Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Out of 85 rabbits 2j received a purified 6% hemoglobin solution free of ghosts (1,8 gHb/Kg) and were compared to 14 animals receiving the same dose of a crude hemoglobin solution containing ghosts. 11 rabbits had 5 infusions with a daily dose of 1,2 g Hb/Kg of the stromafree solution. Controls were partly untreated partly infused with saline. Creatinin, urea, electrolytes, and haptoglobin were determined in the serum oxygen consumption was measured separately in cortex and medulla by Warburg technique, and all kidneys examined histologically. In both groups 20% of the animals died spontaneously. Both groups exhibited the typical morphological and functional signs of acute renal failure. There was an increase in creatinin, urea, and potassium in the serum and a gain in kidney weights. In cortex and medulla we found a 20% drop in O2 consumption in both groups. Thus there was no evidence that ghosts play any role in the pathogenesis of renal failure in hemolysis or in the course of Hb-infusions. even after 5 infusions with lower dose renal damage was demonstrable. The drop in haptoglobin levels indicates, that renal ischemia may be induced by a disturbance in hemoglobin breakdown. The pathogenesis of renal damage has to be elucidated before Hb-solutions come into therapeutical use.
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PMID:[Acute renal failure after the infusion of hemoglobin solutions with or without red cell ghosts in rabbits (author's transl)]. 123 60

Acute renal failure (ARF) is a serious complication in clients who have undergone bone marrow transplantation (BMT). The majority of cases develop as a result of intrarenal damage. Renal ischemia or nephrotoxic drugs, free hemoglobin, and free myoglobin contribute to acute tubular necrosis (ATN), which is the most likely cause of ARF in BMT clients. Nursing care of hospitalized BMT clients is directed toward the prevention of ARF by identifying clients who are at risk, the early diagnosis of renal impairment, and the administration of comprehensive treatment. Nurses play a vital role in the early diagnosis of renal impairment by assessing the client's fluid status, serum and urine electrolyte levels, and daily weights. The nursing role in managing clients with ARF includes preventing drug nephrotoxicity, maintaining fluid and electrolyte balance, preventing infection, and providing emotional support.
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PMID:Acute renal failure in bone marrow transplantation. 143 67

The influence of diltiazem and/or allopurinol on kidney microcirculation was studied in anaesthetized rats, which were subjected to 60 min unilateral renal ischemia followed by 60 min reflow. In histological sections capillary plasma flow patterns were determined based on the distribution of two different fluorochrome-labelled globulins administered i.v.. In the outer medulla (OM) of untreated postischemic kidneys labelling of the capillary network was greatly diminished. Tissue areas occupied by red blood cells increased 4-6 fold. During reperfusion massive penetration of red cells in the urine was demonstrated by the occurrence of hemoglobin in the urine. Maintenance of the rats on allopurinol-saturated drinking water for six days prior to the experiment (daily intake approximately 50 mg allopurinol/kg body wt) combined with the i.v. administration of diltiazem during the pre- and postischemic period (16 mg/kg body wt) resulted in an almost complete normalization of capillary plasma flow patterns in the OM. In this region tissue areas occupied by red blood cells were much lesser in extent than in the untreated controls. Furthermore, urine hemoglobin content after the combined drug regimen was largely decreased when compared to the untreated ischemic group. Effects of the treatment with either of the drugs alone were qualitatively similar, but significantly less pronounced. In conclusion, a synergistic effect of diltiazem and allopurinol in improving postischemic renal microcirculation is clearly evident, whereas no improvement in kidney function was demonstrable. This supports the hypothesis that disturbed microcirculation is not a prerequisite for the generation of the renal functional deterioration in the clamp-induced ischemia model in the rat.
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PMID:Effects of diltiazem and allopurinol in postischemic microcirculatory changes in the rat kidney. 206 Sep 98

In ischemic acute renal failure oxygen free radicals may mediate injury. In addition, iron appears to play a critical role in hydroxyl radical formation and lipid peroxidation during reperfusion of ischemic kidneys. To determine whether iron may play a similar role in pigment (heme protein)-induced acute renal failure, we studied the effects of the iron chelator deferoxamine in two experimental models of pigment-induced acute renal failure, intramuscular glycerol injection and intravenous hemoglobin infusion without and with concurrent ischemia in the rat. Intramuscular injection of 50% glycerol (5 ml/kg) caused inulin clearance to fall to 0.13 +/- 0.03 (SE) ml/min (normal value, 1.0-1.2 ml/min). Continuous infusion of deferoxamine beginning at the time of glycerol injection significantly attenuated this renal dysfunction. Deferoxamine-treated animals had an inulin clearance of 0.37 +/- 0.06 ml/min (P less than 0.01). Glycerol injection was also associated with significant lipid peroxidation, measured as renal malondialdehyde content. Deferoxamine-treated glycerol-injected rats had renal malondialdehyde content not significantly different from control animals. In another model of heme pigment-induced renal injury, hemoglobin was infused to produce hemoglobinuria. Inulin clearance 1 h after hemoglobin infusion was significantly reduced to 0.84 +/- 0.5 ml/min (P less than 0.025). Infusion of deferoxamine after hemoglobin prevented the hemoglobin-induced decrease in inulin clearance. Thirty minutes of renal ischemia followed by infusion of hemoglobin resulted in more severe renal dysfunction with inulin clearance of 0.54 +/- 0.08 ml/min. Deferoxamine infused at the time of reperfusion attenuated the fall in glomerular filtration rate after ischemia and hemoglobin infusion:inulin clearance 1.04 +/- 0.07 (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemoglobin- and myoglobin-induced acute renal failure in rats: role of iron in nephrotoxicity. 341 10

Histological studies have been performed on experimental acute renal failure induced by intravenous injection of hemoglobin in rats. These have been correlated with alterations in renal excretory function, assessed by the measurement of inulin clearance, at various stages of the lesion. The most prominent morphological changes during the first 24 hr after hemoglobin injection, when inulin clearance is most markedly suppressed, are: the presence of hemoglobin within the lumen of small intrarenal vessels, particularly the vasa recta; hemoglobin cast formation involving predominantly the thick ascending limbs of the loops of Henle; and evidence of injury of the epithelium of the proximal tubules and thick ascending limbs. Notably absent during this stage of the lesion are marked tubular dilatation, interstitial edema, and cast formation in the distal collecting ducts. The considerable recovery of function which occurs at 72 hr is accompanied by a marked reduction in involvement of the vasa recta. Standard sections and microdissection reveal many markedly dilated proximal tubules at this stage of the lesion, suggesting obstruction of filtering nephrons. These data have led to a tentative hypothesis regarding the pathogenesis of renal failure in this experimental lesion. It is suggested that renal ischemia and failure of glomerular filtration are the primary factors responsible for the early and severe impairment of renal function, and that these are related to intravascular aggregation of hemoglobin pigment. As this defect recedes, tubular obstruction by hemoglobin casts prevents restitution of excretory function in a variable fraction of the nephrons. The latter accounts for the relatively prolonged, moderate reduction in inulin clearance associated with the late stages of this lesion. These hypotheses form the basis for a continuing study of this renal lesion.
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PMID:The renal lesion associated with hemoglobinemia. II. Its structural characteristics in the rat. 593 61

The role of renal ischemia in the pathogenesis of the renal failure produced by hemoglobin injection in the rat is evaluated. The data indicate that in the initial hours of this lesion renal blood flow is consistently reduced and that during its subsequent evolution blood flow rises towards normal levels, in some animals, while inulin clearance remains severely depressed. Volume expansion during the initial stage of the lesion may effect a rise in renal blood flow to normal levels with little effect on inulin clearance rate, further demonstrating the relative lack of dependence of the excretory defect on concomitant renal ischemia. These observations indicate that renal ischemia is probably a necessary factor in the initial production of the lesion; that it persists during its initial phase, up to 24 hours in most rats; and that, although it may contribute to the observed excretory defect, it is not the predominant etiologic factor. Other functional data indicate that renal blood is perfusing nephrons in which the excretory capacity is impaired but which retain the ability to extract Diodrast from the peritubular capillaries. This functional pattern indicates an excretory defect secondary either to intratubular obstruction or to a primary reduction of glomerular filtration rate of undefined etiology. The morphological findings of numerous dense intratubular hemoglobin casts and, in the well-perfused kidney, dilatation of proximal tubules, are suggestive of an obstructive lesion. However, the data do not conclusively distinguish between these two pathogenetic mechanisms.
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PMID:The renal lesion associated with hemoglobinemia: a study of the pathogenesis of the excretory defect in the rat. 602 73

Ischemic preconditioning has been shown to ameliorate injury due to subsequent ischemia in several organs. However, relatively little is known about preconditioning and the kidney. To address this, rats were randomized to control (C, N = 14), 2 min of ischemic preconditioning (P2 N = 10), 3 periods of 2 min of ischemia separated by 5 min periods of reflow (P2,3 N = 7), or three 5 min periods of ischemia separated by 5 min of reflow (P5,3 N = 6) prior to 45 min of bilateral renal ischemia followed by 24 hours of reperfusion. We observed a lower serum creatinine after 24 hours of reflow in P2, P2, 3 but not P5, 3 rats compared with C. Histology was examined in the C and P2, 3 groups and demonstrated less severe injury in the P2, 3 group. To gain insight into the mechanism by which preconditioning ameliorated ischemic injury, we performed near IR spectroscopy and 31P NMR spectroscopy. Based on near IR spectroscopy, the P2, 3 group had closer coupling of cytochrome aa3 redox state with that of hemoglobin during reflow. In the 31P NMR studies, the changes in ATP and pHi were similar during ischemia, but the P2, 3 group recovered ATP and pHi faster than C. These data suggest that ischemic preconditioning may ameliorate ischemic renal injury as assessed by functional, metabolic and morphological methods. The mechanism(s) by which this occurs requires additional study.
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PMID:Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat. 1008 74

Nitric oxide (NO) is synthesized from l-arginine by nitric oxide synthase (NOS), and nitrite and nitrate are believed to be waste forms of NO. We previously reported an enzyme-independent pathway of NO generation from nitrite in acidic conditions. In this study, we show nitrite-derived NO formation in renal ischemia-reperfusion injury using electron paramagnetic resonance (EPR) spectroscopy. In this experiment, we utilized a stable isotope of [(15)N]nitrite as a source of nitrite to distinguish l-arginine-derived NO from [(15)N]nitrite-derived (15)NO. Intravenous infusion of a stable isotope of [(15)N]nitrite ((15)NO(2)(-)) facilitated the formation of Hb(15)NO during renal ischemia, which demonstrated that the origin of NO was nitrite. The EPR signal of Hb(15)NO in kidney appeared after 40 min of renal ischemia, and renal reperfusion decreased the Hb(15)NO level in the kidney and increased it in blood by contrast. In addition, the amount of HbNO was nitrite concentration dependent, and this formation was NOS independent. Our findings suggest that nitrite can be an alternative source of NO in ischemic kidney and that it binds with hemoglobin and then is spread by the circulation after reperfusion.
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PMID:Nitrite-derived nitric oxide formation following ischemia-reperfusion injury in kidney. 1536 87

Ischemic injury is invoked as a mechanism contributing to end-organ damage and other complications of sickle cell disease (SCD). However, the intrinsic sensitivity of tissues in SCD to ischemic insults has never been addressed. We examined the effect of renal ischemia in a transgenic mouse expressing human sickle hemoglobin. Twenty-four hours after bilateral, total renal artery occlusion for 15 minutes, transgenic sickle mice exhibited worse renal function and more marked histological injury. With bilateral renal ischemia of greater duration (22.5 minutes), and after 6 hours, transgenic sickle mice exhibited massive vascular congestion, sickling of red blood cells, more marked histological injury in the kidney, and more prominent congestion in the capillary beds in the lungs and heart. Additionally, serum amyloid P-component, the murine homologue of C-reactive protein, was markedly increased in transgenic sickle mice as compared to wild-type mice. Twenty-four hours after bilateral renal ischemia for 22.5 minutes, transgenic sickle mice exhibited 28% mortality, with no mortality observed in any other group. With bilateral renal ischemia of short or long duration, renal expression of caspase-3 was most prominent in transgenic sickle mice subjected to ischemia. Thus, renal ischemia in this murine model induces more severe renal injury and extrarenal complications. We conclude that tissues in SCD exhibit heightened vascular congestion and sensitivity to ischemia and that clinically apparent or silent episodes of ischemia may contribute to the complications of SCD.
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PMID:Transgenic sickle mice are markedly sensitive to renal ischemia-reperfusion injury. 1579 78

Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme-iron recovery. We used haptoglobin-null mice to evaluate the impact of haptoglobin gene inactivation on iron metabolism. Haptoglobin deficiency led to increased deposition of hemoglobin in proximal tubules of the kidney instead of the liver and the spleen as occurred in wild-type mice. This difference in organ distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload.
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PMID:Plasma protein haptoglobin modulates renal iron loading. 1579 79


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