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PubMed1991

Electrolyte abnormalities before and after the onset of acute renal failure.

The chemical composition of body fluids, which is regulated by the kidneys, may affect renal function. Conversely, the onset of acute renal failure (ARF) interrupts the normal regulation of the volume and content of the body fluids. In order to further study these relationships and determine the epidemiology and consequences of ARF in a tertiary-care setting, the computerized hospital data base was used to identify and obtain laboratory data on patients with ARF. 9,276 patients, encountered over a 90-day period, were surveyed and 96 were found to have developed ARF in the hospital (3.1% of admissions). The majority of the patients with ARF were found on the medicine service (68%), and sepsis with aminoglycoside use was the single most common of multiple etiologic factors. Patients with ARF experienced an increase in morbidity, as evidenced by an increase in the hospital length of stay and frequent need for ICU care. Mortality (29%) was due to the patients' underlying illnesses, and not uremia. Serum levels of the electrolytes prior to the onset of ARF were within the normal range with the exception of the creatinine (2.04 +/- 0.25 mg/dl) and bicarbonate (22.9 +/- 0.6 meq/l). After the development of ARF (mean creatinine 3.91 +/- 0.03) sodium, chloride, and bicarbonate were decreased, and phosphate, uric acid, and the anion gap were increased (p less than 0.05 for all values). The decrease in serum calcium became significant (p less than 0.05) in those patients whose creatinine increased by a factor of 2 or more.

Acute Kidney Injury↗
PubMed1989

Microinjection of a 19-kDa guanine nucleotide-binding protein inhibits maturation of Xenopus oocytes.

ADP-ribosylation factors (ARFs) are 19-21-kDa proteins purified from bovine brain that bind guanosine 5'-triphosphate (GTP). They exhibit GTP-dependent activity as activators of cholera toxin-catalyzed ADP-ribosylation of the alpha-subunit of the stimulatory guanine nucleotide-binding protein of the adenylyl cyclase system (Gs alpha). ARF, which interacts directly with the catalytic subunit of cholera toxin, has no known physiologic role. Intracellular microinjection of ARF was employed to investigate the effect of ARF on progesterone- and insulin-stimulated maturation of Xenopus oocytes. Maturation was inhibited by injection of ARF 3-8 h before exposure of oocytes to progesterone or insulin. ARF inhibition was dependent on progesterone concentration but not on insulin concentration. Inhibition was enhanced by concomitant injection of GTP and to a greater extent by guanosine 5'-O-(thiotriphosphate) (GTP gamma S) which, in the absence of ARF, inhibited somewhat at early time points. The demonstration of this effect of ARF on both progesterone- and insulin-stimulated oocyte maturation may provide a clue to the physiologic role of this guanine nucleotide-binding protein.

ADP-Ribosylation Factors↗
PubMedDate not supplied

Water immersion induced alterations of atrial natriuretic peptide in patients with noninflammatory acute renal failure.

Water immersion (WI) induced alterations of plasma atrial natriuretic peptide (ANP), circulating plasma volume (PV), plasma, sodium and potassium level and mean blood pressure (MAP) were examined in 12 patients with noninflammatory acute renal failure (ARF) and in 15 healthy persons. In patients with ARF a significantly elevated basal ANP level (138.67 +/- 12.9 pg/ml versus 74.54 +/- 4.1 pg/ml in healthy persons and elevated MAP (111.9 +/- 3.5 mmHg in patients versus 87.3 +/- 1.8 mmHg in healthy persons) were found. WI induced a significant increase of plasma ANP level in both examined groups which was significantly more marked in healthy persons (152.42 +/- 12.82 pg/ml) than in patients with ARF (85.75 +/- 12.62 pg/ml). WI was accompanied by a significantly more marked reduction of MAP (22.6 +/- 2.9 mmHg) and sodium level (6.09 +/- 0.63 mmol/l) in patients with ARF than in healthy persons (12.07 +/- 1.52 mmHg and 4.2 +/- 0.11 mmol/l respectively). In contrast to healthy persons in patients with ARF WI did not induce enhanced diuresis. In patients with ARF a significantly more marked increase of PV was found than in controls. Data obtained in this study seem to prove preservation of the physiological regulatory mechanism of ANP secretion in ARF patients but reduction of ANP release induced by central volume expansion. The importance of elevated basal plasma levels in the maintenance of ARF has not been proven.

Acute Kidney Injury↗
PubMed1988

Chemical and immunological characterization of the 21-kDa ADP-ribosylation factor of adenylate cyclase.

The ADP-ribosylation factor (ARF) is a 21-kDa GTP-binding protein cofactor in the cholera toxin-catalyzed ADP-ribosylation of the stimulatory regulatory subunit of adenylate cyclase. Purified bovine brain ARF was digested with cyanogen bromide, and peptides were purified and sequenced. Approximately 25-30% of the protein was sequenced in this manner. Peptides contained consensus sequences for GTP-binding proteins but were distinct from any of the previously published GTP-binding proteins. Antibodies were raised in rabbits against both protein and synthetic peptide fragments of ARF. Specific ARF immunoreactivity was detected in every eukaryotic tissue or cell examined, including yeast, slime mold, and man. No ARF immunoreactivity was observed when Escherichia coli proteins were tested. Immunoblotting revealed the majority of ARF to be present in the 100,000 x g supernatant. Immunological cross-reactivity with the cytosolic factor indicate that it and ARF are likely to be the same protein. ARF is shown to be myristylated at the amino terminus. The potential role of myristylation in cellular localization is discussed.

ADP-Ribosylation Factors↗
PubMed1986

Acute rheumatic fever in the 1980s.

Acute rheumatic fever (ARF) is an inflammatory sequela which occurs in 1-3% of children afflicted with group A beta-hemolytic streptococcal pharyngitis (strep throat). The major manifestations are carditis, migratory polyarthritis and chorea. ARF recurs with repeated strep throats and frequently leads to rheumatic heart disease (RHD), usually mitral and aortic regurgitation and mitral stenosis. ARF likely results from an abnormal host immune response with a host-antibody/streptococcal antigen production in pharyngeal tissue and subsequent cross-reaction of host antibodies with host end organs. Treatment includes eradication of the streptococcus, use of high doses of salicylates and adrenal corticosteroids, and prolonged bed rest with gradual ambulation after clinical and laboratory signs of the disease are gone. While the incidence and mortality of ARF and RHD have decreased drastically in the affluent industrialized countries of Europe, North America, and in Japan, the disease is a major health problem in the less affluent, 'developing' countries of Latin America, the Middle East, Africa, India and Southeast Asia. The major risk factors for ARF are believed to be genetic or familial, inadequate medical care and crowded conditions. The last two factors are socioeconomic but may also be influenced by ethnic cultural behavior. Genetic propensity for ARF is supported by recent evidence of a specific DR-HLA marker in the majority of people with ARF or RHD. Finally, while ARF appears to be vanishing in most areas of the country, it is still prevalent in some affluent populations and in some disadvantaged minorities.

Acute Disease↗
PubMed1984

[New diagnostic and therapeutic aspects of acute kidney failure].

In a 20 months' period 20 patients were dialyzed at the Cantonal Hospital, Lucerne, because of acute renal failure (ARF). Contrary to expectation, the main cause was not circulatory failure but traumatic and nontraumatic rhabdomyolysis (5 patients), septicemia (9 patients) and endogenous and exogenous intoxications. In only 2 patients did shock seem an important factor in the pathogenesis of ARF. In view of the many causes of rhabdomyolysis, the frequency of patients with myoglobinuric ARF is hardly surprising. Case history, brown-colored urine with a positive reaction for hemoglobin in the absence of significant hematuria and without significant hemolysis (as judged by the color of the plasma or serum) and, most important, high creatine kinase (10(4) to 10(6) U/l) point to the correct diagnosis. In patients who had undergone trauma or surgery the main cause of ARF was uncontrollable infection. A long interval between the accident or operation and the onset of ARF was typical in these cases. Both hemodialysis and peritoneal dialysis are adequate methods of treatment for ARF. For technical reasons, however, in more than 50% of patients with ARF due to trauma or surgery, peritoneal dialysis is not feasible. On the other hand, in patients with cardiovascular instability continuous arterio-venous hemofiltration serves as an alternative to hemodialysis. With the introduction of Y-shaped dialysis catheters and the single needle system with double pump and controlled ultrafiltration, hemodialysis has become an easier and safer procedure. For patients with prolonged-course ARF the authors prefer a combination of initial hemodialysis, followed by peritoneal dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1993

ARD 1, a 64-kDa guanine nucleotide-binding protein with a carboxyl-terminal ADP-ribosylation factor domain.

Clones referred to as ARD 1 were isolated from human and rat cDNA libraries. ARD 1 genes encode a putative 64-kDa protein that contains an 18-kDa ADP-ribosylation factor (ARF) domain at the carboxyl terminus and is much larger than the other monomeric approximately 20-kDa guanine nucleotide-binding ARF proteins thus far identified. ARD 1 mRNAs of 3.7 and 4.1 kilobases were detected in all rat tissues as well as in mouse and rabbit brain, human fibroblasts, and human neuroblastoma cells but not in HL-60 cells. Based on sequence identities, ARD 1 is highly conserved between rat and human. The ARF domain of ARD 1 contains the consensus sequences believed to be involved in guanine nucleotide binding, which are conserved in the ARFs and other GTP-binding proteins. Recombinant ARD 1 or the ARF domain of ARD 1, which lacks the 15 amino acids corresponding to the amino-terminal regions of ARFs stimulated, in a GTP-dependent manner, cholera toxin ADP-ribosyltransferase activity in the presence of 0.3% Tween 20. It had no effect in the presence of SDS, dimyristoylphosphatidylcholine/cholate, or cardiolipin. These observations are consistent with the conclusion that the amino-terminal region of ARF proteins is not required for activation of cholera toxin. In addition, the characteristic features of ARF proteins may be found as domains of larger mammalian proteins.

ADP-Ribosylation Factors↗
PubMed1997

Use of carbamylated hemoglobin concentration to differentiate acute from chronic renal failure in dogs.

OBJECTIVE: To determine usefulness of carbamylated hemoglobin (CarHb) concentration for differentiation of acute renal failure (ARF) from chronic renal failure (CRF) in dogs. SAMPLE POPULATION: Samples from dogs with ARF or CRF and from nonazotemic control dogs. PROCEDURE: CarHb concentration was determined in heparinized blood samples by measuring the micrograms of valine hydantoin (VH) per gram of hemoglobin (Hb), using a high-performance liquid chromatography assay, in which carbamyl valine is converted to VH via acid hydrolysis. RESULTS: CarHb concentration was significantly higher in dogs with ARF and CRF, compared with values in control dogs (ARF vs control, P < 0.05; CRF vs control, P < 0.001). Furthermore, CarHb concentration was significantly (P < 0.001) higher in dogs with CRF, compared with that in dogs with ARF. Carbamylated hemoglobin concentration did not correlate with serum urea nitrogen or creatinine concentration. Using a cutoff value of 100 micrograms of VH/g of Hb, the sensitivity and specificity of CarHb concentration for differentiating ARF from CRF was 96.1 and 84.2%, respectively. CONCLUSIONS: CarHb concentration was useful in the differentiation of ARF from CRF in the dogs of this study. CLINICAL RELEVANCE: CarHb concentration may be used to increase the accuracy of identifying ARF, so that early, aggressive management can be instituted, thereby increasing the chance of recovery.

Acute Kidney Injury↗
PubMed1997

[Medical rhabdomyolysis in the elderly].

BACKGROUND: To investigate the characteristics of medical rhabdomyolysis (RM) in the elderly, as well as differences compared with those observed in younger patients. PATIENTS AND METHODS: Prospective study of 56 elderly patients (> or = 65 years) with RM and 73 younger patients (> 7 years and < 65 years) with RM for 43 months. The RM characteristics were analyzed in the elderly group (ERM) and compared with those in the younger group (YRM). RESULTS: Fifty-six elderly patients with RM (38 males and 18 females, with a mean age of 76.3 +/- 7.6 years; range: 65-92 years) and 73 younger patients (57 males and 16 females, with a mean age of 37.9 +/- 15.6 years; range: 13-63 years), made up the 129 patients in the study. The most common cause for RM in the ERM was muscle compression due to immobilization and the multicausative group, both with 9 (16%) cases, followed by respiratory infection with 8 (14.2%) cases. In the YRM, the most common cause was physical exertion with 15 patients (20.5%) and multicausative with 18 patients (24.6%). Myalgia predominated in the YRM group, with 25 vs. 9 (odds ratio [OR]: 2.7; 95% confidence interval [CI]: 1.0-7.3; p < 0.05). Acute renal failure (ARF) occurred in 13 patients in the ERM group compared with 4 in the YRM group (OR: 5.2; 95% CI: 1.4-23; p < 0.01). In the logistic regression analysis an association was found between hypoalbuminemia and ARF for the ERM group. In the presence of ARF, both ERM and YRM had decreased serum calcium levels, deeper in YRM and more prolonged in the ERM. Six patients in the ERM died, and four of them had developed ARF. In contrast, none of the two deceased patients in the YRM had the complication of ARF. CONCLUSION: Almost half of cases of RM occur in elderly patients, which is mostly due to muscle compression and infections, particularly in the respiratory tract. Symptoms are usually mild and the development of ARF is more common than in younger patients, and its presence is associated with hypoalbuminemia. Hypocalcemia associated with ARF was less deep in the elderly, but more persistent than in younger patients. Most deceased patients in the elderly group previously developed ARF.

Aged↗
PubMed1998

Risk factors for acute renal failure requiring dialysis after liver transplantation.

Acute renal failure (ARF) is a common and severe complication after liver transplantation (LT). The aim of this study was to ascertain the impact of ARF requiring dialysis in the outcome of LT and to analyze the risk factors leading to this event in the early post-operative period. From October 1988 to December 1994, 172 LT were performed in 158 patients. Postoperative ARF occurred in 88 transplants (51.1%) during the early postoperative period: mild ARF was found in 46 (serum creatinine 1.5-3 mg/dl), moderate ARF in 12 (serum creatinine > 3 mg/dl) and severe ARF in 30 (serum creatinine > 3 mg/dl with dialysis requirement). Preoperative, intraoperative, and postoperative variables were studied, comparing patients presenting severe ARF with the remaining patients. Postoperative mortality in the dialysed group was much higher than in the non-dialysis group (50% vs. 13.4%)(p < 0.001) and 1-yr actuarial graft survival was 73.4% for the non-dialysed group compared with 40.9% for the dialysed group (p < 0.05). Among 38 variables investigated, only two factors had independent prognostic value in multivariate analysis: preoperative serum creatinine > 1.5 mg/dl (OR = 4.4, p = 0.006) and graft dysfunction grades III-IV (OR = 8.9, p = 0.001). In conclusion, ARF is a severe complication post-LT; its appearance could be predicted in patients with pre-transplant renal dysfunction, severe graft dysfunction, or both. However, in many cases renal function may revert to normal if treated aggressively with early dialysis support.

Acute Kidney Injury↗
PubMed1998

Protective effect of FK409, a spontaneous nitric oxide releaser, on ischemic acute renal failure in rats.

The contribution of nitric oxide (NO) to ischemic acute renal failure (ARF) is controversial. In the present study, we investigated the effect of FK409 ((+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexanamide ), a spontaneous NO donor, on ischemic ARF in rats. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow, urinary osmolality and fractional excretion of sodium were measured to test the effectiveness of the drug. Renal function in untreated ARF rats markedly decreased at 24 hr after reperfusion and thereafter tended to recover gradually. Intravenous bolus injection of FK409 at a dose of 1 mg/kg before the occlusion markedly attenuated the ischemic ARF-induced decreases in renal function, to the same extent as verapamil (1 mg/kg i.v.). The protective effect of FK409, at a dose of 3 mg/kg, was much more potent than that of the lower dose. Histopathological examination of the kidney of untreated ARF rats revealed severe renal damages, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion. These renal damages were significantly attenuated by treatment with FK409, at each dose given and this attenuation exceeded that seen with verapamil treatment. FK 409 administration led to a dose-dependent increase in NO metabolites concentration in renal venous blood immediately after the reperfusion. These findings suggest that NO has a crucial role in the pathogenesis of ischemic ARF. Spontaneous NO donors may be clinically effective in cases of ischemic ARF.

Acute Kidney Injury↗
PubMed2004

Renal and post-renal causes of acute renal failure in children.

OBJECTIVE: To identify the causes of acute renal failure (ARF) in pediatric population along with the identification of the age and gender most affected by the failure. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: This study was carried out at the Pediatric Medical Ward of National Institute of Child Health (NICH), Karachi over a period of two years from 1996 to 1998. SUBJECTS AND METHODS: The study included children under the age of 12 years who presented with signs and symptoms suggestive of ARF (oliguria/anuria, vomiting, acidotic breathing etc.) along with raised blood urea nitrogen (BUN) serum creatinine and metabolic acidosis as shown by arterial blood gases (ABGs). Patients were divided into two groups on the basis of age; group A consisting of 0-2 years and group B from >2 years. Patients presenting with transient pre-renal azotaemia were excluded from the study. After providing initial emergency cover, detailed history, physical examination and investigations were carried out according to a proforma specially designed to ascertain the cause of ARF. Patients were managed for ARF as per standard recommendations and investigations completed or repeated as and when required. RESULTS: A total of 119 patients with ARF were admitted in the ward over a period of two years constituting 1.36% of the total admissions and 16.39% of the admissions due to renal pathology. Mean age of presentation was 4.5 years with 56.7% of the patients under the age of 5 years. Male predominance was noted in all ages with an overall male to female ratio of 2.3:1. Most common cause leading to ARF in younger age group was found to be hemolytic uremic syndrome [25(54.34%)] followed by septicemia [7(15.21%)]. In older patients renal calculus disease was the most common [22(30.13%)] underlying pathology followed by pre-existing, undiagnosed chronic renal failure [16(21.91%)]. More than 90% of cases were related, directly or indirectly, to infections. CONCLUSION: ARF is fairly common in children especially under the age of 5 years showing a male predominance. More than 90% of the cases can be prevented by improving primary health care and by early and prompt treatment of infections.

Acute Kidney Injury↗
PubMed2006

Fine-mapping loss of gene architecture at the CDKN2B (p15INK4b), CDKN2A (p14ARF, p16INK4a), and MTAP genes in head and neck squamous cell carcinoma.

OBJECTIVE: To identify the extent and the smallest region of loss for CDKN2B(INK4b), CDKN2A(ARF,INK4a), and MTAP. Homozygous deletions of human chromosome 9p21 occur frequently in malignant cell lines and are common in squamous cell carcinoma of the head and neck (HNSCC). This complex region encodes the tumor suppressor genes cyclin-dependent kinase 2B (CDKN2B) (p15(INK4b)) and CDKN2A (p14(ARF), p16(INK4a)) and the housekeeping gene methylthioadenosine phosphorylase (MTAP). DESIGN: A targeted probe panel designed to finely map the region of 9p21 loss comprised 3 probes for CDKN2B(INK4b), 7 for CDKN2A(ARF, INK4a), and 3 for MTAP and was interrogated using the multiplex ligation-dependent probe amplification assay (MLPA). The MLPA genomic copy number alterations for CDKN2A were validated using real-time polymerase chain reaction. SUBJECTS: Six HNSCC primary (A) and recurrent or metastatic (B) cell lines were examined: UMSCC-11A/11B, UMSCC-17A/17B, and UMSCC-81A/81B. RESULTS: Cell line UMSCC-11B retained all 9p loci tested in the region. Cell lines UMSCC-17A/B indicated homozygous deletion of CDKN2A(ARF, INK4a) starting at p16(INK4) exon 1alpha to include exons 2 and 3. Homozygous loss was indicated for CDKN2B(INK4b) and CDKN2A(ARF,INK4a) in UMSCC-11A, and UMSCC-81A. Cell line UMSCC-81B indicated retention of all 9p loci except for exon 1alpha (p16(INK4a)). Selective loss of the 3' end of MTAP was observed in UMSCC-11A. Genomic alterations by fine-mapping MLPA were validated at the DNA level for CDKN2A. CONCLUSIONS: We identified exon 1alpha (p16(INK4a)) as the smallest region of loss in the CDKN2A(ARF, INK4a) gene. The frequency and precise loss of CDKN2B(INK4b), CDKN2A(ARF, INK4a), and MTAP in the prognosis of 9p21-deleted HNSCC may provide impetus for use of these targets as therapeutic biomarkers in head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed1993

Serum cholesterol levels in patients with acute rheumatic fever.

OBJECTIVE: To determine abnormalities of cholesterol metabolism in children with acute rheumatic fever (ARF). DESIGN: Cross-sectional study and prospective study. SETTING: Pediatric ward of the Khon Kaen (Thailand) University Hospital. PARTICIPANTS: Forty-six confirmed patients with ARF (during the acute and recovery phases of disease), 51 siblings, and 92 age- and sex-matched control children. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Serum samples of these children were studied for serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels and liver function tests. No significant differences were found in mean serum total cholesterol levels (3.68 +/- 0.86 mmol/L [142.4 +/- 33.3 mg/dL] vs 3.75 +/- 0.67 mmol/L [145.0 +/- 25.8 mg/dL], 3.79 +/- 0.75 mmol/L [146.4 +/- 29.0 mg/dL], and 3.80 +/- 0.59 mmol/L [146.9 +/- 23.0 mg/dL]) or mean triglyceride levels (1.19 +/- 0.33 mmol/L vs 1.16 +/- 0.51, 1.12 +/- 0.37, and 1.07 +/- 0.41 mmol/L) (during ARF vs after ARF, sibling, and age- and sex-matched control children, respectively). The children with ARF had significantly lower mean levels of high-density lipoprotein cholesterol and of albumin than did the other groups (analysis of variance, P < .0001). In the ARF group, high-density lipoprotein cholesterol and albumin levels varied inversely with the clinical severity of carditis, while, in contrast, triglyceride and alkaline phosphatase levels varied with the clinical severity of carditis. CONCLUSIONS: This study confirms abnormalities of cholesterol metabolism in ARF. Hepatic dysfunction associated with the clinically detectable severity of carditis or inflammation might explain the observed differences in serum high-density lipoprotein cholesterol and triglyceride levels in these children.

Acute Disease↗
PubMed2005

Acute renal failure in critically ill patients: a multinational, multicenter study.

CONTEXT: Although acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world. OBJECTIVES: To determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology, illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes. DESIGN, SETTING, AND PATIENTS: Prospective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries. MAIN OUTCOME MEASURES: Occurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality. RESULTS: Of 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% CI, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03), cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02), and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03). CONCLUSION: In this multinational study, the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.

Acute Kidney Injury↗
PubMed1998

Pharmacokinetic and pharmacodynamic changes of azosemide after intravenous and oral administration of azosemide to uranyl nitrate-induced acute renal failure rats.

The pharmacokinetic and pharmacodynamic differences of azosemide were investigated after intravenous (i.v.) and oral administration of azosemide, 10 mg kg-1, to the control and uranyl nitrate-induced acute renal failure (U-ARF) rats. After IV administration, the plasma concentrations of azosemide were significantly higher in the U-ARF rats and this resulted in a significant increase in AUC (2520 versus 3680 micrograms min mL-1) and significant decrease in Cl (3.96 versus 2.72 mL min-1 kg-1) of azosemide. The significant decrease in Cl in the U-ARF rats was due to the significant decrease in Clr of azosemide (1.55 versus 0.00913 mL min-1 kg-1) due to the decrease in kidney function in the U-ARF rats. After IV administration, the urine output (38.5 versus 8.45 mL 100 g-1 body weight) and urinary excretion of sodium (4.60 versus 0.420 mmol 100 g-1 body weight) decreased significantly in the U-ARF rats. After oral administration, the AUC0-8 h of azosemide decreased significantly (215 versus 135 micrograms min mL-1) in the U-ARF rats possibly due to the decreased GI absorption of azosemide. After oral administration, the 24-h urine output decreased considerably (16.1 versus 11.2 mL 100 g-1 body weight, p < 0.098) and the 24-h urinary excretion of sodium (1.74 versus 0.777 mmol 100 g-1 body weight) decreased significantly in the U-ARF rats. The i.v. and oral doses of azosemide needed to be modified in the acute renal failure patients if the present rat data could be extrapolated to humans.

Acute Kidney Injury↗
PubMed2006

Effects of acute renal failure on the pharmacokinetics of DA-7867, a new oxazolidinone, in rats.

The pharmacokinetic parameters of DA-7867 were compared after intravenous and oral administration at a dose of 10 mg/kg to control rats and rats with acute renal failure induced by uranyl nitrate (rats with U-ARF). After intravenous administration in rats with U-ARF, the time-averaged total body clearance (Cl) was significantly faster (2.45 versus 0.932 ml/min/kg) than controls due to significantly faster nonrenal clearance (2.25 versus 0.855 ml/min/kg) in rats with U-ARF. The faster nonrenal clearance could be due to significantly greater gastrointestinal (including biliary) excretion; the amount of unchanged DA-7867 recovered from the entire gastrointestinal tract at 24 h was significantly greater (30.3% versus 9.38% of intravenous dose) in rats with U-ARF. In rats with U-ARF, the Vss was significantly larger (1420 ml/kg compared with 580 ml/kg), but this was not due to a difference in plasma protein binding; the values were comparable between the two groups of rats. After oral administration to rats with U-ARF, the total area under the plasma concentration-time from time zero to time infinity (AUC) of DA-7867 was significantly smaller than the controls (2560 microg min/ml versus 7440 microg min/ml), and this was not due mainly to a decrease in absorption from the gastrointestinal tract in rats with U-ARF.

Acute Kidney Injury↗
PubMed1998

Analysis of recombinant human ADP-ribosylation factors by reversed-phase high-performance liquid chromatography and electrospray mass spectrometry.

Two complementary approaches utilizing reverse-phase high-performance liquid chromatography and liquid chromatography/mass spectrometry were developed to analyze recombinantly produced Group I and Group II human ADP-ribosylation factors (ARFs). We observe that the NH2 termini of Group II ARFs (ARF4 and ARF5) are efficiently processed by removal of the initiating methionine. In contrast, the NH2 termini of Group I ARFs (ARF1 and ARF3), although fully deformylated, undergo only partial methionine cleavage. This result is unexpected as ARFs are canonical substrates for methionine processing in both bacterial and eukaryotic systems, but it may explain the difficulties encountered by many researchers attempting to produce myristoylated ARFs in Escherichia coli. Additionally, we observe that a significant fraction of purified ARF4 contains a modification which we demonstrate to be consistent with mono-glutathionation. Both methionine retention and glutathione modification may impact ARF function and the methods presented here should be employed to determine the quality of recombinant ARFs.

ADP-Ribosylation Factor 1↗