Norepinephrine-induced acute renal failure: A reversible ischemic model of acute renal failure

Cronin, Robert E.; Erickson, Abby M.; Torrenté, Antoine de; McDonald, Keith M.; Schrier, Robert W.

doi:10.1038/ki.1978.106

Cited by 104 publications

(49 citation statements)

References 7 publications

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“…The absence of inulin extraction during five of these anuric episodes is consistent with cessation ofglomerular filtration due to tubular obstruction with a severe reduction of AP (4,5). Profound reduction of Kf, however, could also explain this finding (2). Similarly, continued formation offiltrate with backleak ofinulin into the peritubular capillaries, and subsequent return to the renal vein, could likewise account for the paradox of negligible renal inulin extraction in the face of adequate renal perfusion during anuria.…”

Section: Discussionmentioning

confidence: 67%

“…Most commonly, renal blood flow has been interrupted either mechanically or pharmacologically for 40-60 min. Transient but total renal ischemia (TRI) of this duration in the dog, rat, or rabbit is followed invariably by a lesion whose clinical manifestations, laboratory features, and pathology resemble closely those of human acute renal failure (1,2). Micropuncture studies in vivo or perfusion of isolated renal tubules in vitro have revealed that an ensuing oliguria is attributable not only to a reduced glomerular filtration rate (GFR) but also to sequestration of tubule fluid within obstructed tubules, and to backleak of tubule fluid across necrotic epithelium into the interstitium (1, [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Nature of the renal injury following total renal ischemia in man.

Myers¹,

Miller²,

Mehigan³

et al. 1984

J. Clin. Invest.

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As bstract. The effects of total renal ischemia (TRI) of 15-87 min duration due to suprarenal clamping of the aorta were studied in 15 mannitol-treated patients undergoing abdominal aortic surgery. 15 patients undergoing similar surgery but requiring only infrarenal clamping served as controls. 1-2 h following TRI, GFR was reduced to only 39% of that in controls, 23±5 vs. 59±7 ml/min (P < 0.001). This could not be ascribed to impaired renal plasma flow (RPF), which was mildly reduced to 331±71 and was not different from the value in controls, 407±66 ml/min. However, impaired PAH extraction (43±7%) and isosthenuria, not present in controls, suggest a primary role for tubular injury in lowering GFR at this time.24 h following TRI, the GFR remained depressed below controls, 45±8 vs. 84±8 ml/min (P < 0.005), while the transglomerular sieving of neutral dextrans was significantly enhanced (radius interval, 24-40 A). A theoretical analysis of transcapillary solute exchange revealed that these findings could be largely explained by a selective reduction of either RPF (-61%) or of transmembrane hydraulic pressure difference (-18%) below control values. Alternately, a combination of these two factors with changes of smaller magnitude could explain the findings. In contrast, a selective increase in oncotic pressure or decrease ofthe glomerular ultrafiltration coefficient could be excluded as a cause of hypofiltration 24 h after TRI. These observations lead us to suggest that the transient azotemia observed following TRI is due to a self-limited

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Nature of the renal injury following total renal ischemia in man.

Myers¹,

Miller²,

Mehigan³

et al. 1984

J. Clin. Invest.

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“…8 Acute renal failure thought to be secondary to ischemia can also be induced with larger intrarenal doses of norepinephrine. 9 One way to examine the effects of chronic adrenergic stimulation is by administering catecholamines chronically to animals. Interestingly, chronic infusions of catecholamines in rats only cause a modest increase (10 to 20 mm Hg) in mean systolic BP, 3,10 which is at a level that is usually not associated with renal damage.…”

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confidence: 99%

Renal Injury and Salt-Sensitive Hypertension After Exposure to Catecholamines

et al. 1999

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Abstract-We investigated whether chronic infusion of phenylephrine could induce structural and functional changes in the kidney of rats with the subsequent development of salt-sensitive hypertension. Rats were infused with phenylephrine (0.15 mmol/kg per day) by minipump, resulting in a moderate increase in systolic blood pressure (BP) (17 to 25 mm Hg) and a marked increase in BP variability as measured by an internal telemetry device. After 8 weeks, the phenylephrine infusion was stopped with the return of BP to normal, and a nephrectomy was performed for histological studies. Glomeruli were largely spared, but focal tubulointerstitial fibrosis was present, with the de novo expression of osteopontin by injured tubules, macrophage and "myofibroblast" accumulation, and focal increases in mRNA for transforming growth factor ␤ by in situ hybridization. Peritubular capillaries at sites of injury had distorted morphology with shrinkage, rounding, and focal rarefaction, and endothelial cell proliferation was also identified. Rats were randomized to a high (8% NaCl or 1.36 mol/kg) or low (0.1% NaCl or 17 mmol/kg) salt diet. After 4 to 8 weeks, phenylephrine-treated rats on a high salt diet developed marked hypertension, which was in contrast with phenylephrine-treated rats placed on a low salt diet or vehicle-treated rats given a high salt diet. Hypertension after phenylephrine exposure correlated with the initial mean systolic BP (r 2 ϭ0.99) and the degree of BP lability (r 2 ϭ0.99) during the phenylephrine infusion, the amount of osteopontin expressed in the initial biopsy/nephrectomy (r 2 ϭ0.74), and the final glomerular filtration rate (r 2 ϭ0.58). These studies provide a mechanism by which a markedly elevated sympathetic nervous system can induce salt-dependent hypertension even when the hyperactive sympathetic state is no longer engaged. (Hypertension. 1999;34:151-159.) Key Words: phenylephrine Ⅲ renal circulation Ⅲ hypertension, episodic Ⅲ sympathetic nervous system T here is ample evidence that a hyperactive sympathetic nervous system (SNS) is present in some forms of human hypertension, especially in early, borderline essential hypertension. 1 In addition to the acute effects of SNS activation to raise blood pressure (BP), adrenergic stimulation may induce target organ damage by both hemodynamic and nonhemodynamic mechanisms. 2 Adrenergic stimulation can be associated with left ventricular hypertrophy as well as hypertrophy and stiffening of large arteries. Adrenergic agents have also been shown to stimulate vascular smooth muscle cell proliferation and hypertrophy both in vivo and in vitro. 3,4 We have been interested in the potential role of the SNS as a mediator of renal injury. It is known that catecholamine infusions can induce acute elevations in glomerular hydrostatic pressure in association with intense renal vasoconstriction and a fall in renal blood flow (RBF). 5,6 Infusions of norepinephrine can also induce microalbuminuria in both normal and diabetic individuals. 7 A combination of intrarenal and i...

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“…Its potential as a general renal pro tective agent has been suggested in several experimental models: Mannitol has been shown to prevent ischemic renal failure in dogs and to maintain glomerular filtration rate during renal hypoperfusion in rats [129,130].…”

Section: Mannitoland Furosemidementioning

confidence: 99%

Current concepts in contrast media-induced nephropathy.

Tublin¹,

Murphy²,

Tessler³

1998

American Journal of Roentgenology

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This phenomenon, termed â€oe¿ contrast media induced nephropathy,â€• has been reported to be the third most common cause of hospital acquired renal failure after surgery and hy potension I I ], making it a significant cause of morbidity andmortality.Although theex istence of contrast mediaâ€"induced nephropa thy is universally accepted, its pathogenesis and the potential benefit, if any, of newer contrast medium formulations and prophy lactic regimens are controversial. This article provides a practical overview of all aspects of contrast mediaâ€"induced nephropathy, in cluding epidemiology, mechanisms, treat ment, and prevention. EpidemiologyEarly case reports noted the ability of ra diographic contrast media to induce renal failure. By the 1950s, contraindication of contrast media in patients with preexisting renal impairment was generally accepted [2, 31. Nevertheless,many researcherscontin ued to advocate high-dose urography to en hance opacitication of the genitourinary tract in patients with renal insufficiency. These re searchers thought that, as long as patients were appropriately hydrated, the nephrotoxic effects of contrast media could be largely dis counted [4â€"7].However, subsequent large scale retrospective and prospective studies have clearly shown the potential of radio graphic contrast media to induce acute renal failure, particularly in patients with preexisting azotemia [8â€"20].Although nearly all studies have confirmed the existence of contrast mediaâ€"inducedneph ropathy, the reported incidence has varied widely. A recent review of seven retrospective and eight prospective studies of contrast me diaâ€"inducednephropathy reported incidence rates ranging from 5% to 17% and from 0% to 22%, respectively [21]. In large measure, the marked variation in the reported incidence of contrast mediaâ€"inducednephropathy can be attributed to the differing criteria used to de fine the disease. Ideally, renal impairment should be assessed by serial measurements of creatinine clearance. However, practical con siderations have forced many investigators to rely on isolated serum creatinine measure ments. Percentage increases in serum creati nine level ranging from 20% to 50% have been arbitrarily chosen as markers for signifi cant renal impairment. Absolute threshold in creases in creatinine from as little as 0.3 mg/dl to as large a.s I .0 mg/dl have also been applied [22]. Differences in the timing of serum creat mine measurements after contrast medium ad ministration have also made comparison of studies difficult. Finally, the presence of mul tiple comorbid risk factors has complicated at tempts to define a global prevalence rate for contrast mediaâ€"induced nephropathy. Retro spective studies of patients without predispos ing risk factors have suggested an incidence rate of less than I% [23, 241, whereas large prospective studies have indicated an average rate of 3% in patients without diabetes or pre existing azotemia [9, 25â€"28]. Controversies about appropriate definitions and measurements should not...

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Norepinephrine-induced acute renal failure: A reversible ischemic model of acute renal failure

Cited by 104 publications

References 7 publications

Nature of the renal injury following total renal ischemia in man.

Nature of the renal injury following total renal ischemia in man.

Renal Injury and Salt-Sensitive Hypertension After Exposure to Catecholamines

Current concepts in contrast media-induced nephropathy.

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