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
Treatment of focal segmental glomerulosclerosis Passerini, Patrizia; Ponticelli, Claudio
Current opinion in nephrology and hypertension,
2001-March, Letnik:
10, Številka:
2
Journal Article
Recenzirano
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.
The term nephrotic syndrome (NS) refers to a condition characterized by heavy proteinuria, hypoalbuminemia, edema and hyperlipidemia. The NS is often seen when the urinary protein excretion exceeds ...3.5 g/day and is almost invariably present when proteinuria is greater than 5 g/day. In the NS there may be a constellation of biochemical and clinical abnormalities that can predispose to disabling and even fatal complications, such as infections, bone disease, arterial or venous thrombosis, cardiovascular disease, etc. In addition, the onset of NS is a marker for bad outcome for most glomerular diseases.
The NS may be caused by a large variety of renal diseases. In this paper, however, we will limit ourselves to reviewing the treatment for those cases of NS associated with primary glomerulonephritis.
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.
The 3 main causes of primary nephrotic syndrome are minimal change nephropathy, focal segmental glomerulosclerosis and membranous nephropathy. Corticosteroids result in remission of proteinuria in ...most patients with minimal change nephropathy. Many patients, however, develop corticosteroid dependency. A course of cytotoxic drugs can also achieve remission but these agents cannot be administered for prolonged periods or in repeated cycles because their toxicity is cumulative. Review of the available literature indicates that cyclosporin may maintain remission of nephrotic syndrome in about 80% of patients with corticosteroid-sensitive disease, indicating an important role for this drug in patients with frequent relapses or corticosteroid dependency. Although cyclosporin is less effective in patients with focal segmental glomerulosclerosis, which is often corticosteroid-resistant, a number of studies indicate that it may be successful both in the few steroid-sensitive patients with frequent relapses and in some corticosteroid-resistant patients. In patients with membranous nephropathy, a 6-month course of corticosteroids and cytotoxic agents may favour remission of nephrotic syndrome and protect renal function. Several studies have shown that cyclosporin can improve proteinuria, and there is a tentative suggestion that it might also protect against renal function deterioration. The risk of nephrotoxicity can be minimised if cyclosporin is used at the correct doses and if renal function is carefully monitored during treatment. In summary, cyclosporin can be considered a useful tool for treating patients with nephrotic syndrome associated with primary glomerulonephritis.
Treatment of membranous nephropathy Passerini, P; Ponticelli, C
Saudi journal of kidney diseases and transplantation,
2000 Jul-Sep, Letnik:
11, Številka:
3
Journal Article
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.
To assess the prognostic significance of complete remission in patients with idiopathic membranous nephropathy, 33 patients were followed for a median of 96 months after remission of proteinuria. All ...patients had had a histological diagnosis of membranous nephropathy and a nephrotic syndrome. Only patients with a complete remission lasting for at least six months and with a follow-up of at least four years after remission were considered. No relapse of proteinuria developed in 17 patients (51%), 7 patients had relapse of non-nephrotic proteinuria (21%) and 9 (27%) relapse of nephrotic proteinuria. However proteinuria disappeared again in some patients so that at follow-up 73% of patients are in complete remission, 21% have non-nephrotic proteinuria and only 6% have nephrotic syndrome. All patients maintained a normal plasma creatinine over the years. It is concluded that complete remission of proteinuria is a strong predictor of long-term favourable outcome in patients with idiopathic membranous nephropathy.
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