ISSN:0886-022X    

DOI:10.3109/08860229309054938

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Inflammatory tubulointestitial nephritis (TIN), either as a primary or as a secondary event, plays an essential role in the development of all forms of chronic renal failure. Experimental models of TIN should help in understanding TIN in humans. As in experimental glomerulopathies, the target antigen can be a kidney structural antigen, from the tubular basement membrane (TBM) or not, or a foreign antigen. While some models are due to deposits of free antibodies or circulating immune complexes, many others involve cell-mediated immunity. This last aspect explains the importance and the originality of experimental TIN.

ISSN:0886-022X    

DOI:10.3109/08860229309054939

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Patients who develop diabetic nephropathy, one of the leading causes of end-stage renal diseases in Western communities, have an increased red cell Li+/Na+countertransport (CT). Li+/Na+CT is a membrane function which exchanges in-tracellular Li for extracellular Na in vitro. High Li+/Na+CT reflects abnormal kinetic properties of red cell membrane Na/H exchange. A widespread abnormality of Na/H exchange could play a major role in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases since Na/H exchange is involved in the regulation of cell pH and cell volume; in the cellular response to hormones, mito-gens, and growth factors; and in the renal reabsorption of Na and bicarbonate. Li+/Na+CT is under genetic control and raised in a subgroup of patients with essential hypertension. Among these patients, high Li+/Na+CT is associated with increased glomerular filtration rate, filtration fraction, proximal fractional Na reabsorption, microalbuminuria, plasma renin activity, and kidney and cardiac volume. Increased Li+/Na+CT is often associated with hyperlipidemia, hyperuri-cemia, reduced insulin sensitivity, and obesity. The whole of these observations may explain why patients with diabetes or essential hypertension and increased Li/ Na CT are at risk of early renal and cardiac impairment.

ISSN:0886-022X    

DOI:10.3109/08860229309054940

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0886-022X    

DOI:10.3109/08860229309054941

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The mechanisms of glomerular injury can be separated into nonimmunologically mediated glomerulonephritis (GN) such as diabetes, leading to glomerular hypertension and into immunologically mediated GN. The immunologically mediated GN may induce chronic glomerulopathy such as membranous GN or proliferative GN. The final pathway of these two types of GN is proteinuria and renal failure linked to glomerulosclerosis. In inflammatory GN, most of the mediators could be synthesized either by infiltrating cells or by resident glomerular cells. They include cytokines, lymphokines, complement activation, generation of superoxyde anions, arachidonic acid metabolites, and fibrin deposition.(a) We have investigated the interaction between isolated glomeruli and platelets and have demonstrated that li-pidic and proteic extracts of glomeruli enhance thromboxane B2 platelet synthesis. This fact is related to the generation by isolated glomeruli of saturated fatty acids and tissue factor, (b) We investigated the interaction between rat isolated glomeruli and peritoneal macrophages. We have demonstrated that 12-HETE synthesized by isolated glomeruli induce macrophage prostaglandin synthesis which, in turn, inhibits the 12-HETE synthesis, (c) We have demonstrated, using human glomerular epithelial cells, thatα-thrombin, the active form of thrombin, generated before fibrin formation, is able to induce cell proliferation and abolishes the profibrinolytic activity of these cells. In summary, the mechanisms of glomerular injury are complex, certainly acting by multiple pathways. So far, the mediators leading to proteinuria and renal failure after glomerular injury remain under investigation.

ISSN:0886-022X    

DOI:10.3109/08860229309054942

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Dialysis arthropathy (DA) and carpal tunnel syndrome are debilitating complications caused by dialysis-associated amyloidosis. They arise after several years of hemodialysis with cuprophane and their onset can be delayed with the use of high-flux dialysis. Serum C-reactive protein is elevated in patients with dialysis arthropathy, indicative of inflammatory processes. X-rays show periarticular bone cysts and erosive spondyloarthropathy. High-flux dialysis improves DA, but transplantation remains the best treatment.

ISSN:0886-022X    

DOI:10.3109/08860229309054943

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

A growing body of evidence supports the notion that calcium antagonists exert a renal protective effect. Calcium antagonists may play an important future role in renal hemodynamics related to their reversal of renal vasoconstrictors. Calcium antagonists are also capable of blocking intracellular calcium overload induced by various types of ischemia or toxic stimuli. Features such as these may be of substantial value in ameliorating acute renal insufficiency secondary to renal ischemia, iodinated radiographic contrast media, or the administration of various nephrotoxic drugs. The latter includes agents such as the aminoglycoside antibiotics, cyclosporine A, and the cancer chemotherapeutic agent cisplatin. Recent prospective, controlled studies from our group indicate that calcium antagonists protected against postischemic acute renal failure in the setting of cadaveric renal transplantation. Moreover, in a prospective, randomized, controlled clinical trial, we were able to demonstrate that the prophylactic use of nitrendipine reduced the decrease in GFR in patients receiving radiographic contrast agents. Such protection may extend to favorably influencing the course of chronic renal insufficiency, particularly when the latter is complicated by hypertension. Seven putative mechanisms have been proposed by which calcium antagonists may ameliorate the decline in GFR associated with renal insufficiency. These are: (a) reduction in blood pressure per se, (b) reduction in renal hypertrophy, (c) modulation of mesangial traffic of macromolecules, (d) reduction in metabolic activity in remnant renal tissue, (e) amelioration of uremic nephrocalcinosis, (f) reduction of pressure-induced calcium entry into vessel walls, and (g) reduction of free radical formation. Experimental investigations in rats with reduced renal mass, desoxycorticosterone-induced hypertension, or chronic angiotensin II infusion, and in spontaneously hypertensive rats support such a view. In three cross-over trials, calcium antagonists reduced proteinuria in patients with type II diabetes mellitus. Preliminary data from a single prospective trial in patients with renal insufficiency offer additional support for a“renoprotective”effect. However, definitive conclusions cannot be reached without further, prospective clinical trials.

ISSN:0886-022X    

DOI:10.3109/08860229309054944

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Calcium antagonists exert several characteristic effects on the kidney that potentiate their antihypertensive effect. The objective of the present study was to investigate the effectiveness of nitrendipine in the presence of different degrees of renal impairment. Two groups of hypertensive patients were included in the study. Group 1: 10 patients with arterial hypertension secondary to chronic renal paren-chymatous disease and adequately controlled with a diuretic and/or a beta-blocker who were switched to nitrendipine. These patients were then followed monthly for I year. Group 2: 24 patients diagnosed as having essential hypertension who presented values of urinary albumin excretion above 30 mglday after a minimum of 3 years of adequate blood pressure control with a diuretic and/or a beta-blocker. Patients were randomly assigned to continue with the same therapy or to switch to nitrendipine for 1 year. In both groups nitrendipine was as efficacious as standard therapy for controlling blood pressure and did not induce changes in renal hemo-dynamics. Nitrendipine did not modify the level of proteinuria in group 1, nor the urinary excretion of albumin in group 2. These results seem to indicate that nitrendipine can be safely used in patients with arterial hypertension and different degrees of renal function impairment.

ISSN:0886-022X    

DOI:10.3109/08860229309054945

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

A monoclonal anti-idiotype antibody (IgGlk MAb 3B11D4) has been raised against theλ-chain dimers isolated from the urine of a patient (DEP) with AL amyloidosis. This antibody binds a conformational idiotope present on the monoclonal DEP IgA, but does not recognize the reduced and alkylatedλ-chain monomers, nor the 15-to 17-kDa light chain fragments obtained from the amyloid fibrils, which have the same N-terminal sequence as the urinary light chains. The nonreactivity of this MAb with amyloid fibrils was confirmed by immunohistochemical examination of cryostatic sections of an amyloidoma surgically removed from the patient's subcutaneous tissue. Our data demonstrate that the deletion of about 70 amino acid residues of the C-terminus of theλchain prevents the formation of the self-limiting dimer and may facilitate the deposition of fragments into amyloid fibrils. With regard to the amyloidogenic clone, MAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning and cytotoxicity experiments demonstrate that this antibody has the capability of selectively eliminating the idiotype-positive cells from peripheral blood. Antibodies with these properties could find application in a new therapeutic strategy which provides high-dose chemotherapy, total body irradiation, and rescue with circulating stem cells. These antibodies could be used in two distinct phases: first, in the purging of the stem cells to be infused from the amyloidogenic clone and, secondly, in an attempt to eliminate residual disease by intravenous infusion.

ISSN:0886-022X    

DOI:10.3109/08860229309054946

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Chronic renal parenchymal disease is the most common cause of secondary hypertension: By the time end-stage renal disease develops, its prevalence approaches 75–85%. It was previously believed that hypertension caused arteriolar nephroscle-rosis and ischemic renal injury superimposed on primary renal parenchymal disease, contributing to progressive renal insufficiency. Recently, the importance of an increased intraglomerular hydraulic pressure due to loss of renal autoregulation has been emphasized. There are several potential explanations concerning clinical studies which have not uniformly demonstrated slowing of progressive renal damage with antihypertensive therapy: Random BP measurements may not adequately reflect average BP levels, or, alternatively, the widely accepted target level of BP control may be inadequate. In a retrospective study, we found that hypertensive nephropathics had higher serum creatinine levels than normotensives; in another prospective trial we have demonstrated that enalapril is an effective anthypertensive agent in patients with IgA nephropathy, and it also ameliorates the evolution of the disease.

ISSN:0886-022X    

DOI:10.3109/08860229309054947

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor