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PubMed1998

Role of angiotensin II, endothelin-1, and nitric oxide in HgCl2-induced acute renal failure.

To elucidate the mechanisms underlying the development of HgCl2-induced acute renal failure (ARF), we examined the expression of endothelin (ET)-1, endothelial (e) nitric oxide synthase (NOS) and inducible (i) NOS, and a role of angiotensin II (ANG II) and tumor necrosis factor (TNF) in glomeruli and cortices from rats at 20 h after exposure of HgCl2. Prepro-ET-1 and iNOS mRNA were significantly increased in glomeruli and cortices from rats with HgCl2-induced ARF. However, eNOS mRNA was markedly decreased in glomeruli of rats with HgCl2-induced ARF. Blockade of the action of endogenous ANG II with TCV-116, an ANG II receptor type 1 antagonist, or prior administration of TNF antibody (Ab) neutralizing TNF bioactivity or aminoguanidine, an iNOS inhibitor, substantially suppressed the increase in the expression of prepro-ET-1 or iNOS mRNA seen in rats with HgCl2-induced ARF. Both TCV-116 and TNF Ab had no effects on the expression of eNOS mRNA. The abundance of ET-1, iNOS, and eNOS proteins was paralleled by the magnitude of each mRNA expression. Additionally, the aggravation of blood urea nitrogen and serum Cr observed in rats with HgCl2-induced ARF were significantly ameliorated together with the alleviation of proximal tubule epithelial cell injury when the expression of prepro-ET-1 or iNOS mRNA was blunted by prior administration of TCV-116 or prior injection of TNF Ab or aminoguanidine. These observations indicate that ANG II, ET-1, and NO may play an important role in the progression of HgCl2-induced ARF through the acceleration of proximal tubule epithelial cell injury and the deterioration of glomerular hemodynamics. In HgCl2-induced ARF, the gene expression of ET-1 or iNOS is at least in part up-regulated at the transcription level by endogenous ANG II or TNF.

Acute Kidney Injury↗
PubMed1990

Decrease of catecholamine and neuropeptide Y-like immunoreactivity in the glycerol-induced acute renal failure of rats.

Changes of catecholamine and neuropeptide Y (NPY) were investigated in experimental acute renal failure (ARF) of rats. Concentrations of noradrenaline (NA) and dopamine (DA) were determined by chromatographic analysis using electrochemical detection. Renal content of NPY, identified by radioimmunoassay, was expressed as NPY-like immunoreactivity (NPY-LI). All animals with a plasma urea value higher than 200 mg/dl induced by injection of glycerol were employed as ARF subjects for the experiment. Formation of ARF was also confirmed by histological findings showing diffused necrosis of tubular epithelia. In ARF rats, renal contents of NA and DA decreased markedly (P less than 0.001), NA (ng/g wet tissue) decreased from 186.3 +/- 19.6 to 2.81 +/- 0.67 (n = 8), and DA (ng/g wet tissue) decreased from 14.69 +/- 4.97 to 4.05 +/- 2.66 (n = 8). Similarly, NPY-LI (pg/g wet tissue) in ARF was reduced significantly (P less than 0.001) from 435.23 +/- 35.82 to 4.61 +/- 0.52 (n = 8). The decrease of NA in ARF was obtained parallel to the change of NPY-LI; degeneration of adrenergic nerve fibers was confirmed by immunohistochemical observation. Results obtained suggest damage to the adrenergic and the dopaminergic innervation in the kidneys during ARF.

Acute Kidney Injury↗
PubMed1987

Acute renal failure: the glomerular and tubular connection.

Acute renal failure (ARF) is a common clinical entity which results from multiple causes. Experimental models in animals have duplicated many of the clinical syndromes which can be classified into (1) ARF due to increased filtered load of endogenous and exogenous materials, (2) ARF associated with exogenous nephrotoxins and (3) ischemic forms of renal failure secondary to hypoperfusion and hypotension. The mechanisms leading to the reduction in GFR are multiple and the alterations in determinants of nephron filtration rate and degree of tubular backleak and obstruction are described for each of these subtypes of experimental ARF. The specific mechanisms whereby tubular damage translates into a reduction in GFR in ARF are discussed for each subtype of ARF. Tubular damage can often be dissociated from the reduction in GFR, possibly by inhibiting tubuloglomerular feedback responses, but such increases in GFR and nephron filtration rate are not necessarily beneficial to the organism because of potential volume depletion and the risk of magnifying further tubular damage. Information on the physiologic role of tubuloglomerular feedback activity in ARF is provided and supports the concept that feedback induced reductions in GFR after tubular injury may preserve extracellular volume and minimize further tubular damage. Reductions in tubular metabolic work appears to prevent and ameliorate further tubular injury after the initial insult. The mechanisms which associate changes in GFR and tubular damage can now be described, and therapies which improve GFR without correcting the tubular damage may compound the clinical problem and increase renal damage.

Acute Kidney Injury↗
PubMed1991

Continuous positive pressure breathing without and with inspiratory pressure support in acute respiratory failure when mean airway pressure is constant.

OBJECTIVE: Mean airway pressure (Pawm) may be a major factor for PaO2, functional residual capacity, and cardiac output in acute respiratory failure (ARF). To clarify effects of inspiratory pressure support (IPS) as a ventilatory mode in ARF, we studied patients in ARF either using IPS or continuous positive pressure breathing (CPAP) at the same level of Pawm, measuring respiratory and circulatory parameters. METHODS: After consent, 10 patients in ARF of moderate severity (PaO2:FiO2 205 +/- 108 at positive end expiratory pressure (PEEP) 8.7 +/- 3.1 cmH2O; mean +/- SD) were investigated. Measurements were on day 7.4 +/- 8.4 after onset of ARF. IPS was 13.5 +/- 3.9 cmH2O above PEEP. To result in constant Pawm, PEEP was reduced for IPS (Pawm IPS 11.1 +/- 3.6 vs. Pawm CPAP 9.9 +/- 3.3 cmH2O, ns; PEEP IPS 8.7 +/- 3.1 vs. PEEP CPAP 10.6 +/- 4.3 cmH2O, p = 0.04). Inspired concentration of oxygen (FiO2) and the ventilator (Siemens 900 C) were not changed for the individual patient. RESULTS: For IPS, tidal volume (VT) increased by +31% and respiratory frequency (RF) decreased by -19% (VT IPS 608 +/- 179 vs. VT CPAP 465 +/- 141 ml, p = 0.01; RF IPS 21.6 +/- 7.6 vs. RF CPAP 26.7 +/- 8.3 breaths per minute, p = 0.02). Also, PaCO2 showed a tendency to be lower for IPS, not reaching significance (PaCO2 IPS 44.3 +/- 5 vs. PaCO2 CPAP 47.4 +/- 4.9 mmHg, p = 0.1). All other parameters were unchanged (expiratory minute volume, PaO2, pH, intravascular pressures, cardiac index, stroke volume index (n = 6), systemic and pulmonary vascular resistances, venous admixture, deadspace (n = 3), oxygen consumption and oxygen delivery). WE CONCLUDE: When Pawm remained constant, IPS added to CPAP improved VT and RF without improving oxygenation or deteriorating circulation in patients with ARF of moderate severity. IPS mainly supports the ability to breathe spontaneously in ARF.

Acute Disease↗
PubMed2005

Evaluation of exercise-induced acute renal failure in renal hypouricemia using Tc-99m DTPA renography.

We present a case of a thirty-eight-year-old man who had exercise-induced acute renal failure (exercise-induced ARF). He experienced oliguria, general fatigue, and vague discomfort in the lower abdomen after he exercised. As he had suffered from hypouricemia before, he was diagnosed as having exercise-induced ARF associated with hypouricemia. Enhanced computed tomography (CT) images showed patchy wedge-shaped contrast enhancement on his bilateral kidneys, consistent with characteristic observations for exercise-induced ARF. Tc-99m diethylene triamine pentaacetic acid (DPTA) renography revealed decreases in both the renal blood flow (RBF) and glomerular filtration rate (GFR), and revealed parenchymal dysfunction of the bilateral kidneys. Renogram revealed a hypofunctional pattern on the bilateral kidneys. CT images and Tc-99m DTPA renography also had improved when the symptoms of exercised-induced ARF indicated improvement. It has been hypothesized that one cause of exercise-induced ARF may be renal vasocontraction. Although CT images are useful in evaluating exercise-induced ARF, Tc-99m DTPA renography can more easily and safely evaluate renal function. We also show that Tc-99m DTPA renography is useful in precisely evaluating the degree of improvement of exercise-induced ARF.

Acute Kidney Injury↗
PubMed2001

Outbreak of acute renal failure due to cefodizime-vancomycin association in a heart surgery unit.

OBJECTIVE: To describe an outbreak of acute renal failure (ARF) occurring in a group of patients undergoing open-heart surgery, simultaneously to a change in perioperative antibiotic prophylaxis. DESIGN: Case series. SETTING: A nine-bed heart surgery intensive care unit, serving a 1,300-bed University teaching hospital. PATIENTS: Thirty-two patients undergoing open-heart surgery during an 11-day period, when the preoperative surgical prophylaxis protocol had been changed from the usual antibiotic association of ceftriaxone + vancomycin to cefodizime + vancomycin. RESULTS: ARF occurred in 16 of the 32 (50%) patients exposed to the new antibiotic prophylaxis regimen; seven patients had oliguric ARF, and nine patients had an increase in serum creatinine (SCr) levels >50% over 24-48 h. In the seven patients with oliguric ARF, SCr increased from a median preoperative level of 88 micromol/l (80-115 micromol/l) to a peak value of 725 micromol/l (521-857 micromol/l) in 5 days (4-6). Eight patients out of the sixteen with ARF (50%) were diabetics, as opposed to none of the 16 patients not experiencing ARF. Renal biopsy (three patients) showed tubular dilation and necrosis, interstitial edema, and lymphomononuclear infiltrate of moderate degree. Only one patient required hemodialysis, and all recovered renal function. No other cases of unexplained ARF occurred in the unit after the original prophylaxis protocol was resumed. CONCLUSION: The simultaneous infusion of cefodizime and vancomycin may involve a high risk of substantial renal function derangement, especially in diabetics.

Acute Kidney Injury↗
PubMed2006

Outcome of assisted ventilation for acute respiratory failure in cystic fibrosis.

OBJECTIVES: To assess outcome of assisted ventilation in cystic fibrosis (CF) patients with acute respiratory failure (ARF), to identify risk factors associated with poor outcome and to compare long-term outcome of CF children who were mechanically ventilated for ARF with unventilated CF controls. DESIGN: Retrospective cohort study. SETTING: Two large CF centres in the Netherlands. PATIENTS: CF patients who required assisted ventilation for ARF and unventilated CF controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Thirty-one CF patients required assisted ventilation for ARF between January 1990 and March 2005. All five children (under 2 years of age) and seven adults (27%) survived. In the total population, age was a statistically significant risk factor for poor outcome (p=0.02). In adult CF patients who required invasive mechanical ventilation, acute on chronic respiratory failure was associated with poor outcome. In children who required mechanical ventilation for ARF, lung function and CF related complications 5 years later were not significantly different compared with controls matched for age, gender and genotype. CONCLUSIONS: CF patients younger than 2 years old, who are ventilated because of ARF, have a good prognosis and their long-term outcome seems identical to unventilated CF controls. ARF in adult CF patients still is associated with high mortality, especially among patients with acute on chronic respiratory failure.

Adolescent↗
PubMedDate not supplied

Percutaneous transvenous mitral commissurotomy in patients with severe mitral stenosis and acute rheumatic fever.

There is a concern that percutaneous transvenous mitral commissurotomy (PTMC) performed during acute rheumatic fever (ARF) may result in adverse outcomes. We performed a retrospective study at a tertiary care center. Ten patients (ages 8-12 years) with severe symptomatic mitral stenosis and ARF who underwent PTMC (ARF group) were compared with 10 controls with similar mitral valve area (MVA). The procedure was successful in all patients. The median MVA increased from 0.7 to 1.5 cm2 following PTMC in the ARF group and from 0.7 to 1.8 cm2 in the control group [p = not significant (NS)]. The median MVA was 1.2 cm2 in the study group compared to 1.6 cm2 in the control group (p = 0.02) over a mean follow-up of 17.5 +/- 11.7 months. Echocardiographic restenosis occurred in 4 patients (40%) in the ARF group compared to 1 patient (10%) in the control group (p = NS). The improvement in the New York Heart Association functional class was maintained in 8 patients of the ARF group and 9 patients of the control group. PTMC can be performed in children with ARF without an increase in procedural complications. However, the restenosis rates appear to be higher.

Acute Disease↗
PubMed2002

Poststreptococcal reactive arthritis in children: is it really a different entity from rheumatic fever?

Poststreptococcal reactive arthritis (PSRA) is an acute, nonsuppurative arthritis following documented streptococcal infections. Although most authors accepted it as a different entity, the differences from acute rheumatic fever (ARF) are not clear. To document and compare the clinical and laboratory characteristics of PSRA and ARF, 24 patients with PSRA and 20 with ARF were enrolled in the study. The latency period from upper respiratory tract infection was shorter in patients with PSRA ( P<0.01). However, 25% of the patients with ARF had also short (<10 days) latency periods. Although symmetric and nonmigratory arthritis were more frequent in patients with PSRA, there was no significant difference for the distribution of mono-, oligo-, and polyarticular disease between PSRA and ARF patients. The frequency of small joint and hip involvement was also similar between the patient groups. Unresponsiveness of articular symptoms to salicylate therapy within 72 h was more frequent in patients with PSRA (P<0.001). However, in a substantial part of the patients with ARF (nine patients, 45%), joint symptoms also had no response during the first 72 h. Since there is a considerable overlap of symptoms, signs, and laboratory features of PSRA and ARF, a line between these two entities could not be easily drawn. We conclude that these two conditions are actually different presentations of the same disease.

Adolescent↗
PubMed2002

Renal failure after anti-D globulin treatment of idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is a disorder of rapid destruction of antibody-coated platelets. Anti-D immune globulin has been used for treatment of ITP in the United States since 1995. Initial studies identified no significant side effects of treatment. However, a recent report highlighted occasional episodes of intravascular hemolysis after anti-D immune globulin. We describe two children with ITP who developed acute renal failure (ARF) after treatment with anti-D immune globulin and also analyze ten additional cases of ARF reported to the manufacturer, Cangene Corporation, through postmarketing surveillance. All episodes of ARF were associated with intravascular hemolysis. Four patients required dialysis. Patient age ranged from 1 to 82 years, but those requiring dialysis were all under age 15 years. Several patients with ARF had preexisting creatinine elevation. Three of the patients with ARF had serologic evidence of acute Epstein-Barr virus (EBV) infection. Renal biopsy in one patient showed acute tubular necrosis, with findings consistent with pigment nephropathy. Anti-D immune globulin, used to treat ITP, may be associated with intravascular hemolysis and resultant ARF. Renal function should be monitored in patients with evidence of intravascular hemolysis. Children and adolescents may have increased risk of ARF requiring dialysis.

Acute Kidney Injury↗
PubMed2004

Genetic polymorphisms and risk for acute renal failure in preterm neonates.

Acute renal failure (ARF) affects about 10% of severely ill neonates. Recent studies have shown that genetic polymorphisms of proteins that play a role in neonatal physiology may contribute to individual susceptibility to both ARF and its risk factors. Our review summarizes the data collected to date. Studies have shown that the risk of preterm neonates for ARF is directly associated with a combination of high tumor necrosis factor-alpha producer and low interleukin-6 producer genotypes, as well as with low heat shock protein 72 producer genotype. Premature birth is itself the most important risk factor for a number of complications, including ARF, and recent studies have also shown an association between several maternal and fetal cytokine genetic polymorphisms and increased inflammatory response in preterm neonates. These polymorphisms could also be associated with increased risk for disorders such as sepsis and necrotizing enterocolitis, which lead to renal hypoperfusion and ARF. Genetic polymorphisms of the renin-angiotensin-aldosterone system have not been shown to directly influence risk for ARF. They may, however, be associated with patent ductus arteriosus, poor postnatal adaptation, and heart failure, which are all prevalent risk factors for ARF.

Acute Kidney Injury↗
PubMed1994

ARF1(2-17) does not specifically interact with ARF1-dependent pathways. Inhibition by peptide of phospholipases C beta, D and exocytosis in HL60 cells.

The small GTP-binding protein ARF has been shown recently to regulate phospholipase D (PLD). In order to investigate the role of ARF proteins in regulated exocytosis, we have used the N-terminal peptide ARF1(2-17) of the ARF1 protein. ARF1 reconstituted PLD activity in cytosol-depleted HL60 cells was inhibited by ARF1(2-17). In the presence of endogenous cytosol, ARF1(2-17) also inhibited GTP-gamma-S-stimulated PLD activity and exocytosis. Mastoparan Politses jadwagae and mastoparan Vespula lewisii which exhibit similar structural properties to ARF1(2-17) also inhibited GTP-gamma-S-stimulated PLD and exocytosis. GTP-gamma-S-stimulated phospholipase C-beta (PLC-beta) was also inhibited by ARF(2-17) and mastoparan. In cytosol-depleted HL60 cells, the ARF(2-17) inhibited the reconstitution of GTP-gamma-S-stimulated PLC-beta activity with exogenously-added PLC-beta 1 and phosphatidylinositol transfer protein. We conclude that the widely-used ARF1(2-17) peptide inhibits both ARF-independent (i.e. PLC-beta) and ARF-dependent pathways (i.e. PLD) and therefore cannot be regarded as a specific inhibitor of ARF function.

ADP-Ribosylation Factor 1↗
PubMed1991

ADP-ribosylation factor is a subunit of the coat of Golgi-derived COP-coated vesicles: a novel role for a GTP-binding protein.

ADP-ribosylation factor (ARF) is an abundant and highly conserved low molecular weight GTP-binding protein that was originally identified as a key element required for the action of cholera toxin in mammalian cells, but whose physiological role is unknown. We report that ARF family proteins are highly concentrated in non-clathrin-coated transport vesicles and are coat proteins. About three copies of ARF are present on the outside of coated vesicles per alpha-COP (and thus per coatomer). ARF is highly enriched in coated vesicles as compared with parental Golgi cisternae, as shown both by biochemical and morphological methods, and ARF is removed from transport vesicles through uncoating during transport. Furthermore, ARF binds to Golgi cisternae in a GTP-dependent manner independently of coated vesicle budding. These observations strongly suggest a new role for GTP-binding proteins: ARF proteins may modulate vesicle budding and uncoating through controlled GTP hydrolysis.

ADP-Ribosylation Factors↗
PubMed1995

Renal hypouricemia: prevention of exercise-induced acute renal failure and a review of the literature.

Isolated renal hypouricemia from defective uric acid reabsorption and/or secretion is a well-described entity, with a prevalence of 0.12% to 0.20% in Japan. It is rarely associated with exercise-induced acute renal failure (ARF). The etiology of ARF is debated. Prevention of ARF in renal hypouricemia has not been previously addressed. A 29-year-old Pakistani man had recurrent exercise-induced ARF. He was found to have isolated renal hypouricemia; serum uric acid 0.5 mg/dL, 24-hour urine uric acid 472 +/- 25 mg (+/- SD), and fractional excretion of uric acid 55.2% to 69.4%. Both pyrazinamide and probenecid decreased fractional excretion of uric acid and uric acid excretion rate (UV(Urate)) in our patient, suggesting either a partial presecretory and postsecretory reabsorption defect or increased secretion. We investigated renal uric acid excretion during exercise in our patient and four control subjects. All five subjects underwent a physical fitness test (PFT). Our patient developed ARF. Uric acid excretion rate increased in our patient, from 0.48 mg/min at baseline to 1.49 mg/min 4 hours after the PFT, as did the urine uric acid to urine creatinine ratio (UUa)/UCr) (0.29 to 1.49). In the controls, UV(Urate) and UUA/UCr were unchanged after the PFT: UV(Urate) was 0.46 +/- 0.10 mg/min at baseline and 0.59 +/- 0.04 mg/min 4 hours after the PFT, while UUA/UCr was 0.30 +/- 0.04 at baseline and 0.36 +/- 0.04 at 4 hours. All five subjects took allopurinol 300 mg daily for 5 days and repeated the PFT. In our patient, allopurinol prevented the ARF as well as the exercise-induced increases in UV(Urate) (0.28 mg/min to 0.22 mg/min) and UUA/UCr (0.25 to 0.17). In the controls, the UV(Urate) and UUA/UCr responses to exercise were not altered. We conclude that increased renal excretion of uric acid during exercise was responsible for the ARF in our patient with renal hypouricemia and that successful prophylaxis with allopurinol is possible.

Acute Kidney Injury↗
PubMed2006

Subclinical carditis in rheumatic fever: a systematic review.

OBJECTIVE: Subclinical carditis (SCC)--pathological valvular regurgitation detected on echocardiography that is not evident clinically--has been reported in acute rheumatic fever (ARF), but its significance is unknown. We aimed to review the existing literature on the prevalence and outcome of SCC in ARF. METHODS: We conducted a systematic literature review using MEDLINE. RESULTS: Prevalences of SCC in ARF ranged from 0% (in one study only) to 53% in 23 articles. The weighted pooled prevalence of SCC in ARF was 16.8% (95%CI 11.9 to 21.6). This increased slightly to 18.1% (95%CI 11.1 to 25.2) by analysing only the 10 studies that applied full World Health Organization criteria for SCC diagnosis. The weighted pooled prevalence of persistence or deterioration of SCC 3 to 23 months after ARF diagnosis was 44.7% (95%CI 19.3 to 70.2) from 11 articles. CONCLUSION: SCC is relatively common in ARF. Although some studies suggest that SCC lesions may persist or deteriorate, the available data are insufficient and of poor quality, so no confident conclusions can be drawn about the prognosis of SCC. Until better studies are conducted, clinicians will have to make management decisions that are not evidence-based. These decisions will have important practical implications for the use of echocardiography acutely and during follow-up, diagnosis of ARF, and duration of secondary prophylaxis in patients with SCC.

Acute Disease↗
PubMed2005

Yukmijihwang-tang ameliorates ischemia/reperfusion-induced renal injury in rats.

The present study was designed to examine whether Yukmijihwang-tang (YJT), which is a Korean decoction for the treatment of renal disease, has an effect on renal functional parameters in association with the expression of aquaporin 2 (AQP 2), Na,K-ATPase, heme oxygenase-1 (HO-1) in rats with ischemia/reperfusion-induced acute renal failure (ARF). Polyuria caused by down-regulation of renal AQP 2 in the ischemia/reperfusion-induced ARF rats was markedly restored by administration of YJT (100 or 200 mg/kg, p.o.) with restoring expression of AQP 2 in the kidney. The expressions of Na,K-ATPase alpha1 and beta1 subunits in the renal medulla and cortex of the ARF rats were also restored in them by the administration of YJT. Administration of YJT lowered the expression of renal HO-1, which was up-regulated in rats with ischemia/reperfusion-induced ARF. The renal functional parameters including creatinine clearance, urinary sodium excretion, urinary osmolality, and solute-free reabsorption were also markedly restored in ischemia-ARF rats by administration of YJT. Histological study also showed that renal damages in the ARF rats were abrogated by administration of YJT. Taken together, these data indicate that YJT ameliorates renal defects in rats with ischemia/reperfusion-induced ARF.

Animals↗
PubMed2006

Continued high caseload of rheumatic fever in western Pennsylvania: Possible rheumatogenic emm types of streptococcus pyogenes.

OBJECTIVE: To evaluate the occurrence of cases of acute rheumatic fever (ARF) in western Pennsylvania although there has been a marked reduction of cases of ARF in the United States overall. STUDY DESIGN: From 1994 to 2003, the cases of ARF evaluated at Children's Hospital of Pittsburgh were reviewed. In addition, throat cultures were performed on a subset of these children and their family members beginning in 1995. Molecular typing was performed on isolates of the group A streptococcus (GAS) recovered, using field inversion gel electrophoresis (FIGE) and emm typing. RESULTS: There were 121 new cases of ARF from 1994 to 2003. Of these, 57% were male. The median age was 10 years. The majority of children (57%) had carditis with or without another manifestation of ARF. The results of throat cultures were available for 231 persons; 36% (30/84) of the children with ARF and 14% (20/147) of family members were positive for GAS. Eight emm types were observed (emm 1, 2, 6, 12, 18, 28, 75, and 89). Data suggest that emm type 12 may be a rheumatogenic strain. CONCLUSION: ARF remains a problem in western Pennsylvania. Identification of emm types associated with cases should enlighten vaccine development.

Acute Disease↗
PubMed2004

Lithospermic acid B isolated from Salvia miltiorrhiza ameliorates ischemia/reperfusion-induced renal injury in rats.

The present study was designed to examine whether lithospermic acid B (LSB) isolated from Salvia miltiorrhiza has an ameliorative effect on renal functional parameters in association with the expression of aquaporin 2 (AQP 2) and Na,K-ATPase in the ischemia-reperfusion induced acute renal failure (ARF) rats. LSB showed strong antioxidant activity against production of reactive oxygen species (ROS), ROS-induced hemolysis, and production of lipid peroxide in a dose-dependent manner. Polyuria caused by down-regulation of renal AQP 2 in the ischemia-reperfusion induced ARF rats was partially restored by administration of LSB (40 mg/kg, i.p.), restoring expression of AQP 2, in renal inner and outer medulla. The expression of Na,K-ATPase alpha1 subunit in outer medulla of the ARF rats was also restored in the ARF rats by administration of LSB, while beta1 subunit level was not altered. The renal functional parameters including creatinine clearance, urinary sodium excretion, urinary osmolality, and solute-free reabsorption were also partially restored in ischemia-ARF rats by administration of LSB. Histological study also showed that renal damages in the ARF rats were abrogated by administration of LSB. Taken together, these data indicate that LSB ameliorates renal defects in rats with ischemia-reperfusion induced ARF, most likely via scavenging of ROS.

Acute Kidney Injury↗