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Immortalization of human mammary epithelial cells is associated with inactivation of the p14ARF-p53 pathway.

Inactivation of the ARF-p53 tumor suppressor pathway leads to immortalization of murine fibroblasts. The role of this pathway in immortalization of human epithelial cells is not clear. We analyzed the functionality of the p14(ARF)-p53 pathway in human mammary epithelial cells (MEC) immortalized by human papillomavirus 16 (HPV16) E6, the p53 degradation-defective E6 mutant Y54D, or hTERT. E6-MEC or E6Y54D-MEC maintains high-level expression of p14(ARF). Late-passage hTERT-immortalized MEC express p53 but down-regulate p14(ARF). Enforced expression of p14(ARF) induces p53-dependent senescence in hTERT-MEC, while both E6-MEC and E6Y54D-MEC are resistant. We show that E6Y54D inhibits p14(ARF)-induced activation of p53 without inactivation of the p53-dependent DNA damage response. Hence, p53 degradation and inhibition of p14(ARF) signaling to p53 are independent functions of HPV16 E6. Our observations imply that long-term proliferation of MEC requires inactivation of the p14(ARF)-p53 pathway.

Cell Transformation, Neoplastic↗

Maintenance and recovery stages of postischemic acute renal failure in humans.

Postischemic injury in 38 recipients of 7-day-old cadaveric renal allografts was classified into sustained (n = 15) or recovering (n = 23) acute renal failure (ARF) according to the prevailing inulin clearance. Recipients of long-standing allografts that functioned optimally (n = 16) and living transplant donors undergoing nephrectomy (n = 10) served as functional and structural controls, respectively. A combination of physiological and morphometric techniques were used to evaluate glomerular filtration rate and its determinants 1-3 h after reperfusion and again on day 7 to elucidate the mechanism for persistent hypofiltration in ARF that is sustained. Glomerular filtration rate in the sustained ARF group on day 7 was depressed by 90% (mean +/- SD); the corresponding fall in renal plasma flow was proportionately less. Neither plasma oncotic pressure nor the single-nephron ultrafiltration coefficient differed between the sustained ARF and the control group, however. A model of glomerular ultrafiltration and a sensitivity analysis were used to compute the prevailing transcapillary hydraulic pressure gradient (DeltaP), the only remaining determinant of DeltaP. This revealed that DeltaP varied between 27 and 28 mmHg in sustained ARF and 32-38 mmHg in recovering ARF on day 7 vs. 47-54 mmHg in controls. Sustained ARF was associated with persistent tubular dilatation. We conclude that depression of DeltaP, perhaps due partially to elevated tubule pressure, is the predominant cause of hypofiltration in the maintenance stage of ARF that is sustained for 7 days.

Acute Kidney Injury↗

Ameliorative effect of hepatocyte growth factor on glycerol-induced acute renal failure with acute tubular necrosis.

BACKGROUND/AIMS: Hepatocyte growth factor (HGF), a multi-potent growth factor, is known to promote regeneration of damaged renal epithelial cells. Glycerol injection into rats induces severe acute renal failure (ARF) with ischemia and tubular necrosis, a model which shares many features with human ARF or rhabdomyolysis. We investigated the efficacy of HGF in this glycerol-induced ARF rat model. METHODS: ARF was induced by intramuscular injection of glycerol into the hind limbs of male Wistar rats. HGF (0.25 mg/kg/shot) or vehicle was administered intravenously 1 h before and 1, 3, 5, 8, 24 and 36 h after glycerol injection. Biochemical parameters for serum and urine were measured and histological analyses of the kidneys were performed. We also analyzed endogenous HGF expression and phosphorylation of c-Met/HGF receptor in the kidneys of glycerol-induced ARF rats. RESULTS: Glycerol treatment caused severe ARF which invariably led to death of the rats. Repeated administration of HGF protected rats from death caused by severe ARF. Histological analyses revealed that HGF treatment reduced necrosis of tubular cells in the renal cortex. Serum/urine biochemical parameters also showed that renal dysfunction was improved by HGF administration. Intravenous administration of HGF enhanced phosphorylation of the c-Met/HGF receptor and mitogen-activated protein kinase in the kidney. In the vehicle-treated group the renal endogenous HGF concentration decreased and there was no change in c-Met/HGF receptor phosphorylation. CONCLUSION: These results indicate that HGF effectively accelerated the recovery of renal function and improved survival in glycerol-induced ARF rats.

Acute Disease↗

Comparison of experimental lung injury from acute renal failure with injury due to sepsis.

BACKGROUND: Acute renal failure (ARF) and acute respiratory distress syndrome (ARDS) coexist frequently, and the mortality rate of this combination is very high. It is well established that cytokines and chemokines play a major role in the pathogenesis of ARDS. In addition, heat shock proteins (HSPs) have been shown to be protective against ARDS. OBJECTIVES: The purpose of this study was to investigate the pathophysiology of ARDS in two different conditions, sepsis and ARF. METHODS: We examined five different rat animal models including sham-operated control, sepsis and three ARF models induced by renal ischemia/reperfusion injury, bilateral nephrectomy or bilateral ligation of renal pedicles. We analyzed pulmonary histology, pulmonary vascular permeability, cellular infiltration, and expression of cytokines, chemokines and HSPs. RESULTS: Like sepsis, the three forms of ARF led to ARDS, as manifested by increased pulmonary vascular permeability and histological changes consistent with ARDS. On the other hand, ARF and sepsis differed in that ARF was associated with markedly lower levels of pulmonary cellular infiltration. Furthermore, while pulmonary expression of tumor necrosis factor-alpha increased in sepsis, cytokine-induced neutrophil chemoattractant 2 increased in nephrectomized rats indicating that different inflammatory mediators were involved in the injury mechanism. Finally, pulmonary expression of multiple HSPs including HSP27-1, HSP70, HSP70-4, HSP70-8 and HSP90 was significantly different between the two conditions. CONCLUSIONS: We conclude that the pathophysiology of ARDS following ARF is distinct from that in sepsis. ARF-induced ARDS is characterized by a low level of cellular infiltration, induction of cytokine-induced neutrophil chemoattractant 2, and a discrete expression profile of HSPs.

Acute Kidney Injury↗

Plasma concentrations of tumor necrosis factor alpha may predict the outcome of patients with acute renal failure.

BACKGROUND/AIMS: Elevated plasma tumor necrosis factor-alpha (TNFalpha) concentration is frequently found in patients with chronic renal failure on hemodialysis (HD) and correlates with their mortality. The present study aimed to analyze the relationship between plasma TNFalpha concentrations and survival of patients with nonseptic acute renal failure (ARF). METHODS: Twenty-seven patients with ARF and 27 HD patients were examined. In ARF the patients' plasma TNFalpha concentrations were assessed 3 times: before the first HD session (phase I), 5 days later at the anuric/oliguric phase (phase II), and at the polyuric phase at discharge of the patients from the hospital (phase III). In 17 ARF patients kidney function recovered and 10 patients died in phase I. RESULTS: In ARF patients plasma TNFalpha concentration was markedly higher [70 pg/ml (37-275)] than reference values (<5 pg/ml) but significantly lower than in HD patients [216 pg/ml (18-350)]. Moreover, also plasma TNFalpha levels at the polyuric phase remained elevated. An initial plasma TNFalpha concentration in ARF patients lower than 70 pg/ml predicted the beneficial outcome with a sensitivity of 64.7% and a specificity of 70.0%. CONCLUSIONS: (1) Plasma TNFalpha concentration may predict the outcome in patients with ARF. (2) Plasma TNFalpha concentration remained elevated at the polyuric phase in ARF despite a marked improvement of excretory kidney function.

Acute Kidney Injury↗

Preoperative renal risk stratification.

BACKGROUND: After cardiac surgery, acute renal failure (ARF) requiring dialysis develops in 1% to 5% of patients and is strongly associated with perioperative morbidity and mortality. Prior studies have attempted to identify predictors of ARF but have had insufficient power to perform multivariable analyses or to develop risk stratification algorithms. METHODS AND RESULTS: We conducted a prospective cohort study of 43 642 patients who underwent coronary artery bypass or valvular heart surgery in 43 Department of Veterans Affairs medical centers between April 1987 and March 1994. Logistic regression analysis was used to identify independent predictors of ARF requiring dialysis. A risk stratification algorithm derived from recursive partitioning was constructed and was validated on an independent sample of 3795 patients operated on between April and December 1994. The overall risk of ARF requiring dialysis was 1.1%. Thirty-day mortality in patients with ARF was 63.7%, compared with 4.3% in patients without ARF. Ten clinical variables related to baseline cardiovascular disease and renal function were independently associated with the risk of ARF. A risk stratification algorithm partitioned patients into low-risk (0.4%), medium-risk (0.9% to 2.8%), and high-risk (> or = 5.0%) groups on the basis of several of these factors and their interactions. CONCLUSIONS: The risk of ARF after cardiac surgery can be accurately quantified on the basis of readily available preoperative data. These findings may be used by physicians and surgeons to provide patients with improved risk estimates and to target high-risk subgroups for interventions aimed at reducing the risk and ameliorating the consequences of this serious complication.

Acute Kidney Injury↗

Severe acute respiratory failure managed with continuous positive airway pressure and partial extracorporeal carbon dioxide removal by an artificial membrane lung. A controlled, randomized animal study.

Using an animal model of acute respiratory failure (ARF), we evaluated two treatments: conventional mechanical pulmonary ventilation (MV) and continuous positive airway pressure (CPAP) with extracorporeal removal of CO2 by an artificial membrane lung. We developed a model of "mild" ARF and a model of "severe" ARF after ventilating healthy sheep at a peak inspiratory pressure of 50 cm H2O for various lengths of time. Sheep from either injury models were randomly assigned to one of the above treatment groups. All 16 sheep from the model with "severe" ARF died, with progressive deterioration in pulmonary function and multiorgan failure irrespective of the treatment. Of 11 sheep from the model with "mild" ARF treated by MV, only three survived, whereas all 11 sheep from the model with "mild" ARF treated with CPAP and extracorporeal removal of CO2 responded well, and nine sheep ultimately recovered. We conclude that CPAP with extracorporeal removal of CO2 provided a better environment for the recovery in our model with "mild" ARF than the conventional arrangement centered on MV alone. Our studies also suggest that lung injury can progress (i.e., model with "severe" ARF) to where neither of the two treatments can succeed.

Acute Disease↗

Increased food intake after the addition of amylase-rich flour to supplementary food for malnourished children in rural communities of Bangladesh.

BACKGROUND: In Bangladesh, as in other developing countries, protein-energy malnutrition is mostprevalent among children during weaning. After weaning, children are often fed cereal-based diluted low-calorie porridge, resulting in growth-faltering. OBJECTIVE: To assess the effect on food intake of adding amylase-rich flour (ARF) from germinated wheat to supplementary food among children in nine rural Community Nutrition Centers under the Bangladesh Integrated Nutrition Project (BINP). METHODS: A total of 166 malnourished children of either sex, aged 6 to 24 months, received one of three diets randomly allocated to the Community Nutrition Centers. The composition of the diets was the same; however, the consistency and calorie density were altered by adding either ARF or water. Thirty-five children received the standard supplementary food of the BINP (S-SF), 65 received supplementaryfood with added ARF (ARF-SF), and 66 received supplementary food with added water (W-SF). The children were studied for six weeks. Results. The mean +/- SD intake of supplementaryfood from a single meal by children completing six weeks on the diets was higher for children receiving ARF-SF (33.91 +/- 8.25 g) than for those receiving S-SF (25.66 +/- 6.73 g) or W-SF (30.26 +/- 8.39g) (p < .05 for both comparisons). The weight of vomited food was significantly higher for children receiving W-SF than for children in the other two groups. Weight gain and increments in length and weight-for-height were higher for children who received ARF-SF than for children in the other two groups, but the differences were not statistically significant. The acceptability ofARF-SF was higher than that of the two other diets. The additional cost of adding 2 g of ARF to the diet was about Taka 0.25 (U.S. dollar 1 = Taka 48). CONCLUSIONS: Addition of ARF to existing standard supplementary food, as used under the BINP program, is a simple and effective means to increase the intake of food by changing its consistency, thus making it easier for malnourished children to ingest.

Amylases↗

Overlapping and non-redundant functions of the Arabidopsis auxin response factors MONOPTEROS and NONPHOTOTROPIC HYPOCOTYL 4.

Transcription factors of the auxin response factor (ARF) family have been implicated in auxin-dependent gene regulation, but little is known about the functions of individual ARFs in plants. Here, interaction assays, expression studies and combinations of multiple loss- and gain-of-function mutants were used to assess the roles of two ARFs, NONPHOTOTROPIC HYPOCOTYL 4 (NPH4/ARF7) and MONOPTEROS (MP/ARF5), in Arabidopsis development. Both MP and NPH4 interact strongly and selectively with themselves and with each other, and are expressed in vastly overlapping domains. We show that the regulatory properties of both genes are far more related than suggested by their single mutant phenotypes. NPH4 and MP are capable of controlling both axis formation in the embryo and auxin-dependent cell expansion. Interaction of MP and NPH4 in Arabidopsis plants is indicated by their joint requirement in a number of auxin responses and by synergistic effects associated with the co-overexpression of both genes. Finally, we demonstrate antagonistic interaction between ARF and Aux/IAA gene functions in Arabidopsis development. Overexpression of MP suppresses numerous defects associated with a gain-of-function mutation in BODENLOS (BDL)/IAA12. Together these results provide evidence for the biological relevance of ARF-ARF and ARF-Aux/IAA interaction in Arabidopsis plants and demonstrate that an individual ARF can act in both invariantly programmed pattern formation as well as in conditional responses to external signals.

Arabidopsis↗

Transport of procainamide and N-acetylprocainamide from blood into the intestinal lumen and intestinal dialysis by oral activated charcoal in rats with acute renal failure.

The characteristics of exsorption and/or excretion of procainamide and its metabolite, N-acetylprocainamide (NAPA), into the small intestinal lumen in both normal rats and rats with acute renal failure (ARF rats) induced by uranyl nitrate were investigated by an in situ single-pass perfusion technique. The exsorption of procainamide and NAPA from blood into the intestinal lumen was increased in ARF rats compared with normal rats. The mean apparent renal, biliary and intestinal clearance values of procainamide were 186, 1.83 and 73.9 ml/h/kg in normal rats, respectively, and were 2.02, 1.37 and 55.8 ml/h/kg in ARF rats respectively. Furthermore, the mean renal, biliary and intestinal clearance values of NAPA were 35.2, 19.4 and 21.1 ml/h/kg in normal rats, respectively, and were 1.12, 21.0 and 26.0 ml/h/kg in ARF rats, respectively. There was little difference in the intestinal clearance values of procainamide and NAPA between normal and ARF rats. The ratio of nonrenal clearance/total body clearance was greater in ARF rats than in normal rats. Treatment with oral activated charcoal reduced the serum NAPA levels in both normal and ARF rats, and had little effect on the serum procainamide levels in normal rats, while it reduced the serum drug levels in ARF rats. Consequently, the increase in both drugs transported into the intestinal lumen induced by renal failure may enhance the intestinal clearance of the drug by oral administration of activated charcoal.

Acecainide↗

Increased availability of propranolol in rats with uranyl nitrate-induced acute renal failure.

The effect of acute renal failure (ARF) on the pharmacokinetics of propranolol was investigated. The model of ARF was produced by the subcutaneous injection of uranyl nitrate to rats (10 mg/kg) and was used 3 d after treatment. Uranyl nitrate-treated rats showed significantly higher plasma concentrations of propranolol after oral administration and the area under the plasma concentration-time curve increased about 3-fold compared to control rats. The plasma disappearance of propranolol after intravenous administration did not differ significantly between control and ARF. The mean availability of propranolol after oral administration increased from 0.120 in control to 0.215 in ARF (p less than 0.005). Absorption of propranolol was almost complete and no significant difference was found between two groups. No changes in plasma protein binding of propranolol and hepatic blood flow were observed in ARF. On the other hand, hepatic clearance of propranolol determined by liver perfusion studies showed a significant reduction in ARF and the calculated intrinsic clearance of unbound propranolol at a dose of 6.25 mg was 26.8 +/- 2.3 ml/min in control and 16.0 +/- 2.3 ml/min in ARF (p less than 0.01). These results demonstrate that the oral availability of propranolol increased in ARF due to a reduction in the hepatic presystemic elimination as compared to healthy control rats.

Acute Kidney Injury↗

Protective effects of KW-3902, an adenosine A1-receptor antagonist, against cisplatin-induced acute renal failure in rats.

We investigated possible renal protective and therapeutic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel and potent adenosine A1-receptor antagonist, on cisplatin-induced acute renal failure (ARF). ARF was induced in rats by a single injection of cisplatin-induced acute renal failure (ARF). ARF was induced in rats by a single injection of cisplatin (5 mg/kg, i.v.). Prophylactic treatment with KW-3902 (0.01-1 mg/kg, p.o., twice a day) significantly attenuated the increases of serum creatinine (S-CRE) and urea nitrogen (S-UN) induced by cisplatin. On the other hand, neither furosemide nor trichlormethiazide showed any ameliorating effects against the cisplatin-induced ARF. In the clearance study, the cisplatin-treatment induced marked decreases of glomerular filtration rate (GFR), renal plasma flow (RPF), and reabsorptions of water, sodium and potassium at tubular sites, in comparison with those in untreated normal rats. KW-3902 (0.1 mg/kg, p.o., twice a day) significantly improved these deteriorated glomerular and tubular functions. In the rats with established cisplatin-induced ARF, KW-3902 ameliorated the cisplatin-induced reductions of GFR, RPF, and reabsorptions of water, sodium and potassium at tubular sites. These results suggest that activation of adenosine A1-receptors is involved in the pathogenesis of cisplatin-induced ARF. The adenosine A1-receptor antagonist may be useful for the treatment of cisplatin-induced ARF.

Absorption↗

Auxin response factor family in rice.

We isolated 11 rice genes homologous to the genes encoding auxin response factors (ARFs) in Arabidopsis. All of the genes encoded a well-conserved amino acid sequence in the N-terminal region, which is considered to be a DNA-binding domain (DBD). Phylogenetic analysis based on comparison of the DBDs indicated that rice has one or two closely related orthologs corresponding to a given respective ARF gene in Arabidopsis. We also analyzed the amino acid sequences of another conserved domain in the C-terminal conserved domain (CTD), which was shared by almost all the rice ARFs, with the exception of OsETTIN1 and OsETTIN2. These results agreed well with the evolutionary relationship deduced from the DBD comparison. In contrast to many ARFs, OsETTIN1 and OsETTIN2 do not contain the conserved C-terminal domain, but do share another consensus motif that is also found in Arabidopsis ETTIN. All of the above observations indicate that rice has functionally diversified ARF genes whose structures and functions correspond to those of various Arabidopsis ARFs, with one or two rice ARFs corresponding to a given Arabidopsis ARF. Thus, auxin signal transduction mechanisms may be well conserved between monocot and dicot plants.

Amino Acid Sequence↗

Role of endothelin in the pathogenesis of acute renal failure.

Shortly after the discovery of endothelin (ET) in 1988, it was suggested that ET might be an important mediator of acute renal failure (ARF) because of its intense renal vasoconstrictive properties. Evidence has accumulated for supporting this hypothesis: Exogenous ET infused into the kidney is able to decrease renal blood flow and glomerular filtration rate to create conditions that can lead to ARF; ET also has glomerular and tubular effects; and ET mRNA expression, ET content and its affinity for ET receptors are elevated in ARF. In addition, since physiological and pathophysiological actions of ET in renal tissue are mediated by interaction with ET(A) and ET(B) receptor subtypes, a number of ET receptor antagonists have been developed and used to deter- mine the pathophysiological role of ET peptide and ET receptor subtypes in the kidney. Many reports confirm beneficial effects of selective ET(A) and nonselective ET(A)/ET(B) receptor antagonists on renal dysfunction and degeneration in ARF. A recent study shows that renal dysfunction and histological damage observed in ischemic ARF are not improved by the treatment with a selective ET(B) receptor antagonist. Although the pathophysiological role of ET(B)-mediated ET action in the development of ARF is not fully understood, these observations strongly suggest that up-regulated endogenous ET contributes to the pathogenesis of ARF exclusively via ET(A) receptors and that compounds with ET(A) receptor antagonism are useful for the treatment of ARF. It is expected that such agents will have clinical applications in the future, and a number of drug candidates are now in development.

Journal Article↗

Models of glycerol-induced acute renal failure in rats.

Acute renal failure (ARF) following rhabdomyolysis is not uncommon in man. The popular model for ARF formation following rhabdomyolysis in experimental animals is glycerol injection into the leg muscle following a 24 hour period of water deprivation. A large percentage of patients developing ARF following rhabdomyolysis do not suffer from such long periods of water deprivation. On the contrary, fluid loss in patients developing ARF is relatively fast and is the result of excessive sweating or hemorrhage. Since it is known that the hydration state of the body during rhabdomyolysis considerably affects the development of ARF, it seems that the popular model of glycerol injection following a prolonged period of water deprivation in experimental animals is, to a certain extent, deficient. The aim of the present study was to examine two models of ARF formation in the rat following glycerol injection and acute diminution of the body's water content: 1) by sucrose injection (200 mg/100 g), 2) by hemorrhage (0.7 ml/100 g). A number of differences were found between the various models of ARF formation by glycerol. The differences are mainly expressed in the urine volume three hours after the glycerol injection. In the sucrose and hemorrhage groups a decrease of 29% and 66% (p < 0.001) in urine volume was found at the end of the experiment. In contradistinction, in the group that underwent water deprivation for a period of 24 hours prior to the glycerol injection, an increase of 46% (p < 0.001) in the urine volume was observed at the end of the experiment. Differences were also found in potassium uptake and in the extent of the decrease in renal cortex blood flow as measured by the laser Doppler flowmetry technique. From this study it may be concluded that glycerol injection to the rat leg muscle results in ARF in all three methods of decreasing the body's fluid content. It is possible that the models of sucrose injection or hemorrhage prior to glycerol injection are better suited for reflecting the hydration condition of humans suffering from rhabdomyolysis than 24 hours of water deprivation prior to this injection.

Acute Kidney Injury↗

Peritoneal dialysis alters tolbutamide pharmacokinetics in rats with experimental acute renal failure.

The plasma concentration profile of the antidiabetic agent tolbutamide was investigated in glycerol-induced acute renal failure (ARF) rats receiving or not receiving peritoneal dialysis (PD) to assess the impact of performing dialysis on tolbutamide pharmacokinetics. It was revealed that the plasma concentration of tolbutamide was decreased by 23.4% by performing PD in ARF rats, while it was not changed by PD in normal rats. The decrease in the plasma concentration of tolbutamide was nearly proportional to the increase in its volume of distribution. To clarify the mechanisms responsible for the decreased tolbutamide concentration caused by PD, the plasma protein binding of tolbutamide was examined in normal and ARF rats. The plasma unbound fraction of tolbutamide was higher in ARF rats than in normal rats, and the dissociation constants were 3.5+/-0.7 and 5.5+/-0.2 microg in normal and ARF rats, respectively. These results indicated that the unbound fraction of tolbutamide was increased in ARF rats because of its protein binding being suppressed. It is therefore likely that since a measurable amount of tolbutamide can distribute in peritoneal dialysate in ARF rats, but not in normal rats, the plasma concentration of tolbutamide was decreased by performing PD only in ARF rats. These findings suggest that diabetes medication with tolbutamide should be carefully performed in patients receiving dialysis treatment.

Acute Kidney Injury↗

[Antistreptolysin O titer profile in acute rheumatic fever diagnosis]

OBJECTIVE: To determine ASO titer profile by establishing ARF differential diagnoses of other diseases with high levels of ASO antibodies. METHODS: We investigated 78 patients with ARF at onset and follow-up, 22 with isolated chorea at onset, 45 with recurrent oropharyngeal tonsillitis, and 23 with recent flare of juvenile idiopathic arthritis. We tested ASO with automated particle-enhanced immunonephelometric assay (Behring(R)-Germany). The ASO (IU/ml) titers were assessed at the following time intervals: 0-7 days, 1-2 weeks, 2-4 weeks, 1-2 months, 2-4 months, 4-6 months, 6-12 months, 1-2 years, 2-3 years, 3-4 years, and 4-5 years after onset of ARF. RESULTS: ASO titers in patients diagnosed with ARF had a significant increase up to the 2-4-month time interval (P<0.0001). Baseline levels were observed afterwards in patients under regular penicillin prophylaxis. The levels of ASO in ARF were also significantly higher than in patients with isolated chorea, recurrent oropharyngeal infections or juvenile idiopathic arthritis (P=0.0025), when age-matched samples of these groups were compared. The testacute;s sensitivity was 73.3% and the specificity was 57.6%, and it was calculated taking into account the upper limit of normality at 320 IU/ml, as well as the established diagnosis of ARF. The testacute;s specificity and positive predictive value increased with rising or higher titers, being higher with titers above 960 UI/ml. CONCLUSION: This reappraisal of ASO profile in ARF patients indicates a remarkable response during the acute phase, and that points to the extent to which ASO levels may differentiate ARF from other diseases with high levels of ASO antibodies, as coincidental but unrelated streptococcal infection or chronic arthritis flareup.

Journal Article↗

The causal role of salt depletion in acute renal failure due to captopril in hypertensive patients with a single functioning kidney and renal artery stenosis.

Captopril (C) causes ARF in hypertensive patients with renal artery stenosis (RAS) with a single functioning kidney (SK). Retrospective studies in two patients showed that episodes of C-induced ARF were preceded by a rise in urinary Na+ excretion and a rapid decrease in body weight. These observations prompted us to investigate whether extracellular fluid volume depletion secondary to C-induced natriuresis can be responsible for ARF. Prospective studies were performed in four patients with RAS-SK treated with C. These studies have shown that: ARF is associated with negative Na+ balance and is corrected by salt replacement, even without interrupting C; ARF is preceded by a rise in urinary prostaglandin (PG) E2 and 6-keto-F1 alpha; ARF is prevented by either saline infusion or aspirin administration; ARF does not occur when the dose of C is not sufficient to raise PGs and urinary N + excretion. We conclude therefore that C-induced ARF in patients with RAS-SK can be secondary to salt depletion dependent on a raised secretion of PGs.

Acute Kidney Injury↗