Alpha-1-antitrypsin deficiency and mesangio-capillary glomerulonephritis in an elderly patient.
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Biomedical subjects
Publications and source records attributed to D Verbeelen.
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The feasibility of a voxel-by-voxel deconvolution analysis of T(1)-weighted DCE data in the human kidney and its potential for obtaining quantification of perfusion and filtration was investigated. Measurements were performed on 14 normal humans and 1 transplant at 1.5 T using a Turboflash sequence. Signal time-courses were converted to tracer concentrations and deconvolved with an aorta AIF. Parametric maps of relative renal blood flow (rRBF), relative renal volume of distribution (rRVD), relative mean transit time (rMTT), and whole cortex extraction fraction (E) were obtained from the impulse response functions. For the normals average cortical rRBF, rRVD, rMTT, and E were 1.6 mL/min/mL (SD 0.8), 0.4 mL/mL (SD 0.1), 17s (SD 7), and 22.6% (SD 6.1), respectively. A gradual voxelwise rRBF increase is found from the center of two infarction zones toward the edges. Voxel IRFs showed more detail on the nefron substructure than ROI IRFs. In conclusion, quantitative voxelwise perfusion mapping based on deconvolved T(1)-DCE renal data is feasible, but absolute quantification requires inflow correction. rRBF maps and quantitative values are sufficiently sensitive to detect perfusion abnormality in pathologic areas, but further research is necessary to separate perfusion from extraction and to characterize the different compartments of the nephron on the (sub)voxel level.
The present case describes the unusual association of a crescentic glomerulonephritis (GN), diabetes mellitus and a monoclonal gammopathy. After an unexplained deterioration of renal function, a kidney biopsy was performed. The finding of crescentic glomerulonephritis was unexpected. This case illustrates the usefulness of kidney biopsy in diabetes to exclude concomittant disease.
A 62-year-old female was admitted for a new episode of ascites, complicated by uremia. She had been treated 6 years earlier for bladder cancer with partial cystectomy and postoperative radiotherapy. At the work-up for both previous episodes of ascites, 6 and 24 months earlier, no definite diagnosis was made, and each time the ascites disappeared spontaneously. Also, at the third episode, the uremia resolved. Finally, explorative laparoscopy demonstrated urinary leakage from the superior portion of the bladder. This feature of vanishing and relapsing ascites is explained by intermittent covering by overlying abdominal structures and subsequent spontaneous healing. The pseudo-renal failure is caused by reabsorption of urine through the peritoneum. Only nine cases of recurring ascites and eight cases of bladder perforation after radiotherapy have been described in the literature.
BACKGROUND: Antioxidant enzyme status changes in experimental models of chronic renal disease with glomerulosclerosis. Most of the studies are performed in rats. We now investigate whether a mouse model with more rapid development of glomerulosclerosis is suitable for the study of radical-associated renal disease. METHODS: Female BALB/c mice are injected intravenously with a single dose of adriamycin (10 mg/kg). The development of glomerular and interstitial injury is evaluated by means of renal function parameters and histology. Renal cortex activities of catalase, Cu/Zn and Mn superoxide dismutase and glutathione peroxidase are measured by enzymatic techniques, and their mRNA levels by Northern blot analysis. RESULTS: The mice develop proteinuria and hypercholesterolaemia; glomerulosclerosis is present 20 days after adriamycin injection. Involvement of reactive oxygen intermediates in the disease process is supported by an increased cortex level of glutathione (1.77+/-0.13 vs 1.31+/-0.12 micromol/g kidney; P = 0.021) and ferric iron deposition in the tubulointerstitial compartment. Glomerulosclerosis and tubulointerstitial lesions are accompanied by decreased cortex activities of catalase (0.19+/-0.01 vs 0.23+/-0.01 U/mg protein; P = 0.024), glutathione peroxidase (0.28+/-0.01 vs 0.32+/-0.01 U/mg protein; P = 0.049) and Mn superoxide dismutase (6.61+/-0.91 vs 9.25+/-0.99 U/mg protein, P = 0.020). We find decreased cortex mRNA levels only for glutathione peroxidase. CONCLUSION: The fast development of glomerulosclerosis combined with an altered antioxidant status makes this mouse adriamycin model a suitable alternative for the slower rat models.
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Excessive generation of reactive oxygen intermediates can induce changes in the cellular antioxidant defence system. In this study we examine the antioxidant enzyme status and the expression of fibrosis-related marker proteins in the Adriamycin model of chronic renal failure in the rat. Twenty weeks after Adriamycin treatment, rats have overt nephrotic syndrome and renal failure with development of tubulo-interstitial fibrosis and glomerulosclerosis. Lipids accumulate in blood and in both glomeruli and tubulo-interstitial tissue. Desmin and alpha-smooth muscle actin expression increases in glomeruli and in the tubulo-interstitial area. Renal cortex antioxidant enzyme activities are decreased 20 weeks after Adriamycin injection (to 41% for catalase, to 56% for total superoxide dismutase and to 69% for glutathione peroxidase). The mRNA levels of catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1 evaluated by Northern blot are decreased by more than 50% for catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1. We conclude that in the rat Adriamycin-induced model of chronic renal failure with fibrosis, the combination of decreased antioxidant enzyme status in renal cortex with high concentrations of lipids in blood and renal tissue facilitates oxidative damage. Development of fibrosis is paralleled by increased expression of desmin and alpha-smooth muscle actin.
BACKGROUND: Cardiac troponin T (cTnT) is a subunit of the cardiac actin-myosin complex, which leaks into the circulation when myocardial necrosis is present. Detection of cTnT is associated with a poor outcome in patients with unstable angina, and is a useful tool for risk stratification. The value of cTnT determination in patients with renal failure has been questioned, and the specificity of cTnT in this particular group has not been established. METHODS: In the present study, 94 patients at a single centre were followed prospectively after three determinations of cTNT, at 1-month intervals. The outcome after 12 months was chosen as the end-point. cTnT was measured using both a quantitative chemiluminiscence immunoassay and a qualitative rapid bedside immunoassay on a test strip. The maximum of three measurements was used and was correlated with different parameters and outcome. The following statistical tests were performed: Kaplan-Meier analysis, Cox's proportional regression analysis for measuring survival and logistic regression for analysing factors influencing cTnT. RESULTS: Forty seven of the 94 patients had a positive cTnT by test strip defined as >0.10 ng/ml. Twenty four patients died in the follow-up period (14 from cardiovascular causes). Twenty of the 24 non-survivors had an increased cTnT by test strip and 23 had increased cTnT by laboratory immunoassay. The outcome analysed by a Cox's proportional regression analysis showed that the factors which influenced survival significantly were cTnT, the presence of ischaemic heart disease, C-reactive protein (CRP) and prealbumin. A logistic multivariate analysis revealed that age and CRP significantly influenced cTnT. A good correlation was found between cTnT determined by test strip and in the laboratory. CONCLUSION: cTnT is elevated in a large number of patients on regular haemodialysis and is a significant independent predictor of outcome. Increased cTnT is significantly predicted by age and CRP.
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Lymphoma in immunocompromised transplant patients is a feared cause of morbidity and mortality. Superimposed on the lymphoma and the transplantation immunosuppression is a rare condition: hemophagocytic syndrome (HS). HS is characterized by fever, hepatosplenomegaly and lymphadenopathy, skin rashes, jaundice, coagulopathy, and phagocytosis of blood elements with pancytopenia. Here we describe a rare but fatal case of a kidney transplant patient who developed T-cell lymphoma and HS, without evidence of EBV replication. A short review of the diagnosis, treatment, and prognosis of HS is given.
The effect of a six-month peritoneal amino acid administration on muscle metabolism at rest and during exercise was examined in 12 patients (4 control and 8 amino acid treated) on continuous ambulatory peritoneal dialysis. 31P-magnetic resonance spectroscopy was used to measure several high-energy phosphates (PCr, Pi) in resting muscle and during exercise and recovery. At rest, no significant changes were detected between the non-treated (control) and the amino acid treated (experimental) group. Before the administration of amino acids, the exercise-induced fall in [PCr], the increase in [ADP] and [Pi] and the pH were not significantly different in the control and experimental group. The initial rate of PCr recovery and the calculated maximal rate of ATP-synthesis (Qmax) for the control subjects was not significantly different at the onset and the end of the study. In the treated group, however, the fall in [PCr] and increase in [ADP] after exercise were significantly lower after than before treatment, while [Pi] and pH were identical. The initial rate of PCr recovery and Qmax were also significantly improved. These changes indicate an improved oxidative phosphorylation under the treatment and suggest that the impaired oxidative metabolism of the dialysis patients could be the result of their bad nutritional state.
An increased H2O2 production and a decreased activity of several peroxisomal oxidases have previously been reported in kidneys of rats with five-sixth nephrectomy, a model for chronic renal failure. We investigated the morphological and morphometric characteristics of peroxisomes, the organelles in which an important part of cellular H2O2 metabolism is localized, in remnant kidneys 16 weeks after operation. The vast majority of renal peroxisomes were found in the epithelial cells of proximal tubules. The organelles were distributed throughout the cells. We observed a significant increase in size, perimeter and volume density of the peroxisomes as compared to normal kidneys. Elongated peroxisomes were less frequent. An inverse linear correlation between mean size and number of peroxisomes was found. In cortex homogenates, the activity of catalase the peroxisomal H2O2-scavenging enzyme, was significantly decreased and was inversely proportional to the mean peroxisomal diameter. The observed morphological adaptations are believed to create an unfavorable situation for the enzymatic activities in remnant kidney peroxisomes.
In rats with five-sixth nephrectomy (remnant kidney), glomerulosclerosis was significantly reduced by dietary administration of vitamin E (alpha-tocopherol) during 11 and 16 weeks after reduction of nephron number. The activity of catalase and the production of H2O2 in remnant kidney cortex homogenate were not influenced by the vitamin E diet; however, the activities of glutathione peroxidase and superoxide dismutase were significantly increased (up to 140 and 180%, respectively, after 16 weeks). Lipid peroxidation, evaluated by malonaldehyde and 4-hydroxynonenal concentrations, was decreased in cortex homogenates and in urine. Though the extent of the effect of vitamin E on antioxidant enzyme levels and lipid peroxidation is small, the important reduction of glomerulosclerosis is in favor of dietary supplementation with vitamin E.
Nephron loss leads to increased production of reactive oxygen intermediates. We measured the effect of carvedilol, a beta-blocking drug with radical scavenging properties, on renal function, glomerulosclerosis, antioxidant enzyme status and in vivo hydrogen peroxide (H2O2) production in rats with chronic renal failure caused by 5/6 nephrectomy (remnant kidney) and compared results to data obtained with propranolol, a beta-blocking drug without scavenging characteristics. Carvedilol and propranolol were administered during 11 weeks following reduction of nephron number. Kidneys were examined using enzymatic and histological techniques. Both carvedilol and propranolol decreased systolic blood pressure. Compared to propranolol, carvedilol offered some additional beneficial effects on renal function, particularly with regard to glomerulosclerosis. Lipid peroxidation, evaluated by malonaldehyde and 4-hydroxynonenal concentration in cortex homogenates, was decreased in carvedilol-treated rats only. Superior beneficial effect of carvedilol treatment is not linked to a significant up-regulation of the activities of the remnant kidney antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase) or to a decreased in vivo H2O2 production.
The biocompatibility of a 1.1% amino acid-containing peritoneal dialysis fluid (AA-PDF) was compared to that of a 2.27% glucose-based peritoneal dialysis fluid (G-PDF). Peritoneal macrophages (PMO), isolated from the peritoneal dialysis (PD) effluents of 10 chronic ambulatory PD patients, were tested for their phagocytosis capacity and peak chemiluminescence response. A subset of PMO was cultured for 24 h with and without lipopolysaccharide (LPS) to study the release of interleukin-1 beta (IL-1 beta) and 8 (IL-8). As control, the interleukin release by blood monocytes of healthy donors was tested. The opsonic activity of the PD effluent was tested as well. Compared to PMO isolated from G-PDF, PMO from AA-PDF showed a significantly better phagocytosis capacity. There was no difference in the peak chemiluminescence response between PMO from AA-PDF and G-PDF. The release of IL-1 beta by unstimulated PMO isolated from the two fluids did not differ. Compared to control monocytes, however, PMO from both fluids showed a considerable spontaneous release of IL-1 beta. When stimulated with LPS, IL-1 beta production by PMO from G-PDF exceeded that of PMO from AA-PDF (p < 0.002). The release of IL-8 by PMO from G-PDF was significantly higher in comparison with PMO from AA-PDF, both spontaneously and after stimulation with LPS (p < 0.02). The opsonic activity of undiluted and to 75% diluted effluents was significantly higher for G-PDF than for AA-PDF (p < 0.01). Thus, compared to the regularly used G-PDF, the phagocytosis capacity as measure for PMO function seems to be better preserved after in vivo exposure to AA-PDF. In addition, the higher release of IL-1 beta and IL-8 by PMO isolated from G-PDF suggests a stronger intra-abdominal activation of PMO, with G-PDF acting as a chemical inflammatory agent. Whether the lower opsonic activity of the AA-PDF is more important for biocompatibility than the other parameters is not clear. Therefore, it is concluded that, although macrophage function is better preserved, it is not proven that the 1.1% AA-PDF studied has an improved biocompatibility compared to 2.27% G-PDF.
We report the case of a 73-year-old man, who developed acute renal failure in association with a Legionella pneumophila serotype 1 pneumonia. Renal biopsy revealed a tubulointerstitial nephritis. Treatment with erythromycin, rifampicin and haemodialysis resulted in a clinical resolution of the pulmonary and renal syndromes.
The effect of two different dialysate solutions with a calcium concentration of 1.25 and 1.75 mmol/l was evaluated in 14 patients, using a cross-over design. Patients were treated with each solution during a period of 6 months. Treatment with calcium supplements, vitamin D and aluminium hydroxide was adapted weekly, according to the results of blood chemistry. PTH, SAP, and ionized calcium were determined monthly, bone density with DXA and QCT before and after 6 months of treatment. During treatment with both 1.25 and 1.75 calcium dialysate (cad), the control of serum calcium and phosphate was similar. PTH did not change during either treatment. SAP decreased during treatment with 1.75, but remained stable with 1.25 mmol/l cad. Bone density evaluated with DXA remained unchanged during both treatments. QCT measured bone density increased from 101.29 +/- 13.50 to 106.79 +/- 13.14 mg/ml in the 1.75 cad group, while it did not vary in the 1.25 cad group, (107.75 +/- 13.48 versus 108.97 +/- 13.40 mg/ml). It is concluded that lowering the calcium content of the dialysate does not negatively influence the control of serum calcium and phosphate, nor does it aggravate hyperparathyroidism when vitamin D is administered simultaneously. Under the present conditions, osteopenia and possibly bone mineralization improve only in the group dialysed with 1.75 Ca.