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T Bertani

Publications and source records attributed to T Bertani.

At least 19 recordsLinked to original sources
PubMed1994

Dissociation between antiproteinuric and antihypertensive effect of angiotensin converting enzyme inhibitors in rats.

To clarify whether angiotensin converting enzyme (ACE) inhibitors prevent progressive renal injury directly by their antihypertensive effect we administered the ACE inhibitor lisinopril to male MWF/Ztm rats as a single daily dose that lowered blood pressure for only 9 of 24 h. We investigated the effects of this treatment in short- and long-term studies and compared them with another antihypertensive drug, the calcium channel blocker nitrendipine, given to partially control blood pressure as done with the ACE inhibitor. In untreated animals systemic hypertension, proteinuria, and glomerulosclerosis developed spontaneously with age, and lisinopril reduced systemic hypertension and prevented proteinuria and glomerular lesions. Nitrendipine, despite similar blood pressure control, was ineffective in preventing both proteinuria and glomerulosclerosis. After 2 mo of treatment glomerular capillary pressure was significantly reduced by lisinopril and slightly but significantly increased by nitrendipine, compared with untreated controls. The ultrafiltration coefficient was significantly higher in lisinopril than in controls and not significantly changed by nitrendipine. With both drugs, however, glomerular hemodynamic effects were observed only at a few hours after administration and were abolished before the next administration. No significant changes in glomerular tuft volume were observed in treated and untreated animals after 2 and 6 mo of observation. Thus ACE inhibitor, despite only partial control of systemic blood pressure, effectively prevented proteinuria and glomerular injury. Comparable blood pressure control obtained with a calcium channel blocker was not associated with renal protection. These results suggest that ACE inhibitors could protect glomerular microcirculation by a mechanism that is not directly related to their antihypertensive action.

Alpha-Globulins↗
PubMed1994

Evidence that an angiotensin-converting enzyme inhibitor has a different effect on glomerular injury according to the different phase of the disease at which the treatment is started.

In rats with streptozotocin-induced diabetes, the effect of an angiotensin-converting enzyme (ACE) inhibitor on the evolution of glomerular injury according to the time at which the treatment is started with respect to the onset of the disease was studied. Three groups of animals were used, a control Group 1 and two groups of diabetic rats treated with insulin (Groups 2 and 3). The latter were monitored until urinary protein excretion reached 40 to 50 mg/24 h (on average, 23 wk after the induction of the diabetes). At this time, Group 2 continued to receive insulin alone, whereas Group 3 was also given the ACE inhibitor moexipril for 8 more wk. Untreated diabetic rats showed a moderate increase in systolic blood pressure that was normalized by moexipril administration. Urinary protein excretion progressively increased during the 8-wk follow-up in untreated diabetics that, at the end of the study, developed moderate glomerular sclerosis. Moexipril treatment lowered urinary protein excretion to a normal range and completely prevented glomerular injury. Three other groups of rats were similarly treated, except that moexipril treatment was started later on (when proteinuria reached 100 to 200 mg/24 h, on average, 32 wk after the induction of diabetes), and were monitored for another 8 wk. Untreated and treated diabetics had comparable blood glucose levels throughout. Systolic blood pressure, significantly increased in untreated diabetic rats, was effectively controlled by moexipril administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Effects of angiotensin-converting enzyme inhibition on glomerular capillary wall ultrastructure in MWF/Ztm rats.

Previous studies have documented that treatment with angiotensin-converting enzyme (ACE) inhibitors prevents spontaneous proteinuria and enhances the glomerular ultrafiltration coefficient in male MWF/Ztm rats. The aim of this study was to study whether these beneficial effects of ACE inhibitors on glomerular capillary wall function are derived from the preservation of its ultrastructure. Conventional morphometrical analysis of kidney tissue, by light and electron microscopy, was used to quantify glomerular structural changes in the male MWF/Ztm rats treated with the ACE inhibitor cilazapril for 2 and 6 months and in age-matched untreated controls. At the end of the observation periods, both systolic blood pressure and urinary protein excretion were significantly reduced in treated animals as compared with controls. Glomerular volume increased significantly with time but was comparable in control and in treated rats. Surface area available for filtration (measured as peripheral capillary wall) was comparable in control and in treated animals at the same time and increased significantly with time only in treated rats. Mesangial volume was significantly higher in cilazapril-treated animals than in controls after 2 months of treatment and was comparable after 6 months. ACE inhibitor treatment did not induce significant ultrastructural changes such as basement membrane thickness, configuration of epithelial podocytes, and the width and the frequency of the epithelial slit diaphragms. These results indicate that the previously observed increase in the glomerular ultrafiltration coefficient by an ACE inhibitor in these animals is not the consequence of changes in filtering surface area but likely reflects an increase in membrane hydraulic permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Prognosis of untreated patients with idiopathic membranous nephropathy.

BACKGROUND: Defining the most appropriate treatment for patients with idiopathic membranous nephropathy is a matter of controversy. The course of the disorder is often benign, and the immunosuppressive regimens used in some patients have uncertain benefits and substantial risks. We studied the natural history of idiopathic membranous nephropathy in patients who received only symptomatic therapy. METHODS: We prospectively studied 100 consecutive patients (68 men and 32 women; mean [+/- SD] age, 51 +/- 17 years) with biopsy-proved idiopathic membranous nephropathy. The patients received diuretic or antihypertensive drugs as needed, but no glucocorticoid or immunosuppressive drugs. We examined the patients and measured their urinary protein excretion and serum creatinine concentrations every 6 months for a mean of 52 months. RESULTS: Twenty-four (65 percent) of the 37 patients followed for at least five years had complete or partial remission of proteinuria; in 6 others (16 percent), end-stage renal disease developed, and they required dialysis. As calculated by the Kaplan-Meier method, the estimated probability (+/- the standard error of the estimate) of retaining adequate kidney function was 88 +/- 5 percent after five years and 73 +/- 7 percent after eight years. The prognosis was poorer in men and in patients over 50 years of age, but not in patients with the nephrotic syndrome, hypertension, or hypercholesterolemia. CONCLUSIONS: Most untreated patients with idiopathic membranous nephropathy maintain renal function for prolonged periods and are likely to have spontaneous remission. These results do not support the use of glucocorticoids and immunosuppressive drugs in patients with idiopathic membranous nephropathy.

Adult↗
PubMed1993

A specific endothelin subtype A receptor antagonist protects against injury in renal disease progression.

We have recently reported that renal preproendothelin-1 gene is up-regulated in rats with renal mass reduction (RMR) and that time-dependent increase in urinary excretion of the corresponding peptide correlates with renal disease progression. Here we evaluated whether a specific endothelin subtype A (ETA) receptor antagonist, FR139317, reduced signs of disease activity in this model. Two groups of rats were given FR139317 or its vehicle (saline) from day 7 to day 60 after the surgical procedure. Sham-operated animals were the control group. Blood pressure, urinary protein excretion and serum creatinine were evaluated at days 0, 7 (before FR139317 or saline administration), 30, 45 and 60. At sacrifice, histological evaluation of renal tissue was performed. The results showed that ETA receptor blocker reduced the abnormal permeability to proteins, limited glomerular injury and prevented renal function deterioration thus confirming the working hypothesis. These findings suggest that this class of compounds may eventually prove useful in the treatment of human progressive nephropathies.

Animals↗
PubMed1993

Glomerulonephritis.

Advances in cell and molecular biology have generated fresh insights into the mechanisms of glomerular injury, a field with very few substantial advances in the past 20 years. Currently, the nature of renal antigens involved in the immune reaction is being identified, as in the case of Goodpasture antigen. Many recent studies focus on T-cell and macrophage functions in glomerulonephritis that initiate acute inflammatory events and determine glomerular disease progression. Recent data established that after inflammatory cell migration to the glomerulus, subsequent damage depends on cell adhesion to cytokine-activated endothelial cells, a process mediated by a variety of specialized molecules. It seems easy to predict that within the next few years these studies will have a major impact on the way these diseases are treated. Already, evidence indicates that, in experimental animals, monoclonal antibodies blocking adhesive molecules prevent or reduce glomerular damage. Cytokines and growth factors, by promoting resident cell proliferation and modulating extracellular matrix synthesis and metabolism, modulate acute glomerular injury and subsequent scarring. Recent studies have established that glomerular injury is related to urinary protein excretion, an issue that has been approached in humans by combining studies on barrier size selectivity with morphometry. An emerging concept suggests that leaking of proteins through the glomerular capillary has an intrinsic renal toxicity that is likely due to proximal tubular over-reabsorption of the abnormally filtered macromolecules. Data are also accumulating that may soon link the degree of tubulointerstitial injury with glomerular damage and subsequent development of renal scarring.

Animals↗
PubMed1993

Heterogeneous nature of renal lesions in type II diabetes.

The nature of renal damage in patients with type II diabetes remains unclear. This study was directed to evaluate pathologic changes in 52 patients affected by type II diabetes with overt clinical nephropathy by conventional and morphometric techniques. The duration of diabetes ranged from 6 to 384 months, urinary protein excretion ranged from 0.9 to 9.2 g/24 h, and serum creatinine ranged from 0.9 to 9 mg/dL. Specimens were examined semiquantitatively by light microscopy, immunofluorescence, and electron microscopy. Glomerular tuft cross-sectional area was measured by a versatile computer system. Pathologic examination revealed three distinct patterns arbitrarily defined as Classes 1, 2, and 3. Class 1 included 19 patients with typical changes of diabetic nephropathy characterized by a high score of glomerulosclerosis (mean score, 2.1), marked glomerular hypertrophy (23,632 microns2), and arteriolar hyalinosis (mean score, 2). There was a positive correlation between glomerulosclerosis and arteriolar hyalinosis scores (P < 0.05). Class 2 included 16 patients showing chronic and aspecific changes. As compared with Class 1 patients, these patients had less glomerulosclerosis (mean score, 1.3) and less arteriolar hyalinosis (mean score, 0.8) but more severe ischemic glomerular lesions (mean score, 1.4) and arteriosclerosis (mean score, 2). Class 3 included 17 patients showing glomerular disease superimposed on diabetic glomerulosclerosis. There were no differences in age, mean duration of diabetes, renal function, urinary protein excretion, and mean arterial pressure among the three classes of patients. This study indicates that renal lesions in patients with type II diabetes manifest in a quite heterogeneous fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Short- and long-term effect of angiotensin II receptor blockade in rats with experimental diabetes.

The short- and long-term effects of specific angiotensin II (AII) receptor blockade on the evaluation of glomerular injury in moderately hyperglycemic diabetic rats were studied. Three groups of animals were used, a control group, a group of diabetic rats treated with insulin, and a group of insulin-treated diabetic rats receiving the AII receptor antagonist losartan in drinking water. After 4 to 6 wk of observation, diabetic rats showed higher systolic blood pressure and GFR than normal controls. Losartan treatment prevented both systolic blood pressure and GFR rise. Three other groups of rats, similarly treated for a 1-yr period, were used for renal functional and morphologic evaluation. Diabetic animals had higher urinary protein excretion and glomerulosclerosis incidence than did normal controls. Losartan significantly prevented proteinuria and glomerulosclerosis. Evaluation of the sieving properties of the glomerular membrane by Ficoll fractional clearance showed an important increase in the filtration of this marker in diabetic animals, as compared with that in controls, and almost complete prevention of this change in losartan-treated animals. Theoretical analysis of fractional clearance data with a heteroporous model of glomerular size-selectivity showed that in diabetic animals the size of membrane pores was increased uniformly, as compared with that in controls. These changes were completely prevented by the AII receptor antagonist. The results presented here strongly indicate that reduction of AII activity plays a crucial role in the preservation of glomerular structure and function and suggest that the favorable effects previously observed with angiotensin-converting enzyme inhibition in this model depend directly on the reduction of AII activity.

Angiotensin Receptor Antagonists↗
PubMed1992

Renal protective effect of angiotensin-converting enzyme inhibition in aging rats.

Aging in rats with intact kidneys is associated with changes in selective glomerular permeability to macromolecules resulting in proteinuria and progressive glomerular sclerosis. We have previously reported that angiotensin-converting enzyme (ACE) inhibition in Munich Wistar Fromter/Ztm (MWF/Ztm) rats resulted in a significant reduction of proteinuria, in respect to untreated animals, and that treated animals were protected against the development of glomerular sclerotic lesions. The present study was designed to establish whether ACE inhibition protects against glomerular injury in male Sprague-Dawley rats, which develop spontaneous proteinuria and glomerulosclerosis with age. The effect of ACE inhibition was tested when proteinuria was already present. Four-month treatment with the ACE inhibitor perindopril prevented the increase in systolic blood pressure, compared with vehicle-treated animals, and significantly decreased urinary protein excretion of aging rats. Partial protection of the development of glomerular sclerosis was also observed.

Aging↗
PubMed1992

Thromboxane receptor blockade attenuates chronic cyclosporine nephrotoxicity and improves survival in rats with renal isograft.

The question of whether pharmacological inhibition of the thromboxane A2 activity prevents cyclosporine-induced chronic renal dysfunction in a Lewis rat model of renal isograft was addressed. Transplanted animals were given a daily oral dose of cyclosporine (20 mg/kg; N = 15), cyclosporine (20 mg/kg) and the thromboxane A2 receptor antagonist GR32191 (3 mg/kg twice daily, by gavage; N = 15), or the vehicle alone (N = 12). Treatments were started the day of kidney transplant, and animals were monitored for 1 year. Cyclosporine-treated animals developed renal insufficiency, as documented by serum creatinine levels of 0.49 +/- 0.09, 0.95 +/- 0.12, and 1.38 +/- 0.15 mg/dL before and after 6 and 12 months of observation, respectively. Cyclosporine and GR32191 used in combination partially but significantly prevented the deterioration of renal function (serum creatinine, basal, 0.52 +/- 0.06; month 6, 0.68 +/- 0.04; month 12, 0.93 +/- 0.10 mg/dL). At the end of the study, GFR, as insulin clearance, was significantly lower in rats given cyclosporine (0.28 +/- 0.09 mL/min/100 g) than in rats given cyclosporine plus GR32191 (0.45 +/- 0.05 mL/min/100 g) or than in vehicle-treated animals (0.56 +/- 0.07 mL/min/100 g). Similar results were obtained for the effective RPF, measured as p-aminohippurate clearance. At the same time points, comparable to whole-blood cyclosporine levels were found in rats receiving cyclosporine alone and in those given cyclosporine plus GR32191. More than 50% of the animals on cyclosporine alone died from uremia before the end of the observation period. By contrast, rats receiving cyclosporine in combination with GR32191 had a prolonged survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Pathophysiologic implications of proteinuria in a rat model of progressive glomerular injury.

BACKGROUND: Males of a substrain of Munich-Wistar rats (MWF/Ztm), selected for their large number of superficial glomeruli, develop spontaneous proteinuria with age, whereas females of this strain have a normal urinary protein excretion rate. EXPERIMENTAL DESIGN: We investigated the relationship between functional and structural glomerular alterations in four groups of male and female MWF/Ztm rats, respectively at 20 and 35 weeks of age. Systolic blood pressure, urinary protein excretion and composition of urinary proteins were periodically measured during the study. At the end of the observation period, renal function was evaluated with solute clearance technique and kidney tissue processed for morphologic and morphometrical analysis using light and electron microscopy. RESULTS: Systolic blood pressure in males was significantly higher than in females, and progressed toward systemic hypertension with age. Urinary protein excretion became spontaneously abnormal in males. About 50% of urinary proteins consisted of albumin, whereas 35% was a sex-dependent low molecular weight protein. Albumin excretion increased with age in these animals, whereas excretion of the sex-dependent protein decreased. Urinary protein excretion in females was significantly lower than in males of the same age, remaining near normal levels. No decline in renal function with age was observed in all animal groups. Glomerular structural alterations developed progressively with age in males, leading to important glomerular and tubular alterations. Female rats maintained almost intact glomerular morphology until the end of the study. Morphometric analysis showed an important increase in glomerular volume with age in males but not in females. This glomerular tuft enlargement was the result of an increase in the number of glomerular cells and a concomitant increase in cell volume. CONCLUSIONS: Male MWF/Ztm rats develop spontaneously systemic hypertension, proteinuria of glomerular origin, and glomerulosclerosis. Female rats develop less severe hypertension and are protected from proteinuria and glomerulosclerosis.

Aging↗
PubMed1992

Chronic dialysis in patients with systemic amyloidosis: the experience in northern Italy.

The clinical outcome of 61 patients with renal amyloidosis treated with chronic dialysis was reviewed. Eighteen patients, 4 with primary or AL amyloidosis and 14 with reactive or AA amyloidosis, died within one month from starting treatment. The other 43 patients were treated with dialysis for 3 to 199 months and are the object of this study. Sixteen patients had AL amyloidosis and 27 had AA amyloidosis. Thirty-five patients were treated with hemodialysis (HD) for a mean period of 40 +/- 47 months and 8 were treated with continuous ambulatory peritoneal dialysis (CAPD) for 20 +/- 15 months. Patient survival rate at 1 and 5 years was 68% and 30% respectively. There was no difference in survival rate between patients treated with HD and those treated with CAPD, while patients younger than 45 had a better 5-year survival rate. Twenty four (60%) patients achieved a satisfactory rehabilitation with dialysis. At the last follow-up, 15 patients (14 on HD, 1 on CAPD) were alive 61 +/- 58 months after starting dialysis. Twenty-eight patients died after 30 +/- 20 months. The main causes of death were: cardiovascular accident (11), stroke (3), sepsis (5) and cachexia (5). The most important extra-renal complications of amyloidosis were related to cardiovascular involvement (heart failures, arrhythmias, hypotension) and gastrointestinal involvement (malabsorption). Intra-dialytic hypotension in patients on HD and peritonitis in patients on CAPD were the main problems related to dialytic procedure. his study confirms that life expectancy and the quality of life of dialysis patients with systemic amyloidosis are poorer than those of general dialysis population.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloidosis↗
PubMed1991

Morphometrical analysis of glomerular changes induced by cyclosporine in the rat.

Functional and morphologic techniques were used to study the renal changes induced by a long-term exposure of normal rats to cyclosporine A (CsA), as well as their potential reversibility. CsA treatment for 3 months resulted in a significant (P less than 0.01) reduction of glomerular filtration rate (GFR) as compared with vehicle-treated animals. Histological examination of the kidneys showed mild glomerular damage characterized by ischemic lesions, increased mesangial matrix, and intracapillary hypercellularity in the CsA-treated group, but not in the vehicle-treated group. Proximal tubular abnormalities and limited areas of interstitial fibrosis were also present in the CsA group. A complete reconstruction of glomerular corpuscle was used to evaluate the consequence of CsA-induced renal ischemia on capillary tuft volume. The results showed that in rats administered CsA for 3 months glomerular volume distribution was shifted toward small glomeruli. Prolongation of CsA administration for 5 months did not result in a further decrease in GFR, and was associated with the appearance of a subset of glomeruli that became larger than normal. We have also investigated whether, once established, CsA-induced renal injury is reversible. In rats that were administered CsA for 3 months and then treatment discontinued for 2 months, GFR returned to pretreatment values and partial reversibility of morphologic changes was observed. Morphometric analysis showed that 2 months after withdrawal of CsA, glomerular volume distribution was almost comparable to that observed in vehicle-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL).

The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Nature and extent of glomerular injury induced by cyclosporine in heart transplant patients.

We sought to clarify whether low-dose cyclosporine (5.0 +/- 2.2 mg/kg/day) given for more than two years to prevent cardiac graft rejection induced glomerular injury and to quantify the extent of the lesions. After renal hemodynamic studies, renal biopsy specimens were obtained from 10 patients on cyclosporine and analyzed by a novel morphometric technique consisting of a tridimensional reconstruction of the glomerular tuft. Autopsy kidney specimens from three patients with no clinical history of renal disease, and from four patients who died with dilatative cardiomyopathy served as controls. The glomerular filtration rate and renal plasma flow were significantly depressed below normal values in transplant recipients given cyclosporine, averaging 35 +/- 8 and 325 +/- 94 ml/min/1.73 m2, respectively. Conventional light microscopy of specimens from controls and from patients who died with dilatative cardiomyopathy did not reveal renal structural abnormalities. By contrast kidney specimens from cyclosporine-treated patients had obliterative arteriolopathy and ischemic-type changes, with thickening and wrinkling of glomerular capillary wall. Morphometrical analysis of 28 control glomeruli and 40 glomeruli from patients with dilatative cardiomyopathy showed glomerular capillary tuft volumes (VCT) ranging between 1.2 and 2.3 microns 3 x 10(-6), whereas of 102 glomeruli from cyclosporine-treated patients 42.1% had VCT lower than 1.2 microns 3 x 10(-6) and 24.4% VCT higher than 2.3 microns 3 x 10(-6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Renoprotective effect of low iron diet and its consequence on glomerular hemodynamics.

It has been reported that anemia limits renal injury in rats with reduced renal mass. We studied the effect of a low iron diet, given to reduce hematocrit, on urinary protein excretion and glomerular function in male MWF/Ztm rats, which spontaneously develop proteinuria and glomerular sclerosis. At 20 weeks of age, micropuncture and glomerular volume measurements were performed in untreated rats fed standard chow and in rats fed an isocaloric diet with low iron (5 mg/kg) content. Two additional groups of rats were used for total kidney function and glomerular volume evaluation at 35 weeks of age. At 20 weeks of age animals on low iron diet showed significantly (P less than 0.01) reduced hematocrit (46 +/- 5% vs. 54 +/- 2%) and proteinuria (60 +/- 15 vs. 225 +/- 34 mg/24 hr) than control animals, and no statistically significant differences were observed in single nephron hemodynamics. At 35 weeks of age rats on low iron diet had significantly lower proteinuria than age matched controls (222 +/- 68 vs. 411 +/- 71 mg/24 hr, P less than 0.01) and developed less glomerular sclerosis (mean percentage of sclerotic glomeruli was respectively 14 +/- 7% and 31 +/- 17%, P less than 0.05). Glomerular volume was comparable in animals on the low iron diet and in controls both at 20 and 35 weeks of age. These data indicate that low iron diet protected male MWF/Ztm rats against glomerular injury without significant effects on glomerular hemodynamics and on glomerular volume.

Anemia, Hypochromic↗