摘要:

During the past two decades, major investigative interest has been focused on the determinants of chronic renal disease and interventions to retard the inexorable progression to end-stage renal disease. Recent studies have provided a theoretic framework for anticipating that angiotensin-converting enzyme (ACE) inhibitors, and possibly calcium antagonists, may preferentially retard the progression of renal disease. Whereas the majority of available clinical trials have assessed the effects of ACE inhibitors in patients with insulin-dependent diabetes mellitus (IDDM), there are relatively few long-term studies that have evaluated the renal protective effects of ACE inhibitors and calcium antagonists inpatients with nondiabetic renal disease. Although clinical trials have been initiated using both of these drug classes as monotherapy, theoretical considerations suggest that fixed-dose combinations of an ACE inhibitor and a calcium antagonist might be appealing as renal protective agents. Several lines of evidence suggest that the renal microcirculatory effects of coadministration of both agents should be complementary. Similarly, recent observations suggest that the two classes may act in a complementary manner to countervail pathogenetic mechanisms at the level of the mesangium. A recent study in type II diabetic patients demonstrated that combination therapy with an ACE inhibitor and a calcium antagonist induced the greatest reduction in proteinuria, and reduced the rate of decline in glomerular filtration rate (GFR) more than did either agent alone at the same level of blood pressure reduction. Based on such considerations, recent randomized prospective studies have been initiated to compare the renal protective effects of combination calcium antagonist-ACE inhibitor therapy versus monotherapy with agents of either of these two antihypertensive classes.

ISSN:0886-022X    

DOI:10.3109/08860229609047709

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

The rate of progression of chronic renal failure (CRF) is similar for many diseases, suggesting a common, perhaps intrinsic, renal signal for its progression. The remnant nephron hypothesis of Bricker suggests that CRF may be the result of persistent compensatory renal growth (CRG). Normally, CRG after unilateral nephrectomy (uniNx) ceases within 1 week. Knowledge of the signals that initiate CRG may therefore shed light on the signals responsible for ongoing CRF. The signals responsible for the initiation of compensatory renal growth after uniNx are unknown. Hemodynamic changes in the remaining renal artery have been observed, but there are as yet no data for the main renal compartment which undergoes hypertrophy, the superficial renal cortex. The noninvasive technique of laser-Doppler flowmetry allows the continuous and independent monitoring of blood velocity and blood volume. The product of the two signals is proportional to tissue blood flow per unit volume of the tissue observed. Under controlled conditions in adult male Sprague-Dawley rats, renal cortical blood velocity increased by 22% within 5 min after uniNx and remained elevated at this level for 60 min. Renal cortical blood volume decreased throughout the experiment. Their product, renal cortical blood flow, increased briefly by 14% 5 min after uniNx but decreased over the time of observation in parallel with renal cortical blood volume. The simultaneous increase in blood velocity and decrease in blood volume in the superficial renal cortex acutely after uniNx suggest that vasoconstriction is an early event in compensatory renal growth.

ISSN:0886-022X    

DOI:10.3109/08860229609047710

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

The influence of magnesium (Mg) deficiency on the concentration of calcium (Ca) in the aorta, heart, and kidney was evaluated in uremic rats. A total of 32 rats were randomly assigned to two groups: one group made uremic by the 5/6 nephrectomy method, and the other serving as sham-operated controls. Both groups were randomly assigned to two subgroups: one group given a Mg-deficient diet and the other fed a Mg-supplemented diet. After 12 weeks on the regimen, all animals were sacrificed. In Mg-supplemented uremic rats, the concentration of Ca in the aorta was higher than in Mg-supplemented control rats. The concentration of Ca in the aorta was further increased in Mg-deficient uremic rats. The concentrations of Ca in the heart and the kidney were also increased in Mg-deficient uremic rats, as compared with Mg-supplemented uremic rats. The concentration of Mg was decreased in the aorta and increased in the kidney of Mg-deficient rats. There was no significant influence of Mg deficiency on the concentration of phosphate in tissue. Results suggest that Mg deficiency in uremia may increase aortic calcification.

ISSN:0886-022X    

DOI:10.3109/08860229609047711

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

In chronic renal failure (CRF), phosphate (Pi) retention may lead to secondary hyperparathyroidism and progression to end-stage renal disease (ESRD). Dietary phosphorus restriction or phosphate binders can slow progression in experimental CRF. Conversely, diets high in phosphorus can accelerate the progression toward ESRD. Phosphate binders reduce intestinal Pi. absorption but have no effect on its renal excretion. Phosphonoformic acid (PFA, foscar-net) is a specific inhibitor of both intestinal and renal brush border Na+-Picotransport. It causes phosphaturia when administered parenterally or orally to rats. To determine the effect of oral PFA on renal function and on phosphate excretion in renal insufficiency, PFA was administered in drinking water to rats with CRF produced by 5/6th nephrectomy. Blood and 24-h urine collections were performed every 2 weeks for determination of plasma Piand creatinine concentrations, urinary protein excretion, and urinary creatinine and Piclearances. PFA, administered for 8 weeks, did not exert any adverse effects on any of the measured parameters. The slopes of the reciprocal of plasma creatinine versus time were not different between control and PFA-treated rats. Although PFA increased Piexcretion over the baseline, it had no persistent effect on plasma Piconcentrations under these experimental conditions.

ISSN:0886-022X    

DOI:10.3109/08860229609047712

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Primary cell culture was utilized to study the relationships between stress protein induction by zinc in vivo and cadmium toxicity in vitro. Effects of cadmium on cell viability were evaluated by the alamar blue assay, in conjunction with the ultrastructural morphology of cells by transmission electron microscopy. The expression of stress protein gene products was evaluated by35S two-dimensional gel electrophoresis. The results showed cytotoxicity of CdCl2 at and above 129μM (14.55μg cadmium/mL medium) following 4 h of exposure. Prior zinc administration (20 mg zinc/kg, s.c, two daily doses) in vivo significantly protected the cells in vitro as demonstrated by improved cell viability. The 35S labeling of proteins induced by CdCl2exposure clearly demonstrated for the first time that gene product of the 70-kDa family was induced in cultured rat proximal tubule cells which are the target cells for cadmium toxicity in vivo. Zinc in vivo pretreatment of animals induced proteins in the 90-, 70-, and 38-kDa families, which may act together with metallothionein to protect cells against cadmium toxicity. The results also indicate that the protective effect of zinc remains after the cells have been put in culture and thus provides a system in which we can study the changes that occur as a result of zinc exposure that decreases cadmium toxicity.

ISSN:0886-022X    

DOI:10.3109/08860229609047713

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We studied the actions of nifedipine and the platelet activating factor (PAF) antagonist BN 52021 on renal and tubular function in glycerol-induced acute renal failure (Gly-ARF). The tubular handling of sodium was evaluated through the lithium clearance method in awake rats in metabolic cages. The sequential analysis of tubular function 3, 6, 12, and 24 h after Gly-ARF showed a sharp decrease in fractional proximal Na reabsorption (FPRNa—control 74.1±12.5%, 3 h: 79.5±6.0%; 6 h: 41.8±15.9%; 12 h: 22.9±17.9%; and 24 h: 31.1±16.2% (p<0.001) while fractional distal Na reabsorption (FDRNa) did not change during the study. The effect of nifedipine (20 mg/kg p.o.) and BN 52021 (1 mg/kg i.p.) were evaluated 24 h after the induction of Gly-ARF. Both drugs attenuated the reduction in creatinine clearance (control 431.8±108.2, glycerol 96.7±43.8, glycerol plus nifedipine 264.9±103.5, and glycerol plus BN 52021 188.9±69.8μL/min/100 g, p<0.001). However, only nifedipine could keep FPRNahigher than untreated rats (58.3±13.2 vs. 31.1±16.2%, p<0.05) and reduced the tubular necrosis on histologic semiquantitative analysis. Our data showed that nifedipine and BN 52021 could protect against filtration failure in Gly-ARF but that only nifedipine reduced the proximal tubular lesion.

ISSN:0886-022X    

DOI:10.3109/08860229609047714

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Effects of ulinastatin (a Kunitz-type proteinase inhibitor) administration was examined in a model of acute ischemic renal injury induced by bilateral renal artery occlusion in rats. Compared with rats administered vehicle, rats administered ulinastatin (150,000 U/kg body weight) intravenously 30 min preischemia had significantly lower serum creatinine and blood urea nitrogen, and much less injury evident by examination of kidney histologies over the course of 48 h postreperfusion. We conclude that ulinastatin exerts a protective effect against ischemic renal injury.

ISSN:0886-022X    

DOI:10.3109/08860229609047715

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

The aim of this study was to investigate the relationship between the urine excretion and kidney activities of enzymes predominantly located in the proximal renal tubule, viz. the lysosomal hydrolase N-acetyl-β-D-glucosaminidase (NAG) and the predominantly brush border enzymes alanine aminopeptidase (AAP) andγ-glutamyltransferase (GGT) in an experimental model of gentamicin nephrotoxicity. Groups of six animals received either gentamicin (50 mg/kg/day by intraperitoneal injection) or saline daily and were killed after 4, 7, 10, or 14 days of treatment. Gentamicin nephrotoxicity was characterized by reduced creatinine clearance rates and increased urinary flow rate and glycosuria, but only on day 14. Structural changes included a similar degree of vacuolation of the renal proximal convoluted tubules (PCT) in all animals sacrificed on days 11 and 14, some evidence of PCT brush border loss, and the presence of protein casts on day 14. Following gentamicin treatment, increased NAG, AAP, and GGT enzymuria were noted at all time points tested. However, while the increases in urine AAP and GGT activity were paralleled by decreased total renal activity, total kidney NAG activity increased on days 4, 7, and 11 before falling back to pretreatment values on day 14. Interestingly, NAG enzymuria was highest in those animals with protein casts in the lumen of the PCT. The results suggest that increased AAP and GGT enzymuria reflect loss of brush border integrity while increased NAG enzymuria is consistent with the autophagic response of the kidney to acute injury.

ISSN:0886-022X    

DOI:10.3109/08860229609047716

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Two dynamic tests (Gn-RHi.v. and clomiphene citrate-CC p.o.) were used to evaluate the hypothalamic-pituitary axis in hemodialysis patients and renal transplant recipients (recipients). In the Gn-RHtest the gonadotropin secretion was maximally decelerated in hemodialysis patients while it was normal in recipients. During the CC test a decrease of gonadotropin secretion, chronically and quantitatively identical for both group, was found; while on the following test days an increase was noted, which was more accelerated in male recipients. In cases with uremia a strong negative feedback dominates at the pituitary level probably owing to testicular inhibin. The estrogenic feedback in uremia was intact, while the antiestrogenic feedback at the level of hypothalamus is partly impaired, owing to altered opioid metabolism.

ISSN:0886-022X    

DOI:10.3109/08860229609047717

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

While captopril-enhanced renal scintigraphy is acknowledged to be a useful screening technique to detect clinically silent obstructive lesions of the main renal arteries, the presence of significant atherosclerosis of distal, smaller renal vessels as a cause of positive scintigraphy scans has not been reported extensively. In a retrospective 2-year analysis of 31 consecutive captopril-enhanced renal scintigrams, we found a total of 13 studies in 11 patients that were classified as“positive“for renal artery stenosis. Of these 11 patients with positive scintigraphic studies, 4 patients underwent 5 renal arteriography procedures; only 1 of these renal arteriograms showed significant stenosis of the main renal artery. In the other 4 cases, an angiographic pattern of diffuse intrarenal distal arterial disease correlated with scintigram lateralization. Angiography was also performed in 4 patients with negative captopril renal scintiscans. In each of these cases the arteriogram was also negative for significant renal artery stenosis, and only 1 patient had diffuse bilateral intrarenal arterial disease. We conclude that distal renal arterial narrowing should be considered in the differential diagnosis of lateralized renal scintigrams. A negative renal scintigraphic study may be more reliable for excluding significant main renal artery obstructive disease.

ISSN:0886-022X    

DOI:10.3109/08860229609047718

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor