Contrast Media-Induced Acute Renal Failure
JM Idée, B Bonnemain
Investigative Radiology 1996
Glomerular filtration and saturable absorption of iohexol in the rat isolated perfused kidney
R Masereeuw, MM Moons, P Smits, FG Russel
British Journal of Pharmacology 1996
Aspects of contrast media nephrotoxicity
SK Morcos, FH Epstein, J Haylor, M Dobrota
European Journal of Radiology 1996
Continuous urine oxygen tension monitoring in patients undergoing cardiac surgery
M Kainuma, M Yamada, T Miyake
Journal of Cardiothoracic and Vascular Anesthesia 1996
Effects of Mannitol and Iohexol Infusions on the Renal Cortical Blood Flow in Dehydrated Mice
B Högström, SO Hietala, P Rooth
Acta Radiologica 1996
Rapid DNA fragmentation from hypoxia along the thick ascending limb of rat kidneys
R Beeri, Z Symon, M Brezis, SA Ben-Sasson, PH Baehr, S Rosen, RA Zager
Kidney International 1995
The effect of contrast agents on renal function
S Dorph
European Radiology 1995
Contrast media injection in the rat after multiple renal insults no evidence of additional nephrotoxicity
A Verbacys, N Lameire, S Ringoir, M Praet, GV Maele
Urological Research 1995
Influence of feeding, blood sampling method and type of anaesthesia on renal function parameters in the normal laboratory rat
A Verbaeys, S Ringoir, GV Maele, N Lameire
Urological Research 1995
Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat
Y Agmon, H Peleg, Z Greenfeld, S Rosen, M Brezis
Journal of Clinical Investigation 1994
Risk of radiocontrast nephropathy in patients with and without diabetes mellitus
LS Weisberg, PB Kurnik, BR Kurnik
Kidney International 1994
Iodinated contrast media-induced nephropathy: pathophysiology, clinical aspects and prevention
JM Idée, H Beaufils, B Bonnemain
Fundamental & Clinical Pharmacology 1994
Physiology of Renal Hypoxiaa
FH Epstein, Y Agmon, M Brezis
Annals of the New York Academy of Sciences 1994
Contrast nephrotoxicity: Predictive value of urinary enzyme markers in a rat model
SG Naidu, FT Lee
Academic Radiology 1994
Current Perspectives on Intravascular Contrast Agents for Radiological Imaging
JJ Keizur, S Das
The Journal of Urology 1994
In Vivo Fluorescence Microscopy of Microcirculation in the Renal Cortex of Mice: Part V. Effects of Mannitol and Iohexol Infusions in Normal, Obese/Hyperglycemic and Diabetic Mice
B Högström, SO Hietala, P Rooth
Acta Radiologica 1994
Role of endothelin and prostaglandins in radiocontrast-induced renal artery constriction
LG Cantley, K Spokes, B Clark, EG McMahon, J Carter, FH Epstein
Kidney International 1993
In Vivo Fluorescence Microscopy of Microcirculation in the Renal Cortex of Mice: Part III. Effects of Mannitol and Iohexol Infusions after Pretreatment with Cyclosporin A
B Högström, SO Hietala, P Rooth
Acta Radiologica 1993
In Vivo Fluorescence Microscopy of Microcirculation in the Renal Cortex of Mice: Part IV. Effects of Mannitol and Iohexol Infusions after Temporary Renal Ischemia
B Högström, SO Hietala, P Rooth
Acta Radiologica 1993
Nephrology and Urology in the Aged Patient
DG Oreopoulos, MF Michelis, S Herschorn
1993
Determinants of Intrarenal Oxygenation: Factors in Acute Renal Failure
S Rosen, FH Epstein, M Brezis
Renal Failure 1992
Forefronts in Nephrology: Summary of the Newer Aspects of Renal Cell Injury
M Brezis
Kidney International 1992
Effect of Glycine and Hypertrophy on Renal Outer Medullary Hypoxic Injury in Ischemia Reflow and Contrast Nephropathy
SN Heyman, M Brezis, FH Epstein, K Spokes, S Rosen
American Journal of Kidney Diseases 1992
Cyclosporine Nephropathy: Morphometric Analysis of the Medullary Thick Ascending Limb
IE Stillman, M Brezis, Z Greenfeld, BJ Ransil, SN Heyman, S Rosen
American Journal of Kidney Diseases 1992
Radiocontrast–induced nephropathy in humans: Role of renal vasoconstriction
LS Weisberg, PB Kurnik, BR Kurnik
Kidney International 1992
International Yearbook of Nephrology 1993
VE Andreucci, LG Fine
1992
Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys
M Brezis, SN Heyman, D Dinour, FH Epstein, S Rosen
Journal of Clinical Investigation 1991
Effects of graded oxygen tension on adenosine release by renal medullary and thick ascending limb suspensions
RE Beach, BA Watts, DW Good, CR Benedict, TD DuBose
Kidney International 1991
Early renal medullary hypoxic injury from radiocontrast and indomethacin
SN Heyman, M Brezis, FH Epstein, K Spokes, P Silva, S Rosen
Kidney International 1991
Diabetic Nephropathy: Changing Concepts of Pathogenesis and Treatment
DS Bell
The American Journal of the Medical Sciences 1991
Absence of Functional Renal Effects of Uro-Angiographic Contrast Media on Post-Ischemic Rat Kidneys
A Verbaeys, GV Maele, WD Sy, S Ringoir, N Lameire
Acta Radiologica 1991
Effect of Indomethacin and Salt Depletion on Renal Proton MR Imaging: An Experimental Study in the Rat
SN Heyman, M Mammen
Acta Radiologica 1991
Use of Iodinated Contrast Media in Patients with Chronic Renal Insufficiency and in End-Stage Renal Disease
NA Nora, FA Krumlovsky
The International Journal of Artificial Organs 1991
Update 1991
JL Vincent
1991
Hypercalcemic nephropathy: Chronic disease with predominant medullary inner stripe injury
S Rosen, Z Greenfeld, J Bernheim, M Rathaus, E Podjarny, M Brezis
Kidney International 1990
Morphometric correlates of renal excretory function
AJ Howie, BK Gunson, J Sparke
The Journal of Pathology 1990
Angiotensin II augments medullary hypoxia and predisposes to acute renal failure
M Brezis, Z Greenfeld, A Shina, S Rosen
European Journal of Clinical Investigation 1990
Ultrastructure of medullary tubules in ischemic acute tubular necrosis and acute interstitial nephritis in man
TS Olsen, HE Hansen
APMIS 1990
Induction and prevention of radiocontrast-induced nephropathy in dogs with heart failure
KB Margulies, LJ Mckinley, PG Cavero, JC Burnett
Kidney International 1990
Experimental contrast-associated nephropathy and its clinical implications
GA Porter
The American Journal of Cardiology 1990
Contrast nephropathy in azotemic diabetic patients undergoing coronary angiography
CL Manske, JM Sprafka, JT Strony, Y Wang
The American Journal of Medicine 1990
Adriamycin Nephrosis and Contrast Media: A Comparison between Diatrizoate and Iohexol in Rats
HS Thomsen, K Golman, L Hemmingsen, S Larsen, P Skaarup
Acta Radiologica 1990
Low Sodium Diet, Indomethacin, and Contrast Media: A Comparison between Renal Effects of Diatrizoate and Iohexol in Rats
HS Thomsen, L Hemmingsen, K Golman, P Skaarup, S Larsen
Acta Radiologica 1990
Acute Renal Failure in the Intensive Therapy Unit
D Bihari, G Neild
1990
Frontiers in European Radiology
AL Baert, FH Heuck
1990
Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure
HD Humes, DA Cieslinski, TM Coimbra, JM Messana, C Galvao
Journal of Clinical Investigation 1989
Renal medullary Na-K-ATPase and hypoxic injury in perfused rat kidneys
FH Epstein, P Silva, K Spokes, M Brezis, S Rosen
Kidney International 1989
Adenine nucleotides, transport activity and hypoxic necrosis in the thick ascending limb of Henle
PF Shanley, GC Johnson
Kidney International 1989
Nephrotoxicity of contrast media
AS Berns
Kidney International 1989
A Closer Look at Radiocontrast-Induced Nephropathy
M Brezis, FH Epstein
New England Journal of Medicine 1989
The Pathophysiological Implications of Medullary Hypoxia
M Brezis, SN Rosen, FH Epstein
American Journal of Kidney Diseases 1989
The Vulnerability of the Thin Descending Limbs of Henle's Loop in the Isolated Perfused Rat Kidney
J Kopolovic, M Brezis, K Spokes, P Silva, F Epstein, S Rosen
American Journal of Kidney Diseases 1989
Protective Role of Furosemide and Saline in Radiocontrast-Induced Acute Renal Failure in the Rat
SN Heyman, M Brezis, Z Greenfeld, S Rosen
American Journal of Kidney Diseases 1989
Southwestern Internal Medicine Conference: Renal Failure Following Radiologic Procedures
RE Cronin
The American Journal of the Medical Sciences 1989
Nephrotoxicity of Cyclosporin a and Contrast Media: A Comparison between Diatrizoate and Iohexol in Rats
HS Thomsen, S Larsen, P Skaarup, L Hemmingsen, H Dieperink, K Golman
Acta Radiologica 1989

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