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Biomedical subjects

P Passerini

Publications and source records attributed to P Passerini.

At least 19 recordsLinked to original sources
PubMed2005

Natural history of hepatitis C virus infection in adult renal graft recipients.

AIM: To study the natural history of hepatitis C virus infection in renal transplantation, 464 HbsAg negative patients were prospectively studied from 1989. METHODS: AntiHCV was tested by ELISA II and HCVRNA by Amplicor HCV RNA tests. RESULTS: Two hundred nine patients were antiHCV positive (C+). HCVRNA was confirmed in 89% of C+ patients. Compared with the 255 anti-HCV negative (C-), C+ had undergone longer periods of dialysis (P = .0001), were more transfused (P = .01), and included more retransplants (P = .002). Immunosuppression was azathioprine (AZA) plus steroids in 133 and cyclosporine (CsA) in 331 patients. Liver biopsy showed chronic active hepatitis in 50, cirrhosis in 8, and fibrosing cholestatic hepatitis in 2 patients. Histologic progression of liver disease was confirmed in 18 of 26 patients. The causes of death in 84 patients (51 C+ vs 33 C-) were cardiovascular disease in 49%, sepsis in 13%, liver failure in 14%, neoplasia in 21%, and hepatocarcinoma in 2%. The 14-year patient survival was 75% in C+ and 86% in C- (P = .002). By multivariate analysis, age (>40) (P = .001) and C+ (P = .019) correlated with a worse patient survival. If patients were stratified according to age (<40 vs > or =40), younger C+ patients had a lower survival probability (P = .03). The 14-year graft survival was 44% in C+ vs 60% in C- patients (P = .001) but pure graft survival was similar (68% in C+ vs 72% in C-) (P = .13). CONCLUSION: The presence of C+ significantly reduced both patient and graft survival in the long-term with liver failure being the second most frequent cause of death.

Adult↗
PubMed2004

From cyclosporine to the future.

Most of the experience acquired in our unit with cyclosporine (CsA) comes from randomized trials. A first trial demonstrated that CsA-treated patients had a better 10-year graft survival than azathioprine-treated patients. A second trial showed equivalence between double therapy with CsA plus steroids and triple therapy with CsA, steroids, and azatioprine. A third trial showed similar 2-year graft survival with CsA monotherapy and triple therapy. A larger multicenter study that compared three different CsA-based regimens showed similar long-term graft survival with monotherapy, double therapy, and triple therapy. However, patients given monotherapy had less frequent steroid-related side-effects. Finally a more recent multicenter international trial showed that the rate of acute rejection can be reduced without increasing side effects by adding the monoclonal antibody basiliximab to the triple therapy. By reviewing our cumulative experience with CsA we found a mean graft half-life of 18.7 years for cadaver renal transplant recipients and 31.9 for the living transplant recipients. No significant attrition of graft function was found for patients with grafts functioning at 15 years. Two important issues with the present immunosuppression concern the long-term nephrotoxicity of calcineurin inhibitors and the cardiovascular disease, which is at least in part related to the use of steroids. To face these problems, we are currently involved in two multicenter trials, one comparing sirolimus plus mycophenolate mofetil to sirolimus plus low-dose CsA, while the other trial compares certican plus CsA to certican plus CsA plus corticosteroids.

Clinical Trials as Topic↗
PubMed2001

Treatment of membranous nephropathy.

Several therapeutic approaches have been tried in patients with membranous nephropathy. Corticosteroids have been largely used, but a meta-analysis of the available controlled trials did not show any benefit of corticosteroids either in favouring remission of the nephrotic syndrome or in preventing renal dysfunction. Controversial results have been obtained with cytotoxic agents. Unfortunately, most of the available trials were small in size and had short-term follow-ups. Three controlled trials evaluated the role of a 6-month treatment with methylprednisolone and chlorambucil. The first trial showed that the 10-year renal survival rate was 92% in treated patients compared with 60% in untreated controls. A second trial compared the effects of methylprednisolone/chlorambucil with those of methylprednisolone alone. The combined treatment achieved remission of nephrotic syndrome in 64% of cases vs 38% in patients given steroids alone. A third trial showed equivalent results in patients randomized to be given methylprednisolone/chlorambucil or methylprednisolone/cyclophosphamide. A number of non-controlled studies and a randomized trial also showed the efficacy of cyclosporine in reducing proteinuria. In many but not all cases, proteinuria reappeared when cyclosporine was stopped. In conclusion, although the treatment of membranous nephropathy remains difficult, some therapeutical approaches have proved to favour remission and protect renal function

Adrenal Cortex Hormones↗
PubMed2001

Treatment of focal segmental glomerulosclerosis.

The prognosis of untreated patients with focal segmental glomerulosclerosis is poor, as the disease progress to end-stage renal disease in approximately 50--70% of nephrotic patients. Although focal segmental glomerulosclerosis was initially considered to be a steroid-resistant disease, several studies have shown a better responsiveness to more prolonged courses of steroids. For patients with steroid-resistant or -dependent focal segmental glomerulosclerosis, cyclosporine A and cytotoxic agents have shown efficacy in clinical trials. Plasmapheresis or LDL-apheresis may represent a rescue treatment in patients who do not respond to other therapies. The role of other agents used in focal segmental glomerulosclerosis, including azathioprine, mycophenolate mofetil, tacrolimus, pefloxacin or vitamin E is still poorly defined.

Adrenal Cortex Hormones↗
PubMed2001

Alternative treatments for focal and segmental glomerular sclerosis.

Corticosteroids represent the first therapeutic approach for patients with focal and segmantal glomerulosclerosis. What to do in patients who do not respond to corticostetoids is still uncertain. Cytotoxic agents have been tried. The results are usually poor when these drugs are given for short periods but almost half of patients may enter remission ir treatment is prolonged. Some decrease in proteinuria may be obtained with mycophenolav, mofetil but the available reports are still scanty and the follow ups are short. Cyclosporine has been largely used both in controlled and non controlled trials with favorable results. However, being the drug nephrotoxic caution should be recommended with its use. Plasma-exchange and lipopheresis may attempted in resistant cases.

Glomerulosclerosis, Focal Segmental↗
PubMed1999

Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis?

Eighty nephrotic adults with focal segmental glomerulosclerosis (FSGS) and plasma creatinine lower than 3 mg/dL were given corticosteroids (53 patients) or immunosuppressive agents (27 patients) for a median of 16 and 75 weeks, respectively. Forty-two patients responded with complete remission (29 patients, 36%) or partial remission (13 patients, 16%). Twenty-six patients who did not respond were treated again. Two patients obtained complete remission and 13 partial remission. The probability of remission was associated with treatment with corticosteroids (P = 0.0001; RR, 3. 93; 95% CI, 2.00 to 7.72), absence of arterial hypertension (P = 0. 0023; RR, 2.59; 95% CI, 1.41 to 4.79), and a percentage of hyaline glomeruli lower than 5% (P = 0.0152; RR, 2.04; 95% CI, 1.15 to 3.64). The probability of being alive at 110 months without doubling of plasma creatinine was 69%. The risk of renal insufficiency was correlated with mesangial proliferation (P = 0.0025; RR, 5.50; 95% CI, 1.82 to 16.60) and with interstitial fibrosis (P = 0.0231; RR, 4. 44; 95% CI, 1.23 to 16.08) at initial biopsy. Considering partial or complete remission as a time-dependent variable, only the lack of remission (P = 0.0027; RR, 7.23; 95% CI, 1.98 to 26.33) and mesangial proliferation (P = 0.0069; RR, 4.59; 95% CI, 1.52 to 13. 88) were correlated with renal failure. Major side effects were observed in 11 patients (5 infections, 1 peptic ulcer, 2 diabetes, 3 neoplasias). This study shows that 70% of nephrotic adults with FSGS may obtain complete or partial remission and maintain stable renal function for about 10 years when given a prolonged therapy with corticosteroids or immunosuppressive drugs.

Adrenal Cortex Hormones↗
PubMed1998

A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.

To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.

Adolescent↗
PubMed1997

Validation of a predictive model of idiopathic membranous nephropathy: its clinical and research implications.

Although a number of factors have consistently correlated with progression to chronic renal insufficiency (CRI) in idiopathic membranous glomerulonephropathy (IMGN), they appear late, are not quantitative in nature and have not been validated. We have determined that the highest sustained six-month period of proteinuria is an important predictor of progression. Using multiple logistic modelling, the only additional prognostic variables of importance in 184 Canadian patients were the initial creatinine clearance and the rate of change in function over this six-month interval. Independent data from Italy (101 patients) and Finland (78 patients) were obtained for comparison. Sensitivity, specificity, negative and positive predictive values and overall accuracy, as well as Pearson's goodness-of-fit and Harrell's "C" statistic were used to assess the fits of the model. Accuracy of prediction was > or = 85% in all three countries. Pearson's Chi-square goodness-of-fit showed good agreement across the spectrum and Harrell's "C" statistic was > or = 90%. Therefore, a predictive, semiquantitative algorithm in IMGN has been validated. Its relevance in patient management and in clinical trials is illustrated.

Algorithms↗
PubMed1995

A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy.

The natural course of idiopathic membranous nephropathy is variable, with some patients slowly progressing to renal failure while others maintain normal renal function over the entire time. Whether to treat this disease or not is controversial due to the lack of controlled data about the long-term effects of treatment. We updated at 10 years the results of a controlled trial in which 81 patients with idiopathic membraneous nephropathy and nephrotic syndrome were randomly assigned to receive symptomatic therapy (39 patients) or a treatment of six months with methylprednisolone and chlorambucil (42 patients). The probability of surviving without developing end-stage renal disease at 10 years was 92% in patients given methylprednisolone and chlorambucil versus 60% in controls (P = 0.0038). The slope of the reciprocal of plasma creatinine up to 10 years was significantly better in treated patients than in controls (P = 0.035). The probability of having a complete or partial remission of the nephrotic syndrome was significantly higher in treated patients (P = 0.000). Patients assigned to therapy spent significantly longer time without nephrotic syndrome than untreated patients (P = 0.0001). Four patients had to stop treatment because of reversible side-effects. In the long-term one treated patient developed diabetes and another one became obese. In conclusion, a six-month therapy with methylprednisolone and chlorambucil increases the probability of remission of proteinuria and protects from renal function deterioration even in the long-term. This treatment may avoid dialysis or death within 10 years to about one third of nephrotic patients with membranous nephropathy.

Adult↗
PubMed1994

Therapy for idiopathic membranous nephropathy: tailoring the choice by decision analysis.

Two Italian controlled trials demonstrated that the difference in remission rates obtained with six months of methylprednisolone and chlorambucil (MP+Ch) compared to MP was smaller than MP+Ch versus symptomatic therapy in the treatment of idiopathic membranous nephropathy nephrotic syndrome (NS). A decision analysis was used to compare the three treatment strategies, assuming triple probabilities and costs for MP+Ch complications compared to MP, with no risk for supportive therapy, referring to an average 40-year-old patient and using the quality-adjusted life expectancy year (QALY) as the utility scale. With MP+Ch the difference in expected QALY was 7.2 years compared to supportive therapy, and 2.6 years compared to MP. To offset the longer survival obtained with MP+Ch versus MP, it was assumed that all patients treated with MP+Ch would undergo either fatal (5% vs. 0.3% with MP) or non-fatal complications (95% vs. 15% with MP). This threshold denotes a great stability of the inequality in the expected QALY. Consequently, treatment with MP or with MP+Ch is justified if their side effects are considered to be a suitable trade-off for a five or seven QALY, respectively, longer survival. Only an absurd increase in the death rate with MP+Ch could offset the difference.

Adolescent↗
PubMed1994

[Nephritic sedimentation findings].

The urinary nephritic sediment represents a well defined microscopic pattern, which indicates an active renal disease or its relapse. Therefore, once a nephritic sediment is found, the physician should immediately proceed to further diagnostic steps to define the renal disease and to start treatment.

Adult↗
PubMed1993

Idiopathic membranous nephropathy in the elderly.

In this retrospective non-randomized study we reviewed the outcome for 41 patients with membranous nephropathy older than 65 years at onset and followed for at least 1 year. Twelve of the patients never received any specific treatment (group A), 15 were treated with a 6-month course of methylprednisolone alternated to chlorambucil every other month (group B), and 14 received corticosteroids alone for 3-12 months (group C). At the end of a mean follow-up of 92 +/- 61 months in group A, 53 +/- 35 in group B, and 38 +/- 25 in group C there were significantly more remissions of nephrotic syndrome in group B than in group A (P = 0.035) or in group C (P = 0.010). Moreover patients in group B spent a significantly longer period without nephrotic syndrome than patients in group A (P = 0.000) and C (P = 0.000). Three patients in group A and one in group B died. During the follow-up six patients of group A, two of group B, and five of group C developed renal function deterioration. In patients followed for at least 5 years the mean plasma creatinine increased from a basal of 112 +/- 29 to 239 +/- 287 mumol/l at the 5th year in group A and from 113 +/- 14 to 124 +/- 30 mumol/l in group B. The mean urine protein excretion remained unchanged in group A (basal 4.6 +/- 2.3 versus 4.8 +/- 5.7 g/day at 5 years) while it decreased in group B (from a basal of 6.8 +/- 3.5 to 1.1 +/- 0.4 g/day at 5 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Methylprednisolone plus chlorambucil as compared with methylprednisolone alone for the treatment of idiopathic membranous nephropathy. The Italian Idiopathic Membranous Nephropathy Treatment Study Group.

BACKGROUND AND METHODS: Treatment with methylprednisolone and chlorambucil may protect renal function and increase the chance of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy. To determine whether similar results might be obtained with methylprednisolone alone, we compared the effects of methylprednisolone and chlorambucil with those of methylprednisolone alone in 92 patients with the nephrotic syndrome caused by idiopathic membranous nephropathy. The patients were randomly assigned to receive either alternating one-month courses of methylprednisolone and then chlorambucil for a total of six months (group 1) or methylprednisolone alone for six months at the same cumulative dosage (group 2). RESULTS: Four of the 45 patients in group 1 (9 percent) and 1 of the 47 in group 2 (2 percent) stopped treatment because of side effects. At one, two, and three years, the percentage of patients who did not have the nephrotic syndrome was significantly higher in group 1 than in group 2. It was 58, 54, and 66 percent, respectively, in group 1, as compared with 26, 32, and 40 percent in group 2 (P = 0.002, 0.029, and 0.011). By year 4, the difference was no longer statistically significant: 62 percent of the patients in group 1 and 42 percent of those in group 2 did not have the nephrotic syndrome (P = 0.102). The patients in group 1 were in remission longer than those in group 2 (P = 0.008). CONCLUSIONS: In patients with the nephrotic syndrome caused by idiopathic membranous nephropathy, treatment with methylprednisolone and chlorambucil for six months induces an earlier remission of the nephrotic syndrome than methylprednisolone alone, but the difference may diminish with time.

Adolescent↗
PubMed1992

Remissions and relapses in idiopathic membranous nephropathy.

To assess the significance of remissions and relapses in idiopathic nephrotic syndrome the outcome of 169 patients was reviewed of them III had either a complete or partial remission. The probability of obtaining a complete remission within 5 years was 44% for the whole group, being significantly higher (P = 0.015) for those patients who had been treated with steroids plus cytotoxic drugs. Of the 74 patients who had complete remission only two showed renal function deterioration over time. Relapse of non-nephrotic proteinuria occurred in 22 patients. Of these, 12 again entered complete remission spontaneously, which persisted in nine until the last observation. Relapse of nephrotic syndrome occurred in 42 of III patients. Six patients showed a moderate renal function deterioration. Of 27 untreated patients, 17 had again a partial or complete remission that persisted in 13 until the last observation. All the 15 patients submitted to treatment again entered remission, which persisted in nine of 11 patients given prednisolone and chlorambucil and only in one of four given steroids alone. In conclusion, (a) the development of complete remission is a good marker of an excellent renal outcome, (b) patients with relapse of non-nephrotic proteinuria usually carry a good prognosis, (c) about half of patients with relapse of nephrotic syndrome show a spontaneous remission, and (d) the chances of a stable remission may be increased by treatment with steroids and cytotoxic agents.

Adolescent↗