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C Marcantoni

Publications and source records attributed to C Marcantoni.

13 recordsLinked to original sources
PubMed2001

Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects against nondiabetic glomerulosclerosis in rats.

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a member of the nuclear receptor superfamily of ligand-dependent transcriptional factors with beneficial effects in diabetes mediated by improved insulin sensitivity and lipid metabolism, but potential adverse effects in atherosclerosis by promoting in vitro foam cell formation. We explored whether a PPAR gamma agonist, troglitazone (TGL), affects sclerosis by mechanisms unrelated to insulin and lipid effects in a model of nondiabetic glomerulosclerosis. METHODS: Adult male Sprague Dawley rats underwent 5/6 nephrectomy and were treated for 12 weeks as follows: control (CONT), no further treatment; triple antihypertensive therapy (TRX); and TGL or TGL + TRX. Functional, morphological, and molecular analyses were performed. RESULTS: Systolic blood pressure (SBP) was increased in CONT and TGL groups (161 +/- 1 and 160 +/- 3 mm Hg), but not in TGL + TRX and TRX (120 +/- 3 vs. 126 +/- 1 mm Hg, P < 0.0001 vs. non-TRX). Serum triglyceride and cholesterol levels in all groups remained normal except for slightly higher serum cholesterol levels in TRX group. TGL groups had reduced proteinuria, serum creatinine, and glomerulosclerosis versus CONT, in contrast to no significant effect with TRX alone (sclerosis index, 0 to 4+ scale: CONT 1.99 +/- 0.42, TGL 0.85 +/- 0.12, TGL + TRX 0.56 +/- 0.14, TRX 1.30 +/- 0.21; TGL, P < 0.05; TGL + TRX, P = 0.01 vs. CONT). Glomerular cell proliferation, assessed by proliferating cell nuclear antigen (PCNA), was decreased after treatment with TGL or TGL + TRX, in parallel with decreases in glomerular p21 mRNA and p27 protein compared with CONT and TRX (PCNA + cells/glomerulus: CONT 2.04 +/- 0.64, TGL 0.84 +/- 0.21, TGL + TRX 0.30 +/- 0.07, TRX 1.38 +/- 0.37; TGL, P < 0.05, TGL + TRX, P < 0.01 vs. CONT). Glomerular plasminogen activator inhibitor-1 (PAI-1) immunostaining was decreased in TGL or TGL + TRX groups (0 to 4+ scale, CONT 2.42 +/- 0.32, TGL 1.40 +/- 0.24, TGL + TRX 1.24 +/- 0.17, TRX 2.53 +/- 0.24; TGL or TGL + TRX vs. CONT, P < 0.05), with a parallel decrease in PAI-1 mRNA by in situ hybridization. Glomerular and tubular transforming growth factor-beta (TGF-beta) mRNA expression was decreased with TGL treatment. Glomerular macrophages, present in CONT and TRX rats, did not express PPAR gamma, in contrast to PPAR gamma + macrophages in control carotid artery plaque. PPAR gamma was expressed in resident cells. CONCLUSIONS: Our results demonstrate in vivo that the PPAR gamma ligand TGL ameliorates the progression of glomerulosclerosis in a nondiabetic model. Macrophages show phenotypic diversity in glomerular versus vascular sclerosis, with macrophage PPAR gamma expression in only the latter. PPAR gamma beneficial effects are independent of insulin/glucose effects and are associated with regulation of glomerular cell proliferation, hypertrophy, and decreased PAI-1 and TGF-beta expression.

Animals↗
PubMed2001

Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients. METHODS: Data were analyzed from 1860 patients enrolled in 11 randomized controlled trials comparing the effect of antihypertensive regimens, including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during follow-up. The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during follow-up and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease. RESULTS: Mean (median) baseline urine protein excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the follow-up in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher level of urine protein excretion during follow-up (baseline minus change) was associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the current level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52 to 0.83)], but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion. CONCLUSIONS: The antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion. The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Regression of sclerosis in aging by an angiotensin inhibition-induced decrease in PAI-1.

BACKGROUND: Glomerular and vascular sclerosis increase with aging, and angiotensin inhibitors ameliorate progression of this injury. We investigated the potential for achieving regression of existing age-related sclerosis, and the mechanisms by which angiotensin type 1 receptor antagonist (AIIRA) may affect remodeling of this sclerosis. We focused on plasminogen activator inhibitor-1 (PAI-1) because it is directly induced by angiotensin, inhibits matrix degradation, and may thus be pivotal in remodeling. METHODS: Eighteen-month-old male Sprague-Dawley rats were treated with the AIIRA losartan (N = 8, 80 mg/L, dry weight), sacrificed at age 21 and 24 months, and compared with age-matched untreated controls (N = 15). Blood pressure and renal function were monitored, and morphological, biochemical, and molecular analyses were done on aorta and kidney. RESULTS: Body weight increased in both groups. Mean arterial pressure (MAP) and serum creatinine remained normal (24-month MAP 115 +/- 8 vs. 113 +/- 6 mm Hg, controls vs. AIIRA, P = NS). Aorta wall thickness ratio was reduced by AIIRA at 21 and 24 months vs. age-matched controls (21 months 0. 12 +/- 0.01 vs. 0.15 +/- 0.01, P = 0.006; 24 months 0.10 +/- 0.005 vs. 0.14 +/- 0.003, AIIRA vs. controls, respectively, P = 0.0027). The aorta wall thickness ratio after treatment with AIIRA for six months was even lower than that of 18-month control rats (P = 0.018). AIIRA reduced proteinuria versus age-matched control at 24 months (253 +/- 62 vs. 390 +/- 51 mg/24 h, P = 0.0017). AIIRA at 24 months decreased glomerulosclerosis versus age-matched control (sclerosis index, 0 to 4+ scale: 0.06 +/- 0.02 vs. 0.49 +/- 0.12, P = 0.0082) to levels even lower than the 18-month baseline (0.37 +/- 0.14, P = 0.014). Renal collagen content increased with aging and was decreased by AIIRA at 24 months (5.0 +/- 0.7 vs. 3.1 +/- 0.5% collagen, P < 0.05). Apoptosis, assessed by TUNEL, was increased in tubular and interstitial cells in aging and was reduced by AIIRA versus control and baseline, respectively (TUNEL scoring, AIIRA 24 months 0.33 +/- 0.16 vs. 1.06 +/- 0.23 and 0.80 +/- 0.05, P < 0.05). PAI-1 mRNA in kidney was decreased at 24 months in AIIRA versus age-matched controls (PAI-1/GAPDH density ratio: AIIRA 24 months 0. 34 +/- 0.05 vs. 24-month controls 0.99 +/- 0.05, P < 0.05). Increased glomerular PAI-1 immunostaining with aging was decreased by AIIRA at 24 months versus age-matched controls, even below baseline (staining score 0 to 4+, 0.57 +/- 0.15 vs. control 0.90 +/- 0.07, P < 0.05; baseline 1.05 +/- 0.02, P < 0.01). CONCLUSION: We conclude that AIIRA not only slows the progression of glomerular and vascular sclerosis in aging, but can also induce regression of these processes. The mechanisms appear to involve modulation of cortical cell turnover and inhibition of PAI-1 expression.

Aging↗
PubMed2000

The role of systemic hypertension in the progression of nondiabetic renal disease.

BACKGROUND: A role for hypertension in the progression of renal disease has been convincingly shown in experimental animals only. In human studies, the relation between hypertension and progression is difficult to demonstrate due to several confounding factors: age, gender, race; the difficult choice of blood pressure (BP) parameters that correlate with progression; the abnormal circadian BP pattern; and the many non-hemodynamic factors of progression. An important role for hypertension in progressive nondiabetic renal disease has been suggested by observational studies and clinical trials originally intended to evaluate the effect of dietary protein restriction on progression. In addition, several studies, summarized by a recent meta-analysis, have shown that pharmacological agents which lower both BP and proteinuria, mainly the angiotensin-converting enzyme inhibitors (ACEI), significantly slow the rate of progression in these diseases. METHODS: In this article we review the effect of lowering BP on the progression of nondiabetic chronic renal disease, the patient characteristics that are associated with a greater or lesser benefit of blood pressure reduction, and the choice of antihypertensive regimens associated with better outcomes in patients with renal disease. RESULTS: Lower levels of achieved BP are associated with a slower decline in renal function, both in patients with and without proteinuria. ACEI are effective BP lowering agents and are associated with better preservation of renal function as opposed to antihypertensive regimens without ACEI. This protective effect of ACEI is in addition to their BP and urine protein lowering effects. The protective effect of ACEI on renal function is more pronounced in patients with proteinuria. CONCLUSION: In patients with nondiabetic renal disease and proteinuria, the risk of progression can be minimized by lowering both BP and proteinuria. ACEI have an additional beneficial effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Progression of renal failure in diabetic nephropathy.

The onset of renal damage in diabetes mellitus may be influenced by several factors which largely result from genetic predisposition, hereditary factors and the early appearance of microalbuminuria and/or systemic hypertension. Most of these factors are also implicated in the progression of nephropathy from microalbuminuria to overt proteinuria and to end-stage renal failure (ESRF). Over the last few years, the role of hyperglycaemia has emerged as critical in mediating the progressive renal damage in diabetes. However, hyperglycaemia leads to increased formation of glycated proteins which may act as promoters of progression by localizing in renal tissue. In addition, hyperglycaemia may have a synergistic effect with some other risk factors, such as growth factors and the renin angiotensin system, in accelerating renal deterioration.

Albuminuria↗
PubMed1998

Angiotensin converting enzyme inhibitors in nondiabetic renal disease.

The class of antihypertensive agents that act by blocking angiotensin II has been shown in several experimental models to have the interesting ability to protect the kidney. In patients with nondiabetic renal disease, a number of controlled clinical trials have shown angiotensin converting enzyme inhibitors to achieve a better control of blood pressure and significantly reduce the rate of progression of renal failure in comparison with conventional agents. In addition, treatment with angiotensin converting enzyme inhibitors has helped to achieve new information on the optimal blood pressure target to be reached in order to protect the residual renal function maximally.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

A prospective, randomized trial of two antibiotic regimens in the treatment of peritonitis in CAPD patients: teicoplanin plus tobramycin versus cephalothin plus tobramycin.

A multicentre, comparative, randomized study was performed to compare the efficacy and tolerability of two antibiotic regimens in the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients: teicoplanin plus tobramycin versus cephalothin plus tobramycin. After informed consent had been obtained, 68 patients were randomized prospectively to receive either teicoplanin plus tobramycin or cephalothin plus tobramycin. Patients were followed throughout the study and for up to 4 weeks after the end of treatment, when clinical and microbiological parameters were assessed again. The incidence of clinical failure was 4.6 times higher in the cephalothin plus tobramycin group than in the teicoplanin plus tobramycin group (7/28 versus 2/37; P < 0.05). There was no significant difference in bacterial eradication between the two groups. Local and systemic tolerability were good for both regimens. The study shows that teicoplanin plus tobramycin is more effective than cephalothin plus tobramycin and might become a 'first-line' treatment for peritonitis in CAPD patients.

Aged↗
PubMedDate not supplied

Management of hypertension in renal disease.

The treatment of systemic hypertension in chronic renal disease is now mostly based on the administration of drugs which are able to reduce proteinuria and to slow down the progressive functional deterioration. Angiotensin-converting-enzyme inhibitors (ACEI), which lower both proteinuria and blood pressure, have emerged as drugs of choice in proteinuric patients with either normal renal function or mild to moderate chronic renal failure. In non proteinuric nephropathies no controlled studies exist demonstrating the superiority of ACEI over other drugs. In these conditions calcium antagonists might also be used. The approach to patients with hypertension and renal disease should always take into consideration the quality of the results that are to be achieved. If the aim is to control blood pressure and to protect other organs at risk, then a variety of drugs can be used. If the aim is to reduce proteinuria and slow down progression, then ACEI, possibly associated with calcium antagonists, are the drugs of choice.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Hypertension and progression of renal disease.

That systemic hypertension is involved in the progression of human renal disease is mostly suggested by the way anti-hypertensive treatment affects the course of the disease. Clinical evidence has been obtained from observational studies as well as from studies of dietary protein restriction. In addition, several trials have compared the effects of different antihypertensive agents. The angiotensin-converting-enzyme inhibitors have the best renoprotective effect when compared to conventional agents and calcium channel blockers. In most studies, ACE-inhibitors approximately halved the risk of progressive renal functional deterioration in patients with non-diabetic nephropathies; this protection was associated with a significant reduction in systemic blood pressure and proteinuria. Statistical analysis, however, also suggests a direct effect of ACE-inhibitors on the kidney.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Resolution of renal disease: mission impossible?

Several studies have extensively shown that both dietary and pharmacological intervention can prevent the progression of renal damage. The best results may be obtained by optimizing blood pressure control, reducing proteinuria levels in non diabetic nephropathies, and further achieving a good glycemic control in diabetic nephropathies. The earlier the treatment is started, the better the results. Since slowing progression of renal disease has been established, the challenge of the future seems to be the resolution of an established renal damage. Few studies have suggested that this process of regression is possible. Experimental animal studies, based on repeated renal morphological investigations, showed resolution of glomerular lesions in 40% of animals treated with either ACEI or AIIRA. Resolution of renal lesions (62%) has been claimed in a single study and in a small number of patients with diabetic nephropathy after 10-year pancreas transplantation. Confirmation studies are awaited.

Clinical Trials as Topic↗