Biomedical subjects
Publications and source records attributed to Dierik Verbeelen.
Acute interstitial nephritis (AIN) is a common cause of acute renal failure. We report a case of AIN, confirmed by renal biopsy, that developed in a patient with typhoid fever due to a Salmonella hadar infection. AIN secondary to Salmonella infection is a rare complication that has only been described twice in the literature. Salmonella should be added to the list of possible causes of AIN.
BACKGROUND: Conversion from cyclosporine (CsA) to sirolimus (SRL) has mainly been done in clinical conditions warranting calcineurin inhibitor discontinuation. Little is known about the clinical outcome of conversion in renal transplant recipients without transplant dysfunction. METHODS: This prospective, open-label, multicentric pilot study evaluates the safety and efficacy of converting patients with stable renal function from CsA to SRL. RESULTS: Forty stable patients on CsA, mycophenolate mofetil (MMF) (1.5 g/day), and steroids (ST) were converted at 7.6+/-1.4 months after renal transplantation. At 1 year, graft and patient survival was 100% and the incidence of acute rejection 5%. Calculated glomerular filtration rate (GFR) increased from 54+/-18 to 66+/-16 ml/min (P<0.0001). Blood pressure remained unchanged. A gradual increase in the incidence and severity of proteinuria was observed from month 6 onwards with de novo proteinuria in 30% of the patients at 1 year. Protein excretion was below 1 g/day in 12.5%, between 1 and 3 g/day in 17.5% and above 3 g/day in 7.5% of the proteinuric cohort (P=0.0043, compared to baseline). No predictors could be identified for the development of proteinuria. All patients had a reduction in protein excretion following renin-angiotensin blockade and were continued on SRL. CONCLUSION: Conversion of stable renal transplant recipients from a CsA-MMF-ST to a SRL-MMF-ST regimen is safe and results in improved renal function but is associated with the development of proteinuria in 30% of the patients requiring renin-angiotensin blockade.
Chronic renal failure evolves inevitable towards glomerular and tubulo-interstitial sclerosis. This pathological process involves a disturbed redox status of the kidney tissue, leading to irreversible damage. In this study we investigate in an adriamycin model of chronic renal failure in mice the evolution of in vivo hydrogen peroxide production, and the possible role of gamma-glutamyl transpeptidase and ferric iron in the process. Histological changes and ferric iron deposits are evaluated by histochemical staining. To evaluate oxidative stress residual catalase activity, TBARS formation and gamma-glutamyl transpeptidase activity are measured spectrophotometrically. While catalase activity remains the same, a decreased residual catalase activity indicates an increased formation of hydrogen peroxide. Both the activity of gamma-glutamyl transpeptidase and TBARS formation is increased at early stages of the disease. Ferric iron is clearly present in the proximal tubule. Twenty days after adriamycin injection all parameters decrease, probably due to the destruction of the tissue. Our data show the involvement of oxidative stress in the progression of adriamycin induced renal failure in mice. Both radical production and oxidative damage are measurable, while the altered activity of gamma-glutamyl transpeptidase and the deposition of ferric iron suggest the involvement of these factors in the development of a disturbed redox status in the kidney cortex.
BACKGROUND: In patients with end-stage renal disease (ESRD), treated with haemodialysis, a high overall mortality is observed. A previous study showed that cardiac troponin T (cTnT) is a strong independent predictor of outcome in this population. In this study we investigated possible causes of cTnT increase and its relationship with a marker of oxidative stress. METHODS: In a group of 71 haemodialysis patients (36 male, 35 female, mean age 68.7+/-1.5 years) we determined cTnT and compared its presence with several biochemical parameters and with malondialdehyde (MDA), which is an indicator of oxidative stress. None of the patients suffered an acute coronary event during the observation period. Three measurements of cTnT and MDA were performed with a 2-week interval. Forty-nine patients underwent a transthoracic echocardiography. RESULTS: Twenty-nine patients (or 40.8%) had a positive cTnT determination (defined as cTnT >/=0.10 ng/ml). cTnT positive patients had significantly higher levels of MDA (P=0.0125), C-reactive protein (CRP) (P=0.04) and pre-dialysis urea (P=0.04). Regression analysis showed that both pre-dialysis urea and MDA independently influenced cTnT. No correlation was found with age, dialysis adequacy, post-dialysis urea, total cholesterol, white blood cell count, fibrinogen or any of the echocardiographical parameters. Presence of heart failure, diabetes or use of medication could not discriminate between cTnT positive and cTnT negative patients. MDA levels correlated positively with time on haemodialysis (P=0.0021). Echocardiography showed left ventricular hypertrophy in 88% of the examined patients and impaired wall motion in 35%. Patients with clinical signs of heart failure had a lower ejection fraction and worse wall motion score index. No correlation existed between echocardiographic findings and cTnT or MDA. Survival was independently predicted by cTnT (P=0.0025), MDA (P=0.0007), CRP (P=0.006) and age (P=0.0143). Patients with both cTnT and CRP increase had a survival of <50% at 1 year, compared with 90% in patients with both cTnT and CRP within the normal range and 80% when either CRP or cTnT was increased (chi(2)=12.127; P=0.0023). CONCLUSIONS: This study confirms that the presence of cTnT predicts prognosis in ESRD. The presence of cTnT is linked to oxidative stress, inflammation and uraemia. The absence of specific findings on EKG and echocardiography points towards subclinical myocardial damage caused by endothelial disturbances.
BACKGROUND/AIMS: Mycophenolate mofetil (MMF) is known to attenuate glomerulosclerosis in experimental models of renal failure. We investigated whether this is mediated by reduction of oxidative stress. METHODS: Effects of MMF on oxidative stress are studied in an experimental rat model (NA model) involving unilateral nephrectomy and two intravenous injections with adriamycin (2 mg/kg). Rats are sacrificed after 2 and 6 weeks. Glomerulosclerosis and tubulointerstitial lesions are demonstrated by histological techniques. Presence of macrophages/monocytes (ED1) and myofibroblasts (alpha-SMA) is demonstrated by immunohistochemistry. Oxidative stress is evaluated by enzymatic measurements (AOE), spectrofluorometry (TBARS), immunohistochemistry (MDA and HNE) and histology (ferric iron deposition). RESULTS: The NA model shows proteinuria, hypercholesterolemia, beginning glomerulosclerosis, tubulointerstitial sclerosis and tubular dilatation, glomerular, periglomerular and interstitial presence of alpha-SMA and increased presence of macrophages/monocytes after 6 weeks. Oxidative stress in renal cortex is apparent (increased cortex TBARS concentration, increased glomerular presence of MDA and HNE, decreased activity of antioxidant enzymes, ferric iron deposition in proximal tubules) after 6 weeks. MMF administration results in a decrease of glomerulosclerosis, interstitial sclerosis, glomerular and periglomerular expression of alpha-SMA and the number of ED1-positive cells in tubulointerstitium and glomeruli. Proteinuria and cholesterolemia are not decreased. TBARS level, and activities of catalase, Mn and Cu/Zn superoxide dismutase as well as the presence of ferric iron in the proximal tubules are not changed by MMF treatment. Cortex activity of glutathione peroxidase returns to normal. CONCLUSION: MMF has a favorable effect on glomerular and interstitial fibrosis in the NA model of kidney disease, but not on proteinuria and cholesterolemia. Improvement of fibrosis cannot be explained by major changes in oxidative stress or antioxidant defense.
BACKGROUND: Patients with end-stage renal disease (ESRD) undergoing hemodialysis have severe alterations in cell-mediated immunity (CMI) that increases their risk of contracting chronic hepatitis B virus (HBV) infection and decreases their protective responses to HBV vaccine. In an effort to improve the humoral response to an accelerated HBV vaccine protocol in these patients, the ability of an immunomodulator, AM3, to improve seroconversion was investigated. METHODS: A total of 269 patients were enrolled in a multicenter trial. All patients received a DNA recombinant vaccine (40 microg HBsAg/dose/day) on days 0, 10, 21, and 90. AM3 or placebo (3 g/day) was given orally for 30 consecutive days beginning 15 days prior to the first vaccine dose. Anti-HBsAg titers were measured on days 120 and 270 after the beginning of the trial. RESULTS: After one month, 207 patients could be evaluated and 132 patients after six months. The placebo and AM3-treated groups had comparable seroconversion and protective response rates one month after the final vaccine dose. The AM3 treatment group, but not the placebo group, maintained these protective titers up to six months after the final vaccine dose. At this time, the percentage of high responders (anti-HBsAg>100 IU/L) and mean anti-HBsAg titers in the AM3 group was significantly higher than in the placebo group. CONCLUSIONS: AM3 is a safe and easily tolerated oral agent that potentiates long-term serological immunity to hepatitis B in hemodialysis patients after vaccination.
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BACKGROUND/AIMS: In the rat Adriamycin model of chronic renal failure, the development of glomerulosclerosis and tubulointerstitial lesions is accompanied by decreased activities and mRNA levels of the antioxidant enzymes. In this study, we investigated the effect of oral vitamin E supplementation on antioxidant enzyme activities in both the cortex and isolated glomeruli from Adriamycin-treated rats. METHODS: Glomerulosclerosis, tubulointerstitial lesions and ferric iron deposits were evaluated by histochemical staining methods, and antioxidant enzyme activities were measured by spectrophotometry. RESULTS: Vitamin E supplementation of the normal diet attenuates Adriamycin-induced glomerulosclerosis and tubulointerstitial lesions, but not proteinuria and serum total cholesterol, low-density lipoprotein cholesterol, triglycerides and total protein concentrations. In the cortex, vitamin E completely prevented a decrease in enzyme activity for Cu/Zn superoxide dismutase and catalase, and partly for Mn superoxide dismutase and glutathione peroxidase. In the glomeruli, vitamin E completely prevented a decrease in activity for Cu/Zn superoxide dismutase, catalase and glutathione peroxidase, and partly for Mn superoxide dismutase. CONCLUSION: Dietary supplementation of vitamin E protects the activities of antioxidant enzymes in the kidney cortex and glomeruli, and attenuates the evolution towards terminal renal failure in rats treated with Adriamycin.