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PubMed2005

Renal artery stenosis is not associated with the development of acute renal failure following coronary artery bypass grafting.

BACKGROUND: Acute renal failure (ARF) is a frequent complication of coronary artery bypass grafting (CABG) surgery and is strongly associated with perioperative morbidity and mortality. We hypothesized that renal artery stenosis (RAS), causing occult renal ischemia, may be an important factor contributing to development of ARF after CABG surgery. METHODS: Preoperative and intraoperative data on 798 consecutive adult patients undergoing CABG surgery with cardiopulmonary bypass from February 1, 1995 to February 1, 1997 (who had also undergone an abdominal aortogram for the evaluation of RAS) were recorded and entered into a computerized database. The development of ARF was defined as a rise in serum creatinine of 1 mg/dL (88.4 micromol/L) above baseline postoperatively. The association between the presence of renal artery stenosis together with preoperative and intraoperative variables and the development of ARF was assessed by multivariate logistic regression. RESULTS: A total of 798 patients underwent isolated coronary bypass grafting, of which 18.7% demonstrated 50% or more RAS. ARF developed in 82 patients (10.2%), of which three (0.3%) required dialysis support. The mortality for patients who developed ARF was 14% (OR 15, P=0.0001) compared to 0.2% among those who did not develop ARF. The presence of renal artery stenosis of any severity ranging from unilateral 50% RAS to bilateral 95% RAS was not associated with the subsequent development of ARF. CONCLUSIONS: The development of ARF following CABG surgery is associated with high mortality. The presence of RAS does not appear to increase the risk for developing ARF.

Acute Kidney Injury↗
PubMedDate not supplied

[Guidelines for dialysis. Replacement therapy for acute renal failure in critically ill patients].

Acute renal failure (ARF) in patients admitted to the intensive care unit (ICU) is mostly caused by ischemic or toxic injury, with a higher incidence in the latest years due to the growing number of interventions in cardiac and vascular surgery and to the general enhancement of reanimation techniques, which allow a better outcome among ICU patients. In critically ill patients, the ARF incidence reported in the literature ranges between 1 and 25%. Among ICU patients with ARF the mortality is between 40 and 65%, much more than in patients without this complication. Higher mortality rates, longer hospitalisation times and higher therapy costs demand from us an early diagnosis and treatment of ARF. Due to the lack of controlled and randomized proofs, recommended criteria for starting renal replacement therapy (RRT) in critical ARF patients might overlap with those for ESRD therapy. Moreover, randomised and controlled trials, confirming the actual efficacy of early onset of RRT on the mortality rate, are not yet available. As for stable ESRD patients, a direct relationship between dialytic doses and mortality and morbidity has been established for ARF patients. For ARF patients, as well as for ESRD patients, a minimum Kt/V of 1.2 three times a week should be ensured, although higher doses for critical ARF patients may achieve better results. The choice between intermittent (IRRT) and continuous renal replacement therapy (CRRT) in these patients is still a controversial issue. In spite of the fact that most studies report a better outcome in patients treated with CRRT, a recent meta-analysis failed to demonstrate any difference on the relative risk (RR) of mortality and on the rate of renal recovery between patients treated with either IRRT or CRRT. Furthermore, the use of peritoneal dialysis for the treatment of ARF patients in ICU has not been dismissed yet; so far this is indeed considered to be the technique of choice in some specific clinical situations. The intrinsic urgency of dialysis in ARF patients entails the use of temporary central venous catheters. The internal right jugular vein is usually preferred for these catheters because of the easier insertion and the lower risk of stenosis and thrombosis. The anticoagulant procedure should be chosen on the basis of patient characteristics, treatment typology and the likelihood of effectively monitoring its action. The choice of buffers in the dialysate, mostly lactate or bicarbonate, should depend on patient characteristics; so far, however, controlled but not randomized studies do not show any significant difference in the correction of metabolic acidosis between lactate and bicarbonate.

Acute Kidney Injury↗
PubMed1992

Guanine nucleotide-binding proteins in the intestinal parasite Giardia lamblia. Isolation of a gene encoding an approximately 20-kDa ADP-ribosylation factor.

Giardia lamblia is a protozoan intestinal parasite that has characteristics of both eukaryotes and prokaryotes. To determine whether genes for guanine nucleotide-binding proteins are present in Giardia, genomic DNA and cDNA libraries were screened by polymerase chain reaction and by hybridization with mixed oligonucleotide probes complementary to sequences encoding conserved GTP-binding domains. A gene with a high degree of sequence identity with mammalian ADP-ribosylation factors (ARFs), believed to be important in vesicular transport, was identified. The Giardia ARF gene had a 573-base open reading frame encoding 191 amino acids which are 63-70% identical with known mammalian and yeast ARFs. Sequence conservation among ARFs was greatest in putative GTP-binding domains. A single ARF mRNA species of approximately 750 bases was found in two different Giardia isolates. Primer extension and RNA sequencing of the Giardia ARF transcript revealed a short (6-base) 5'-untranslated region similar in size to those found in other Giardia transcripts. Giardia extracts contained ARF activity, as shown by stimulation of cholera toxin-catalyzed ADP-ribosylation and a Giardia ARF expressed in Escherichia coli as a fusion protein likewise exhibited biochemical activity. Its presence in Giardia is consistent with the view that ARF emerged before the divergence of this protozoan from other eukaryotes (approximately 1.5 billion years ago), and that an ARF-like protein may have been the ancestor of several other classes of signal-transducing guanine nucleotide-binding proteins, including the alpha subunits of the heterotrimeric G proteins.

ADP-Ribosylation Factors↗
PubMed1992

[Respiratory insufficiency in acute pancreatitis].

BACKGROUND: Acute respiratory failure (ARF) is one of the systemic complications of acute pancreatitis (AP). The severity of AP may be objectified by the Ranson index and the radiologic alterations showed by abdominal computerized tomography (CT). The aim of the present was to study the relation between both problems. METHODS: Two hundred ninety-five cases of AP attended between November 1983 and August 1987 were revised. Ranson criteria were used to qualify the 295 AP and the abdominal CT in 85 cases. ARF was defined as PaO2 less than 60 mmHg breathing air at room temperature. The severity of ARF was classified by the respiratory index (RI: PaO2/FIO2) with ARF being considered as severe when less than 200. In 100 cases of AP the thoracic radiologic alterations were objectified and evaluated in order to know their relation with ARF. RESULTS: ARF was the most frequent complication (28%) of AP, being severe in 8%. Pleural effusion was the radiologic alteration most frequently observed (23 patients). In 28% there was no correlation between the radiology and the presence of ARF. The correction of ARF was achieved in 85% of the patients with a mask of O2 less than 40%. Mean ARF was 227. A correlation was found between ARF and the severity of the episode of AP and the changes observed in the abdominal CT. CONCLUSIONS: Acute respiratory failure is the most frequent complication of acute pancreatitis and correlates with the severity of the episode of the latter; classification of the episode of acute respiratory failure by respiratory index is of use.

Acute Disease↗
PubMed1992

GTP but not GDP analogues promote association of ADP-ribosylation factors, 20-kDa protein activators of cholera toxin, with phospholipids and PC-12 cell membranes.

ADP-ribosylation factors (ARFs) are a family of approximately 20-kDa guanine nucleotide-binding proteins initially identified by their ability to enhance cholera toxin ADP-ribosyltransferase activity in the presence of GTP. ARFs have been purified from both membrane and cytosolic fractions. ARF purified from bovine brain cytosol requires phospholipid plus detergent for high affinity guanine nucleotide binding and for optimal enhancement of cholera toxin ADP-ribosyltransferase activity. The phospholipid requirements, combined with a putative role for ARF in vesicular transport, suggested that the soluble protein might interact reversibly with membranes. A polyclonal antibody against purified bovine ARF (sARF II) was used to detect ARF by immunoblot in membrane and soluble fractions from rat pheochromocytoma (PC-12) cell homogenates. ARF was predominantly cytosolic but increased in membranes during incubation of homogenates with nonhydrolyzable GTP analogues guanosine 5'-O-(3-thiotriphosphate), guanylyl-(beta gamma-imido)-diphosphate, and guanylyl-(beta gamma-methylene)-diphosphate, and to a lesser extent, adenosine 5'-O-(3-thiotriphosphate). GTP, GDP, GMP, and ATP were inactive. Cytosolic ARF similarly associated with added phosphatidylserine, phosphatidylinositol, or cardiolipin in GTP gamma S-dependent fashion. ARF binding to phosphatidylserine was reversible and coincident with stimulation of cholera toxin-catalyzed ADP-ribosylation. These observations may reflect a mechanism by which ARF could cycle between soluble and membrane compartments in vivo.

ADP-Ribosylation Factors↗
PubMed1991

[Myoglobinuria and acute renal failure].

Clinical and experimental studies on the development of myoglobinuria-associated acute renal failure (ARF) were reviewed. ARF developed in 30% of the cases of rhabdomyolysis. Rhabdomyolysis-associated ARF accounted for 5-10% of all ARF. The presence of dehydration or hypotension at the presentation of rhabdomyolysis seems to be a risk factor in the development of rhabdomyolysis-associated ARF. ARF occurred more frequently in the rhabdomyolysis caused by sepsis or burns. Glycerol-induced ARF in rats or rabbits has been studied to investigate the pathogenesis of myoglobinuria-associated ARF. The early decrease in inulin clearance (Cin) in glycerol-induced ARF was dependent upon the decrease in renal blood flow, but the decrease in Cin in the late phase could not be attributed to the decrease in renal blood flow. Diminished glomerular permeability and cast formation might play important roles in the decrease in Cin in the late phase of glycerol-induced ARF.

Acute Kidney Injury↗
PubMed1985

Post-heparin lipolytic activity in acute renal failure.

Total post-heparin lipolytic activity (PHLA), hepatic triglyceride lipase (HTGL) and protamine inactivated lipoprotein lipase (LPL) and plasma lipoprotein pattern were investigated in 8 patients with acute renal failure (ARF). PHLA was determined at 5, 10, 15, 30, 45 and 60 minutes after heparin administration (100 U/kg b.w.). Maximal PHLA in ARF was 6.12 +/- 1.56 mumol FFA/ml/h at 10 minutes versus 14.62 +/- 4.29 at 45 min in controls (= 42%, p less than 0.001). PHLA was reduced in ARF throughout the study period (p less than 0.001). Maximal HTGL activity (3.06 +/- 0.84 mumol FFA/ml/h) was obtained at 10 min in ARF versus 8.97 +/- 3.11 after 15 min in controls (= 34%, p less than 0.001). HTGL in ARF differed from controls at all points of determination (p less than 0.001). LPL maximum was 3.12 +/- 1.93 mumol FFA/ml/h at 15 min in ARF and 7.65 +/- 3.44 at 45 min in controls (= 40%, p less than 0.001). LPL activity was different from controls at 30, 45 and 60 min (p less than 0.001) but not at 5, 10 and 15 min after heparin injection. Due to a rapid decrease of LPL activity (half maximal activity after 34 min in ARF versus 94 min in controls, p less than 0.05) activity half life of PHLA was diminished in ARF (49 min in ARF versus 112 min in controls, p less than 0.01). Thus both the activity of HTGL and LPL is impaired in ARF. Because of the different activation kinetics of the two PHLA fractions no conclusions concerning maximal enzyme activities can be drawn from single determinations as suggested in previous studies on chronic renal failure.

Acute Kidney Injury↗
PubMed1983

Fibrinogen degradation products in acute renal failure of the newborn.

Acute parenchymal renal failure (ARF) in the newborn infant has emerged as a major problem since the advent of neonatal intensive care units. Because intravascular and/or intrarenal coagulation may be important in the development of ARF, a prospective study of coagulation was performed on 20 babies with ARF, with particular emphasis on the measurement of fibrinogen degradation products (FDP) in serum and urine. Thirteen babies with respiratory distress syndrome (RDS) and 40 healthy neonates served as controls. Initial serum FDP levels were significantly higher in ARF than in RDS or normals (P less than 0.001); initial urine FDP levels were higher in ARF than in normals (P less than 0.01). Levels of FDP did not differentiate among the various etiologies of ARF. Since initial urine FDP levels are high in normal newborns, serial urine FDP were compared among patient groups and found to be highest in ARF. Initial serum and urine FDP levels could not differentiate among the 11 survivors and 9 nonsurvivors, but FDP levels declined as the duration of ARF (e.g., survival) increased, often antedating the recovery of renal function. We conclude: (1) serum and urine FDP are significantly elevated in most newborns with ARF; (2) factors other than hypoxia may be involved in the pathogenesis of elevated serum FDP in RDS with ARF newborns, indicating the importance of coagulation; (3) serial measurements of serum and urine FDP may be early indicators of recovery of renal function.

Acute Kidney Injury↗
PubMed1996

Pharmacokinetic and tissue distribution changes of adriamycin and adriamycinol after intravenous administration of adriamycin to uranyl nitrate-induced acute renal failure rats.

The pharmacokinetic and tissue distribution changes of adriamycin (ADM) and adriamycinol were investigated after intravenous (i.v.) administration of ADM, 16 mg/kg, to the control and the uranyl nitrate-induced acute renal failure (U-ARF) rats. After 1 min i.v. infusion of ADM, apparent 'constant' plasma levels of ADM were maintained from 2 to 12 hr in the U-ARF rats, whereas the levels were detected for only up to 3 hr in the control rats. Adriamycinol was detected in plasma for up to 180 min for the U-ARF rats, but, it was detected for only up to 1 min for the control rats with significantly higher levels in the U-ARF rats. The mean amount of both ADM and adriamycinol excreted in urine were significantly smaller in the U-ARF rats than those in the control rats due to the decreased kidney function in the U-ARF rats. In tissue distribution studies, the amount of ADM obtained from the heart, liver, spleen, small intestine, large intestine, and fat were significantly higher in the U-ARF rats than those in the control rats. The tissue to plasma ratios of the liver, spleen, large intestine, and fat also increased significantly in the U-ARF rats than those in the control rats. The amount of adriamycinol obtained from the heart, spleen, and liver were significantly higher in the U-ARF rats. All 7 control rats survived over 48 hr whereas 6 out of 8 U-ARF rats died between 36-48 hr after i.v. administration of ADM, suggesting that the i.v. doses of ADM in acute renal failure patients may need modification if the present rat data could be extrapolated to humans.

Acute Kidney Injury↗
PubMed1998

The spectrum of acute renal failure in the intensive care unit compared with that seen in other settings. The Madrid Acute Renal Failure Study Group.

Acute renal failure (ARF) is at a crossroads between nephrology and intensive care medicine. However, there seems to be wide differences between the ARF observed in the intensive care unit (ICU) compared to that observed in other areas of the hospital, particularly when examining the mortality rate. Among the ICU patients the 70% mortality rate is higher to the 50% found in an overall series of studies. Recently, Druml proposed that there is a changing trend in the clinical spectrum of ARF as a convincing reason to justify these differences. According to him, we are moving from an ARF seen as a mono-organ failure to another one observed in a multiorgan dysfunction syndrome (MODS) context. Although extremely coherent, this hypothesis has not been fully confirmed in a prospective study. In fact, most authors seem to look at the problem from opposite sides of the river, either from the critical medicine or the nephrological bank. To the best of our knowledge, only one retrospective study has dealt with this topic by comparing outcome of ARF in ICU and non-ICU patients. In this article we aim to overcome this problem by reviewing the data of the prospective epidemiological ARF study carried out in Madrid using two different approaches: (1) comparing the ARF cases observed in the ICU setting with those ARF studied outside the ICU, and (2) comparing the outcome of isolated ARF with the outcome of ARF as part of a MODS in patients treated in both settings.

Acute Kidney Injury↗
PubMed2004

Exercise-induced acute renal failure associated with renal hypouricaemia: results of a questionnaire-based survey in Japan.

BACKGROUND: A retrospective investigation was conducted to define the clinical features of exercise-induced acute renal failure (ARF) associated with renal hypouricaemia with the aim of clarifying further the clinical features of the disease entity. METHODS: A questionnaire was mailed to 43 institutions in Japan that had experienced case(s) of exercise-induced ARF associated with renal hypouricaemia. Fifty-four patients (48 males and six females) were identified from 38 institutions. RESULTS: Median age at the first episode of ARF was 17 years (range 11-46). The maximal serum uric acid and creatinine levels were 4.40+/-2.49 (range 0.4-13.3) and 5.45+/-3.33 mg/dl (range 1.10-17.7), respectively. The serum uric acid level after recovery was 0.70+/-0.25 mg/dl (range 0.1-1.4). The short-term prognosis seemed to be good and histological findings in 28 patients showed minimal change or acute tubular necrosis except for one patient with chronic lesions. ARF episodes occurred predominantly in September, October and May, mostly after strenuous exercise such as a short-distance race. The first symptoms were nausea/vomiting in 51 episodes, loin pain in 35, abdominal pain in 22, general fatigue in 16 and low-grade fever in seven. Thirteen patients (24.1%) experienced recurrent ARF at various intervals. Univariate and multivariate analyses failed to demonstrate any risk factor of ARF recurrence, although no female patients experienced ARF recurrence. CONCLUSIONS: The reason for the heterogeneity in ARF associated with renal hypouricaemia remains unknown. Further studies, especially on molecular mechanisms, are required to establish the best guidance against ARF recurrence.

Acute Kidney Injury↗
PubMed2003

Effects of glucose on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate.

The effects of glucose on CYP2E1 expression in rats with acute renal failure induced by uranyl nitrate (U-ARF) have been reported. CYP2E1 was significantly induced (2.3-fold) in rats with U-ARF compared with that in control rats. In contrast, CYP2E1 expression was significantly decreased in rats with U-ARF supplied with glucose (dissolved in tap water to make 10%, w/v) in their drinking water for 5 days (U-ARFG) compared with that in rats with U-ARF. However, CYP2E1 in rats with U-ARFG was significantly greater than that in control rats. Chlorzoxazone (CZX) primarily undergoes hydroxylation, catalyzed mainly by CYP2E1, to form 6-hydroxychlorzoxazone (OH-CZX) rats. Hence, it could be expected that in rats with U-ARFG, formation of OH-CZX could significantly decrease and increase compared with those in rats with U-ARF and control rats, respectively. This expectation is proven by the following results of a study of intravenous administration of CZX at a dose 20 mg/kg to control rats and rats with U-ARF and U-ARFG. First, the total area under the plasma concentration-time curve from time zero to 8 h (AUC(0-8 h)) of OH-CZX in rats with U-ARFG (8730 microg x min/mL) was significantly greater than that in control rats (414 microg x min/mL) and significantly smaller than that in rats with U-ARF (11500 microg x min/mL). Second, the AUC(0-8 h, OH-CZX)/AUC(CZX) ratio in rats with U-ARFG (10.0) was significantly greater than that in control rats (0.252) and significantly smaller than that in rats with U-ARF (17.5). Finally, the in vitro intrinsic OH-CZX formation clearance (CL(int)) in rats with U-ARFG (27.9 mL/min/mg protein) was significantly slower than that in rats with U-ARF (36.7 mL/min/mg protein) and significantly faster than that in control rats (17.7 mL/min/mg protein).

Acute Kidney Injury↗
PubMed2002

Invasive mechanical ventilation for acute respiratory failure in children with cystic fibrosis: outcome analysis and case-control study.

The outcome for cystic fibrosis (CF) patients requiring intubation and invasive mechanical ventilation (IMV) due to acute respiratory failure (ARF) has been poor. Mortality rates have been reported as high as 60-90%. However, a review of mortality in children has not been published in 20 years. Our objectives were to study outcomes in CF patients requiring IMV due to ARF between 1988-1998, compare recent outcomes with those previously reported, and identify risk factors associated with poor outcome. We additionally attempted to identify factors suggesting an increased risk of developing ARF requiring IMV. A retrospective cohort study design was used, comparing IMV survivors and nonsurvivors with a nested case-control study to identify risk factors for ARF leading to IMV. All patients cared for at our Center who required IMV for ARF between 1988-1998 were identified. Outcome, age, steroid use, forced vital capacity (FVC), forced expired volume in 1 sec (FEV(1)), microbiology, nutritional status, CF-related diabetes (CFRD), liver dysfunction, and history of major hemoptysis (HEM) or pneumothorax (PTX) were recorded. Cases were matched for gender and age with CF controls identified through a clinical database.Thirty-eight episodes of IMV due to ARF were reported in 33 patients. Three subjects underwent IMV on two or more occasions, but only the first episode was included in analysis. Older age was the only factor that was significantly associated with mortality: 9 subjects were <5 years of age (mortality, 22%), while 24 were 5-34 years old (mortality, 75%) (P = 0.013). There was an increased risk of having an episode of ARF requiring IMV in malnourished subjects (OR = 4.2; 95% CI = 1.66-10.51) and in those with a history of HEM (OR = 6.3; 95% CI = 1.75-22.65). Infants and young children with CF requiring IMV due to ARF have a favorable prognosis, whereas those >or=5 years of age suffer significantly higher mortality. Malnutrition and a history of HEM are important risk factors for having an episode of ARF requiring IMV.

Acute Disease↗
PubMed2003

Leukocyte recruitment and acute renal failure.

Despite advances in medical technology, acute renal failure (ARF) still represents a major challenge in clinical medicine, as morbidity and mortality have remained unchanged over the past two decades. The pathophysiology of ARF is highly complex and only poorly understood; new insights into the pathophysiology of ARF are therefore of utmost importance to develop better understanding and therapies. Acute tubular necrosis (ATN) is the predominant cause of ARF and often arises as a consequence of septic, toxic, or ischemic insults. The recruitment of leukocytes into the kidney has recently emerged as a key event in the development of experimental ischemic and septic ARF. A few descriptive clinical studies support this idea. However, the clinical relevance of various animal models remains unclear, as does the importance of different leukocyte subsets, and even methodological aspects as how to quantify renal leukocyte recruitment. This review summarizes and critically evaluates experimental findings that provide insight into the role of leukocytes and their recruitment during ARF. We aim to provide a valid description of ARF, illustrate animal models of ARF, review qualitative and quantitative methods to assess renal leukocyte recruitment, and discuss the components of the leukocyte recruitment cascade and their role in ARF.

Acute Kidney Injury↗
PubMed2000

The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy.

The healthy term, and particularly the premature infant, is born with a very low glomerular filtration rate (GFR), controlled by a delicate balance of intrarenal vasoconstrictor and vasodilator forces. Vasoactive disturbances can easily further reduce the already low GFR. The newborn infant is thus prone to develop vasomotor nephropathy (VMNP) or acute renal failure (ARF). The main causes for ARF at this young age are prerenal mechanisms, and include hypotension, hypovolemia, hypoxemia perinatal asphyxia, and neonatal septicemia. Other causes include the administration of angiotensin converting enzyme inhibitors, indomethacin and tolazoline. The most-important factors governing the ultimate renal prognosis are the severity of the underlying disorder, the rapidity of an accurate diagnosis, prompt treatment, and avoidance of severe iatrogenic complications. The immediate treatment is of particular importance in VMNP, i.e., prerenal ischemic ARF, and consists of correcting abnormalities in fluid homeostasis and reduction of the complications of the acute azotemic state (uremia, hyperkalemia, acidosis, and hypertension). In severe and prolonged (established) ARF, temporary dialysis therapy may be indicated. Prerenal ARF with oliguria or anuria warrants immediate volume resuscitation. Special attention should be given to infants with congestive heart failure (CHF). The sick neonate with persistent oliguria and CHF should be treated with intravenous dopamine. Furosemide (FM) is the second line of therapy for babies with indomethacin-induced ARF. In most other conditions, the therapeutic effect of FM is limited to a transient increase in urine flow, without improving basic renal function. The special conditions of the maturing kidney have to be appreciated in order to protect babies from undue renal injury. With the increasing knowledge of the mechanisms governing the development of ARF, progress has been made in the development of new treatment modalities. For example theophylline, calcium antagonists, ATP-MgCl2, thyroxine, and a variety of cytokines may in the near future be used to prevent or ameliorate VMNP and/or recently established ARF. With a combination of time-honored and new therapeutic strategies, there may well be a brighter future for neonates with vasomotor, prerenal, ischemic ARF.

Humans↗
PubMed2005

Alterations in band 3 protein and anion exchange in red blood cells of renal failure patients.

The precise nature of band 3 protein and its involvement in oxalate exchange in the red blood cells (RBCs) of renal failure patients has not been studied in detail. Therefore, here we studied the oxalate exchange and binding by band 3 protein in RBCs of humans with conditions of acute and chronic renal failure (ARF and CRF). The RBCs of ARF and CRF patients exhibited abnormal red cell morphology and an increased resistance to osmotic hemolysis. Further, an increase in the cholesterol content and decrease in the activities of Na(+)-K(+)-, Ca(2+)-, and Mg(2+)-ATPases of membranes were observed in the RBCs of ARF and CRF patients. A decrease in the oxalate flux was observed in the RBCs of ARF and CRF patients. The oxalate-binding activities of the RBC membranes were significantly lower in ARF (20 pmoles/mg protein) and CRF (5.3 pmoles/mg protein) patients as compared to that in the normal subjects (36 pmoles/mg protein). DEAE-cellulose and Sephadex G-200 column chromatography purification profiles revealed a distinctive shift in oxalate-binding activity of band 3 protein of RBCs of ARF and CRF patients as compared to that of the normal subjects. It was also observed from the binding studies with a fluorescent dye, eosin-5-maleimide, which specifically binds to band 3 protein, that the RBCs of ARF and CRF patients exhibited only 53 and 32% of abundance of band 3 protein, respectively, as compared to that in the RBCs of the normal subjects, thus revealing a decrease in the band 3 protein content in ARF and CRF patients. These results for the first time showed a decrease in the oxalate exchange in RBCs of patients with ARF and CRF, which was also concomitant with the low levels of abundance of band 3 protein.

Acute Kidney Injury↗
PubMed1992

Cloning and characterization of the gene encoding the ADP-ribosylation factor in Candida albicans.

We have cloned and sequenced the gene (ARF) encoding the ADP-ribosylation factor (ARF) of Candida albicans. The gene contains an open reading frame of 537 nucleotides (nt) that codes for a protein with an Mr of 20,259. The C. albicans ARF gene is 67-70% identical at the nt level to other ARF sequences including those of humans; the deduced amino acid sequence of C. albicans ARF shows a 78-83% identity and 89-92% similarity to the other ARFs. Southern analysis of C. albicans genomic DNA suggested the presence of a second ARF gene. The presence of multiple ARF genes is a consistent finding among the other organisms previously shown to have ARFs.

ADP-Ribosylation Factors↗
PubMed2006

p14ARF inhibits the growth of p53 deficient cells in a cell-specific manner.

While p14(ARF) suppression of tumorigenesis in a p53-dependent manner is well studied, the mechanism by which p14(ARF) inhibits tumorigenesis independently of p53 remains elusive. A variety of factors have been reported to play a role in this latter process. We report here that p14(ARF) displays different effects on the anchorage-dependent and -independent growth of p53-null/Mdm2 wild type cells. p14(ARF) blocks both the anchorage-dependent and-independent (soft agar) proliferation of 293T and p53(-/-) HCT116, but not p53-null H1299 lung carcinoma cells. While p14(ARF) had no effect on the anchorage-dependent proliferation of p53(-/-) MEFs and Ras12V-transformed p53(-/-) MEFs, it inhibited the growth of Ras12V-transformed p53(-/-) MEFs in soft agar. Furthermore, ectopic expression of p14(ARF) did not lead to degradation of the E2F1 protein and did not result in the reduction of E2F1 activity detected by two E2F1 responsible promoters, Apaf1 and p14(ARF) promoter, in 293T, p53(-/-) HCT116, and H1299 cells. This is consistent with our observations that p14(ARF) did not result in G1 arrest, but induced apoptosis via Bax up-regulation. Taken together, our data demonstrate that the response of p53-null cells to ARF is cell type dependent and involves factors other than Mdm2 and E2F1.

Animals↗