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Claudio Ponticelli

Publications and source records attributed to Claudio Ponticelli.

At least 37 records · Page 2Linked to original sources

Acute post-bacterial glomerulonephritis in renal transplant patients: description of three cases and review of the literature.

Only a few cases of acute post-infectious glomerulonephritis have been described in renal transplant patients. We report here three cases of acute post-bacterial glomerulonephritis in renal transplants. In contrast to the classic cases of post-streptococcal glomerulonephritis the type of infection was heterogeneous: respectively, Escherichia coli bacteremia, a skin abscess, and cholangitis. The clinical presentation was characterized by a deterioration of graft function in two of our three patients. Acute renal dysfunction recovered in both patients, but in the long term the outcome was severe; two of the three patients lost their graft function. It is difficult to ascertain whether progression was due to chronic allograft nephropathy, to glomerulonephritis, or both. It may be concluded that acute post-infectious glomerulonephritis is a possible, although rare, complication in renal transplant recipients. It has an unusual presentation and may have a poor outcome in the long term. The role of therapy, if any, is still undefined.

Acute Disease↗

Antiphospholipid antibodies are associated with an increased risk for chronic renal insufficiency in patients with lupus nephritis.

BACKGROUND: Previous studies have documented the high frequency of thrombosis and fetal loss in patients with lupus nephritis and antiphospholipid (aPL) antibodies, but there is little information on the impact of aPL antibodies on the outcome of lupus nephritis. The aims of this study are to evaluate the prevalence of aPL antibodies in patients with lupus nephritis and assess their prognostic value for thrombosis and pregnancy morbidity and impact on long-term renal outcome. METHODS: One hundred eleven patients with lupus nephritis followed up for a mean of 173 +/- 100 months were tested regularly for immunoglobulin G (IgG) and IgM anticardiolipin antibodies and lupus anticoagulant. RESULTS: The overall prevalence of aPL antibodies was 26%. In follow-up, 79% of aPL antibody-positive patients experienced thrombotic events and/or fetal losses, and aPL antibodies were associated significantly with arterial or venous thrombosis (P = 0.00001), pregnancy morbidity (P = 0.045), thrombocytopenia (P = 0.0015), and persistent arterial hypertension (P = 0.028). aPL antibodies were significantly more frequent in patients with biopsy-proven membranous lupus nephritis (P = 0.01). A strong association between aPL antibodies and the development of chronic renal insufficiency in the long-term outcome also was found (P = 0.01). With multivariate analysis, aPL antibody positivity (P = 0.02), high plasma creatinine level at presentation (P = 0.01), and chronicity index (P = 0.00004) were independent predictors of chronic renal function deterioration. CONCLUSION: Detection of aPL antibodies in patients with lupus nephritis is useful not only to identify patients at risk for vascular and obstetric manifestations, but also for their potential deleterious impact on renal outcome.

Adolescent↗

Renal transplantation 2004: where do we stand today?

In spite of considerable progress in immunosuppressive and supportive treatment, numerous problems persist which interfere with the success of renal transplantation. Before transplantation has been performed, factors impacting on outcome include the donor (living vs cadaver, age and HLA system) as well as the recipient (age, immunological reactivity, potential sensitization and duration of dialysis). These are the main factors that affect the outcome of the transplant, particularly in the long-term. After transplantation a number of events may put graft function at risk: potential recurrence of the primary renal disease in the allograft; 'de novo' renal disease triggered by infections, drugs or autoimmunity; and non-specific progression promoters, such as diabetes, hypertension, proteinuria, nephrotoxic agents and/or viral infections. The two most frequent causes of chronic allograft dysfunction are (i) chronic rejection (often triggered by preceding acute rejection, delayed graft function or poor compliance) and (ii) calcineurin-inhibitor nephrotoxicity (more likely to develop in kidneys of older donors or in marginal kidneys). The differential diagnosis between these two entities is generally difficult, but some histological clues (reduplication of glomerular basement membrane, obliterating vasculopathy and C4d deposits) as well as the demonstration of humoral antibodies are pointers suggesting rejection. Treatment of chronic graft dysfunction is difficult, whatever the cause, particularly in cases with advanced renal lesions. Therefore, early diagnosis is of paramount importance. In this regard, graft biopsy can be of great help. In spite of many problems and complications, not only short-term but also long-term results of renal transplantation are improving progressively, as documented by CTS data showing that in Europe for transplants performed between 1982 and 1984 the mean graft half-life was 7 years, while for transplants performed between 1997 and 1999 it was 20 years.

Age Factors↗

Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial.

Proteinuria plays a causal role in the progression of IgA nephropathy (IgAN). A previous controlled trial showed that steroids are effective in reducing proteinuria and preserving renal function in patients with IgAN. The objective of this study was to evaluate the long-term effectiveness of steroids in IgAN, examine the trend of proteinuria during follow-up (starting from the hypothesis that the degree of reduction in proteinuria may influence IgAN outcome), and evaluate how histologic scores can influence steroid response. A secondary analysis of a multicenter, randomized, controlled trial of 86 adult IgAN patients who were receiving supportive therapy or intravenous methylprednisolone plus oral prednisone for 6 mo was conducted. Ten-year renal survival was significantly better in the steroid than in the control group (97% versus 53%; log rank test P = 0.0003). In the 72 patients who did not reach the end point (doubling in baseline serum creatinine), median proteinuria significantly decreased (1.9 g/24 h at baseline, 1.1 g/24 h after 6 mo, and 0.6 g/24 h after a median of 7 yr). In the 14 progressive patients, proteinuria increased from a median of 1.7 g/24 h at baseline to 2.0 g/24 h after 6 mo and 3.3 g/24 h after a median of 5 yr. Steroids were effective in every histologic class. Cox multivariate regression analyses showed that, in addition to steroids, a low baseline histologic score, a reduction in proteinuria after 6 mo, and no increase in proteinuria during follow-up all were independent predictors of a beneficial outcome. Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN. The histologic picture and proteinuria during early and late follow-up improve the prediction of outcome, but considerable variability remains outside the model.

Adrenal Cortex Hormones↗

Renal transplantation in patients with IgA mesangial glomerulonephritis.

Most patients with IgA nephritis are suitable candidates for renal transplantation. In about 33% of patients the disease may recur after transplantation, although there are differences in the various series because of the different criteria for biopsy, the different length of follow-up and the different ethnicities. Living donation, genetic factors and time of progression of original disease have been found to be related with the risk of recurrence by some investigators, but these associations were not confirmed by other studies. The graft survival in patients with IgA nephritis is similar or even better than that observed with other renal diseases. The available data indicate that recurrence has a little impact on the 10-yr graft survival. However, a minority of patients may show a rapid progressive course after recurrence. Little information is available on the impact of recurrence in the very long term. There is no established treatment for preventing or treating the recurrence of IgA nephritis.

Child↗

Oxidative stress in kidney transplant patients.

BACKGROUND: Little information is available about the role of oxidative stress in renal transplant patients. To evaluate the prevalence and severity of oxidative stress in renal transplantation, the authors conducted a cross-sectional study. METHODS: In 112 cadaver or living-donor kidney transplant recipients with a follow-up of at least 6 months and with plasma creatinine less than or equal to 2.5 mg/dL, complete blood count, serum vitamin B12, serum folate (s-F), reactive oxygen species (ROS), thiol groups (-SH), total antioxidant activity (TAOC), serum homocysteine (Hcy), and intraerythrocyte folate (ery-F) were measured. RESULTS: The mean levels of Hcy (21.1 microM vs. <10 microM), ROS (302.7 U. Carr (Carratelli units) vs. 250-300 U. Carr), and TAOC (410.6 micromol/HclO/mL vs. >350 micromol/HclO/mL), were higher than the reference interval, whereas -SH groups, vitamin B12, s-F, and ery-F were within the normal range. In the multivariate model, plasma creatinine (P=0.0062), vitamin B12 (P=0.0121), and TAOC (P=0.0007) were independently associated with oxidative stress. At multiple regression analysis, -SH groups and ROS were directly and inversely related to hematocrit (P=0.0007 and P=0.0073). There was also a negative correlation between -SH groups and blood pressure levels (P=0.0095). CONCLUSIONS: Renal transplant patients have a pattern of increased oxidant stress that is counterbalanced by an enhancement of the antioxidant mechanisms. Besides the well-known risk factors, the authors found that anemia is an independent risk factor for an increase of ROS. Further studies are needed to evaluate whether the correction of anemia might prevent or reduce the oxidative stress in renal transplant patients.

Adult↗

Corticosteroids, cyclophosphamide, and chlorambucil therapy of membranous nephropathy.

Corticosteroids and cytotoxic agents have been studied widely in membranous nephropathy (MN). However, controlled studies with corticosteroids have not shown a clear benefit of these agents on the outcome of the disease. Some controlled trials reported that cytotoxic agents can reduce proteinuria significantly, but it was difficult to assess the efficacy of these drugs in protecting renal function because of the short follow-up period of the studies. Three randomized controlled trials showed that a 6-month treatment regimen based on corticosteroids and a cytotoxic agent, giving each for 1 month at a time in an alternating schedule, could favor remission of the nephrotic syndrome and protect renal function. Taken together, the results of these trials at the end of the follow-up period, 74% of the 174 treated patients were without nephrotic syndrome, 4 patients were on chronic dialysis, and 2 patients died. Good results with cytotoxic drugs, often associated with corticosteroids, also have been reported in progressive membranous nephropathy. However, in patients with renal insufficiency side effects were frequent and severe. Moreover, in most cases renal function improved but did not return to normal.

Antineoplastic Agents, Alkylating↗

Biological dynamics of hepatitis B virus load in dialysis population.

BACKGROUND: Control of the spread of hepatitis B virus (HBV) infection in dialysis units has been one of major advances in the management of end-stage renal disease. However, the natural history of HBV in dialysis patients remains unclear. The aim of this study is to measure monthly HBV viral load (HBV DNA) in a large cohort (n = 29) of hepatitis B surface antigen (HBsAg)-positive chronic dialysis patients during 12 months. METHODS: HBV DNA was measured using the Amplicor HBV Monitor Test (Roche Diagnostics, Branchburg, NJ), an in vitro assay using polymerase chain reaction nucleic acid amplification and DNA hybridization for the quantitative measurement of HBV DNA in serum. RESULTS: We observed three HBV DNA patterns: (1) patients persistently positive by Amplicor HBV Monitor Test (persistent HBV DNA; 7 of 29 patients; 24.1%), (2) individuals with alternatively positive and negative results (intermittent HBV DNA; 18 of 29 patients; 62.1%), and (3) patients persistently negative by Amplicor HBV Monitor Test (4 of 29 patients; 13.8%). HBV viral load was greater in patients with persistent compared with intermittent HBV DNA (persistently HBV DNA positive; 2.686 x 10(4) copies/mL; 95% confidence interval [CI], 5.2499 x 10(4) to 1.8158 x 10(4)copies/mL) versus intermittently HBV DNA positive (1.071 x 10(3) copies/mL; 95% CI, 8.524 x 10(3) to 4.09 x 10(2) copies/mL; P = 0.0001). In the entire group, HBV load at study entry was low and did not change versus the end of follow-up. CONCLUSION: Three patterns of HBV viremia in dialysis patients over time were assessed; HBV load was not high and was relatively stable. HBsAg-positive patients who were intermittently HBV DNA positive had less HBV viral load than persistently HBV DNA-positive patients. Periodic testing for HBV DNA to assess the virological status of HBsAg-positive dialysis patients is recommended.

Aged↗

Changes in viremia and circulating interferon-alpha during hemodialysis in hepatitis C virus-positive patients: only coincidental phenomena?

BACKGROUND: It has been hypothesized that hemodialysis (HD) treatment per se can preserve patients from an aggressive course of hepatitis C virus (HCV) infection by reduction of viral load. The aim of the present study in HCV-positive (HCV+) HD patients is to determine whether HD induces the production of interferon-alpha (IFN-alpha) and if such production can contribute to viremia reduction. METHODS: To address this issue, HCV RNA and IFN-alpha levels were determined in 11 HCV+ patients immediately before and at the end of a 4-hour dialysis session using cellulosic membranes and 24 and 48 hours later, ie, immediately before the subsequent dialysis session using the same membrane and at the end of the dialysis session. The same protocol was repeated 1 week later using a high-biocompatibility synthetic membrane. RESULTS: HCV titer decreased in all patients after dialysis (range, 3% to 95%; P = 0.001) and thereafter progressively increased and returned to basal levels within 48 hours, with a new reduction during the next dialysis treatment. There was no significant difference in the magnitude of changes in HCV titers in tests performed using cellulosic or synthetic membranes. Plasma IFN-alpha levels increased markedly after dialysis using both cellulosic (in 9 of 11 cases) and synthetic membranes (in 10 of 11 cases; P < 0.01) and returned to basal levels within 48 hours; thereafter, IFN-alpha levels increased again during the next dialysis session. In some patients, plasma IFN-alpha levels after HD were approximately 50% of the level observed after therapeutic administration of 6 million units of IFN-alpha to 4 HD patients with chronic hepatitis. CONCLUSION: Although without a proven direct cause-effect relationship between HCV level reduction and induction of IFN-alpha after dialysis, our observation suggests an additional new mechanism for the unusually mild course of HCV infection in HD patients.

Adult↗

Prevalence and management of anemia in renal transplant recipients: a European survey.

The TRansplant European Survey on Anemia Management (TRESAM) documented the prevalence and management of anemia in kidney transplant recipients. Data from 72 transplant centers in 16 countries were screened, involving 4263 patients who had received transplants 6 months, 1, 3 or 5 years earlier. The mean age of transplant recipients was 45.5 years at transplantation. The most common etiology was chronic glomerulonephritis. The most common comorbidities were coronary artery disease, hepatitis B/C, and type 2 diabetes. The mean hemoglobin levels before transplantation were significantly higher in the more recently transplanted recipients. At enrollment, 38.6% of patients were found to be anemic. Of the 8.5% of patients who were considered severely anemic, only 17.8% were treated with epoetin. There was a strong association between hemoglobin and graft function; of the 904 patients with serum creatinine > 2 mg/dL, 60.1% were anemic, vs. 29.0% of those with serum creatinine <or= 2 mg/dL (p < 0.01). Therapy with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, mycophenolate mofetil (MMF) or azathioprine was also associated with a higher likelihood of anemia. The prevalence of anemia in the transplant recipients was remarkably high and appeared to be associated with impaired renal function and with ACE inhibitors and angiotensin II receptor antagonist use. Further studies should be carried out to interpret whether appropriate management of anemia after kidney transplantation may improve long-term outcome.

Adult↗

Other immunosuppressive agents for focal segmental glomerulosclerosis.

A prolonged course with corticosteroids represents the first therapeutic approach for nephrotic patients with focal segmental glomerulosclerosis (FSGS). In patients with contraindications to steroids or in those who do not respond to steroids or cyclosporine, cytotoxic agents, mycophenolate mofetil (MMF), plasmapheresis, and low-density lipoprotein (LDL) apheresis have been tried as alternative treatments. A short-term treatment with cytotoxic agents often is ineffective in steroid-resistant patients However, an aggressive and prolonged treatment with cytotoxic agents combined with corticosteroids proved to be effective in more than half of steroid-resistant children. In adults, the response to cytotoxic agents was good in steroid-responsive patients, but was poor in steroid-resistant patients. Better results were observed when cytotoxic therapy was prolonged for several months. The problem with these drugs is that long-term immunosuppression may be complicated by severe side effects including a major risk for cancer. Uncontrolled studies reported that MMF can induce some reduction of proteinuria, but complete remission of proteinuria was rare and no data on long-term follow-up evaluation with this drug are available. Good results have been reported with plasmapheresis, immunoadsorption, and lipopheresis. However, all the reports were uncontrolled, small sized, and with short-term follow-up evaluation. In conclusion, there are several therapeutic options for patients who respond to steroids and have further relapses of nephrotic syndrome, but how to treat steroid-resistant patients is still a matter of debate. Nevertheless, a 6-month trial with cytotoxic agents or MMF can be offered to steroid-resistant patients to identify the few patients who respond to these agents. The preliminary results with plasmapheresis or lipopheresis are promising but further studies are needed to assess the role of these treatments.

Disease Progression↗

[Acute post-infective glomerulonephritis].

In children post-infectious acute glomerulonephritis is usually caused by beta-hemolytic streptococcus and has a fair prognosis with spontaneous remission in most cases. Rarely, however, the disease may be complicated by oliguria and/or severe hypertension which can cause cardiac congestion or cerebral edema. In adults the acute glomerulonephritis may be caused by a number of different micro-organisms and it often develops in patients with other diseases. The prognosis may be severe and is worsening over the years. The risk of chronic renal failure is increased in patients with crescents and with large interstitial infiltrates. A renal biopsy is recommended in adults with acute glomerulonephritis to make possible a differential diagnosis with other diseases presenting with a nephritic syndrome, to assess the prognosis and to evaluate the pro's and the con's of a treatment with steroid and/or immunosuppressive agents.

Acute Disease↗

Risk factors for late kidney allograft failure.

BACKGROUND: While graft survival rates in the short term have improved dramatically, only a modest improvement has been shown in long-term graft survival rates. We evaluated the causes of late failure in renal allograft recipients treated with cyclosporine A (CsA). METHODS: A total of 864 adults with a functioning graft at one year were evaluated. The end points were dialysis or death with a functioning graft. RESULTS: The 13-year patient and graft survival probabilities were 0.82 and 0.64, respectively. The graft half-life was 20.1 years and the pure graft half-life was 31.1 years. At multivariate analysis, plasma creatinine at one year (P = 0.0006; RR 1.72), low-density lipoproteins (LDL) at one year (P = 0.0014; RR 1.65), older age (P = 0.0128; RR 1.50) and delayed graft function (P = 0.0350; RR 1.45) were associated with the end point. Chronic allograft nephropathy was the cause of failure in 97 patients, death in 70, recurrence of glomerulonephritis in 24, other events in 6. Cardiovascular complications were the most frequent cause of death. Post-transplant cardiovascular events were associated with: pre-transplant cardiovascular events (P = 0.0012; RR 2.65), older age (P = 0.0001; RR 2.46), pre-transplant arterial hypertension (P = 0.0249; RR 1.57), smoking (P = 0.0235; RR 1.29), duration of dialysis (P = 0.0229; RR 1.28). Mean serum cholesterol, LDL and triglycerides were each significantly associated post-transplant cardiovascular events. CONCLUSIONS: The graft half-life was 20 years. Chronic allograft nephropathy was the leading cause of late failure, followed by death. If the data were censored by death, the projected pure graft half-life would be 31.1 years. Pre-transplant selection and preparation of the candidate as well as appropriate life style are recommended to improve life expectancy and extend graft survival.

Adolescent↗

Depletion of clusterin in renal diseases causing nephrotic syndrome.

BACKGROUND: Clusterin is a lipoprotein that has anti-complement effects in membranous nephropathy (MN). In focal segmental glomerulosclerosis (FSGS), it inhibits permeability plasma factor activity and could influence proteinuria. Moreover, with aging, knockout mice for clusterin develop a progressive glomerulopathy with sclerosis. METHODS: Since little is known about clusterin metabolism in humans, we determined clusterin levels and composition in the sera and urine of 23 patients with MN, 25 with FSGS and 23 with steroid-responsive nephrotic syndrome (NS). Renal localization was evaluated by immunofluorescence and morphometry. RESULTS: Serum clusterin was markedly reduced in active MN, in FSGS and in children with NS compared to controls; after stable remission of proteinuria, nearly normal levels were restored. Among various biochemical variables, serum clusterin was inversely correlated with hypercholesterolemia. Urinary clusterin, representing a 0.01 fraction of serum, was higher in the urine from normal subjects and FSGS patients in remission with proteinuric MN, FSGS and idiopathic NS; clusterin was inversely correlated with proteinuria. In all cases, urinary and serum clusterin was composed of the same 80 kD isoforms. Finally, a decrease in focal segmental or global clusterin staining was found in FSGS glomeruli, especially in areas of sclerosis. Instead, in MN an overall increment of staining was observed that ranged from mild/focal to very intense/diffuse. CONCLUSIONS: The overall pool of clusterin is reduced in glomerular diseases causing nephrotic syndrome, with hypercholesterolemia appearing as the unifying feature. Depletion of clusterin should negatively affect the clinical outcome in nephrotic patients and efforts should be aimed at normalizing clusterin overall pool.

Adolescent↗

Outcome of peritoneal dialysis in cirrhotic patients with chronic renal failure.

BACKGROUND: Results of peritoneal dialysis (PD) in cirrhotic patients with renal failure are debated. The aim of the present study is to assess the outcome of PD patients with liver cirrhosis. METHODS: A retrospective study based on clinical records was performed in 21 cirrhotic and 41 PD patients without liver disease followed up at our PD unit. RESULTS: Five-year patient and technique survival were similar in the two groups. Seven cirrhotic patients (33%) died of liver failure (5 patients), liver cancer (1 patient), and peritonitis (1 patient). Ten controls (24%) died of cardiovascular complications (6 patients), pneumonia (1 patient), cachexia (1 patient), and unknown reasons (2 patients). Six cirrhotic patients discontinued PD therapy after 44.3 +/- 24.7 months because of inadequate dialysis (2 patients), sclerosing peritonitis (2 patients), dementia (1 patient), or patient choice (1 patient). Twelve controls discontinued PD therapy after 33 +/- 25.9 months because of peritonitis (6 patients), exit-site infection (1 patient), inadequate peritoneal clearance (3 patients), catheter malfunction (1 patient), and patient request (1 patient). The peritonitis rate was 0.31 episodes/y in cirrhotic patients and 0.53 episodes/y in controls (P = not significant). The hospitalization rate was similar (16.5 d/y in cirrhotic patients, 15.4 d/y in controls). In cirrhotic patients, complications were leakage (3 patients), symptomatic hypotension (5 patients), anemia (5 patients), severe malnutrition (14 patients), sclerosing peritonitis (2 patients), and hepatic encephalopathy (3 patients). CONCLUSION: The outcome of PD and risk for bacterial peritonitis or other dialysis complications are not worsened by the presence of liver cirrhosis.

Female↗

Pregnancy in lupus nephritis.

BACKGROUND: Fetal and maternal outcomes of 70 pregnancies in 48 women with lupus nephritis were retrospectively analyzed. METHODS: In 13 women, lupus nephritis developed during pregnancy (group A). In 38 patients with known lupus nephritis (including 3 patients in group A who had another pregnancy), 57 pregnancies occurred. In 6 patients, a therapeutic abortion was performed. The remaining 51 pregnancies were considered pregnancies in lupus nephritis (group B). RESULTS: Fetal loss was 36% (38%, group A; 35%, group B); it decreased from 46% in the 1970s to 30% in the last decade. Among 41 live births, there were 13 preterm deliveries and 28 full-term deliveries. At multivariate analysis, proteinuria (P = 0.025), arterial hypertension (P = 0.05), and antiphospholipid antibodies (P = 0.01) were independent predictors of fetal loss. In group A, 3 patients developed acute renal failure, irreversible in 1 patient (7.7%); all other patients recovered after steroid and immunosuppressive therapy. In group B, 12 renal flares and 1 extrarenal flare developed during pregnancy or the postpartum period. Two patients progressed to irreversible renal failure (3.9%), and 1 of the 2 patients died. All other patients recovered. The incidence of renal flares before or during pregnancy was not different (P = 0.51). Renal quiescence at the onset of pregnancy was the only predictor of favorable maternal outcome. CONCLUSION: Proteinuria, hypertension, and positivity of antiphospholipid antibodies are independent predictors of adverse fetal outcome. Quiescence of renal disease is the only predictor of favorable maternal outcome.

Abortion, Spontaneous↗