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PubMed2006

Ethnic differences for developing rheumatic fever in a low-income group living in Hawaii.

UNLABELLED: The risk factors responsible for acute rheumatic fever (ARF) are complex, in part, because group A streptococcus (GAS) infection is a prerequisite for this disease. We attempted to differentiate socioeconomic from genetic risk factors by studying subjects in a Hawaii pediatric cardiology clinic who qualified for Medicaid. This ethnically diverse group was unique because they maintained a low socioeconomic but generally healthy lifestyle with more limited risks than those living in extremely impoverished conditions. METHODS: Questionnaires were administered to consenting subjects in the clinic, who were divided into those diagnosed with ARF (n = 26) and those with other (primarily congenital) heart diseases (n = 41). RESULTS: The socioeconomic status of the ARF and non-ARF groups was lower than that of the Hawaii population in general, and little differences were noted between the groups. The ARF group, however, had slightly larger household sizes and more children than the non-ARF group. The greatest difference was in ethnicity. By the Fisher exact test, the number of Polynesians belonging to the ARF group was significantly greater than all other ethnicities (P = .005). Polynesians had an odds ratio > 4.80 of developing ARF, which increased to 6.33 when number of children per household was considered. CONCLUSION: The potential contribution of genetic predisposing factors for developing ARF was analyzed in subjects living in a homogeneously low socioeconomic level relative to the general Hawaii population. Polynesians were at highest risk when compared to other ethnicities living in similar socioeconomic conditions.

Acute Disease↗
PubMed1991

Human ADP-ribosylation factors. A functionally conserved family of GTP-binding proteins.

A new member, hARF4, of the ADP-ribosylation factor (ARF) family, a subset of the superfamily of regulatory GTP-binding proteins, has been cloned from a cDNA expression library. Two other human ARF cDNA sequences, designated human ARF1 and ARF3, have been reported previously and are 96% identical in amino acid sequence. A human ARF1 cDNA, significantly longer than previously described clones, was obtained, by cross-species hybridization using a bovine ARF1 cDNA probe. Bovine ARF1p and human ARF1p are 100% identical while each is only 80% identical to hARF4p. Thus, hARF4p is the most divergent of the mammalian ARF proteins identified. Northern blot analysis revealed the expression of at least three different ARF messages in human placenta and adrenal carcinoma cells. Both hARF1 and hARF4 encode GTP-binding proteins with predicted molecular masses of 20,000-21,000 Da. Biochemical analysis of the purified recombinant proteins revealed a high degree of conservation of nucleotide binding properties and in vitro ARF activities. ARF is an essential gene in the yeast, Saccharomyces cerevisiae, and is encoded by two genes. Expression of either hARF1p or hARF4p in yeast was found to rescue the lethal double mutant, arf1-arf2-, thus demonstrating the functional conservation of ARF functions between yeast and man. The combination of in vivo and in vitro assays for ARF function provides a specific and unambiguous means of determining bona fide ARF proteins from divergent species from among the rapidly increasing number of structurally related, small molecular weight GTP-binding proteins.

ADP-Ribosylation Factor 1↗
PubMed1990

[Acute renal failure in patients with hematologic neoplasms].

The retrospective study of acute renal failure (ARF) in patients with hematologic neoplasms was carried out. ARF occurred in 32 (6.1%) of 526 patients with hematologic neoplasms. Twenty-one (66%) patients recovered from ARF, but only 7 (22%) survived and were discharged from the hospital and 25 (78%) died of ARF or other complications. In 17 patients with leukemia or malignant histiocytosis, sepsis and/or disseminated intravascular coagulation were the most common causes of ARF, and all 17 patients died. In 11 patients with multiple myeloma, ARF was always attributable to the underlying disease, and the clinical course improved with the initiation of blood purification therapy (hemodialysis, plasma exchange) and chemotherapy. Five patients in blast crisis of chronic myelogenous leukemia or non-Hodgkin's lymphoma developed ARF as a result of tumor lysis syndrome. In this group, renal function improved with hemodialysis but only 2 patients survived. Patients with oliguria had worse outcomes than those without oliguria. Survival appeared to depend not on renal function but on the underlying disease, the cause of ARF, and other complications. These findings suggest that, in patients with hematologic neoplasms complicated by ARF, early initiation of blood purification therapy will improve the prognosis.

Acute Kidney Injury↗
PubMed1986

[Physiopathology of acute renal insufficiency].

Various physiopathological mechanisms are involved in acute renal failure (ARF). Renal cortical ischemia is frequent but is not a constant finding. The fall in glomerular filtration rate is related to the decrease in glomerular capillary pressure, the increase in tubular pressure, and/or the decrease in ultrafiltration coefficient. Emphasis is placed on the role of tubular obstruction (in some toxic and in postischemic ARF), and of imbalance between pre- and postglomerular vascular resistance (as in captopril or enalapril-induced ARF in patients with artery stenosis of a solitary kidney). Recently attention has been focused on cellular events in ARF. In aminoglycoside-induced ARF, phospholipids accumulate in tubular cell lysosomes. In post-ischemic ARF, cell depletion in adenine nucleotides (ATP, ADP) and increase in Ca++ play a role. Administration of calcium antagonists improves experimental post-ischemic ARF. In conclusion, there is no single physiopathological mechanism of ARF. It should be borne in mind that the mechanisms triggering ARF may be different from those perpetuating it, and may necessitate different preventive and therapeutic measures.

Acute Kidney Injury↗
PubMed1994

Nephrotoxicity following orthotopic liver transplantation. A comparison between cyclosporine and FK506.

Nephrotoxicity represents a serious side effect of immunosuppression following liver transplantation. In order to compare the nephrotoxic action of CsA and FK506 in a clinical setting, we evaluated the incidence of early and late nephrotoxicity in 121 patients, 60 of whom were randomly assigned to CsA- and 61 to FK506-based immunosuppression. Early postoperative renal insufficiency (between PODs 0 and 30; SCr 1.5-3 mg/dl) was observed to a similar extent in patients treated with CsA (38.3%) and FK506 (42.6%). Early postoperative acute renal failure (ARF) (SCr > 3 mg/dl) was observed in 18.0% of patients in the FK506 treatment group and 18.3% of patients receiving CsA therapy. Approximately half the patients with ARF required hemodialysis (CsA: 11.7%; and FK506: 8.2%). All patients with early postoperative ARF requiring hemodialysis survived for more than one year. New onset of late ARF (between PODs 30 and 365) was observed in 6.6% of patients receiving FK506 therapy and in 1.7% in the CsA treatment group as a result of severe infection with multiple organ failure syndrome (MOFS). There was 100% mortality in patients with late ARF requiring hemodialysis. Etiology and prognosis of early and late ARF seem to be completely different. Early ARF was associated with severe coagulopathy and a rise in bilirubin and free hemoglobin, and was accompanied by impaired liver function. Mean onset of hemodialysis in CsA-treated patients was POD 1 and in FK506-treated patients POD 6, which disclosed a different time course of drug-specific nephrotoxicity of CsA and FK506 in early ARF. In contrast, late ARF occurred in both treatment groups only as a part of the MOFS in association with severe infections, an observation consistent with the assumption of overimmunosuppression rather than a primary nephrotoxic effect. Late renal insufficiency appeared in 23.3% of CsA- and in 29.4% of FK506-treated patients, and represented a slowly progressing form of drug-specific nephrotoxicity of CsA and FK506. These preliminary results demonstrate a similar outcome in terms of both early and late nephrotoxicity, but longer follow-up will delineate the overall efficacy and toxicity in humans.

Acute Kidney Injury↗
PubMed1994

Characterization of a glucose-repressible ADP-ribosylation factor 3 (ARF3) from Saccharomyces cerevisiae.

ADP-ribosylation factors (ARFs) are highly conserved approximately 20-kDa guanine nucleotide-binding proteins that enhance the ADP-ribosyltransferase activity of cholera toxin, and are believed to participate in vesicular transport in both exocytic and endocytic pathways. Based on size, phylogenetic analysis, amino acid sequence, and gene structure, mammalian ARFs fall into three classes (class I, ARFs 1, 2, 3; class II, ARFs 4, 5; class III, ARF6). Two ARF genes (yARF1, yARF2) are known in Saccharomyces cerevisiae and believed to participate in vesicular trafficking in the Golgi system; the double deletion mutant is not viable. A third yeast ARF (yARF3) cDNA has been cloned by polymerase chain reaction-based procedures. It contains an open reading frame of 549 bases encoding a protein of 183 amino acids, with a deduced amino acid sequence more identical (60%) to that of the class III mammalian ARF than to those of the other two classes (52-56%). The yARF3 protein, however, reacted poorly with antibodies against any of the three classes of mammalian ARFs. In the presence of GTP, recombinant yARF3 protein stimulated cholera toxin-catalyzed auto-ADP-ribosylation. yARF3 gene transcription, similar to that of yARF2, was repressed by glucose. As yARF3 was not essential for cell viability and was not required for endoplasmic reticulum to Golgi protein transport, it may provide an opportunity to define an ARF function in another kind of vesicular trafficking.

ADP-Ribosylation Factors↗
PubMed1994

Characterization of class II and class III ADP-ribosylation factor genes and proteins in Drosophila melanogaster.

ADP-ribosylation factors (ARFs) are ubiquitous approximately 20-kDa guanine nucleotide-binding proteins that enhance the ADP-ribosyltransferase activity of cholera toxin and are involved in intracellular vesicular transport. Based on size, phylogenetic analysis, amino acid identity, and gene structure, mammalian ARFs fall into three classes (class I, ARF1, -2, and -3; class II, ARF4 and -5; class III, ARF6). A class I ARF had been identified in Drosophila melanogaster. To search for ARFs of other classes in Drosophila, polymerase chain reaction-based techniques were used, resulting in cloning of Drosophila ARF (dARF) II and dARF III with deduced amino acid sequences similar to those of class II and class III mammalian ARFs, respectively. The three Drosophila ARF genes map to different chromosomes and the coding regions have different splicing sites. dARF II mRNA, like ARF I mRNA, is fairly uniformly distributed throughout adult flies, whereas dARF III mRNA is significantly more abundant in heads than in legs or bodies. Recombinant dARF II and dARF III have biochemical and immunological properties similar to those of human ARF5 (hARF5) and hARF6, respectively. These observations are consistent with the conclusion that the three classes of ARFs are present in non-mammalian as well as mammalian species.

ADP-Ribosylation Factor 1↗
PubMed1994

Cloning of two novel ADP-ribosylation factor-like proteins and characterization of their differential expression in 3T3-L1 cells.

A polymerase chain reaction-based cloning approach was employed in order to identify ADP-ribosylation factors (ARF) in murine 3T3-L1 cells and to study their expression before and after differentiation of cells to the adipocyte-like phenotype. Partial sequences comprising the effector domains of ARF were amplified with degenerate primers and cloned. Five of these sequences were identified as murine homologues of known human ADP-ribosylation factors (ARF 1, 2, 4, 5, and 6). In addition, partial sequences of two previously unknown isoforms were found, and complete cDNA clones were isolated from a rat fat cell library and were sequenced. Both sequences harbor a putative myristoylation site in position 2, the known consensus sequences presumably involved in GTP binding and hydrolysis, and lack cysteine residues in the C terminus. Their amino acid sequences share a 56 and 41% identity, respectively, with human ARF 1. Based on a comparison with the known ARF isoforms, the first clone appears to represent the mammalian homologue of a known sequence from Drosophila (dARL 1, 79% identity) and was therefore designated rARL 1. The second clone resembled none of the known ARF-like proteins and was designated rARL 4. mRNA of ARL 4 was undetectable in the fibroblasts but abundant in the adipocyte-like phenotype, its expression starting on day 6 of the differentiation. In contrast, ARF 1, 2, and 5 were unaltered by differentiation of the 3T3-L1 cells; mRNA levels of ARF 6, and also of ARL 1 and ARF 4, were reduced after differentiation. It is suggested that the function of ARL 4 is related to the adipocyte-like phenotype of 3T3-L1 cells.

3T3 Cells↗
PubMed1993

[Acute renal failure in severe pregnancy induced hypertension: a report of 19 cases].

Twenty-six pregnant women complicated with acute renal failure (ARF) were admitted to Beijing Friendship Hospital during Jan. 1972 to Dec. 1990, the incidence rate was 0.045%. Among them, 4 cases of ARF were due to non-specific factors to pregnancy (15.4%) and 22 cases (84.6%) were due to factors correlated with pregnancy. Severe pregnancy induced hypertension (PIH) was the main cause of ARF in late pregnancy accounting for 86.4% (19 cases). In this series, 7 cases with eclampsia and 12 cases with preeclampsia, the incidence rate of ARF in preeclampsia and eclampsia was 0.91% and 11.3% respectively. The average age was 28.3 yr. 9 out of 19 cases were parous women. During pregnancy and labour, patients had more than one complications. 4 cases each were complicated with abruptio placentae, postpartum hemorrhage, intracranial hemorrhage and serious puerperal infection respectively. 3 cases were complicated with HELLP syndrome and one each with acute fatty liver, hypertension or gentamycin nephrotoxicity. 10 cases had deliveries preceded admission. The cesarean rate was 52.6% (10 cases). ARF onset before labour in 9 cases and postpartum in 10 cases. Developed only in 1 case of postpartum ARF in our department, this patient had a twin gestation, also complicated with severe PIH and acute fatty liver. Auria and oliguria ARF were found in 18 cases, nonauria in only 1 case. In this study, the highest serum BUN was 7.5-39.3 mmol/L (21-110 mg/dl). Medical management and rectal dialysis or peritoneal dialysis were performed in 10 cases who were in early stage, mild ARF or those ARF occurred before admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1993

[Evaluation of blood purification in perioperative acute renal failure].

The technical aspects of blood purification have made a great progress during 1980's. We reviewed our experiences of blood purification for the past six years. Between 1986 to 1991, we treated 48 perioperative patients with acute renal failure (ARF). Four were intraoperative cases and 46 were postoperative cases. Three of four intraoperative patients received major cardiovascular surgery, and hemodialysis was connected directly to ECC in these three cases, and in other one case, ARF was treated with continuous hemofiltration (CHF). There was no intraoperative complication. One patient died of septic multiple organ failure (MOF), but other three patients were discharged uneventfully. Thirty five postoperative ARF patients showed oliguric ARF, and their major causes were LOS (65%) and septic shock (29%). We treated these ARF patients with CHF combined with HD (63%), CHF only (28%) and HD only (9%). There were 21 deaths (60%) in this group and most common cause of death was septic MOF. Eleven postoperative ARF patients showed non-oliguric renal failure, and major cause of this type of ARF was thought to be aortic dissection and relative hypotension (45%). We treated these non-oliguric ARF patient with HD only (73%) and HD combined with CHF (27%). One of these non-oliguric ARF patients died from ARDS.

Acute Kidney Injury↗
PubMed1993

Binding of coatomer to Golgi membranes requires ADP-ribosylation factor.

Coatomer, a complex of seven proteins, appears to be the precursor of the coat structure of non-clathrin-coated Golgi-derived vesicles. Another component of this vesicle coat is the cytosolic protein ADP-ribosylation factor (ARF). Like coatomer, ARF appears to reversibly associate with Golgi membranes. We now report that ARF is required for coatomer binding to Golgi membranes and that myristoylated, but not non-myristoylated, ARF is the required species. We utilize an antibody directed against the beta-subunit of coatomer (beta-COP) to follow coatomer binding. ARF and beta-COP bind stoichiometrically to Golgi membranes. ARF-dependent beta-COP binding requires a membrane-associated protein, is saturable, and is enhanced in the presence of stable GTP analogues like guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). ARF and beta-COP bind sequentially to Golgi membranes, since beta-COP can be bound to reisolated membranes that had been previously incubated with ARF and GTP gamma S. We conclude that membrane-bound ARF confers to Golgi membranes all of the requirements for specific beta-COP binding.

ADP-Ribosylation Factors↗
PubMed1996

[Peritoneal dialysis in the treatment of acute renal insufficiency].

106 patients with acute renal failure (ARF) treated with peritoneal dialysis (PD) for the last 15 years (except for postrenal ARF treated only with HD, or ARF with conservative treatment) were analyzed. The commonest causes were sepsis (3), hemorrhagic fever (17) and complications of some internal or surgical disease (28). ARF appeared more frequently in older ages (> 50 y). Some causal diseases had closer relationship with sex like sepsis (22 women vs 8 men) and hemorrhagic fever (16 men vs 1 woman). The treatment was started on time (2-3 day after onset of ARF). In most of the patients stabilization of uremic symptoms was achieved in five days (average). The duration of oliguric phase, polyuric phase and treatment with PD where closely related to the causal disease. Mortality of ARF was 60% in patients with causal disease. Mortality of ARF was 60% in patients with surgical or internal complications, in patients with sepsis and 20-30% in others (complications during ARF were most frequently observed in patients with sepsis). Hemodialysis was used in severe cases and we were unable to determine its role in survival of patients with ARF.

Acute Kidney Injury↗
PubMed1997

Acute renal failure--etiologic and therapeutic considerations. A five-year experience at a single institution.

In the present study we highlight the epidemiology, etiologic spectrum, and evaluation of ARF in adults. We then expand on the pathophysiologic mechanisms of renal failure and discuss the rationale for current therapeutic strategies in ARF patients. A total of 79 patients (45 male, female 34), aged 18-75 years (median age 51.2 +/- 17.7 years) with acute renal failure were studied in 5 years (January 1990 through October 1995). Emergency hemodialysis sessions following an acute anuric episode were instituted in 39 cases (49.3% of all patients). The median number of hemodialysis procedures per patient treated at our institution was 3.2 +/- 1.9. The total number of acute interstitial nephritis-associated ARF was 40. In 30 of them (75%) the acute renal insult included a combination of several therapeutic antimicrobial agents, in 2 cases (5%) ARF followed the administration of nonsteroidal anti-inflammatory drugs, in 1 (2.5%) it resulted from a combined therapeutic regimen and in the remaining 5 (12.5%) from the application of a single drug. Acute interstitial nephritis developed in 2 patients following a viral infection. In the hemodialysis-treated ARF group 12 patients (29.77%) had interstitial nephritis and 2 patients (5.13%) presented with renal impairment for an unspecified period of time preceding the development of overt ARF. In a subset of this group of patients, ARF occurred in 7 patients (17.95%) following an urologic intervention, in 8 patients (20.51%) as a consequence of thermal or mechanical trauma or intoxication and in 3 cases (7.69%) it resulted from fever of unknown origin. Three patients with postoperative peritonitis and 4 other (10.26%) with postoperative complications were encountered in our series. No cases of septic abortion-related or obstetric-related ARF were recorded. 92.3% of all hemodialysis-treated patients seen at our Institution had received a combination of antibiotics and only 2 patients had been pre-treated with a single antimicrobial agent. Our results underscore the strong tendency towards diversity in the etiologic spectrum of clinical entities causing ARF and the increase in the number of acute interstitial nephritis. These factors highlight the importance of precise dosing and administration of drugs, especially antibiotics, as well as the duration of antibiotic treatment.

Acute Kidney Injury↗
PubMed1998

Acute renal failure: controversies, clinical trials, and future directions.

Acute renal failure (ARF) is an important clinical syndrome. Despite the frequent occurrence of ARF, nephrologists have not made major therapeutic inroads in the treatment or prevention of ARF. This article will speculate as to why it has been so difficult to gain a substantial foothold in the ongoing battle against ARF. First, some of the major controversies regarding the pathogenesis of ARF will be considered. Scientific debates regarding the mechanisms of ARF have greatly enriched the scientific literature, but may have slowed the development of clinically applicable therapies. Controversies regarding the treatment of ARF will then be discussed. Next, the fate of several recent clinical trials in ARF will be examined. Finally, the future directions that research in ARF may pursue will be contemplated.

Acute Kidney Injury↗
PubMed1999

Monosodium urate-crystal-stimulated phospholipase D in human neutrophils.

Protein kinase Calpha (PKCalpha) and small GTPases of the Rho and ADP-ribosylation factor (Arf) family are implicated in the regulation of phospholipase D1 (PLD1) activity. Although they are involved in fMet-Leu-Phe (fMLP)-mediated PLD activation, their role in monosodium urate (MSU)-stimulated PLD1 activity in human neutrophils is not clear. The translocation of PKCalpha, RhoA and Arf from the cytosol to the membranes was monitored. fMLP induced a cytochalasin B (CB)-dependent recruitment of Arf, RhoA and PKCalpha to neutrophil membranes. CB also increased the activation of PLD 10-fold. In contrast with fMLP, MSU stimulated a sustained and time-dependent relocalization of Arf and PKCalpha, but not of RhoA, to the membrane fraction. MSU-stimulated PLD was activated with a time course preceding membrane recruitment of Arf and PKCalpha in the absence of CB. Furthermore, MSU-induced PLD activation and the membrane recruitment of PKCalpha, but not that of Arf, were inhibited by CB. An anti-FcgammaRIIIB antibody, VIFcRIII, prevented the membrane relocalization of Arf and PKCalpha and the stimulation of the levels of tyrosine phosphorylation and of PLD activity induced by MSU. Erbstatin and ST-638, two inhibitors of tyrosine kinases, inhibited the MSU-induced translocation of Arf and PKCalpha but not MSU-induced tyrosine phosphorylation and PLD activation. Furthermore MSU crystals did not cause the tyrosine phosphorylation of PLD1. The present study indicates that soluble and particulate agonists show selectivity in inducing the translocation of RhoA in neutrophils and that the ability of MSU to increase PLD activation was independent of the membrane relocalization of Arf and PKCalpha.

ADP-Ribosylation Factors↗
PubMed1996

Nonsteroidal anti-inflammatory drugs and the risk of hospitalization for acute renal failure.

BACKGROUND: Few studies have evaluated the association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of idiopathic acute renal failure (ARF) in the general population. METHODS: Population-based case-control study among persons in the Canadian province of Saskatchewan who received at least 1 NSAID prescription between January 1, 1982, and December 31, 1986. Health department databases were used for case detection, as the sampling frame for selecting controls (n = 1997), and as the primary source of information on drug use and comorbidity. A total of 306 hospital records were reviewed. Twenty-eight patients who were hospitalized fulfilled the diagnostic criteria for ARF. RESULTS: The incidence rate of hospitalization for ARF among the general population not exposed to NSAIDs was 2 per 100000 person-years. Current exposure to NSAIDs, acetylsalicylic acid and other nephrotoxic drugs, male gender, increasing age, cardiovascular comorbidity, and recent hospitalization for disorders other than renal were found to be independent risk factors for ARF. Current NSAID users had an adjusted odds ratio for ARF of 4.1 (95% confidence interval, 1.5-10.8). The risk of ARF was especially high during the first month of use (odds ratio, 8.5). For prescribed dose, we found that users of high daily doses of NSAIDs experienced an odds ratio of 9.8 for ARF. CONCLUSIONS: In the general population, hospitalizations for ARF were found to be a rare condition. The 4-fold increase in risk associated with NSAID use was dose-dependent and occurred especially during the first month of therapy. Concurrent comedication with other potentially nephrotoxic agents should be prescribed with care, especially in the elderly.

Acute Kidney Injury↗
PubMed2004

Pharmacokinetic changes of DA-8159, a new erectogenic, after intravenous and oral administration to rats with acute renal failure induced by uranyl nitrate.

The pharmacokinetic parameters of DA-8159, a new erectogenic, were compared after intravenous and oral administration of the drug at a dose of 30 mg/kg to control rats and rats with acute renal failure induced by uranyl nitrate (U-ARF). After intravenous administration to rats with U-ARF, the plasma concentrations of DA-8159 were higher than those in control rats. This resulted in a significantly greater area under the plasma concentration-time curve from time zero to time infinity (AUC) of DA-8159 in rats with U-ARF (304 compared with 365 microg min/ml for control rats and rats with U-ARF). The significantly greater AUC in rats with U-ARF was due to significantly slower total body clearance (Cl) of DA-8159 (98.6 compared with 82.2 ml/min/kg). The significantly slower Cl in rats with U-ARF was due to slower renal clearance (1.07 ml/min/kg compared with not calculable, due to impaired kidney function) and nonrenal clearance (97.5 compared with 82.2 ml/min/kg due to slower metabolism) than those in control rats. After oral administration of DA-8159 to rats with U-ARF, the AUC (122 compared with 172 microg min/ml) was significantly greater and Cl(R) was slower (3.47 ml/min/kg compared with not calculable) than those in control rats. The significantly greater AUC in rats with U-ARF could be due to slower Cl of DA-8159 in the rats.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2002

Decreased expression of brain nitric oxide synthase in macula densa cells and glomerular epithelial cells of rats with mercury chloride-induced acute renal failure.

To elucidate the mechanisms responsible for the development of HgCl(2)-induced acute renal failure (ARF), we examined the expression of brain type (b) nitric oxide synthase (NOS), which is involved in the generation of the vasodilator nitric oxide (NO), in the renal cortex of rats at 20 h after exposure to 7.5 mg/kg HgCl(2). Both blood urea nitrogen and serum creatinine were significantly increased in rats exposed to HgCl(2) relative to control rats, indicating the induction of ARF resulting from HgCl(2) exposure. Histopathological analysis demonstrated that, in addition to necrosis of proximal tubule epithelial cells, necrosis of macula densa cells and swelling of glomerular epithelial cells were observed in the renal cortex of rats with HgCl(2)-induced ARF. Consequently, the number of pars maculata segments was decreased by 42% in rats with HgCl(2)-induced ARF compared to control rats. The primary sites of bNOS mRNA and protein expression were macula densa cells and glomerular epithelial cells in the renal cortex of control rats and rats with HgCl(2)-induced ARF. The abundance of the bNOS mRNA and protein was significantly decreased in rats with HgCl(2)-induced ARF relative to control rats. These observations suggest that the production of the vasodilator NO derived from bNOS is decreased at the glomerulus level in the HgCl(2)-induced ARF setting. Thus, the reduction in bNOS expression may in part contribute to the progression of HgCl(2)-induced ARF through the deterioration of glomerular hemodynamics. In addition, the decrease in bNOS expression may be primarily the result of cell injury caused by the cytotoxic effect of HgCl(2).

Acute Kidney Injury↗