Pathogenetic mechanisms in experimental hemoglobinuric acute renal failure

1989 ◽  
Vol 256 (3) ◽  
pp. F446-F455 ◽  
Author(s):  
R. A. Zager ◽  
L. M. Gamelin
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renal Damage ◽  
Iron Chelation ◽  
Proximal Tubular Cell ◽  
Radical Scavenger ◽  
Heme Uptake ◽  
Hydroxyl Radical Scavenger ◽  
Proximal Tubular ◽  
Hemoglobin Production

To evaluate mechanisms in hemoglobinuric acute renal failure (ARF) rats were infused with hemoglobin under aciduric or alkalinuric conditions. Aciduric rats developed azotemia, distal heme casts, and proximal tubular cell (PTC) necrosis, whereas alkalinuric rats developed no renal damage. Aciduria converted hemoglobin to met-hemoglobin, which precipitated, forming distal casts and inducing ARF. Hematin formation was not observed. The importance of met-hemoglobin production was indicated by its greater toxicity than hemoglobin during aciduria and by its ability to induce ARF even under alkalinuric conditions. A link between obstructing casts and PTC necrosis was identified; tubular obstruction induced by various mechanisms (met-hemoglobin casts; ureteral ligation; ischemic ARF) increased PTC hemoglobin uptake, producing lysosomal overload (giant endolysosomes) and PTC necrosis. This worsened ischemic ARF despite an otherwise subtoxic hemoglobin dose being used that had no discernible acute renal vasoconstrictive effect. Iron chelation (deferoxamine)/hydroxyl radical scavenger (Na benzoate) therapy did not mitigate this exacerbation of ischemic injury, suggesting a nonoxidant mechanism. We conclude that H is nephrotoxic, particularly when intratubular obstruction facilitates PTC heme uptake. Thus aciduria-induced met-hemoglobin cast formation and concomitant ischemic renal injury predispose to its nephrotoxic effect.

Evidence suggesting a role for hydroxyl radical in glycerol-induced acute renal failure

1988 ◽  
Vol 255 (3) ◽  
pp. F438-F443 ◽  
Author(s):  
S. V. Shah ◽  
P. D. Walker
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Hydroxyl Radical ◽  
Tissue Injury ◽  
Iron Chelator ◽  
Radical Scavenger ◽  
Reactive Oxygen Metabolites ◽  
Protective Effects ◽  
Hydroxyl Radical Scavenger ◽  
Hydroxyl Radical Scavengers

Reactive oxygen metabolites, in particular hydroxyl radical, have been shown to be important mediators of tissue injury in several models of acute renal failure. The aim of the present study was to examine the role of hydroxyl radical in glycerol-induced acute renal failure, a model for myoglobinuric renal injury. Rats injected with glycerol alone (8 mg/kg im following dehydration for 24 h) developed significant renal failure compared with dehydrated controls. Rats treated with glycerol and a hydroxyl radical scavenger, dimethylthiourea (DMTU), had significantly lower blood urea nitrogen (BUN) and creatinine. In contrast, urea, which is chemically similar to DMTU but is not a hydroxyl radical scavenger, provided no protection. In addition, DMTU prevented the glycerol-induced rise in renal cortical malondialdehyde content (a measure of lipid peroxidation that serves as a marker of free radical-mediated tissue injury). A second hydroxyl radical scavenger, sodium benzoate, had a similar protective effect on renal function (as measured by both BUN and creatinine). Because the generation of hydroxyl radical in biological systems requires the presence of a trace metal such as iron, we also examined the effect of the iron chelator, deferoxamine on glycerol-induced renal failure. Deferoxamine was also protective. The interventional agents were also associated with a marked reduction in histological evidence of renal damage. The protective effects of two hydroxyl radical scavengers as well as an iron chelator implicate a role for hydroxyl radical in glycerol-induced acute renal failure.

Uroangiographic Contrast Media-Induced Nephropathy: Correlations between Their Physicochemical Properties and Renal Damage

2005 ◽  
Vol 72 (4) ◽  
pp. 446-456
Author(s):  
C. Alberti ◽  
M. Piovano ◽  
A. Tizzani
Keyword(s):  
Diabetes Mellitus ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Chronic Renal Failure ◽  
Contrast Media ◽  
Renal Damage ◽  
Contrast Material ◽  
Vasoactive Mediators ◽  
Adequate Hydration ◽  
Hospital Acquired

Contrast media-induced nephropathy (CN) is an important cause of hospital-acquired acute renal failure. Patients with both diabetes mellitus and renal impairment are at high risk. CN pathophysiology involves activation of the tubulo-glomerular feedback and vasoactive mediators such as renin-angiotensin 2, endothelin, adenosine, ADH, etc. The risk of CN can be minimized by the use of non-ionic, low or isoosmolar, contrast material, adequate hydration and prophylactic pharmacological measures. In patients with chronic renal failure who are undergoing arteriography (e.g. coronary angiography and angioplasty), periprocedural hemofiltration appears effective in preventing further renal damage due to contrast agents.

Role of volume depletion in the glycerol model of acute renal failure

1986 ◽  
Vol 250 (2) ◽  
pp. F315-F321
Author(s):  
H. M. Cushner ◽  
J. L. Barnes ◽  
J. H. Stein ◽  
H. J. Reineck
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Volume Expansion ◽  
Ringer Solution ◽  
Inulin Clearance ◽  
Constant Infusion ◽  
Volume Depletion ◽  
Renal Histology ◽  
Proximal Tubular ◽  
Group Averaging

Previous studies have demonstrated significant volume depletion early in the course of glycerol-induced acute renal failure. In addition, it has been shown that acute volume expansion within 6 h of glycerol administration reverses the fall in inulin clearance but volume expansion 12-24 h after glycerol fails to restore that parameter to normal. The current studies were performed to determine whether chronic volume expansion would prevent the fall in inulin clearance normally observed 18-20 h after the insult. Inulin clearance was therefore compared 18-20 h after glycerol in hydropenic rats and in rats undergoing chronic volume expansion by the constant infusion of Ringer solution at a rate of 5 ml/h initiated at the time of the glycerol injection. Inulin clearance was well maintained in the latter group, averaging 1.77 compared with 0.22 ml/min in the hydropenic group. Renal histology revealed no difference in the degree of tubular necrosis between groups but did show a marked decrease in cast formation in the animals undergoing chronic volume expansion. To determine the possible significance of these casts, micropuncture studies were carried out to measure proximal tubular pressures. Under hydropenic conditions these pressures were not different control animals and rats receiving glycerol when studied 18-20 h after glycerol. Following acute volume expansion, however, glycerol-treated rats demonstrated significantly higher pressures than control rats. On the other hand, proximal tubular pressures were comparable in glycerol-treated and control animals receiving the chronic volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

A1 adenosine receptor knockout mice are protected against acute radiocontrast nephropathy in vivo

2006 ◽  
Vol 290 (6) ◽  
pp. F1367-F1375 ◽  
Author(s):  
H. Thomas Lee ◽  
Michael Jan ◽  
Soo Chan Bae ◽  
Jin Deok Joo ◽  
Farida R. Goubaeva ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Proximal Tubule ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Proximal Tubule Cells ◽  
Proximal Tubular ◽  
Tubule Cells

The role of renal A1 adenosine receptors (A1AR) in the pathogenesis of radiocontrast nephropathy is controversial. We aimed to further elucidate the role of A1AR in the pathogenesis of radiocontrast nephropathy and determine whether renal proximal tubule A1AR contribute to the radiocontrast nephropathy. To induce radiocontrast nephropathy, A1AR wild-type (WT) or knockout (KO) mice were injected with a nonionic radiocontrast (iohexol, 1.5–3 g iodine/kg). Some A1WT mice were pretreated with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; a selective A1AR antagonist) before iohexol injection. A1AR contribute to the pathogenesis of radiocontrast nephropathy in vivo as the A1WT mice developed significantly worse acute renal failure, more renal cortex vacuolization, and had lower survival 24 h after iohexol treatment compared with the A1KO mice. DPCPX pretreatment also protected the A1WT mice against radiocontrast-induced acute renal failure. No differences in renal cortical apoptosis or inflammation were observed between A1WT and A1KO mice. To determine whether the proximal tubular A1AR mediate the direct renal cytotoxicity of radiocontrast, we treated proximal tubules in culture with iohexol with or without 2-chloro- N6-cyclopentyladenosine (a selective A1AR agonist) or DPCPX pretreatment. We also subjected cultured proximal tubule cells overexpressing A1AR or lacking A1AR to radiocontrast injury. Iohexol caused a direct dose-dependent reduction in proximal tubule cell viability as well as proliferation. Neither the A1AR agonist nor the antagonist treatment affected proximal tubule viability or proliferation. Moreover, overexpression or lack of A1AR failed to impact the iohexol toxicity on proximal tubule cells. Therefore, we conclude that radiocontrast causes acute renal failure via mechanisms dependent on A1AR; however, renal proximal tubule A1AR do not contribute to the direct tubular toxicity of radiocontrast.

Inhibition of bFGF-receptor type 2 increases kidney damage and suppresses nephrogenic protein expression after ischemic acute renal failure

2008 ◽  
Vol 294 (3) ◽  
pp. R819-R828 ◽  
Author(s):  
Sandra Villanueva ◽  
Carlos Cespedes ◽  
Alexis A. Gonzalez ◽  
Eric Roessler ◽  
Carlos P. Vio
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Growth Factor ◽  
Renal Damage ◽  
Kidney Development ◽  
Smooth Muscle Actin ◽  
Ischemia Reperfusion ◽  
Recovery Process ◽  
Time Frame ◽  
Altered Expression

Recovery from acute renal failure (ARF) requires the replacement of injured cells by new cells that are able to restore tubule epithelial integrity. We have recently described the expression of nephrogenic proteins [Vimentin, neural cell adhesion molecule, basic fibroblast growth factor (bFGF), Pax-2, bone morphogen protein-7, Noggin, Smad 1-5-8, p-Smad, hypoxia-inducible factor-1α, vascular endothelial growth factor], in a time frame similar to that observed in kidney development, after ischemic ARF induced in an ischemia-reperfusion (I/R) model. Furthermore, we show that bFGF, a morphogen involved in mesenchyme/epithelial transition in kidney development, induces a reexpression of morphogenic proteins in an earlier time frame and accelerates the recovery process after renal damage. Herein, we confirm that renal morphogenes are modulated by bFGF and hypothesized that a decrease in bFGF receptor 2 (bFGFR2) levels by the use of antisense oligonucleotides diminishes the expression of morphogenes. Male Sprague-Dawley rats submitted to ischemic injury were injected with 112 μg/kg bFGFR2 antisense oligonucleotide (bFGFR2-ASO) followed by reperfusion. Rats were killed, and the expression of nephrogenic proteins and renal marker damage was analyzed by immunohistochemistry and immunoblot. Animals subjected to I/R treated with bFGFR2-ASO showed a significant reduction in morphogen levels ( P < 0.05). In addition, we observed an increase in markers of renal damage: macrophages (ED-1) and interstitial α-smooth muscle actin. These results confirm that bFGF participates in the recovery process and that treatment with bFGFR2-ASO induces an altered expression of morphogen proteins.

scholarly journals Acute renal failure after rifampicin

1984 ◽  
Vol 26 (6) ◽  
pp. 341-345 ◽  
Author(s):  
Adriana Weinberg ◽  
A. Barone ◽  
Luis B. Saldanha ◽  
Mario Shiroma
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Renal Damage ◽  
Miliary Tuberculosis ◽  
Granulomatous Lesion ◽  
Granulomatous Interstitial Nephritis ◽  
The Third ◽  
Tubular Necrosis ◽  
High Incidence

A patient with miliary tuberculosis and a chronic urogenital focus is described, who had a borderline renal function at diagnosis and developed overt renal failure upon daily treatment with rifampin (RMP), isoniazid (INH) and ethambutol (EMB). This is the first Brazilian report of BMP induced renal damage. A renal biopsy taken on the third day of oliguria showed recent tubular necrosis with acute interstitial inflammation and granuloma formation. The aspect of the granulomatous lesion hightly suggested drug etiology because of the lack of palisading, high incidence of neutrophils and absence of facid-fast bacilli. This is the first presentation of an acute granulomatous interstitial nephritis probably due to RMP. Furthermore the pathogenesis of the renal damage caused by tuberculosis and RMP are discussed.

N-acetyl-l-cysteine improves renal medullary hypoperfusion in acute renal failure

2001 ◽  
Vol 281 (3) ◽  
pp. R730-R737 ◽  
Author(s):  
Erica López Conesa ◽  
Fernando Valero ◽  
José Carlos Nadal ◽  
Francisco J. Fenoy ◽  
Bernardo López ◽  
...  
Keyword(s):  
Renal Failure ◽  
Blood Flow ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Renal Blood Flow ◽  
Vena Cava ◽  
Laser Doppler ◽  
Radical Scavenger ◽  
Outer Medulla ◽  
Doppler Flowmetry

This study evaluated the effects of N-acetyl-l-cysteine (NAC), a free radical scavenger, and N ω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthesis inhibitor, on the changes in renal function, intrarenal blood flow distribution (laser-Doppler flowmetry), and plasma peroxynitrite levels during the acute renal failure (ARF) produced by inferior vena cava occlusion (IVCO; 45 min) in anesthetized rats. Renal blood flow fell on reperfusion (whole kidney by −45.7%; cortex −58.7%, outer medulla −62.8%, and papilla −47.7%); glomerular filtration rate (GRF) also decreased (−68.6%), whereas fractional sodium excretion (FENa%) and peroxynitrite and NO[Formula: see text]/NO[Formula: see text] plasma levels increased (189.5, 46.5, and 390%, respectively) after ischemia. Pretreatment with l-NAME (10 μg · kg−1 · min−1) aggravated the fall in renal blood flow seen during reperfusion (−60%). Pretreatment with NAC (150 mg/kg bolus + 715 μg · kg−1 · min−1 iv) partially prevented those changes in renal function (GFR only fell by −29.2%, and FENa% increased 119.4%) and laser-Doppler blood flow, especially in the outer medulla, where blood flow recovered to near control levels during reperfusion. These beneficial effects seen in rats given NAC seem to be dependent on the presence of NO, because they were abolished in rats pretreated with l-NAME. Also, the antioxidant effects of NAC prevented the increase in plasma peroxynitrite after ischemia. In conclusion, NAC ameliorates the renal failure and the outer medullary vasoconstriction induced by ICVO, effects that seem to be dependent on the presence of NO and the scavenging of peroxynitrite.

Prevention of ischemic acute renal failure with impermeant solutes

1983 ◽  
Vol 244 (6) ◽  
pp. F646-F649 ◽  
Author(s):  
T. J. Burke ◽  
P. E. Arnold ◽  
R. W. Schrier
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Hydrostatic Pressure ◽  
Glomerular Filtration ◽  
Hypertonic Saline ◽  
Saline Group ◽  
Solute Permeability ◽  
Filtration Pressure ◽  
Proximal Tubular ◽  
Ischemic Acute Renal Failure

Studies were performed to evaluate the effect of solute permeability and extracellular osmolality in protecting against ischemic acute renal failure. The functional protective effect of a 1-min intrarenal perfusion (prior to intrarenal norepinephrine 0.75 micrograms . kg-1 . min-1) of a hypertonic permeant solute (hypertonic saline, 1,400 mosmol/kg H2O) and an isotonic impermeant solute (isotonic mannitol, 280 mosmol/kg H2O or isotonic polyethylene glycol, IPEG, 300 mosmol/kg H2O) was evaluated. Three hours after ischemia, the glomerular filtration rate was significantly lower in hypertonic saline group vs. either the isotonic mannitol- or IPEG-treated animals (2.4 vs. 8.9 and 10.4 ml/min, respectively; both P less than 0.05). Mean renal blood flow was similar in all three groups. The effects of hypertonic saline and IPEG on glomerular filtration pressure and tubular obstruction were also evaluated. Stop-flow pressure, as an index of glomerular filtration pressure, was higher in the IPEG- vs. the hypertonic saline-treated animals (40 vs. 35 mmHg, P less than 0.001). Although proximal tubular pressure was increased in both groups, transglomerular hydrostatic pressure was higher in the IPEG vs. the hypertonic saline group (13 vs. 6 mmHg, P less than 0.01). Tubular microperfusion studies demonstrated increases in proximal tubular pressure in the hypertonic saline but not the IPEG studies. The present results indicate that isotonic, impermeant solutes provide functional protection against ischemic acute renal failure. The beneficial effect of impermeant solute is mediated, at least in part, by better maintenance of transglomerular hydrostatic pressure and prevention of secondary tubular obstruction.

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