If contraindications, especially high blood pressure and abnormal haemostasis, are respected, ultrasound-guided percutaneous renal biopsy with an automated biopsy device is safe. Skilled operators obtain satisfactory amounts of kidney tissue in almost all cases.
Patients with type 2 diabetes on dialysis are at a substantially increased risk of cardiovascular and cerebrovascular diseases. Dyslipidemia characterized by moderately elevated low-density lipoprotein cholesterol and high triglycerides and low high-density lipoprotein cholesterol levels is common in this population. We hypothesized that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors would reduce vascular morbidity and mortality in this patient group. The ‘Deutsche Diabetes Dialyse Studie’ (4D study) is a prospective, randomized, double-blind study involving 178 dialysis centers throughout Germany. Between March 1998 and October 2002, 1,255 patients were randomized to either atorvastatin 20 mg or placebo; 677 men and 578 women, aged 30–83 years, have been enrolled. The study will be terminated as soon as the predefined number of 424 patients with primary combined end points (i.e., cardiovascular death, nonfatal myocardial infarction, or fatal/nonfatal stroke) will have occurred. The total cohort had the following characteristics at baseline: the mean age was 65.7 years, 54% were men, 89% had a history of hypertension, 21% had coronary artery disease, 17.8% had a history of stroke or a transient ischemic attack, and 45% suffered from peripheral arterial disease. The mean time interval between the diagnosis of diabetes and the onset of dialysis was 17.4 years. On average, the patients were on hemodialysis for 8.3 months. Mean lipid and lipoprotein levels were: total cholesterol 219 ± 43 mg/dl, low-density lipoprotein cholesterol 126 ± 30 mg/dl, high-density lipoprotein cholesterol 36 ± 13 mg/dl, and triglycerides 264 ± 167 mg/dl. The results of the study will provide important information on the efficacy and safety of atorvastatin to support its use in patients with an impaired renal function who are at a high risk of vascular morbidity and mortality.
Stimulation of the renin-angiotensin system is a major side effect of the fungoid immunosuppressant cyclosporine A (CyA). The aim of this study was to find out whether or not this effect of CyA results from a direct interaction with renal juxtaglomerular (JG) cells, which are the site of renal renin synthesis and release. Using primary cell cultures from rat renal cortex containing more than 80% JG cells, we found that CyA (0.01 to 10 micrograms/ml) stimulated renin secretion threefold. This stimulation was paralleled by a dose-dependent twofold increase of inactive renin within the cells, while the active intracellular renin remained the same. In order to identify a possible second messenger which could mediate the effects of CyA on JG cells, we examined the simultaneous effects of a single concentration of CyA (1 microgram/ml) on renin secretion, prostaglandin formation and intracellular cAMP concentration. However, prostaglandin formation and cAMP were not detectably altered by CyA in experiments where renin secretion was significantly enhanced. Our results indicate that cyclosporine A stimulates renin secretion and renin synthesis by a direct effect on renal juxtaglomerular cells. This action of CyA is not mediated by changes in cellular prostaglandin or intracellular cAMP.
Intermittent bolus administration of calcitriol – i.e., 1,25-dihydroxycholecalcife-rol or 1,25-(OH)2D3 – is highly efficacious in dialysis patients. In experimental studies, intermittent administration of calcitriol is superior to continuous administration in suppressing preproparathyroid hormone (PTH) mRNA and circulating PTH concentrations. In a randomized, prospective, open multicenter trial 45 dialysis patients with elevated 1,84-iPTH ( > 20 pmol/l, normal 1-6 pmol/l) levels were randomly allocated to daily administration of 0.75 μg calcitriol (continuous) or twice weekly administration (intermittent); the two protocols provided an identical total weekly doses of 5.25 μg calcitriol. Patients were dialyzed with a dialysate Ca concentration of 1.75 mmol/l and had oral CaCO3 or Ca acetate. 1,84-iPTH (immunoradiometric assay) and serum Ca and Pi levels were measured weekly. At the beginning of the study, the median 1,84-iPTH value was 37 pmol/l (range 20-115) in the intermittent versus 36 pmol/l (range 21-72) in the continuous calcitriol group. After 2 weeks, the median 1,84-iPTH level was 18.5 pmol/l (range 1.4-106) versus 18 pmol/l (range 1.2-48). After 12 weeks, 11 of 21 of the patients in the intermittent and 18 of 24 patients in the continuous group had reached the treatment goal, i.e., 1,84-iPTH < 10 pmol/l without hypercalcemia or hyperphosphatemia. There were seven episodes of hypercalcemia ( > 2.7 mmol/l) in the intermittent versus two in the continuous group; the mean peak Ca level was 2.8 mmol/l (range 2.76-3.0) versus 2.9 mmol/l (range 2.74-3.06). There were 21 versus 17 episodes, respectively, of hyperphosphatemia ( > 2.2 mmol/l).
While articular cartilage changes are considered to be one of the initial events in the pathological cascade leading to osteoarthritis, these changes remain difficult to detect using conventional diagnostic imaging modalities such as plain radiography. The aim of this prospective, experimental, methods comparison study was to compare the sensitivity of magnetic resonance imaging (MRI), magnetic resonance arthrography, computed tomography (CT), and CT arthrography in the detection of artificially induced articular cartilage defects in the equine carpal joints. Defects were created in the antebrachiocarpal and middle carpal joint using curettage by a board-certified equine surgeon. Normal articular cartilage thickness varied from a maximum of 1.22 mm at the level of the distal aspect of the radius to a minimum of 0.17 mm in the proximal articular surface of the third carpal bone. Regarding cartilaginous defect measurements the remaining cartilaginous bed range from a maximum of 0.776 mm in the partial thickness defects, and 0 mm (defect reaches the subchondral bone) when total thickness defect were made. Computed tomography and magnetic resonance imaging were performed followed by CT arthrography and magnetic resonance arthrography after antebrachiocarpal and middle carpal intraarticular contrast administration. All images were reviewed by two board-certified veterinary radiologists, both of whom were blinded to the location, presence of, and thickness of the cartilage defects. A total number of 72 lesions in nine limbs were created. Mean sensitivity for localizing cartilage defects varied between imaging modalities with CT arthrography showing the best sensitivity (69.9%), followed by magnetic resonance arthrography (53.5%), MRI (33.3%), and CT (18.1%) respectively. The addition of contrast arthrography in both magnetic resonance and CT improved the rate of cartilage lesion detection although no statistical significance was found. Computed tomographic arthrography displayed the best sensitivity for detecting articular cartilage defects in the equine antebrachiocarpal and middle-carpal joints, compared to magnetic resonance arthrography, MRI, and CT.
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