Biomedical subjects

M Dalla Vestra

Publications and source records attributed to M Dalla Vestra.

10 recordsLinked to original sources

PubMed2004

Effect of lercanidipine compared with ramipril on albumin excretion rate in hypertensive Type 2 diabetic patients with microalbuminuria: DIAL study (diabete, ipertensione, albuminuria, lercanidipina).

Microalbuminuria and hypertension are risk factors for diabetic nephropathy in Type 2 diabetic patients. Recent data suggest that blockade of the renin-angiotensin system slows the progression of diabetic nephropathy; in contrast, the results on the renoprotective effect of calcium channel antagonists are conflicting. We evaluated the effectiveness of lercanidipine, in comparison with ramipril, on the reduction in albumin excretion rate (AER) and blood pressure in mild-to-moderate hypertensive patients with Type 2 diabetes and persistent microalbuminuria. A total of 277 patients were enrolled in a multicentric, randomized, double-blind, active-controlled, parallel-group trial; 180 were randomized to receive 10-20 mg/day of lercanidipine or 5-10 mg/day of ramipril and followed up for 9-12 months. The primary outcome was the change in AER from baseline. After 9-12 months of follow-up, a reduction in AER of -17.4+/-65 microg/min (p<0.05) and -19.7+/-52.5 (p<0.05) in the lercanidipine and ramipril group, respectively, was observed, without differences between the groups. A significant reduction in systolic and diastolic blood pressure was observed in both the lercanidipine and ramipril-based treatment groups (p<0.0001 for both). This study demonstrated that treatment with lercanidipine 10-20 mg/day does not worsen albuminuria in microalbuminuric Type 2 diabetic patients with hypertension. Indeed, both lercanidipine and ramipril treatments resulted in a significant reduction in AER without a statistically significant difference between the two groups.

Adult↗

PubMed2002

The angiotensin-converting enzyme DD genotype is associated with glomerulopathy lesions in type 2 diabetes.

Genetic factors are important in conferring diabetic nephropathy (DN) risk. The insertion/deletion (I/D) polymorphism of the ACE gene has been described to be associated with DN risk and progression. The renal lesions underlying DN in type 2 diabetes are heterogeneous; only a subset of patients, characterized by a faster decline of renal function, have diabetic glomerulopathy. This study explored the relations between diabetic glomerulopathy and the ACE genotype distribution in 77 type 2 diabetic patients with an albumin excretion rate > or = 20 microg/min. Using morphometric analysis of kidney biopsies, mesangial and mesangial matrix fractional volumes [Vv(mes/glom) and Vv(MM/glom)] and glomerular basement membrane (GBM) width were estimated. We found that 13 patients were II, 30 were ID, and 34 were DD. Clinical features and renal function were similar in the three groups; in contrast, the DD patients had the highest Vv(MM/glom) and GBM width. Subdividing patients in tertiles of GBM width and Vv(MM/glom), from the lowest (I) to the highest (III) values, the DD carriers had an odds ratio of 6.11 (95% CI 1.84-20.3) and 10.67 (2.51-45.36), respectively, for the likelihood of being in tertile III than I for GBM width and Vv(MM/glom). Multiple regression analysis revealed the I/D polymorphism as an independent determinant of GBM thickening in addition to diabetes duration and HbA(1c). In conclusion, the ACE DD genotype is associated with diabetic glomerulopathy lesions, making the study of this polymorphism helpful in identifying those type 2 diabetic patients at higher risk of fast DN progression.

Albuminuria↗

PubMed2001

Risk predictors in patients with diabetic nephropathy.

Diabetic nephropathy is currently the most common cause of end-stage renal disease in the Western countries. Only approximately one third of patients with type 1 diabetes develop nephropathy; thus, because it is not feasible to aggressively treat all patients, it becomes very important to find early markers in order to identify patients at high nephropathy risk. To date the best available predictor of overt nephropathy is microalbuminuria. In this article we review the validity of microalbuminuria as a predictor of overt nephropathy and consider other markers of nephropathy risk.

Albuminuria↗

PubMed2000

Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate.

Heterogeneity in renal structure has been described in type 2 diabetic patients with both microalbuminuria and proteinuria; in fact, only a subset of type 2 diabetic patients have the typical diabetic glomerulopathy. However, it is currently unknown whether abnormalities in albumin excretion rate (AER) have a different renal prognostic value depending on the underlying renal structure. Aims of this study were: 1) to study the course of renal function in type 2 diabetic patients with altered AER; 2) to evaluate the relationship between the course of glomerular filtration rate (GFR) and renal structure; and 3) to evaluate the relationship between the course of GFR and baseline AER levels, metabolic control, and blood pressure levels during a follow-up period of 4 years. A total of 108 type 2 diabetic patients, 74 with microalbuminuria (MA) and 34 with proteinuria (P), were recruited into a prospective study that encompassed: 1) a baseline kidney biopsy with morphometric measurements of glomerular parameters; 2) intensified antihypertensive treatment for an average 4-year period (blood pressure target <140/90 mmHg); and 3) determinations of GFR at baseline and every 6 months. Mean (+/- SD) GFR significantly decreased from baseline in both MA (-1.3+/-9.4 [95% CI -3.51 to +0.86], P < 0.05) and P (-3.0+/-13.0 ml x min(-1) x 1.73 m(-2) per year [-7.71 to +1.61], P < 0.01). However, the changes in GFR were quite heterogeneous. Thus, on the basis of percent GFR change per year from baseline (delta%GFR), both MA and P patients were defined as progressors or nonprogressors when they were below or above the median, respectively. Baseline parameters of glomerular structure had a strong influence on the course of GFR. Indeed, the odds ratios of being progressors significantly increased across the quartiles of baseline glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(mes/glom)], being 2.71 and 2.85 higher, respectively, in the fourth quartile than in the first quartile (P < 0.01 for both). Conversely, nonprogressors outnumbered progressors in the first quartile of GBM width (odds ratio: 2.14, P < 0.05) and in the first quartile of Vv(mes/glom) (odds ratio: 2.28, P < 0.01). Baseline albumin excretion rate (AER) did not influence delta%GFR; in fact, the number of progressors did not increase across quartiles of baseline AER among either MA or P. Similarly, mean blood pressure levels during follow-up (and intensified antihypertensive therapy) did not affect the course of GFR: the number of progressors and nonprogressors did not change across quartiles of mean blood pressure. In contrast, HbA1c during follow-up had an impact on delta%GFR: the odds ratio for being a progressor increased across quartiles of HbA1c, particularly for the highest quartile (HbA1c >9.0%). In conclusion, the course of renal function is heterogeneous in type 2 diabetic patients with microalbuminuria or proteinuria. In fact, a subset of patients has a rapid decline in GFR over a 4-year follow-up period; these patients have more advanced diabetic glomerulopathy and worse metabolic control than the remaining patients, whose GFR remains stable. These two cohorts are otherwise undistinguishable as regards the degree of AER at baseline and tight blood pressure control. Kidney biopsy has an important prognostic role in these patients. Thus, tight blood pressure control, when not associated with satisfactory glycemic control, is unable to prevent rapid GFR decline in type 2 diabetic patients with typical diabetic glomerulopathy.

Adult↗

PubMed2000

Structural involvement in type 1 and type 2 diabetic nephropathy.

Structural changes underlying diabetic nephropathy in Type 1 diabetes are prodominant in the glomerulus [thickening of glomerular basement membrane (GBM) and mesangial expansion], but also include arteriolar, tubular and interstitial lesions. The structural measure that correlates best with all renal functional parameters in Type 1 diabetes is mesangial fractional volume [Vv(mes/glom)], an estimate of mesangial expansion. Structural-functional relationships in Type 2 diabetes are much less known. These studies investigated renal structure in the early stages of nephropathy [microalbuminuria (MA)] in patients with Type 1 and Type 2 diabetes. Diabetic glomerulopathy was quite advanced in Type 1 diabetic patients with MA, and both Vv (mes/glom) and GBM width were increased as compared to normoalbuminuric (NA) patients when the albumin excretion rate (AER) was > 30 microgram/min. Serial renal biopsies were performed 5 years apart in 11 Type 1 diabetic patients to evaluate whether glomerular and interstitial lesions progress jointly. AER increased significantly in 5 years, while the glomerular filtration rate remained unchanged. All structural parameters were initially abnormal. Vv(mes/glom) and mean glomerular volume increased significantly, whereas GBM width and the interstitial volume fraction were unchanged. Moreover, the change in Vv (mes/glom) was correlated with the change in AER (r =0.64, p <0.05). Thus, at the disease stage during which some patients progress to MA or proteinuria, continuing mesangial expansion is the main variable, whereas further interstitial expansion does not occur. A large number of Type 2 patients were also studied. Early diabetic glomerulopathy was detected by electron microscopy in NA patients and found to be more advanced in those with MA and proteinuria. However, lesions were milder than in Type 1 diabetic patients, and there was considerable overlap between groups. Morphometric results by electron microscopy were similar to those by light microscopy, demonstrating the heterogeneity of renal structure in Type 2 diabetic patients. In fact, only 30% of MA patients had typical diabetic glomerulopathy, while 40% had more advanced tubulo-interstitial and/or vascular lesions and 30% had normal renal structure.

Basement Membrane↗

PubMed1998

Efficacy of antihypertensive therapy in decreasing renal and cardiovascular complications in diabetes mellitus.

The mechanism underlying the pathogenesis of microangiopathy and macroangiopathy in diabetes mellitus is hypothesized to be chronic hyperglycaemia. However, the values of blood glucose at which chronic diabetic complications develop at the renal and cardiac level are quite different. It is not clear whether this is due to different responses of kidney and heart tissues to the metabolic challenge of diabetes, or to the simultaneous role of other mechanisms contributing differently to the pathogenesis of chronic diabetic complications in renal and cardiac tissues. One of these mechanisms could be the simultaneous occurrence of arterial hypertension along with hyperglycaemia in diabetic patients. We reviewed the available evidence in the recent medical literature and provide information on the relationships between hyperglycaemia and cardiovascular and renal complications in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). The majority of reports indicate that the values of blood glucose appearing to be at threshold level for the development of cardiovascular complications are significantly lower than those determining renal complications (5.4 vs 10.0 mmol/l blood glucose concentrations 2 h after an oral glucose tolerance test). This was the case both in cross-sectional and prospective studies and also in intervention studies aimed at decreasing blood glucose concentrations by using strict metabolic control methods (The Diabetes Control and Complications Trial Research Group), which succeeded in delaying the rate of occurrence of microangiopathic complications at the kidney and retinal level but not so effectively at the cardiac level. Therefore, alternative therapeutic or supplementary strategies to blood glucose control should be adopted in diabetes to prevent diabetic complications. To date, the most effective approach, from our point of view, is antihypertensive therapy in order to prevent end-stage renal disease. We extensively reviewed the available literature which reported comparisons between angiotensin-converting enzyme inhibitors (ACE inhibitors) and calcium channel blockers (CCBs) in the treatment of arterial hypertension in diabetes. Intensified antihypertensive therapy achieving a blood pressure level below 130/85 mmHg has been shown to be useful in decreasing the rate of occurrence of chronic diabetic complications in diabetes mellitus. Both ACE inhibitors and CCBs have been shown to significantly improve the course of renal function in diabetic patients with incipient and overt nephropathy.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of vascular risk factors.

In this study we assessed whether widely accepted risk factors for atherosclerotic vascular diseases such as lipoprotein(a) [Lp(a)], a cholesterol-rich lipoprotein under strict genetical control, and other lipid parameters change with age. The variations of blood levels and the pathophysiological role of Lp(a) in old people, and particularly in the oldest old, are unknown. Accordingly, we measured Lp(a) levels as well as total, LDL, and HDL cholesterol (CT), and triglycerides (TG) in sera from 75 healthy centenarians, 114 randomly selected subjects under 65 years, 73 randomly selected elderly people, and 30 healthy selected elderly people. The results showed that Lp(a) serum levels did not vary by age group, including centenarians. Remarkably, one-quarter of the centenarians had high Lp(a) serum levels even though they never suffered from atherosclerosis-related diseases. At variance with young and aged people, centenarians with high Lp(a) serum levels also had high plasma concentrations of the proinflammatory cytokine IL-6, suggesting that genetic control of the Lp(a) serum level may attenuate with age and that environmental factors such as chronic subclinical inflammatory processes may play a role. We also showed that most centenarians are paradoxically characterized by low HDL-CT and relatively high TG levels, which together are considered to be strong risk factors for coronary heart disease. On the whole, these data support the hypothesis that a continuous and complex reshaping of lipid metabolism occurs in physiological aging, likely contributing to successful aging.

Aged↗

PubMed1998

Renal function in noninsulin-dependent diabetes mellitus patients treated with angiotensin-converting enzyme inhibitors and calcium channel blockers.

BACKGROUND: Data have not shown consistent effects with calcium channel blockers on the course of renal function in patients with noninsulin-dependent diabetes mellitus (NIDDM) who have hypertension alone or in association with renal damage. The differences between the antiproteinuric effects of subclasses or formulations of calcium channel blockers and the heterogeneity of renal lesions may contribute to the discrepancy in these data. Clinical studies conducted by the authors and other recent data that describe the course of renal dysfunction in hypertensive NIDDM patients treated with antihypertensive agents are reviewed. Renal structural changes were also evaluated. RESULTS: Most available data indicate that angiotensin-converting enzyme inhibitors and dihydropyridine and nondihydropyridine calcium channel blockers produce similar effects on glomerular filtration rate. In one study of patients achieving intensified, strict control of blood pressure (target<140/85 mmHg) with either cilazapril or amlodipine, glomerular filtration rate declined by 2.03+/-0.66 ml/ min/1.73 m2 per year and 2.01+/-0.71 ml/min/1.73 m2 per year, respectively, in the subgroup with normoalbuminuria and by 2.15+/-0.69 ml/min/1.73 m2 per year and 2.33+/-0.83 ml/min/ 1.73 m2 per year, respectively, in the subgroup with microalbuminuria. Renal lesions in NIDDM patients were found to be structurally heterogeneous and glomerular filtration rate appeared to decline only in patients with renal structural changes typical of NIDDM. CONCLUSIONS: The extent of blood pressure control, rather than the method by which this is accomplished, is the most important factor in determining the evolution of incipient nephropathy in hypertensive NIDDM. The kidneys of microalbuminuric NIDDM patients are structurally heterogeneous with less than one-third of patients having 'typical' diabetic nephropathology.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Vascular endothelial growth factor (VEGF) and VEGF receptors in diabetic nephropathy: expression studies in biopsies of type 2 diabetic patients.

Vascular endothelial growth factor (VEGF) is involved in the pathogenesis of diabetic retinopathy but its role in diabetic nephropathy is only speculative so far. It has been shown that in renal cortex of normal kidneys, glomerular and tubular epithelial cells express VEGF and that VEGF 165 is the predominant isoform. Two VEGF receptors, KDR (kinase domain region) and Flt-1 (fms-like tyrosine kinase) are co-expressed by glomerular and peritubular capillary endothelial cells. However, VEGF and VEGF receptors are predominantly expressed at glomerular level. We recently demonstrated that in type 2 diabetic patients glomerular qualitative and quantitative changes of VEGF mRNA expression are associated with functional and structural renal changes. In the present work we focused on the tubulo-interstitial compartment; by reverse transcription/polymerase chain reaction (RT/PCR) we evaluated the expression of VEGF, KDR, Flt-1 and the relationship between the two main type of VEGF isoforms, VEGF121 and VEGF165 in the tubulo-interstitium of type 2 diabetic patients. Patients were divided in three category on the basis of renal structure pattern: CI, with normal or near normal renal structure; CII, with glomerular and tubulo-interstitial lesions occurring in parallel (typical diabetic nephropathology); CIII, with atypical pattern of renal injury, i.e., more severe tubulo-interstitial and vascular than glomerular changes. Comparison between the two cortical compartments revealed that, both in glomeruli and in tubulo-interstitium. VEGF121 isoform exceed VEGF165 while Flt-1 was significantly lower in glomeruli. CIII patients had the lowest tubulo-interstitial level of VEGF and Flt-1 mRNAs. These results suggest that the transcriptional shifting from VEGF165 to VEGF121 isoform and the unbalanced FIt-1 expression between tubulo-interstitium and glomeruli could be involved in the pathogenesis of diabetic nephropathy. Furthermore, at least in CIII patients, down-regulation of the VEGF-Flt-1 system could be involved in the mechanisms leading to tubulointerstitial diabetic lesions.

Adult↗

PubMedDate not supplied

Role of mesangial expansion in the pathogenesis of diabetic nephropathy.

Glomerulopathy, characterized by thickening of the glomerular basement membrane (GBM) and mesangial expansion, is the most important renal structural change in type 1 diabetic patients with diabetic nephropathy. Morphological lesions develop concomitantly in the arterioles, tubules and interstitium. Mesangial fractional volume [Vv(mes/glom)], an estimate of mesangial expansion, is the structural parameter that best correlates with glomerular filtration rate (GFR) and it is also closely related to the presence of proteinuria and hypertension. Diabetic glomerulopathy has also been described in type 2 diabetic patients, but glomerular lesions are milder than in type 1 diabetic patients. In type 2 diabetes glomerular structural parameters are, on average, altered. However, despite persistent microalbuminuria or proteinuria, several patients have normal glomerular structure. Renal structure is, in fact, heterogeneous in type 2 diabetic patients: only a subset has typical diabetic glomerulopathy, while a substantial proportion has more advanced tubulo-interstitial and vascular rather than glomerular lesions, or has normal or near normal renal structure. Also in type 2 diabetes mesangial expansion is related to renal functional parameters, but although significant, these structural-functional relationships are less precise than in type 1 diabetes. Thus, both in type 1 and in type 2 diabetes, mesangial expansion is the most important structural change. Finally, we have recently demonstrated that, the lesions of diabetic glomerulopathy can be reversed in humans. This amelioration in glomerular structure was observed after long-term normoglycemia obtained by pancreas transplantation. This is a new concept in nephrology, and the understanding of the mechanisms involved in the glomerular architectural remodelling might have important clinical and therapeutic implications.

Diabetes Mellitus, Type 1↗