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Biomedical subjects

Claudio Ponticelli

Publications and source records attributed to Claudio Ponticelli.

At least 19 recordsLinked to original sources
PubMed2006

Long-term outcome of idiopathic retroperitoneal fibrosis treated with surgical and/or medical approaches.

BACKGROUND: Retroperitoneal fibrosis is a severe disease that affects the ureters, causing renal insufficiency in three-quarters of patients. The optimal treatment is far from being established. METHODS: Seventeen patients with idiopathic retroperitoneal fibrosis and ureteral entrapment followed in our unit for at least 1 year were selected for this study. At presentation 13 patients had renal insufficiency. All patients received steroids, associated with ureterolysis in five (group 1), with azathioprine in six (group 2) and with tamoxifen in six (group 3). Four patients of group 2 and five of group 3 received ureteral stenting or nephrostomy. There were no significant differences among the three groups or the clinical and biochemical characteristics at presentation. RESULTS: All patients of groups 1 and 2 entered remission after therapy. One patient from group 3 did not respond to therapy. During a mean follow-up of 56 +/- 41 months, three patients (two from group 1, one from group 2, 18%) had a recurrence of the disease, which fully responded to retreatment in all three cases. At the last observation, all patients were alive; three patients (18%) had renal insufficiency, of them one from group 1 had to start dialysis 6 years after ureterolysis, one patient from group 2 and one from group 3 had serum creatinine of 1.5 mg/dl. Renal survival was 100% at 5 years and 80% at 10 years. CONCLUSIONS: In most patients, each of the three different therapeutic approaches restored renal function and significantly reduced the fibrotic mass in the short-term and maintained stable serum creatinine in the long-term.

Adult↗
PubMed2006

Withdrawal of therapy in patients with proliferative lupus nephritis: long-term follow-up.

BACKGROUND: Whether corticosteroid and immunosuppressive therapy may be safely withdrawn in patients with proliferative lupus nephritis is still unclear. METHODS: In 32 patients with biopsy-proven proliferative lupus nephritis previously put into remission, therapy was gradually tapered off. RESULTS: When immunosuppressive therapy was stopped (median: 38 months; 25th-75th percentile: 24-81 months, after biopsy), 24 patients were in complete remission and eight had a median proteinuria of 1.05 g/24 h (25th-75th percentile: 0.91-1.1 g/24 h) with normal renal function. After stopping therapy, patients were followed for a median of 203 months (25th-75th percentile: 116-230 months). Fifteen patients (Group 1) never developed lupus activity. The other 17 patients (Group 2) developed lupus exacerbations in a median of 34 months (25th-75th percentile: 29-52 months) after stopping therapy and were re-treated. The only significant differences between the two groups were the longer median durations of treatment, 57 months (25th-75th percentile: 41.5-113.5 months) vs 30 months (25th-75th percentile: 18-41 months; P<0.009), and remission, 24 months (25th-75th percentile: 18-41) vs 12 months (25th-75th percentile: 7-20 months; P<0.02), before stopping therapy in Group 1 than in Group 2. At last follow-up, 12 patients of Group 1 were in complete remission, two had mild proteinuria and one had died. In Group 2, one patient died, 14 were in complete remission, one had mild proteinuria and in another patient serum creatinine doubled. CONCLUSIONS: Some patients with severe lupus nephritis who enter stable remission can be maintained without any specific treatment for many years. Those patients who have new flares can again go into remission with an appropriate treatment. The longer the treatment and remission before withdrawal, the lower the risk of relapse.

Adrenal Cortex Hormones↗
PubMed2006

A randomized pilot trial comparing methylprednisolone plus a cytotoxic agent versus synthetic adrenocorticotropic hormone in idiopathic membranous nephropathy.

BACKGROUND: We conducted a pilot trial to compare the effectiveness and safety of 2 different treatments in patients with membranous nephropathy and nephrotic syndrome. METHODS: To validate the hypothesis that the 2 treatments were equivalent, patients with biopsy-proven membranous nephropathy and nephrotic syndrome were randomly assigned to methylprednisolone alternated with a cytotoxic drug every other month for 6 months (group A) or to intramuscular synthetic adrenocorticotropic hormone administered twice a week for 1 year (group B). RESULTS: The primary outcome measure is cumulative number of remissions as a first event. Fifteen of 16 patients in group A and 14 of 16 patients in group B entered complete or partial remission as a first event. After a median follow-up of 24 months (interquartile range, 15 to 25 months), there were 4 complete remissions and 8 partial remissions in group A versus 8 complete remissions and 6 partial remissions in group B. Median proteinuria decreased from protein of 5.1 g/d (interquartile range, 4.0 to 7.3 g/d) to 2.1 g/d (interquartile range, 0.4 to 3.8 g/d; P = 0.004) in group A and 6.0 g/d (interquartile range, 4.4 to 8.5 g/d) to 0.3 g/d (interquartile range, 0.2 to 1.9 g/d; P = 0.049) in group B. Two patients from each group interrupted treatment because of side effects or inefficacy. CONCLUSION: Most nephrotic patients with membranous nephropathy responded to either treatment. Proteinuria was significantly decreased with both methylprednisolone and cytotoxic agents or prolonged administration of synthetic adrenocorticotropic hormone, without significant differences between these 2 therapies.

Adrenocorticotropic Hormone↗
PubMed2006

Thrombotic microangiopathy after kidney transplantation.

Two forms of post-transplant thrombotic microangiopathy (TMA) may be recognized: recurrent TMA and de novo TMA. Recurrent TMA may occur in patients who developed a nondiarrhoeal form of haemolytic uraemic syndrome (HUS) being particularly frequent in patients with autosomal recessive or dominant HUS. The recurrence is almost the rule in patients with mutation in complement factor H gene. Most patients eventually lose the graft. Treatment with plasma infusions or plasmapheresis is often disappointing, but few cases may be rescued. Intravenous immunoglobulins and rituximab have also been successful in anedoctic cases. De novo TMA is rarer. A number of factors including viral infection may be responsible of de novo TMA, but in most cases TMA is triggered by calcineurin inhibitors or mTOR inhibitors. The clinical presentation of de novo TMA may be variable with some patients showing clinical and laboratory features of HUS while others showing only a progressive renal failure. The prognosis is less severe than with recurrent TMA. Complete withdrawal of the offending drug may lead to improvement in many cases. The addition of plasma exchange may result in graft salvage in about 80% of cases.

Calcineurin Inhibitors↗
PubMed2005

The clinical impact of chronic transplant glomerulopathy in cyclosporine era.

BACKGROUND: The clinical impact of chronic transplant glomerulopathy (CTG) on the outcome of kidney allograft receiving calcineurin inhibitors (CNIs) remains uncertain. A retrospective study of renal transplant recipients at Ospedale Maggiore of Milan was undertaken to evaluate the clinical outcome of patients with CTG. METHODS: Among 666 biopsies taken at least 6 months after transplantation (Tx) in 498 transplant patients treated with CNIs, 28 cases (5.6%) of chronic transplant glomerulopathy (CTG) were identified and their clinical features at Tx, at follow-up and graft survival were compared with those of 56 controls transplanted in the same period and with kidney functioning 12 months after Tx. Clinical characteristics at biopsy and at 1 year after Tx were similar in the two groups. RESULTS: After diagnosis graft function deteriorated in 22 patients (78.5%), while it remained stable in 6. Graft loss developed in 92 % of patients with proteinuria >2.5 g/day and in 33 % of those with lower proteinuria (P<0.005). In cases with more severe CTG the rate of graft loss was higher, though not significantly. Graft survival at 10 years was 48% in patients with CTG and 88% in controls (P<0.0001). CONCLUSIONS: The incidence and clinical course of CTG do not seem to be modified by CNI-based immunosuppression. The evolution is unpredictable but the severity of glomerulopathy and proteinuria at follow-up are associated with progression to graft failure. Patients with CTG have a graft survival significantly worse than that of the general population of transplanted patients.

Adolescent↗
PubMed2005

Natural history of hepatitis B and C in renal allograft recipients.

BACKGROUND: In renal allograft recipients, most cases of liver dysfunction are caused by hepatitis B virus and hepatitis C virus (HCV). The natural history of hepatitis C and B was studied in 286 renal allograft recipients who received a kidney allograft between 1972 and 1989 when tests for anti-HCV became available. METHODS: In all patients, hepatitis B (HB) surface (s) antigen (Ag) was tested before and anti-HCV (by enzyme-linked immunosorbent assay II) after transplantation. RESULTS: At enrollment in 1989 (5.5+/-4 years after transplantation), 209 patients were anti-HCV positive (C+), 42 patients were HBsAg-positive (B+), and 35 patients were both B+ and C+ (C+B+). One hundred four patients were receiving azathioprine (AZA) and 182 were on cyclosporine A (CsA). Since transplantation, the median follow-up was 18 years in AZA-treated and 13 years in CsA-treated patients. Liver biopsy showed chronic hepatitis in 73 patients, cirrhosis in 20 patients, and fibrosing cholestatic hepatitis in 2 patients. In 34 patients, liver biopsy was repeated, and progression of fibrosis was observed in 24 patients. The 12-year patient survival rate was similar in B+, C+, and B+C+ patients (67%, 78%, and 71%, respectively; P=not significant). Liver-related death was the first cause of death in B+ and B+C+ infected patients (58% and 72%, respectively), whereas cardiovascular disease was the leading cause of death in C+ patients (40%). Multivariate analysis showed that older age (>40 years) (relative risk [RR], 2.8), B+ status (RR, 2.36), and C+ status (RR, 1.65) were independently associated with a worse patient survival. CONCLUSIONS: In the long term, B+ patients had a higher risk of death related to liver disease than C+ patients, and co-infection did not worsen patient survival.

Follow-Up Studies↗
PubMed2005

The long-term prognosis of renal transplantation in patients with lupus nephritis.

BACKGROUND: Few data are available about the long-term outcome of renal transplantation in patients with systemic lupus erythematosus (SLE). METHODS: Between June 1982 and 2004, a total of 33 adults with lupus nephritis received 35 kidney allografts. Outcomes of these grafts and those of 70 controls matched for age, sex, and donor source who underwent transplantation during the same period were compared. RESULTS: Mean follow-up after renal transplantation was 91 +/- 59 months for patients with lupus and 90 +/- 64 months for controls. Actuarial 15-year patient (80% versus 83%) and death-censored graft survival rates (69% versus 67%) were not significantly different between patients with lupus and controls. Risks for acute and chronic rejection, arterial hypertension, and infection were not different between the 2 groups. Mean serum creatinine levels also were similar in the 2 groups at the last follow-up visit. Intravascular thrombotic events occurred in 9 patients with SLE (26%) and 6 controls (8.6%; P = 0.038). In the SLE group, 6 of 7 antiphospholipid (aPL) antibody-positive versus 3 of 17 aPL antibody-negative patients experienced thrombotic events ( P = 0.015). Recurrence of lupus nephritis was documented in 3 renal grafts (8.6%), but no graft was lost because of recurrent lupus nephritis. CONCLUSION: Long-term patient and graft survival probabilities were similar in patients with SLE and matched controls. The risk for thrombotic complications was greater in patients with SLE, particularly aPL-positive patients. Nephritis recurred in less than 10% of patients with SLE and did not influence graft survival.

Adult↗
PubMed2005

Therapeutic drug monitoring for everolimus in kidney transplantation using 12-month exposure, efficacy, and safety data.

The aims of the current study were to determine whether therapeutic drug monitoring (TDM) might benefit kidney transplant recipients receiving everolimus, and to establish dosage recommendations when everolimus is used in combination with cyclosporine and corticosteroids. The analysis was based on data from 779 patients enrolled in two 12-month trials. Everolimus trough concentrations >/=3 ng/mL were associated with a reduced incidence in biopsy-proven acute rejection (BPAR) in the first month (p = 0.0001) and the first 6 months (p = 0.0001), and reduced graft loss compared with lower concentrations (4% vs. 20%, respectively). By contrast, cyclosporine in the standard concentration range had no impact on BPAR within the same timeframes. Most patients receiving everolimus 1.5 or 3 mg/d achieved trough concentrations above the therapeutic threshold of 3 ng/mL, regardless of reductions in cyclosporine dose. TDM simulation showed that just two dose adjustments would achieve median everolimus trough values >/=3 ng/mL in 95% of patients during the first 6 months. This investigation indicates that improved efficacy is likely when TDM is considered as an integral component of the immunosuppressive strategy of everolimus.

Biopsy↗
PubMed2005

Gastrointestinal complications in renal transplant recipients.

Gastrointestinal complications are frequent in renal transplant recipients and can include oral lesions, esophagitis, peptic ulcer, diarrhea, colon disorders and malignancy. Oral lesions may be caused by drugs such as cyclosporine and sirolimus, by virus or fungal infections. Leukoplakia may develop in patients with Epstein-Barr virus (EBV) infection. The commonest esophageal disorder is represented by fungal esophagitis usually caused by candida. A number of patients may suffer from nausea, vomiting and gastric discomfort. These disorders are more frequent in patients treated with mycophenolate mofetil (MMF). Peptic ulcer is more rare than in the past. Patients with a history of peptic ulcer are particularly prone to this complication. Other gastroduodenal disorders are caused by cytomegalovirus (CMV) and herpes simplex infection. Diarrhea is a frequent disorder which may be caused by pathogen microorganisms or by immunosuppressive agents. The differential diagnosis may be difficult. Colon disorders mainly consist of hemorrhage, usually sustained by CMV infection, or perforation which may be caused by diverticulitis or intestinal ischemia. Colon cancer, anal carcinoma, and EBV-associated lymphoproliferative disorders are particularly frequent in transplant recipients. A particular gastric lymphoma called mucosa-associated lymphoid tissue (MALT) lymphoma may develop in renal transplant patients. It usually responds to the eradication of Helicobacter pylori.

Colonic Diseases↗
PubMed2005

Increased levels of circulating endothelial cells in chronic periaortitis as a marker of active disease.

BACKGROUND: The pathogenesis of chronic periaortitis (CP) has not been clarified. The histologic features and the association with autoimmune diseases suggest an immune-mediated disorder with marked inflammatory vascular and perivascular lesions. To clarify the role of vascular damage we looked for the presence and the surface phenotype of circulating endothelial cells (CECs) in the peripheral blood of patients with chronic periaortitis. METHODS: Eleven patients with CP were evaluated for the presence of CECs; 9 patients had active and 2 inactive disease. Three patients with active disease were also evaluated 3 months after therapy. Ten atherosclerotic patients, 10 patients with renal insufficiency of variable degree and etiology, and 40 healthy subjects were evaluated as controls. Five-parameter, 3-color flow cytometry was performed with a FACScan. CECs were defined as CD45 negative, CD31, P1H12, and CD36 positive, and activated CECs as CD45 negative and P1H12, CD62 positive. RESULTS: The median number of CECs in patients with CP (10(6) cells/mL) was significantly higher than in healthy controls (16 cells/mL, P= 0.0004) and atherosclerotic patients (25 cells/mL, P= 0.0005) Two patients with inactive disease had a CEC count comparable to that of normal subjects. In 2 of the 3 patients reevaluated, 3 months after therapy CEC numbers normalized. Almost all CECs were microvascular in origin and showed an activated phenotype. CONCLUSION: The presence of a high number of CECs in the active phase of chronic periaortitis and their normalization during inactive disease suggest that endothelial damage may play a role in the pathogenesis of the disease.

Aged↗
PubMed2005

Cyclosporine: from renal transplantation to autoimmune diseases.

Over the last 20 years, cyclosporine (CsA) has been the mainstay of immunosuppression in renal transplantation. Initially, CsA was administered at high doses, which enhanced its potential nephrotoxicity. Better handling of the drug was obtained by lowering the dose, monitoring CsA concentration and renal function, and using graft biopsy in difficult cases. In the early 1990s, a new microemulsion showed better pharmacokinetics and efficacy than did the previous formulation. A few years later, evidence showed that checking blood levels 2 hours after administration was a more reliable indicator of CsA exposure than were trough blood levels. The combination with newer immunosuppressive drugs allowed further reduction in the doses of CsA to maintain stable renal allograft function and to improve long-term graft survival. CsA has largely been used in autoimmune diseases. There is concern about its nephrotoxicity, however, as in some studies control renal biopsies showed that CsA-treated patients developed progressive interstitial fibrosis. The risk of nephrotoxicity was related to the initial doses of CsA and to the increase in serum creatinine. Avoiding CsA in patients with creatinine clearance <60 mL/min and in those with uncontrolled hypertension, starting with CsA microemulsion at doses not higher than 4 mg/kg, and reducing the doses whenever serum creatinine increases to 30% or more over baseline may prevent deterioration of renal function. If these guidelines are followed, CsA may be safely used in autoimmune diseases.

Autoimmune Diseases↗
PubMed2005

Long-term lamivudine monotherapy in renal-transplant recipients with hepatitis-B-related cirrhosis.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is an important cause of morbidity and mortality in renal-transplant recipients. The aim of the study was to assess the efficacy and safety of long-term lamivudine monotherapy in renal-transplant recipients with HBV-related cirrhosis. METHODS: Seventeen such patients [median age: 45 years; 7 with hepatitis B e antigen (HBeAg)] received daily oral doses of 75-150 mg lamivudine for a median of 48 (range 11-81) months. All patients had baseline serum levels of HBV DNA of over 6 log10 copies per ml and of alanine transaminase (ALT) of over 1.5 times the upper normal limit (UNL). Clinical lamivudine resistance was defined as a rebound of serum HBV DNA above 5.3 log10 copies per ml and of serum ALT of over 1.5 times the UNL in patients who initially responded with HBV DNA levels of less than 5.3 log10 copies per ml and normal ALT values. Controls were 14 renal-transplant patients (median age 44 years; 3 with HBeAg) with HBV-related cirrhosis, naive to any anti-HBV therapy, followed for 58 months (4-135). RESULTS: Thirteen (77%) treated patients had a persistent response throughout the study period, including three (18%) who developed genotypic resistance, compared with none of the untreated controls (77% versus 0%, P < 0.0001). Four (23%) developed clinical resistance. Two of three patients with initially decompensated cirrhosis had a durable response and clinical improvement compared with the transient responder, whose liver function worsened following lamivudine resistance. Two responders developed chronic rejection requiring chronic haemodialysis. Overall, one treated patient developed liver-related complications, compared with eight untreated controls (6% versus 57%, P < 0.01). CONCLUSIONS: Most renal-transplant patients treated with lamivudine achieved a rapid and durable suppression of HBV, which substantially lowered the risk of liver decompensation and death.

Adult↗
PubMed2004

Everolimus and reduced-exposure cyclosporine in de novo renal-transplant recipients: a three-year phase II, randomized, multicenter, open-label study.

BACKGROUND: Everolimus and cyclosporine (CsA) exhibit synergistic immunosuppressive activity when used in combination. We explored the use of everolimus with a CsA-sparing strategy in de novo renal-transplant recipients. METHODS: A phase II, randomized, open-label 3-year study was performed in 111 patients to compare the efficacy and tolerability of everolimus (3 mg/day) in combination with basiliximab, steroids, and either full-dose Neoral (FDN) or reduced-dose Neoral (RDN) (CsA trough levels 125-250 ng/mL and 50-100 ng/mL, respectively). Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated at 6, 12, and 36 months. A protocol amendment allowed further reduction of CsA exposure after 12 months. RESULTS: Efficacy failure was significantly higher in FDN than in the RDN group at 6 (15.1% vs. 3.4%; P=0.046), 12 (28.3% vs. 8.6%; P=0.012), and 36 (35.8% vs. 17.2%; P=0.032) months. Mean creatinine clearance was higher in the RDN group at 6 (59.7 mL/min vs. 51.1 mL/min; P=0.009), 12 (60.9 mL/min vs. 53.5 mL/min; P=0.007), and 36 (56.6 mL/min vs. 51.7 mL/min; P=0.436) months. Discontinuations and serious adverse events were more frequent in the FDN group. Reduction of CsA exposure for 6 months during the amendment improved renal function in the FDN group. CONCLUSIONS: In de novo renal-transplant recipients, the regimen of everolimus plus RDN was well tolerated, with low efficacy failure and better renal function in comparison with everolimus plus FDN.

Adolescent↗
PubMed2004

Is cyclosporine in renal-transplant recipients more effective when given twice a day than in a single daily dose?

BACKGROUND: It is still unknown whether it is better to administer cyclosporine (CsA) once or twice a day to renal-transplant patients. METHODS: Fifty-four patients were randomized to receive CsA once a day (OD group, 28 patients) or twice a day (BD group, 26 patients). Clinical parameters and pharmacokinetic studies were regularly monitored over the first year. RESULTS: Two patients lost their grafts because of renal vascular thrombosis. A patient in the BD group died. The other 51 patients were alive with graft functioning after a minimum follow-up of 1 year. Five patients per group had reversible acute rejection. There was a not significant trend toward a lower mean serum creatinine in OD than in BD (1.38 +/- 0.38 and 1.7 +/- 0.80 mg/dL at 1 year posttransplant, respectively). In 47 patients, 319 pharmacokinetic studies were performed. We measured the area under the concentration-time curve during the first 4 hours (AUC0-4) and CsA blood levels at 0, 2, and 4 hours after dosing. C0 was significantly lower in OD than in BD (P=0.0011), whereas C2 (P<0.0001) and C4 (P<0.0001) were significantly higher in OD than in BD. In OD, the AUC was higher than in BD (P<0.0001). OD allows us to reach high levels of C2 and AUC for several hours after dosing, whereas BD showed persistently high levels throughout the whole day. CONCLUSION: No difference in survival and rejection rates were observed between OD and BD groups.

Adult↗
PubMed2004

Impact of chronic allograft nephropathy and subsequent modifications of immunosuppressive therapy on late graft outcomes in renal transplantation.

BACKGROUND: Chronic allograft nephropathy (CAN) is the leading cause of organ failure in renal transplant recipients. We retrospectively evaluated the impact of varying immunosuppression in CAN patients on long-term graft survival. METHODS: We retrospectively analysed 158 cyclosporin (CsA)-treated renal transplant recipients with biopsy-proven CAN with follow-up of >1 year. Immunosuppression remained unchanged in 75 (NOVAR) and was modified in 83 patients (VAR). In 36.1% of VAR patients, it was increased; in 63.8%, the addition of other immunosuppressants was associated with a 20% reduction in or withdrawal of CsA. A regression model, for creatinine clearance (CrCl) slope analysis after therapy variation, and Cox's analysis were applied. RESULTS: In VAR patients, two-phase regression did not show a correlation between the inflection point in the CrCl slope and treatment variation. Changing immunosuppression gave a borderline advantage in long-term graft survival compared with NOVAR (P = 0.088). In univariate analysis, severe histological lesions, proteinuria >0.5 g/day and CrCl <25 ml/min at biopsy correlated with poor graft outcome (P = 0.0009). In multivariate analysis, only proteinuria and low CrCl remained significative. Stratifying histological lesions in relation to therapy variation showed that severe lesions significantly decreased survival in both VAR and NOVAR groups; however, the highly negative impact of severe lesions in NOVAR patients on graft survival [relative risk (RR) 3.602] was reduced in VAR patients (RR 1.951), with a 10 year graft survival since biopsy of 0.16 vs 0.34 (P = 0.0001). CONCLUSIONS: In transplant patients with CAN, variation of immunosuppression can reduce the negative impact of severe chronic lesions.

Adult↗