Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
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The prevalence of hepatitis C infection and possible predisposing factors was assessed in a renal unit. Of 343 patients at our renal dialysis centre, 37 (10.8%) were anti-HCV positive by a 1st-generation assay (ELISA, Ortho/Chiron) and confirmed positive in 35 (10.2%) with a 2nd-generation test (UBI, New York). Anti-HCV positivity was significantly associated with: duration of renal replacement therapy (P < 0.0001); quantity of blood transfused (P < 0.002); duration of hospital haemodialysis (P = 0.0001); duration with a functional renal transplant (P = 0.039); and aspartate aminotransferase (P < 0.0001). Logistic regression determined the following variables to be independent risk factors: duration of renal replacement therapy with a relative risk of 34.3 for 5-9 years and 87.4 when the duration was in excess of 10 years; renal transplant for less than 1 year (relative risk of 5.0); transfusion in excess of 50 units of blood (relative risk of 11.6). Clinical assessment of anti-HCV-positive patients revealed peripheral signs of chronic liver disease in 40%, hepatomegaly in 34%, and splenomegaly in 9%. This prevalence of hepatitis C infection is similar to other European and North American centres, but contrasts with low prevalence rates reported from dialysis populations in the UK. It adds further support for routine screening of blood and possibly organ donors and implementation of further infection control measures in dialysis centres.
Nephrol Dial Transplant 1992
PMID:Prevalence of antibodies to hepatitis C in dialysis patients and transplant recipients with possible routes of transmission. 827 37

Fifty-two patients on regular haemodialysis at our institution were evaluated for the presence of HCV infection. Evaluation included detailed history, clinical examination, and monthly screening for anti-HCV antibody, liver enzymes (ALT, AST), serum iron and ferritin. Also, three-monthly screening for other viral markers, HBV (HBsAg, HBsAb, HBcAb), CMV (IgG and IgM), EBV, and HIV. Anti-HCV antibody was found in 21 patients (40.4%). There was a significant (P less than 0.05) relationship between presence of anti-HCV antibody and proportion of patients who received blood transfusion. During a 12-month follow-up, four (11.4%) patients seroconverted to be Anti-HCV positive while one case (4.8%) seroconverted to be anti-HCV negative. The frequency of elevation of liver enzymes was significantly higher in Anti-HCV positive cases (14/18) than in negative cases (11/28, P = 0.01). Evaluation of liver biopsies of 13 patients showed chronic persistent hepatitis in six and chronic active hepatitis in seven cases. We concluded that hepatitis C is a common problem among chronic haemodialysis patients at our institution; HCV infection is documented in 70% of all clinically diagnosed NANB hepatitis. Presence of anti-HCV antibodies cannot differentiate between active and past infection and cases with early HCV infection can be missed when relying on the mere detection of anti-HCV antibodies.
Nephrol Dial Transplant 1992
PMID:Hepatitis C virus infection in chronic haemodialysis patients, a clinicopathologic study. 128 48

Serum indoxyl sulphate, which is markedly accumulated in haemodialysis patients, cannot be removed efficiently by haemodialysis due to its albumin-binding property. To determine whether an oral adsorbent (AST-120) can decrease its serum concentration, AST-120 was administered to haemodialysis patients. The patients given AST-120 showed significantly reduced serum concentration of indoxyl sulphate as compared to control haemodialysis patients, even though the serum concentrations of urea nitrogen and creatinine did not decrease significantly in the patients treated with AST-120. The haemodialysis patients with generalised pruritus showed an amelioration of itching after administration of AST-120. These results showed that AST-120 was effective in reducing the serum concentration of albumin-bound indoxyl sulphate in haemodialysis patients by adsorption of indole, a precursor of indoxyl sulphate, in the intestines, and that it relieved itching in haemodialysis patients with generalised pruritus.
Nephrol Dial Transplant 1991
PMID:Oral sorbent suppresses accumulation of albumin-bound indoxyl sulphate in serum of haemodialysis patients. 190 99

In order to examine the mechanism by which the oral carbonaceous adsorbent, AST-120 delays the appearance of glomerular sclerosis, experiments were carried out in 120 male Sprague-Dawley rats weighing 285-320 g. The rats were first subjected to 2/3, 3/4, and 4/5 nephrectomy (n = 40). The experiments were begun at 2 weeks after the surgery, and were performed over an 8-week period. Half of each group (n = 20) was administered 1 g/day of liquid AST-120, and the other half received liquid vehicle solution with pair feeding in each group. In the 2/3 nephrectomized group the administration of AST-120 delayed the occurrence of glomerular hypertrophy and prevented the appearance of glomerular sclerosis without any significant differences in renal function, systemic blood pressure (SBP), and urinary protein excretion (U-P). In the 3/4 nephrectomized group the administration of AST-120 delayed the appearance of glomerular hypertrophy and sclerosis with significant decreases in SBP and U-P. In the 4/5 nephrectomized group the administration of AST-120 delayed the appearance of glomerular sclerosis and prevented a decrease in renal function. It is concluded that administration of the oral adsorbent AST-120 delays the occurrence of glomerular sclerosis by delaying the appearance of glomerular hypertrophy, systemic hypertension, and the increase in proteinuria. It can be therefore mentioned that the accumulating substances in the digestive tract worsen the abnormal milieu of chronic renal failure.
Nephrol Dial Transplant 1995
PMID:Correction by oral adsorbent of abnormal digestive tract milieu in rats with chronic renal failure. 756 81

Clinical and biochemical parameters associated with the removal of the peritoneal catheter and death following continuous ambulatory peritoneal dialysis (CAPD) peritonitis were analyzed in 120 episodes of peritonitis. Episodes resulting in catheter removal (n = 24, 20%) and those ending in patient death (n = 12, 10%) were respectively compared with episodes in which peritoneal catheters were saved and from which the patients survived. Variables associated with catheter removal included advanced age, long duration of peritonitis, coexisting exit-site/tunnel infection, infection caused by pseudomonas or fungi, elevated aspartate aminotransferase (AST) and malnutrition at presentation with peritonitis (serum albumin 29.5 +/- 7.6 g/L vs 33.8 +/- 4.8 g/L in episodes in which the catheters were saved, p = 0.014), and worsening malnutrition during peritonitis. Variables associated with death from peritonitis included diabetes mellitus, persistence of the infection, removal of the peritoneal catheter, infection with pseudomonas, malnutrition prior to the infection (serum albumin 29.5 +/- 3.2 g/L vs 34.7 +/- 4.2 g/L in survivors, p < 0.001), presentation with elevated AST and worsening malnutrition, and the development of pronounced malnutrition during infection (serum albumin 18.1 +/- 4.1 g/L vs 28.9 +/- 5.8 g/L in survivors, p < 0.001). Deaths were caused primarily by cardiovascular events. Both removal of the peritoneal catheter and death as consequences of CAPD peritonitis are associated with malnutrition and pseudomonas infection. In addition, death is more frequent in diabetic patients.
Perit Dial Int 1993
PMID:Peritoneal catheter loss and death in continuous ambulatory peritoneal dialysis peritonitis: correlation with clinical and biochemical parameters. 839 4

Nineteen haemodialysis (HD) patients with chronic hepatitis C were treated with interferon-alpha 2b (IFN-alpha) at a dose of 3 or 1 MU thrice weekly for 6 months and were followed-up for another 14 months without treatment. Six patients discontinued treatment because they either presented severe side-effects to IFN-alpha or had complications of their primary disease. Levels of AST and ALT were within normal limits on the 2nd month of treatment and remained so throughout the treatment and the follow-up period in all patients except one who showed an elevation of transaminase levels 2 months after the end of treatment. Serum HCVRNA became negative in 10/13 patients at the end of treatment and was negative in all patients on the 6th month and in 12/13 patients on the 14th month during the follow-up period. Levels of 2'5' oligosynthetase were increased significantly on the 2nd and 4th month of treatment and returned to pretreatment values the 2nd month after treatment. These findings demonstrate that haemodialysis patients with chronic hepatitis C respond well to interferon treatment and that a long-term response is achieved in a high proportion of patients.
Nephrol Dial Transplant 1995 Oct
PMID:Interferon-alpha 2b treatment of chronic hepatitis C in haemodialysis patients. 859 90

Large-scale clinical trials have shown that the oral adsorbent AST-120 improves renal function and delays the initiation of dialysis in chronic renal failure (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via common mechanisms, then the same effects can be expected in diabetic nephropathy. However, no study on diabetic nephropathy has been reported. Thus, we enrolled patients with statistically significant progression of CRF secondary to diabetic nephropathy, and analyzed the changes in renal function after AST-120 therapy, and the clinical factors associated with response to therapy. We enrolled 276 patients with diabetic nephropathy, whose serum creatinine (Scr) had increased from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical data were analyzed by dividing the patients into three groups based on the changes in Scr after AST-120 therapy, with responders showing a decrease (N = 82), partial responders showing <1.5-fold increase (N = 144), and non-responders showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of 1/Scr-time line, suggesting that AST-120 suppressed the progression of renal impairment. No responders required dialysis, whereas 24.3% of the partial responders and 36.0% of the non-responders started dialysis therapy. In responders, the 1/Scr-time slope showed a negative-to-positive shift and serum urea nitrogen decreased significantly, whereas the improvement was moderate in partial responders and minimal in non-responders. Among responders, AST-120 therapy significantly improved renal function despite the presence of hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The beneficial effect of AST-120 was significantly more marked in patients with blood pressure controlled within the normal ranges and hematocrit maintained at 30% or above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis therapy in patients with progressive aggravation of CRF secondary to diabetic nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and hypertension. Active use of AST-120 may be recommended in patients with good control of blood pressure and hematocrit above 30%.
Ther Apher Dial 2004 Jun
PMID:Protective effect of an oral adsorbent on renal function in chronic renal failure: determinants of its efficacy in diabetic nephropathy. 1515 77

The effects of an oral adsorbent, AST-120, in chronic kidney disease (CKD) patients was evaluated by the 24-month dialysis-free rate and 50% dialysis-free period. This study retrospectively analyzed 193 patients admitted to the Osaka Medical College Hospital between January 1994 and December 2001 because of CKD and who later started dialysis. The propensity score on multiple factors was used to match two groups of patients (AST-120 group, n = 78; non-AST-120 group, n = 78). Then, the proportion of patients remaining dialysis-free and the 50% dialysis-free period during the 24 months after starting treatment with or without AST-120 were analyzed. The impact of AST-120 on the risk of dialysis initiation was also determined by multivariate analysis. There were no significant differences in the clinical background and laboratory values after matching the two groups using the propensity score. The 50% dialysis-free period was significantly prolonged in the AST-120 group compared to the non-AST-120 group for all patients analyzed, as well as for the subgroup with diabetic or non-diabetic renal disease. When AST-120 treatment was started at a serum creatinine level below 3 mg/dL, the dialysis-free period was longer than 24 months in the AST-120 group, compared with 16.2 months in the non-AST-120 group. The 24-month dialysis-free rate was higher in the AST-120 group in every patient category. The risk of dialysis initiation was increased 3.48-fold in patients who were not administered AST-120. These results show that AST-120 delays the initiation of dialysis in CKD patients. Thus, AST-120 is an effective supplementary therapy to prevent the initiation of dialysis in CKD patients.
Ther Apher Dial 2007 Jun
PMID:AST-120, an oral adsorbent, delays the initiation of dialysis in patients with chronic kidney diseases. 1749

Protein-energy malnutrition and inflammation are among the leading causes of poor outcome in hemodialysis patients. Hepatitis C virus (HCV) infection is accompanied by elevated proinflammatory mediators, also found in dialysis patients with malnutrition-inflammation complex syndrome. We aimed to study the rate and characteristics of malnutrition-inflammation complex syndrome (MICS) in hemodialysis patients, especially those with hepatitis C. The study included 147 patients (mean age 55.1 +/- 12.9 years), 24.5% of whom were HCV-positive, undergoing adequate hemodialysis three times a week for the last 52.7 +/- 52.5 months. Parameters of nutrition and inflammation were investigated to evaluate MICS. HCV-positive vs. HCV-negative patients had significantly higher hematocrit (29.6 +/- 4.5 g/dL vs. 28.1 +/- 4.3, P < 0.05), uric acid (345.8 +/- 96.5 vs. 321.3 +/- 118.8 micromol/mL, P < 0.05), aspartate aminotransferase (AST, also known as serum glutamic oxaloacetic transaminase [SGOT]) (23.3 +/- 14.9 vs. 17.8 +/- 9 U/L, P < 0.008), alanine aminotransferase (ALT, also known as serum glutamic pyruvic transaminase [SGPT]) (41.2 +/- 28.7 vs. 26.6 +/- 17.1 U/L, P < 0.0003), serum creatinine (980.4 +/- 219.1 vs. 888.4 +/- 202.9 micromol/mL, P < 0.022), intact parathyroid hormone (329.7 +/- 630.5 vs. 110.2 +/- 145.3 pg/mL, P < 0.002), malnutrition-inflammation score (7.4 +/- 5.2 vs. 5.6 +/- 4.1, P < 0.038), and Charlson comorbidity index (4.5 +/- 1.5 vs. 4 +/- 1.4, P < 0.05). MICS had a prevalence of 20-40% in our study. HCV-positive patients had a significantly higher prevalence of MICS than HCV-negative patients (30-40% vs. 20-30%).
Ther Apher Dial 2009 Apr
PMID:Malnutrition-inflammation complex syndrome and hepatitis C in maintenance hemodialysis patients. 1937 50

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Occult HBV infection harbors potential risk of HBV transmission through hemodialysis (HD). The aim of this study was to assess the occult HBV infection in hemodialysis patients with isolated hepatitis B core antibody (anti-HBc). A total of 289 HD patients from five dialysis units in Tehran, Iran, were included in this study. Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (anti-HBs), anti-HBc, Hepatitis C antibody (anti-HCV), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of HD patients with isolated anti-HBc (HBsAg negative, anti-HBs negative and anti-HBc positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler. Of 289 patients enrolled in this study, 18 subjects (6.2%, 95% confidence interval (CI), 3.5%-8.9%) had isolated anti-HBc. HBV-DNA was detectable in 9 of 18 patients (50%, 95% CI, 27%-73%) who had isolated anti-HBc. Plasma HBV-DNA load was less than 50 IU/ml in all of these patients. Our study showed that detection of isolated anti-HBc could reflect unrecognized occult HBV infection in HD patients. The majority of these infections are associated with low viral loads.
Ther Apher Dial 2010 Jun
PMID:Occult hepatitis B virus infection in hemodialysis patients with isolated hepatitis B core antibody: a multicenter study. 2111 74


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