[Nephropathy: current aspects and therapeutic prospects].
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Biomedical subjects
Publications and source records attributed to G Savazzi.
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In this review we describe what is known about nitric oxide (NO), focusing on its clinical significance. It is now well appreciated that NO is a pivotal endogenous messenger molecule in a variety of physiological and pathophysiological processes. In the cardiovascular system NO participates in the paracrine regulation of vascular tone, body fluid homeostasis and platelet aggregation and adhesion. In the nervous system NO is a neurotransmitter that underpins several functions, including the formation of memory. In addition, NO is produced in large quantities during host defense and immunologic reactions. Perturbation in NO bioactivity has been shown to represent an important pathophysiologic mechanism underlying a number of disease states, such as atherosclerosis, hypertension, diabetes mellitus, and septic shock.
Contrast-media associated nephropathy (CMAN) consists in a sudden impairment of glomerular filtration rate following exposure to radiographic contrast materials. Damage may be limited to an asymptomatic mild increase of blood creatinine, or reach the highest levels of nitrogen retention compatible with acute renal failure. Some preexisting clinical conditions or pathologies may lead to CMAN: not only renal insufficiency, diabetes mellitus, multiple myeloma, congestive heart failure and severe hypertension, but also simple dehydration and a growing series of immunologic diseases are recognized as predisposing condition. The exact mechanism responsible for renal injury is still doubtful but recently animal models have shown substantial ischemic changes that may be added to the traditional presumed pathogenesis of direct tubular toxicity and intra-tubular obstruction. As renal ischemia stimulates both endogenous vasoconstrictor and vasodilator substances, it is now supposed that CMAN acts similarly to non-steroidal anti-inflammatory agents, selectively inhibiting the vasodilatory prostaglandin phase and therefore causing a derangement of the physiologic vasoconstriction/vasodilatation balance of renal circulation. The role of oxygen free radicals to contribute to renal dysfunction is considered. Low osmolality non ionic contrast media when compared to conventional high osmolality ionic contrast media have reduced but not eliminated CMAN. Simple but effective lines of prevention include the previous selection of patients predisposed to CMAN for concomitant pathology, suspension of FANS or any other recognized nephrotoxic substance, the least amount of contrast media compatible with radiologic visualization of the patient's problem, careful hydration of the patient before contrast injection and sustained diuresis afterwards. The usefulness of pre-treatment with Ca-channel blockers or atrial natriuretic factors remains sub judice.
BACKGROUND: In this study we investigated whether the increase in proteinuria induced by an oral protein load may be prevented by the angiotensin-converting enzyme inhibitor (ACEI) captopril in patients with nephrotic syndrome, and whether the effects of captopril on renal haemodynamics and/or glomerular selectivity are comparable to those obtained with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin and the calcium-channel blocker (CaCB) nifedipine. METHODS: Twelve subjects underwent the following treatments: (1) low-protein meal (0.2 g protein/kg body wt), (2) high-protein meal (1.3 g protein/kg body wt), (3) high-protein meal plus oral captopril (50 mg), (4) high-protein meal plus oral nifedipine (10 mg), (5) high-protein meal plus oral indomethacin (50 mg). Urine and blood samples were obtained after meals and tested for total protein, immunoglobulin G and albumin. GFR and renal plasma flow (RPF) were calculated from iothalamate and p-aminohippuric acid clearances respectively. RESULTS: Mean arterial pressure decreased significantly after both captopril (-4%, P = 0.001) and nifedipine (-5%, P = 0.0019). Compared with the low-protein meal, mean values of GFR and RPF increased significantly after the high-protein meal alone (+21%, P = 0.0002; +10%, P = 0.0491 respectively), and after captopril (+18%, P = 0.0025; +24%, P = 0.0034 respectively) or nifedipine administration (+30%, P = 0.0001; +21%, P = 0.0036 respectively), whereas they remained unchanged after the high-protein meal plus indomethacin administration. FF did not change significantly under the five experimental conditions. The increase in urinary protein excretion induced by the meat load (total protein +18%, P = 0.0102; albumin +26%, P = 0.0316; IgG +28%, P = 0.0203) was entirely blocked by both captopril and indomethacin, whereas it was further increased by nifedipine administration. CONCLUSIONS: Both captopril and indomethacin, but not nifedipine, are able to prevent the increase in urinary protein excretion rate following a meat meal. The antiproteinuric effect of captopril is comparable to that of indomethacin, but the renal haemodynamic changes induced by these drugs differ considerably, because the filtration capacity and the renal functional reserve were preserved by captopril and decreased by indomethacin. The reduction in systemic blood pressure following administration of both captopril and nifedipine does not account for changes in proteinuria, since, with a similar degree of blood pressure lowering, urinary protein excretion is reduced by captopril and increased by nifedipine.
A case of actinomycosis is reported in a 17-years-old woman with pleural and pericardial effusions and anterior mediastinal mass. Histopathological diagnosis of actinomycosis was performed by mediastinal mass biopsy. There was no evidence of immunodeficit or neoplasia. Probably a dental manipulation favoured the Actinomyces infection. Treatment with antibiotics resulted in a reduction of mediastinal mass and in a complete resolution of pleural and pericardial effusions.
Recent studies indicate that arterial hypertension in diabetes mellitus is a paramount pathogenetic step in the evolution and acceleration of diabetic macro- and microangiopathy and in particular in the development of nephropathy and uremia. This paper deals with the clinical problems of antihypertensive treatment in diabetic patients and discusses the antihypertensive repertory with the aim at determining the best drug choice in the individual case. In the light of our present pathophysiologic knowledges of the intrarenal effects of the various classes of antihypertensive drugs the possibility of preventing diabetic nephropathy is discussed.
Heymann's nephritis can be induced in rats by injection of antibodies (Ab) against the major nephritogenic antigen (Ag) (gp330). We previously reported on a 90-kD tubular-glomerular glycoprotein (gp90) having enzymatic activity (dipeptidyl-peptidase IV) which, after antibody interaction, induces a transient Heymann-like immunofluorescence pattern. In the present study we have analysed the ultrastructural features of the renal immune reaction occurring in rats after injection of a monoclonal antibody to gp90, revealed by a pre-embedding immunogold staining (5-nm particles). In the early stage (10-60 min) gold granules were found along the glomerular capillary walls mainly in the endothelial region. During the intermediate stage (24-48 h) the brush border microvilli were diffusely labelled. In the late stage (1-2 weeks) gold particles were still noticed at the tubular level. This work suggests that the immune reaction in Heymann's nephritis also occurs on the endothelial side of the glomerular capillary walls, thus facilitating the passage of epithelial-specific antibody. The tubular kinetics confirms that gp90 may play a role in the metabolic activity of tubular proximal cells. Because this antigen has been demonstrated in human kidney as well, it may be relevant to some membranous or other human nephropathies.
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Association cases of tuberous sclerosis (ST) and renal displasia-tumors are infrequently seen in literature. These tumors are bilateral renal cystic displasia (RP) rare hamartomas, p.e. angiomyolipomas, and malignant neoplasms, p.e. renal clear cell carcinomas. There therefor as to the frequency of those pathological associations with ST, AML are frequently seen (50-80%). Reports of polycystic renal disease with ST are rare, whereas occasional associations of renal cell carcinomas with ST are founded out. By extensive literature examination of it's evident that the synchronous association of these pathological lesions is exceptional. This report describes one case of AML, RP and renal clear cell carcinoma in a female, 22 years old, with ST; the pathological, clinical and pathogenetic features are discussed.
A case of reversible renal failure due to sarcoid granulomatous nephritis is described. The patient, a 21-year-old student, was admitted with renal insuffciency (GFR = 25 ml/min); no damage was found in any organ except for slightly enlarged pulmonary hilar lymph nodes. Repeated percutaneous renal biopsies showed an interstitial noncaseating granulomatous nephritis. Steroid therapy provided rapid improvement and the diagnosis of sarcoidosis was established. Complete recovery of renal function with normal urinalyses was seen.
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The authors, on personal experience, based on parathyroidectomies for secondary hyperparathyroidism, relate the surgical anatomic findings after a brief discussion on indications. They relate beside some atypical seats of parathyroid glands, observed in 11 glands of the 59 removed. Finally they emphasize the importance of accuracy of surgical exploration because that cannot be helped by instrumental methods or by gross pathologic observation.
The clinical experience obtained with 2 hours every other day recirculation dialysis, using 20-40 liters of dialysate, without sorbents, and standard cuprophane dialyzers of 1.0-1.5 sq.mt. is reported. So far, over 350 treatments in 8 patients have been performed. After 2 hours of treatment the removal of urea, creatinine, phosphate and uric acid, is similar to that obtained by 4-6 hours of haemofiltration. The alkalinazation of the patient through direct venous infusion of bicarbonate, makes predialysis acid-base significantly better than in standard haemodialysis and haemofiltration. Asymptomatic correction of severe fluid overload is easily obtained like in isolated ultrafiltration. The role of osmolality and vasopressors are discussed. A dry weight below the value obtained by previous dialysis treatment is achieved, and volume dependent hypertensions as in haemofiltration are corrected after 2-8 weeks. As an additional advantage, this method offers a highly semplified technical approach and a further reduction of the dialysis time.
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One hundred and one patients were treated for up to two years for three hours every other day (10.5 hr/week), or four hours thrice-weekly with conventional disposable 1m2 dialysers have been investigated. Rigorous control of water balance and the maintenance of predialysis serum K and PO4 within normal limits were the main criteria for judging the adequacy of the treatment. The results regarding blood pressure, phosphate problems, haematocrit, peripheral nerve status, pericarditis and range of rehabilitation are discussed.