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Biomedical subjects

T Bertani

Publications and source records attributed to T Bertani.

90 records · Page 5Linked to original sources
PubMed1984

Steroids and Adriamycin nephrosis.

Adriamycin induces a nephrotic syndrome in rats characterized by severe ultrastructural changes of visceral epithelial cells similar to those observed in puromycin aminonucleoside (PA) nephrosis and in human 'minimal changes' glomerulopathy. Since steroids have been shown to be effective in human 'minimal changes' glomerulopathy and in PA nephrosis, we undertook the present study to assess whether steroids had a therapeutic effect on adriamycin nephrosis. Groups of rats injected with different doses of adriamycin were subsequently treated with prednisolone. No significant differences were observed in proteinuria and in ultrastructural findings between the control and the steroid-injected animals. This study suggests that the mechanism underlying adriamycin-induced nephrotic syndrome might be different from that responsible for PA nephrosis or human 'minimal changes' glomerulopathy.

Animals↗
PubMed1983

Focal segmental membranous glomerulonephropathy associated with other glomerular diseases.

In four patients with the nephrotic syndrome, renal biopsy revealed focal segmental membranous glomerulonephropathy (FSMGN) associated with the histologic patterns of "nil" disease (two cases), hereditary nephritis and diffuse diabetic glomerulosclerosis. The occurrence of FSMGN in association with other glomerular diseases, presumably unrelated to immune complex deposition, is infrequent in our experience. Rather than necessarily representing an early stage or milder form of membranous glomerulonephropathy, it may be an epiphenomenon. This interpretation has prognostic and therapeutic implications and raises important pathogenetic questions. In particular, this study suggests that in some instances, preexisting functional and structural abnormalities may play a role either in the deposition of preformed circulating immune complexes or in the local formation of immune complexes.

Adolescent↗
PubMed1983

Concomitant presence of three different glomerular diseases in the same patient. Report of a case and review of the literature.

A 51-year-old man with diabetes mellitus and the nephrotic syndrome on renal biopsy was found to have diabetic glomerulosclerosis, amyloidosis and membranous glomerulopathy. The presence of three distinct glomerular diseases in the same patient is unique. Possible factors involved in their pathogenesis are discussed and the literature on concomitant glomerular diseases is reviewed.

Amyloidosis↗
PubMed1983

Severe glomerular epithelial cell damage does not prevent passive Heyman nephritis in rats.

Passive Heymann nephritis (PHN) is an experimental model of membranous glomerulopathy in the rat ascribed to in situ formation of immune complexes. Very recently the demonstration that the aminonucleoside of puromycin provides some protection against PHN has highlighted the role of intrinsic properties of the glomerulus in immune complex formation. Adriamycin, a widely employed chemotherapeutic agent, is known to induce a nephrotic syndrome in rats characterized by severe ultrastructural changes of glomerular epithelial cells and by loss of glomerular polyanionic charges. We have studied the effect of pre-treatment with adriamycin on glomerular immune deposits in PHN using immunomorphological and quantitative techniques. In normal rats (group 1) injection of heterologous antibodies to proximal tubular brush border antigen (anti-FxIA), rapidly induces subepithelial immune deposits, as observed by immunofluorescence. Pre-treatment of rats with adriamycin (group 2) 48 hr before injection of anti-FxIA antibodies, when proteinuria is absent, does not alter the immunohistological findings of PHN. Heavily proteinuric rats (group 3) pre-treated with adriamycin 13 days before injection of anti-FxIA did not show any significant difference from groups 1 and 2. Species binding of injected anti-FxIA antibodies, studied by paired label techniques, was similar in normal rats and in proteinuric and non-proteinuric rats treated with adriamycin. The only difference was in the group of proteinuric rats treated with adriamycin, in which at 5 hr binding in the kidney was higher, due to tubular brush border binding as shown by immunofluorescence. This study indicates that local changes of the glomerulus and loss of glomerular histochemical properties do not invariably alter the glomerular deposition of immune complexes.

Animals↗
PubMed1982

Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events.

Adriamycin has been suspected of causing experimental nephrotoxicity. We report here that adriamycin induces a nephrotic syndrome in rats, proteinuria beginning 4 to 5 days after a single intravenous injection (7.5 mg. per kg. of body weight). The full expression of the syndrome develops 13 to 15 days later. Minimal alterations at light microscopy, negative immunofluorescence, and only some focal "fusion" of foot processes can be observed by electron microscopy in the early phase after injection (28 hours). At 13 days, loss of foot process architecture, and replacement by flattened epithelial cytoplasm, was invariably found. These ultrastructural findings became extensive at 28 days follow-up. Colloidal iron staining of kidney biopsies revealed loss of glomerular polyanions as early as 3 hours and very marked loss at 28 hours after adriamycin injection. Polyanions were totally absent at 13 days and were still undetectable at 28 days. Thus, the loss of polyanionic charges associated with the sialic acid coat precedes the ultrastructural changes and the onset of proteinuria. These changes appeared similar to those reported in rats treated with daunomycin or puromycin animonucleoside. The present study supports in a different animal model the concept that both morphologic changes and proteinuria are the consequence of a common primary event that is the loss of glomerular fixed negative charges.

Animals↗
PubMed1979

Plasmapheresis in the treatment of acute renal failure in multiple myeloma.

Three patients with multiple myeloma and severe acute renal failure were treated by repeated plasmapheresis. Recovery of renal function was observed in all. The pathogenetic role of light chains and the possible mechanisms responsible for renal damage are discussed. It is suggested that the removal of light chains by plasmapheresis may be of therapeutic value in this condition.

Acute Kidney Injury↗
PubMed1979

The effect of puromycin on subepithelial deposits induced by antibodies directed against tubular antigens: a quantitative study.

The mechanism of the GN induced by the intravenous injection of antibodies directed against renal tubular epithelial antigens (RTE) was studied by the use of antibody specifically purified by affinity chromatography. With this reagent RTE antigens could be demonstrated on frozen sections of glomeruli as well as on glomerular cells in culture. The antibodies were radiolabelled, and using paired label techniques glomerular binding could be measured in vivo. In normal rats, approximately 4% of the antibody injected was specifically bound in the glomeruli. Binding was not detectable on proximal tubular brush borders. In rats treated with 100 mg/kg of aminonucleoside of puromycin, a substance known to induce alterations of glomerular epithelial cells, it could be shown that glomerular binding was selectively decreased. These observations indicate that immune deposits in passive Heyman nephitis are formed mainly in situ and that local alteration of the glomerulus can markedly influence deposit formation.

Animals↗
PubMed1978

Factor VIII--related protein on vascular intima of patients with chronic renal failure and prolonged bleeding times.

To determine whether the prolonged bleeding time so common to chronic renal failure (CRF) was due to defective factor VIII-related activities, as in von Willebrand's disease, vascular-factor VIII-related protein was measured in patients with CRF. Factor VIII-related protein was detected by immunofluorescence on the vascular intima of all 13 patients with CRF and greatly prolonged bleeding times. This protein was also present on the vascular intima of a patient with CRF and moderate von Willebrand's disease. These findings support a previous suggestion that the disturbed haemostasis in patients with CRF is not linked to defective factor VIII-related activities.

Adult↗
PubMed1978

Vascular factors in the pathogenesis of uraemic bleeding.

To determine the possible role of vascular factors in the bleeding tendency of uraemic patients, three major factors of the haemostatic system normally present in vascular tissues were studied. Factor VIII-related protein (F VIII) was detected on the vascular intima of 13 patients and 10 normal subjects. Comparable values of plasminogen activator (PA) were found in tissue slices from 7 patients and 7 controls. In contrast, prostacyclin like (PGI2) activity, measured as platelet aggregation inhibitory potency, was significantly higher in specimens from 15 patients with either acute or chronic uraemia than in 10 controls. The latter abnormality, leading to impaired platelet-vessel wall interaction, might contribute to the disturbed haemostasis of uraemic patients.

Adult↗
PubMedDate not supplied

Prevention of renal injury in diabetic MWF rats by angiotensin II antagonism.

We studied the effect of the combination of streptozotocin-induced diabetes and spontaneous renal injury in male MWF rats. Renal hemodynamics was studied by micropuncture 1 month after streptozotocin administration, and kidney morphological evaluation was performed after 4 months of diabetes. We also studied the effect of angiotensin II antagonism on development of renal lesions. Untreated animals developed mild hypertension, proteinuria, and glomerulosclerosis. Induction of diabetes, and maintenance of a moderate hyperglycemic state, was associated with slight but significant elevation in systemic and glomerular capillary blood pressure. Development of proteinuria was not accelerated or exacerbated by diabetes. Glomerular and tubular structural changes were also not worsened by diabetes. Antihypertensive treatment with an ACE inhibitor (benazepril) or with an AII receptor antagonist (valsartan) almost completely prevented systemic and glomerular capillary hypertension, proteinuria and renal structural changes. No significant differences in glomerular volume were observed among the four groups. That induction of experimental diabetes, although associated with glomerular capillary hypertension, did not aggravate the rate of progression of renal dysfunction would suggest that glomerular injury is not directly influenced by glomerular hemodynamic conditions in these animals. Prevention of renal functional and structural abnormalities by antagonism of AII activity in diabetic MWF rats suggests a pathogenetic role for angiotensin in inducing the renal disease in these animals.

Angiotensin II↗
PubMedDate not supplied

[Renal damage in type 2 diabetes].

Renal involvement in patients with type 2 diabetes will (probably) be one of the most important clinical problems for nephrologists to face during the next few years. Unlike type 1 diabetes, in type 2 diabetes the renal damage has not yet been well defined at both clinical and pathological levels. Pathological examination of renal biopsies has displayed different patterns of renal damage including diabetic glomerulosclerosis (Class 1), mostly chronic vascular changes (Class 2) and superimposed glomerular diseases (Class 3a) or unrelated to diabetic glomerulosclerosis (Class 3b). Despite the large number of papers published in this field, the actual prevalence and outcome of the different histological classes still remain to be established. Reported discrepancies are most likely caused by ethnic and geographic factors. However, as documented by a recent study carried out on a large number of patients, the prevalence of histological patterns is also greatly influenced by the policy for performing renal biopsies adopted at the various nephrological centers. Although the natural history of type 2 glomerulosclerosis (Class 1) still remains to be defined, those patients with clinical nephropathy and impairment of renal function have very poor outcome with a high rate of mortality and progression to uremia. Moreover, when diabetic glomerulosclerosis is complicated by superimposed glomerular diseases (Class 3a) the prognosis is much worse. On the contrary, when glomerular diseases are not associated with glomerulosclerosis lesions (Class 3b) the prognosis is markedly better. During the last ten years controlled studies have shown that the outcome in type 1 diabetic nephropathy has improved as a result of the use of drugs inhibiting the renin-angiotensin system. Although it is likely that this type of drug might also favourably influence the outcome of type 2 diabetic nephropathy, any conclusive evidence is presently still lacking.

Diabetes Mellitus, Type 2↗
PubMedDate not supplied

[What type of neprologist for the beginning of the third millennium?].

During the last 10-15 years the International, but especially, the American Nephrology have been more and more colonized by the basic sciences. This has led to advocate for the future a nephrologist oriented towards the basic sciences. While nobody would deny that the basic sciences will be useful for the development of nephrolologic knowledge in the next decades, there are very urgent clinical problems in the present that should alert against this attitude. The most actual problem is represented by the new kind of patients affected by renal diseases who are older and much more complicated than in the past. Furthermore, todays patients need to interact with the clinician and require to be informed about the diagnostic and therapeutic procedures proposed. Although it is obvious that a deep knowledge in the basic sciences may be useful in improving the clinical care, the existing situation makes it impossible to propose a nephrologist being able at the same time to take care of all clinical and relational problems of patients with renal diseases and also to be well oriented in the basic sciences. This imposes a choice: If the aim of nephrologist involved in the clinical care is directed to the development of nephrologic knowledge to be applied in the next decades, then it may be reasonable to have more and more people oriented towards the basic sciences. On the contrary, if the aim of nephrologist is directed to offer the best available care to the patients, then there is no choice: no chance for a basic sciences oriented nephrologist.

Forecasting↗
PubMedDate not supplied

Angiotensin-converting enzyme inhibition and calcium channel blockade both normalize early hyperfiltration in experimental diabetes, but only the former prevents late renal structural damage.

We studied the potential renoprotective properties of a calcium channel blocker in moderately hyperglycemic diabetic rats both in the early phase of the disease and in the very long term, and compared such an effect with that of an angiotensin-I-converting enzyme (ACE) inhibitor. Three groups of diabetic rats, one receiving no therapy except insulin and the remaining two receiving insulin and the ACE inhibitor enalapril or the calcium blocker lacidipine and one group of nondiabetic control rats were followed for 4-6 weeks. Both antihypertensive drugs lowered systolic blood pressure comparably. At the end of the observation period, untreated diabetic rats exhibited elevation of glomerular filtration rate and renal plasma flow. Both enalapril and lacidipine treatment completely prevented whole-kidney hyperfiltration and hyperperfusion. Four additional groups of rats, similarly treated, were followed for 1 year. A comparable control of systolic blood pressure and blood glucose level was achieved with the two antihypertensive regimens throughout the whole study period. At 12 months, the average kidney weight was elevated to similar values in all diabetic groups relative to control rats. Untreated diabetic rats had progressive proteinuria and developed glomerulosclerosis. Enalapril markedly limited the development of proteinuria. By contrast, urinary protein excretion in diabetic rats given lacidipine markedly increased with time, and values were as high as those in untreated diabetic animals. Similarly, only enalapril was effective in limiting glomerular injury. These results indicate that ACE inhibition but not calcium channel blockade has a favorable effect in preventing renal disease progression in diabetic rats and suggest that the various antihypertensive regimens are not equally beneficial in protecting against diabetic glomerulopathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Comparison of the effects of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade on the evolution of spontaneous glomerular injury in male MWF/Ztm rats.

The mechanism by which angiotensin-converting enzyme (ACE) inhibitors prevent proteinuria and glomerulosclerosis in experimental nephropathies is not yet clear. Experimental evidence is available that the effect of ACE inhibitors on the glomerular function depends on the inhibition of angiotensin II generation, but it is possible that inhibition of the bradykinin breakdown also plays a relevant role. To establish the mediators of the effects of ACE inhibitors in glomerular injury, we compared the effects of the ACE inhibitor lisinopril with those of a specific angiotensin receptor (AT1) antagonist (ZD7155) on the renal function in male MWF/Ztm rats. After 4 months (end of the study), the untreated animals developed hypertension and proteinuria (160 +/- 10 mm Hg and 214 +/- 92 mg/24 h, respectively). In the lisinopril- and in the ZD7155-treated rats, a comparable systolic pressure control was achieved (121 +/- 12 and 118 +/- 14 mm Hg, respectively), and proteinuria was significantly prevented (averaging only 38 +/- 23 and 30 +/- 8 mg/24h, respectively) at the end of the study. The glomerular filtration rate was comparable in control and lisinopril-treated rats and significantly increased in ZD7155-treated rats. Both treatments significantly reduced the glomerular capillary pressure and significantly increased the ultrafiltration coefficient (Kf) as compared with untreated animals. In ZD7155-treated rats the Kf was also significantly higher than in untreated animals glomerular sclerosis and tubulointerstitital damage developed. Structural changes were absent in lisinopril- and ZD7155-treated animals. These results show that the antihypertensive and renal protective effects of ACE inhibitors are shared by the angiotensin receptor antagonist. Thus, angiotensin II is the likely mediator of proteinuria and glomerulosclerosis which develop spontaneously with age in this model.

Angiotensin Receptor Antagonists↗
PubMedDate not supplied

Passive Heymann nephritis: evidence that angiotensin-converting enzyme inhibition reduces proteinuria and retards renal structural injury.

In nonimmunological models of renal damage, abnormal traffic of proteins through the glomerular capillary is one of the possible causes of renal disease progression. Here we investigated whether in a model of immune-mediated glomerulonephritis long-lasting proteinuria resulted in renal structural damage and whether chronic treatment with perindopril, an angiotensin-converting enzyme (ACE) inhibitor, lowered proteinuria and retarded disease progression. Passive Heymann nephritis (PHN), a model of human membranous nephropathy, was induced with 0.5 ml/100 g of rabbit anti-Fx1 A antibody in 26 male Sprague-Dawley rats. Animals were then divided into two groups of 13 rats each, given daily vehicle or perindopril (1 mg/kg p.o). Treatment started at day 7 when proteinuria was already present and lasted 12 months. An additional group of normal rats was used as control. Renal biopsies were taken at months 8 and 12. Untreated PHN rats showed a significant increase in systolic blood pressure starting from month 8, that was normalized by perindopril administration. Urinary protein excretion progressively increased with time in untreated PHN rats that developed focal and segmental glomerulosclerosis and tubulointerstitial damage. Perindopril significantly reduced proteinuria and limited glomerular and tubulointerstitial injury. Urinary excretion of endothelin-1 (ET-1) and transforming growth factor-beta 1 (TGF-beta 1), two major mediators of renal damage in other models of glomerulonephritis, increased with time in PHN but only the former correlated with the degree of glomerulosclerosis. The effect of perindopril on proteinuria and renal structural damage was associated with a significant reduction in urinary ET-1 but not TGF-beta 1, suggesting that ET-1 may be an important determinant of disease progression in experimental membranous nephropathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Selective dietary restriction of protein and calorie intakes prevents spontaneous proteinuria in male MWF rats.

BACKGROUND/AIMS: Previous observations indicate that protein and calorie restrictions can affect the course of renal disease progression. We compared the effects of selective protein and calorie restriction on glomerular hemodynamics and proteinuria in a model of spontaneous glomerular injury in the rat. METHODS: Three groups of male MWF rats were assigned to three different diets: standard diet (ST, 19% protein, 3.4 kcal/g), low protein (LP) and low calorie (LC). Proteinuria and systolic blood pressure were periodically measured. Glomerular hemodynamics and tuft volume were determined after 2 months of dietary treatment. RESULTS: The effective mean protein intake was 3.4 +/- 0.4, 1.6 +/- 0.2, and 3.2 +/- 0.2 g/day/rat, respectively, for the ST, LP, and LC diets, while caloric intake averaged 60 +/- 7, 59 +/- 9, and 30 +/- 2 kcal/day/rat. Both LP and LC diets significantly prevented proteinuria (104 +/- 32, 36 +/- 9, and 18 +/- 8 mg/day, respectively, in the three groups). The systolic blood pressure was unaffected by the diets. The LC diet induced lower body and kidney weights than the ST diet. The glomerular filtration rate was slightly but significantly increased by the LP diet, but not by the LC diet (0.64 +/- 0.14, 0.81 +/- 0.08, and 0.67 +/- 0.12 ml/min, respectively, for ST, LP and LC diets). The glomerular hydraulic pressures were not affected by the diets. No differences were also observed in glomerular volume. The incidences of glomerulosclerosis and tubulointerstitial changes were comparable in ST and LP diets and completely absent in the LC diet group. CONCLUSION: These results indicate that restriction of both protein and calorie intakes prevents spontaneous proteinuria in male MWF rats by preventing deterioration of glomerular perm-selective functions.

Albuminuria↗