Donata Cresseri

Cancer among patients on renal replacement therapy: a population-based survey in Lombardy, Italy.

Longer and better survival of End‐Stage Renal Disease (ESRD) patients undergoing renal replacement therapy (RRT) is now associated with a higher prevalence of new elderly patients receiving renal replacement therapy (dialysis). In order to help clarify the association of cancer risk with RRT, the incidence of cancer in a population‐based cohort of uraemic patients in the Region of Lombardy, northern Italy, was undertaken using data from the Lombardy Regional Dialysis and Renal Transplant Registry. A total of 479 cases of cancer of all sites was recorded in this population. There were statistically significantly elevated risks of primary liver cancer, kidney cancer, thyroid cancer, lymphoma and multiple myeloma. When the data were examined according to primary renal diseases, there did not appear to be any particular association between excess cancer risk and the underlying pathology. While some caution must be expressed in interpreting these data, due to the relatively small numbers of cases expected in many of the disease entities, the results indicate an excess of renal‐cell and liver carcinomas and lymphomas in patients receiving RRT and highlight the necessity of careful follow‐up and awareness of these associations, together with the need for early detection of such tumours.

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.

Effects of Calcifediol Treatment on the Progression of Renal Osteodystrophy during Continuous Ambulatory Peritoneal Dialysis

Mineral metabolism was studied in 31 patients with chronic renal failure on continuous ambulatory peritoneal dialysis (CAPD) for a year. After baseline observations, 1-year calcifediol treatment was started in all the patients (100 micrograms/day). After therapy, progressive normalization of calcium levels was found in all the patients, while plasma phosphate did not change. After therapy, plasma alkaline phosphatase and parathyroid hormone decreased significantly. 1,25-Dihydroxyvitamin D showed a slight increase, and 25-hydroxyvitamin D (extremely low at the start of the study) rose, reaching normal levels, after 1 year of treatment. Bone mineral density and bone biopsy indexes showed general improvement after calcifediol. In conclusion, calcifediol seems to act positively on the disorders of mineral metabolism in CAPD.

Remission of HCV-associated glomerulonephritis with pegylated ifn and ribavirin therapy after liver transplantation: case report and literature review

Background Hepatitis C virus infection is associated with a variety of extrahepatic disorders such as membrano-proliferative glomerulonephritis, which is generally due to cryoglobulinemia. Setting We describe the case of one liver transplant recipient who received antiviral therapy (subcutaneous administration of peg-IFN-alpha-2a 180 mcg weekly and oral ribavirin 200 mg thrice a day) for HCV-related membrano-proliferative glomerulonephritis. He presented normal kidney function, non-nephrotic proteinuria (2 g/24 h) and mild hematuria. Results Urinary abnormalities disappeared within a few weeks after the initiation of antiviral therapy; however, combination antiviral therapy was not able to obtain viral clearance. After 11 months, IFN-therapy was interrupted and the patient continued low-dose ribavirin monotherapy (200 mg once per day) for one additional year- remission of proteinuria (<0.3 g/24 h) and hematuria persisted with intact kidney function. Although other mechanisms cannot be excluded, we suggest that ribavirin therapy was critically implicated in the remission of urinary abnormalities in our patient. The existing literature on the association between HCV-associated glomerulonephritis and therapy with ribavirin is reviewed. Conclusions Antiviral therapy may be effective in patients with HCV-induced glomerulonephritis. Further evidence is needed to evaluate efficacy and safety of ribavirin monotherapy for HCV-related glomerulonephritis.

Antiviral therapy for HCV-associated cryoglobulinemic glomerulonephritis: case report and review of the literature.

We describe the case of a 51-year-old woman with HCV-associated cryoglobulinemic glomerulonephritis (GN). She presented mild deterioration of kidney function, non-nephrotic proteinuria, and active urinary sediment. Kidney biopsy showed features of membranoproliferative changes with some sclerosis. Sustained viral response (SVR) was obtained by 6 months of antiviral therapy (peg-IFN-α2a plus ribavirin). SVR was linked with improvement of kidney function and remission of proteinuria. Clinical and virological remission persists over a 25-month follow-up. This case report emphasizes efficacy and safety of antiviral treatment of HCV-associated glomerulonephritis – preliminary but encouraging results exist. We identified by systematic review of the literature 9 studies (156 unique patients); the pooled estimate of frequency of sustained virological response after IFN-based therapy was 0.49 (95% confidence interval, CI: 0.21, 0.77; p < 0.0005; random effects model). Heterogeneity was found (I2 = 98.9%, p < 0.0001). Two possible regimens should be considered for the treatment of HCV-associated cryoglobulinemic GN according to the clinical presentation. Immunosuppressive therapy is recommended for HCV-related kidney disease having aggressive course, and recent evidence supports rituximab (RTX) use with a reduced exposure to corticosteroids. We identified six studies (66 unique patients) on RTX therapy for HCV-associated kidney disease; at the end of RTX therapy, the pooled estimate of the mean decrease in proteinuria was 1.4 g/24 h (95% CI: 0.75, 2.05, p < 0.001); The p test for heterogeneity gave a value of 0.94 (I2 = 0). Several questions related to RTX use remain. HCV-induced GN is uncommon among CKD patients of developed countries, and this clearly hampers prospective controlled clinical trials aimed to evaluate efficacy and safety of antiviral or immunosuppressive therapy in this population.

Rituximab therapy for primary glomerulonephritis: Report on two cases

The evidence in the medical literature on the efficacy and safety of rituximab therapy for primary glomerulonephritis is limited and controversial. We describe two male Caucasian patients with rapidly progressive kidney failure due to primary proliferative glomerulonephritis. Both of them received high-dose intravenous corticosteroids and oral cyclophosphamide with limited benefit. The first patient (hepatitis C virus-negative mixed cryoglobulinemia) underwent plasma-exchange with intravenous immunoglobulins; he showed significant benefit on kidney function (he became dialysis independent with serum creatinine going back to 1.6 mg/dL) after one rituximab pulse even if urinary abnormalities were still present. No improvement in renal function or urinary changes occurred in the second patient. Both these individuals developed sepsis over the follow-up, the first patient died two months after rituximab therapy. This report is in keeping with the occurrence of severe infections after rituximab therapy in patients with renal impairment at baseline and concomitant high-dose steroids.

Antiviral therapy of symptomatic HCV-mixed cryoglobulinemia after liver transplant: case report and literature review.

Hepatitis C virus (HCV) infection may be associated with extra-hepatic illness including mixed cryoglobulinemia (MC). Consistent evidence exists on HCV-MC in the non-transplantation setting but information on HCV-related cryoglobulinemia after solid organ transplantation is limited, particularly after liver transplantation (LT). We report on a 48-year-old man who developed HCV-associated cryoglobulinemic vasculitis with recurrent hepatitis after liver transplant. One year after transplant for HCV-positive cirrhosis, he presented severe cutaneous manifestations, and biopsy-proven cryoglobulinemic membrano-proliferative glomerulonephritis (MPGN). HCV RNA clearance occurred within a few weeks of antiviral therapy; sustained viral response (SVR) was obtained by one year of anti-HCV combination therapy (eight months of pegylated IFN/ribavirin and four months of standard IFN/ribavirin). SVR was linked to complete remission of skin, liver, and kidney abnormalities. Tolerance to the pegylated IFN/ribavirin regimen was not excellent due to the occurrence of lobar pneumonia with anemia; thus, peg-IFN was replaced by recombinant IFN, with a favorable outcome. Clinical and viral remission persisted over a 48-month follow-up. HCV-associated mixed cryoglobulinemia flareups following LT were successfully managed with combined antiviral therapy. HCV-related MC is uncommon in developed countries and this clearly hampers randomized controlled clinical trials aimed at evaluating the efficacy and safety of anti-HCV therapy after solid organ transplantation or in the non-transplantation setting.

Primary glomerular diseases in the elderly Glomerulonephritis in the elderly

Recent studies have pointed out that the incidence of primary glomerular diseases is similar in the elderly and in younger populations. However the clinical characteristics of the different subtypes may be different in the advanced age. Minimal change nephropathy responds favorably to corticosteroids and/or cyclophosphamide, but many untreated or non-responder patients progress to end-stage renal disease or die from nephrotic complications. Focal and segmental glomerulosclerosis also has a severe prognosis in older patients but some 50% of patients may attain remission of the nephrotic syndrome with a prolonged corticosteroid treatment. The responders tend to maintain normal renal function over time. Membranoproliferative glomerulonephritis and IgA nephritis have a severe prognosis and do not respond to treatment. The clinical presentation and the outcome of membranous nephropathy are similar in the elderly and in younger adults. Corticosteroids are of little benefit while a 6-month treatment with chlorambucil and methylprednisolone may obtain remission of the nephrotic syndrome in about 2/3 of older patients. Crescentic glomerulonephritis has an ominous prognosis in older patients but some patients may improve if treatment with methylprednisolone pulses is started early. Acute postinfectious glomerulonephritis is often associated with renal failure in older patients. The prognosis may be severe.

Kinetics of Anti-Xa Activity during Combined Defibrotide - Heparin Administration in Hemodialysis

Defibrotide, a polydesoxyribonucleotide derivative with antithrombotic and fibrinolytic activity, capable of inducing the release of PGI2 from vascular endothelia, was proposed as an alternative to standard heparin coverage during blood dialysis for patients at risk of bleeding. The original procedure featured the preliminary washing of the dialysis circuit with heparin, which was then recirculated and eliminated, and the two drugs, heparin and defibrotide, are known to interact with each other. The purpose of this present study was to explore the ex-vivo heparin activity (assessed as anti-Xa activity) in diverse hemodialysis models using defibrotide (800 mg intravenous, in 4 bolus injections) and various dosages of heparin. Anti-Xa activity is negligible in dialysis conducted with defibrotide alone. When the circuit was prewashed with heparin (5000 and 2500 IU), there was evident anti-Xa activity (0.3-0.5 U/ml) in the first 30-60 minutes of dialysis; continuous heparin infusion (500 U/hour) resulted in high anti-Xa activity levels at the end of dialysis. Thus the best hemodialysis procedure for patients at high risk of bleeding should be one utilizing only defibrotide, or defibrotide plus small amounts of calcium heparin infused at the rate of 500 U/hour for not more than two hours.

Immunosuppressive and antiviral treatment of hepatitis C virus–associated glomerular disease: A long-term follow-up

Background: The evidence in the medical literature on the treatment of hepatitis C virus–associated glomerular disease is extremely limited. The advent of nonconventional immunosuppressive agents and direct-acting antivirals promises high efficacy and safety. Aims: We conducted an open-label, single-arm clinical study to examine the efficacy and safety of a combined approach for hepatitis C virus–associated glomerular disease. Methods: In the first phase of the study, patients with hepatitis C virus–associated glomerular disease received interferon-based antiviral therapy and immunosuppressive agents; since 2013, interferon-free antiviral therapy was adopted and novel immunosuppressants (including B-cell depleting agents and mycophenolate mofetil) or immunomodulators (ribavirin) were choiced. Virological and clinical responses were evaluated over a long observation period (median follow-up of 60 weeks and 46.5 months after the end of treatment with interferon and direct-acting antiviral agents, respectively). Results: We enrolled 25 consecutive patients with hepatitis C virus–associated glomerular disease, 8 being liver transplant recipients for hepatitis C. A total of 13 patients received therapy with direct-acting antivirals and experienced sustained viral response (serum hepatitis C virus RNA <12 IU/mL, 12 weeks after treatment ended, sustained viral response12). The mean (±standard deviation) proteinuria decreased from 2.61 ± 1.01 at baseline to 1.71 ± 1.43 (g/day) at sustained viral response 48, p = 0.031; microscopic hematuria and serum cryoglobulins disappeared in six (50%) and seven (64%) patients, respectively, after sustained viral response by direct-acting antivirals. Adverse events occurred in 69% (9/13) of patients and were mild, with four cases of ribavirin-related anemia requiring blood transfusions (no drop-outs). After sustained viral response by direct-acting antivirals, immunosuppressive and immunomodulatory agents were initiated in clinical relapsers (n = 2) and nonresponders (n = 3) with some benefit. Among patients on interferon-based regimens (n = 12), viral response (sustained viral response 24) and dropout rates were 58% (7/12) and 33% (4/12), respectively. After sustained viral response by interferon-based therapy, clinical relapsers (n = 3) were successfully managed with immunosuppressive agents in two patients. Conclusion: Treatment with direct-acting antivirals provides excellent rates of viral response and safety in patients with hepatitis C virus–related glomerular disease; viral response was frequently accompanied by clinical improvement. The absence of hepatitis C virus RNA from serum allowed immunosuppressive and immunomodulatory therapies with benefits for glomerular abnormalities and no concern on hepatitis C virus replication.