Biomedical subjects

Y G Kim

Publications and source records attributed to Y G Kim.

At least 19 recordsLinked to original sources

PubMed2004

Prognostic factors affecting graft and patient survival in cadaveric and living kidney transplantation.

Numerous studies have reported various prognostic factors that affect graft and patient survival in living and cadaveric donor kidney transplantation (KT). The purpose of this study was to evaluate the clinical outcomes and prognostic factors affecting graft and patient survivals in living and cadaveric donor KT. Between February 1995 and December 2001, 421 patients who had undergone cadaveric donor KT (group I: 216 cases, 51.3%) or living donor KT (group II: 205 cases, 48.7%), were retrospectively analyzed. Five-year overall graft survival rates in living was significantly better than that in cadaveric donor KT, respectively (P = .0234). There was no difference in patient survival rates between the two groups. Such factors as absence of rejection, female donor, female recipient, adult KT according to recipient age (>14 years), and donor serum creatinine level just before transplantation (< 2.5 mg/dL) were significantly associated with good graft survival among cadaveric donor KT, whereas two factors-absence of rejection and adult KT according to recipient age (>14 years)-influenced graft survival in living donor KT. In multivariate analysis, the only significant prognostic factor related to graft survival was the presence of rejection. In conclusion, we suggest that the presence of rejection is the only factor that impairs graft survival in both cadaveric and living donor KT, while other factors affected graft survival differently in the two groups.

Adult↗

PubMed2004

Polymerase chain reaction for the diagnosis of human polyomavirus-associated nephropathy in renal transplant recipients.

Human polyomavirus type BK may be related to interstitial nephropathy or renal-allograft dysfunction. Patients with nephropathy due to infection with human polyomavirus may be identified early using the polymerase chain reaction(PCR). We attempted to evaluate whether the positive response in the PCR test of BK virus DNA in the plasma of renal transplant recipients affects the function of the renal allograft. Seventy-seven patients were prospectively analyzed according to the operative sex, age, sources of allograft, serum creatinine levels during PCR test for BK virus, postoperative type of immunosuppressant, and presence of graft rejection. Two groups were distinguished according to the PCR result for BK virus: group 1 (n = 12) positive PCR reaction and group 2 (n = 65) negative reaction. The mean follow-up was 32.6 weeks. The incidence of positive PCR tests for BK virus replication after renal transplantation was 15.6%. Decoy cells in the urine were detected in 20.7%. The incidence of BK virus nephropathy was 1.3%. The mean serum creatinine levels of group 1 and 2 at the time of the PCR tests were 1.34 and 1.22, respectively. The rejection rates in group 1 and 2 were 8% and 4.5%, respectively (P > .05). We consider that a PCR assay to detect BK virus in renal recipients blood may be useful to identify patients at risk for nephropathy. It may serve as a noninvasive indicator of BK virus replication, although this study is limited by the short follow-up and small numbers.

Adolescent↗

PubMed2004

Effect of panel-reactive antibody positivity on graft rejection before or after kidney transplantation.

INTRODUCTION: Because it is well known that kidney transplant recipients with preformed lymphocytotoxic antibodies against HLA antigens have increased graft rejection rates, a serological crossmatch is routinely performed before kidney transplantation. But, the presence of these antibodies is not routinely monitored after transplantation. We investigated the panel-reactive antibody (PRA) response to know whether variations before or after kidney transplantation were associated with graft rejection. METHODS: We prospectively analyzed sera from 350 renal allograft recipients from September 1998 to March 2003. Pretransplantation and posttransplantation sera at 3 or 5 weeks postoperatively were tested in PRA. Recipients were stratified into 3 groups according to their PRA levels group I, PRA = 0; group II, PRA = less than 50%, and group III, PRA = more than 50%. RESULTS: The total graft rejection rate among 350 recipients was 9.4% (n = 33). Twenty-four pretransplantation PRA-positive recipients had a graft rejection rate of 20.8% (n = 5), compared with an 8.6% (n = 28) rate among 326 pretransplantation PRA-negative recipients. Six of 24 posttransplantation PRA-positive recipients (25%) experienced a graft rejection versus 27 (8.3%) of 326 posttransplantation PRA-negative subjects. Among the pretransplantation PRA stratae, the rejection rate in group III was 25% (1 of 4) versus 20% (4 of 20) in group II and 8.6% (28 of 326) in group I (P < .05). According to the postransplantation PRA level, 37.5% (3 of 8) in group III versus 18.8% (3 of 16) in group II and 8.3% (27 of 326) in group I (P < .05) had a graft rejection. CONCLUSION: Our study suggests that the PRA response pretransplantation and in the early posttransplantation period correlates with the kidney allograft rejection rate.

Adolescent↗

PubMed2004

Bioequivalence of pravastatin tablet formulations assessed in Korean males.

AIM: Determination of the bioequivalence of 2 pravastatin tablet formulations manufactured in Korea. PATIENTS AND METHODS: Twenty-three healthy male Korean volunteers received each of the 2 pravastatin formulations at a dose of 20 mg in a 2 x 2 crossover study. There was a 1-week washout period between doses. Plasma concentrations of pravastatin were monitored using high-performance liquid chromatography over a period of 8 hours after administration. AUC(0-8h) (the area under the plasma concentration-time curve from time zero to the last measured time in plasma, 8 h) was calculated using the linear-log trapezoidal method. Cmax (maximum plasma drug concentration) and tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(0-8h) and Cmax and untransformed tmax. RESULTS: The point estimates and 90% confidence intervals for AUC(0-8h) (parametric) and Cmax (parametric) were 1.067 (0.968 to approximately 1.176) and 1.074 (0.999 to approximately 1.155), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. The corresponding value of tmax was 0.000 (-0.250 to approximately 0.250). CONCLUSION: These results indicate that the 2 medications of pravastatin are bioequivalent and, thus, may be prescribed interchangeably.

Adult↗

PubMed2004

Bioequivalence of a prednisolone tablet administered as a single oral dose in healthy male volunteers.

OBJECTIVE: A bioequivalence study ofprednisolone as Nisolone (test) tablets versus Delta-Cortef (reference) tablets was conducted. PATIENTS AND METHODS: Eighteen healthy male Korean volunteers received both 20 mg formulations of prednisolone in this 2 x 2 crossover study with a 1-week washout period between the doses. Plasma concentrations of prednisolone were monitored over a period of 12 hours after the administration using high-performance liquid chromatography. The AUC (area under the plasma concentration-time curve from time zero to infinity) and AUCt (area under the plasma concentration-time curve from time zero to the last sampling time) were calculated using the trapezoidal rule-extrapolation method. The Cmax (maximum plasma drug concentration) and t(max) (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC, AUCt and Cmax and untransformed t(max). RESULTS: The geometric mean of AUCt was 1,786 ng/ml x h (test medication) and 1,787 ng/ml xh (reference medication). A Cmax of 409 ng/ml and 404 ng/ml was achieved for the test and the reference medication, respectively. Point estimates and 90% confidence intervals for AUCt (parametric) and Cmax (parametric) were 0.989 (0.942 approximately 1.039) and 1.013 (0.934 approximately 1.100), respectively. These results satisfy the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of t(max) was -0.221 (-0.415 approximately 0.000). CONCLUSION: The 2 medications of prednisolone examined are bioequivalent and, thus, may be prescribed interchangeably.

Administration, Oral↗

PubMed2003

Comparative bioavailability of silibinin in healthy male volunteers.

AIM: To study a comparative bioavailability of Liverman capsule to Legaion capsule and Silymarin tablet (which contain silibinin) in 24 healthy volunteers. VOLUNTEERS AND METHODS: Twenty-four healthy male Korean volunteers received each medicine at the silibinin dose of 120 mg in a 3 x 3 crossover study. There was a 1-week washout period among the doses. Plasma concentrations of silibinin were monitored by a high-performance liquid chromatography for over a period of 12 hours after the administration. AUCinf (the area under the plasma concentration-time curve from time zero to time infinity) was calculated by the trapezoidal rule extrapolation method. Cmax (maximum plasma drug concentration) and tmax (time to reach a Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCinf, AUC(0-12h), and Cmax and untransformed tmax. RESULTS: After an oral administration of Liverman capsule, the pharmacokinetic parameters of silibinin, such as AUC(0-12h) (5.59, 4.24 and 13.9 microg/ml x h for Legalon capsule, Silymarin tablet and Liverman capsule, respectively) and AUCinf (6.00, 4.63 and 15.1 microg/ml x h) were significantly greater, Cmax (1.33, 1.13 and 6.04 microg/ml) was significantly higher and tmax (1.83, 2.10 and 0.875 h) was significantly faster than those after Legalon capsule and Silymarin tablet. CONCLUSION: These results indicate that the absorption and the extent of relative oral bioavailability of silibinin after Liverman capsule were significantly faster and greater, respectively, than those after Legalon capsule and Silymarin tablet.

Absorption↗

PubMed2002

Comparison of effects of angiotensin peptides in the regulation of clitoral cavernosum smooth muscle tone.

The isometric tension measurement and in vitro autoradiography were used in clitoral cavernosum smooth muscle (CSM). Angiotensin ANG III, ANG IV, ANG II and ANG I induced contractions in clitoral CSM strips. ANG III and ANG I- induced contraction was five times less active than ANG II, whereas ANG IV-induced contraction was 1181-fold less potent than ANG II. Contractile responses to ANG III, ANG IV, ANG II and ANG I were significantly inhibited by type 1 ANG II (AT 1) receptor antagonist Dup 753 but not by type 2 ANG II (AT2) receptor antagonist PD 123,319. Pre-treatment with Nomega-nitro-L-arginine methyl ester, nitric oxide (NO) synthase inhibitor accentuated force of contraction induced by ANG III, ANG IV and ANG II. Amastatin, an aminopeptidase inhibitor enhanced ANG III- and ANG IV-induced contractions. Specific binding sites for 125I-ANG II were found in the clitoral CSM. Specific binding of 125I-ANG II was displaced by unlabeled ANG peptides. This study suggests that the contractile responses to all four peptides of the ANG family are mediated via AT1 receptors but not AT2 receptors. Further, the rank order of potency of contraction was as follows, ANG II> ANG I>ANG III>ANG IV. It is also suggested that peptides of the ANG family have a cross-talk with the NO system and aminopeptidase is involved in the modulation of the tone of clitoral CSM by ANG III and ANG IV.

Acetylcholine↗

PubMed2002

Role of rho-kinase activity in angiotensin II-induced contraction of rabbit clitoral cavernosum smooth muscle.

Isometric tension measurement using a selective Rho-kinase inhibitor (+)- (R)-trans4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632) and a selective myosin light chain kinase (MLCK) inhibitor 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML7) were used in rabbit clitoral cavernosum smooth muscle (CSM). N(G)-nitro-L-arginine methyl ester (L-NAME) was used to evaluate the relationship between NO release and Rho-kinase. Y-27632 significantly attenuated contractions induced by ANG II, dose-dependently. However, ML7 did not affect the contractile response to ANG II except in the high concentrations of ML7. Y-27632 inhibited contraction with phenylephrine (PhE), but ML7 did not inhibit contraction with PhE. Nitric oxide synthase inhibitor (NAME) did not affect the Y-27632-induced relaxation in the pre-contracted strip with PhE. The present study demonstrates that G-protein-coupled increase in myofilament Ca(2+) sensitivity mediated through the RhoA/Rho-kinase signal pathway is involved in the control by ANG II of the clitoral CSM tone. RhoA/Rho-kinase pathway acts in the ANG II-induced contraction independently of the NO pathway.

Amides↗

PubMed2002

Laser mediated production of reactive oxygen and nitrogen species; implications for therapy.

Laser therapy has gained wide acceptance applications to many medical disciplines. The side effect-effects from laser therapy involve the potential for interaction with cellular and extracellular matrix molecules to generate reactive oxygen species and reactive nitrogen species which in turn can initiate lipid peroxidation, protein damage or DNA modification. These issues are addressed in this short overview in the context of experimental models of laser-induced thrombosis.

Animals↗

PubMed2001

Effects of cysteine on the pharmacokinetics of intravenous phenytoin in rats with protein-calorie malnutrition.

The effects of cysteine on the pharmacokinetics of phenytoin and one of its metabolites, 5-(p-hydroxyphenyl)-5-phenylhydantoin (pHPPH) were investigated after intravenous administration of phenytoin, 25 mg/kg, to control rats (4-week fed on 23% casein diet) and rats with PCM (protein-calorie malnutrition, 4-week fed on 5% casein diet) and PCMC (PCM with oral cysteine supplementation, 250 mg/kg, twice daily starting from the fourth week). In rats with PCM and PCMC, the phenytoin hydroxylation (to form pHPPH) activities were significantly smaller (164, 103 and 95.3 pmol/min per mg protein for the control rats, and rats with PCM and PCMC, respectively) than that in control rats. In rats with PCMC, the intrinsic clearance of phenytoin, CL(int) was significantly slower than those in control rats and rats with PCM (0.175, 0.131 and 0.044 ml/min). The above data suggested that the formation of pHPPH could be reduced in rats with PCM and PCMC. This was supported by significantly smaller 24-h urinary excretion of pHPPH (54.7, 35.6 and 32.5% of intravenous dose of phenytoin) in rats with PCM and PCMC than that in control rats. In rats with PCM, the maximum velocity (0.344, 0.203 and 0.196 microg/min), apparent volume of distribution in central compartment (44.4, 65.4 and 72.2 ml/kg) of phenytoin, and total area under the plasma concentration-time curve from time zero to time infinity (609, 714 and 1210 microg min/ml), renal clearance (20.5, 13.4 and 4.67 ml/min per kg) and 24-h urinary excretion (54.7, 35.6 and 32.5% of intravenous dose of phenytoin) of pHPPH were not returned to control levels by cysteine supplementation (rats with PCMC). This could be mainly due to the fact that the phenytoin hydroxylation activity in rats with PCMC was not returned to control level.

Algorithms↗

PubMed2001

Hyperuricemia exacerbates chronic cyclosporine nephropathy.

BACKGROUND: Hyperuricemia frequently complicates cyclosporine (CSA) therapy. The observation that longstanding hyperuricemia is associated with chronic tubulointerstitial disease and intrarenal vasoconstriction raised the hypothesis that hyperuricemia might contribute to chronic CSA nephropathy. METHODS: CSA nephropathy was induced by the administration of CSA (15 mg/kg/day) for 5 and 7 weeks to rats on a low salt diet (CSA group). The effect of hyperuricemia on CSA nephropathy was determined by blocking the hepatic enzyme uricase with oxonic acid (CSA-OA). Control groups included rats treated with vehicle (VEH) and oxonic acid alone (OA). Histological and functional studies were determined at sacrifice. RESULTS: CSA treated rats developed mild hyperuricemia with arteriolar hyalinosis, tubular injury and striped interstitial fibrosis. CSA-OA treated rats had higher uric acid levels in association with more severe arteriolar hyalinosis and tubulointerstitial damage. Intrarenal urate crystal deposition was absent in all groups. Both CSA and CSA-OA treated rats had increased renin and decreased NOS1 and NOS3 in their kidneys, and these changes are more evident in CSA-OA treated rats. CONCLUSION: An increase in uric acid exacerbates CSA nephropathy in the rat. The mechanism does not involve intrarenal uric acid crystal deposition and appears to involve activation of the renin angiotensin system and inhibition of intrarenal nitric oxide production.

Animals↗

PubMed2001

Effects of cysteine on the pharmacokinetics and pharmacodynamics of intravenous and oral azosemide in rats with protein-calorie malnutrition.

The effects of cysteine on the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous (10 mg/kg) and oral (20 mg/kg) administration to male Sprague-Dawley rats fed on 23% protein diet (control rats), and 5% protein diet with (rats with PCMC) or without (rats with PCM) oral cysteine (250 mg/kg, twice daily for the fourth week) for 4 weeks. After intravenous administration to rats with PCMC, some pharmacokinetic parameters restored fully or more than the level of control rats; the time-averaged nonrenal clearance (2.70 versus 2.32 ml/min/kg) and apparent volume of distribution at steady state (160 versus 189 ml/kg) were comparable to those in control rats, however, the terminal half-life (34.7 versus 57.2 min) and mean residence time (73.3 versus 99.3 min) were significantly shorter, area under the plasma concentration-time curve from time zero to time infinity (AUC, 1930 versus 2680 microg min/ml) was significantly smaller, and time-averaged renal (2.24 versus 1.21 ml/min/kg) and total body (CL, 4.98 versus 3.65 ml/min/kg) clearances were significantly faster than those in control rats. This could be mainly due to significantly faster renal clearance and at least partly due to increased cytochrome P450 1A2 activity by cysteine supplementation. After intravenous administration to rats with PCMC, the total amount of 8-hr urinary excretion of unchanged azosemide was significantly greater (457 versus 305 microg/g body weight), however, the 8-hr urine output (15.3 versus 31.1 ml/g kidney) was not significantly different between control rats and rats with PCMC. This could be due to the fact that urine output seemed to reach an upper plateau from 10 mg/kg dose of azosemide in rats.

Administration, Oral↗

PubMed2001

Comparative mutational analysis of cis-acting RNA signals for translational frameshifting in HIV-1 and HTLV-2.

Human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type II (HTLV-2) use a similar mechanism for -1 translational frameshifting to overcome the termination codon in viral RNA at the end of the gag gene. Previous studies have identified two important RNA signals for frameshifting, the slippery sequence and a downstream stem-loop structure. However, there have been somewhat conflicting reports concerning the individual contributions of these sequences. In this study we have performed a comprehensive mutational analysis of the cis-acting RNA sequences involved in HIV-1 gag-pol and HTLV-2 gag-pro frameshifting. Using an in vitro translation system we determined frameshifting efficiencies for shuffled HIV-1/HTLV-2 RNA elements in a background of HIV-1 or HTLV-2 sequences. We show that the ability of the slippery sequence and stem-loop to promote ribosomal frameshifting is influenced by the flanking upstream sequence and the nucleotides in the spacer element. A wide range of frameshift efficiency rates was observed for both viruses when shuffling single sequence elements. The results for HIV-1/HTLV-2 chimeric constructs represent strong evidence supporting the notion that the viral wild-type sequences are not designed for maximal frameshifting activity but are optimized to a level suited to efficient viral replication.

Base Sequence↗

PubMed2001

Prevention of c-Jun/activator protein-1 activation and microsomal epoxide hydrolase induction in the rat liver by cysteine during protein-calorie malnutrition.

Protein-calorie malnutrition (PCM), a major global health problem, arises during protein and/or energy deficit due to disease and nutritional inadequacy. To date, cellular adaptive responses and gene expression associated with PCM remain poorly understood. In view of the primary role of the liver in energy conversion, the present study was designed to investigate changes in hepatic morphology and molecular alterations during PCM. PCM caused marked decreases in the cytoplasmic eosinophilic content and nuclear shrinkage in the hepatocytes with a decrease in glutathione content. The nuclear activator protein-1 (AP-1) complex was activated in the liver of PCM rats. AP-1-binding activity of nuclear extracts produced from PCM rats was reduced by the presence of anti-c-Jun antibody. Microsomal epoxide hydrolase (mEH), a phase II detoxifying enzyme, was 4-fold induced, with a 20-fold increase in the mRNA level during PCM. In contrast to the PCM-induced changes in hepatic morphology, PCM rats supplemented with cysteine showed an increase in the GSH level and well-preserved hepatic structures with mild fat degeneration. Cysteine supplementation inhibited the activation of AP-1 and the induction of mEH in PCM rats. These results provided evidence: (i) that PCM alters liver morphology with a decrease in the glutathione level; (ii) that cysteine may serve as a key element responsible for preserving hepatic morphology and maintaining the glutathione level; and (iii) that cysteine was active in preventing the activation of AP-1 and mEH induction in the liver during PCM.

Animals↗

PubMed2001

Genomic clustering of tRNA-specific adenosine deaminase ADAT1 and two tRNA synthetases.

Human tRNA-specific adenosine deaminase (hADAT1) specifically converts A37 in the anticodon loop of human tRNA(Ala) to inosine via a hydrolytic deamination mechanism. The enzyme is related to a family of RNA editing enzymes (ADARs) specific for pre-mRNA, and it has been cloned based on its sequence homology to the catalytic domain of ADARs. In the present study we have analyzed the 5'-flanking sequence of the murine ADAT1 gene, revealing that the first transcribed exon is located 1.1 kb downstream from the polyadenylation site of lysyl tRNA synthetase (KARS). The close proximity is conserved in the human genome with an intergenic distance of 5.5 kb. We determined the complete cDNA sequence as well as exon/intron organization of murine KARS. Significant sequence similarities between KARS and ADAT1 are apparent within their substrate interaction domains. Radiation hybrid panel analysis mapped human ADAT1 and human KARS to region q22.2--22.3 of Chromosome (Chr) 16 with alanyl tRNA synthetase (AARS) positioned centromeric to the KARS and ADAT1 genes. 16q22--24 has recently been recognized as a susceptibility candidate locus for several autoimmune inflammatory diseases. The clustering of three tRNA specific genes, of which two are specific for tRNA(Ala), may indicate their evolutionary relatedness or common factors involved in regulating their expression.

Adenosine Deaminase↗

PubMed2001

Optimization of fermentation conditions for the production of bacterial cellulose by a newly isolated Acetobacter sp. A9 in shaking cultures.

The optimum fermentation conditions for the production of cellulose by a newly isolated Acetobacter sp. A9 were determined by shaken cultures. The strain was able to produce cellulose at 25-30 degrees C with a maximum at 30 degrees C. Cellulose production occurred at pH 4.5-7.5 with a maximum at pH 6.5. The improved medium composition was 4% (w/v) glucose, 0.1% (w/v) yeast extract, 0.7% (w/v) polypeptone and 0.8% (w/v) Na(2)HPO(4).12H(2)O. Under these culture conditions, 3.8 g/l cellulose was produced after 7 days of cultivation, although this strain produced only 2.2 g/l in the standard medium. The addition of ethanol to the improved medium enhanced cellulose production: in an improved medium containing 1.4% (v/v) ethanol, cellulose production was 15.2 g/l, which was about four times higher than that without ethanol. Addition of ethanol was found to eliminate the spontaneous mutation of Acetobacter sp. A9.

Acetobacter↗

PubMed2001

Vascular endothelial growth factor (VEGF121) protects rats from renal infarction in thrombotic microangiopathy.

BACKGROUND: Renal thrombotic microangiopathy, typified by the hemolytic uremic syndrome, is associated with endothelial cell injury in which the presence of cortical necrosis, extensive glomerular involvement, and arterial occlusive lesions correlates with a poor clinical outcome. We hypothesized that the endothelial survival factor vascular endothelial growth factor (VEGF) may provide protection. METHOD: Severe, necrotizing, thrombotic microangiopathy was induced in rats by the renal artery perfusion of antiglomerular endothelial antibody, followed by the administration of VEGF or vehicle, and renal injury was evaluated. RESULTS: Control rats developed severe glomerular and tubulointerstitial injury with extensive renal necrosis. The administration of VEGF significantly reduced the necrosis, preserved the glomerular endothelium and arterioles, and reduced the number of apoptotic cells in glomeruli (at 4 hours) and in the tubulointerstitium (at 4 days). The prosurvival effect of VEGF for endothelium may relate in part to the ability of VEGF to protect endothelial cells from factor-induced apoptosis, as demonstrated for tumor necrosis factor-alpha (TNF-alpha), which was shown to be up-regulated through the course of this model of renal microangiopathy. Endothelial nitric oxide synthase expression was preserved in VEGF-treated rats compared with its marked decrease in the surviving glomeruli and interstitium of the antibody-treated rats that did not receive VEGF. CONCLUSIONS: VEGF protects against renal necrosis in this model of thrombotic microangiopathy. This protection may be mediated by maintaining endothelial nitric oxide production and/or preventing endothelial cell death.

Animals↗

PubMed2001

Intravenous immunoglobulin protects against experimental thrombotic microangiopathy.

BACKGROUND: Intravenous immunoglobulin (IVIG) has been utilized in several forms of vasculitis and has many potential mechanisms of action, including the inhibition of C3 activation. We have previously demonstrated that IVIG can reduce glomerular injury in a model of membranous nephropathy mediated by C5b-9 [1]. C5b-9 has also been shown to mediate the thrombotic microangiopathy (TMA) induced by antibody to glomerular endothelial cells leading to a hemolytic uremic syndrome-type lesion [2]. METHODS: To test the hypothesis that IVIG might be effective in treating antibody-induced TMA, male uninephrectomized rats underwent right renal artery perfusion with goat anti-rat glomerular endothelial cell (GEN) antibody (20 mg/kg). Sheep IgG (200 mg/kg) was administered either 30 minutes before the renal artery perfusion (group I, N = 6) or 30 minutes postperfusion (group II, N = 9). A third control group received phosphate-buffered saline (PBS; group III, N = 12). A survival biopsy was performed at 15 minutes, and the animals were sacrificed on day 2. RESULTS: There were no significant differences in proteinuria or hematocrit between the groups. Animals pretreated with IVIG had significantly improved survival and renal function, which was associated with a decrease in glomerular C3 deposition. The protective effect of IVIG was abolished if the administration was delayed 30 minutes after perfusion. CONCLUSIONS: IVIG is effective in reducing injury in experimental TMA only if given prophylactically. The effect is mediated by inhibition of local intraglomerular complement activation.

Animals↗