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

Abstract

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.

Prophylactic Anticoagulation in Nephrotic Syndrome

“…A survey of all such trials reported between 1979 and 2001 revealed an extraordinarily low rate of thromboembolism (one case in Ͼ500 randomly assigned patients who were followed for Ͼ2000 patient-years). [23][24][25][26][27][28][29] Subtle selection forces operating at the enrollment level may have contributed to this finding. Natural history studies of untreated patients have also noted a low prevalence of thromboembolism in membranous nephropathy.…”

“…A possible argument against "routine" prophylactic anticoagulants in idiopathic membranous nephropathy is that none of the randomized therapeutic trials in membranous nephropathy reported between 1979 and 2001 required that enrolled patients be routinely treated with prophylactic anticoagulants. [23][24][25][26][27][28][29] Because ethical considerations demand that participants in such trials receive standard of care, one would have to conclude that prophylactic anticoagulation of patients with membranous nephropathy (and by inference other patients with nephrotic syndrome) has not yet reached a uniform level of standard of care.…”

Have We Changed the Outcome in Membranous Nephropathy? A Propensity Study on the Role of Immunosuppressive Therapy

“…The design and conduct of therapeutic studies for treatment of MGN remains a challenge because of its relatively slow evolution and highly variable natural history. Long-term follow-up publications of randomized controlled trials (RCTs) on cytotoxic therapy have demonstrated a reduction of ESRD in some (4,5) but not all studies (6). The effect of calcineurin inhibitors on remission of proteinuria is clear, but their effect on renal survival is uncertain (7).…”

Balancing Cancer Risk and Efficacy of Using Cyclophosphamide to Treat Idiopathic Membranous Nephropathy

“…Following this, a variety of immunosuppressive strategies have been explored in IMN patients with underlying renal insufficiency at high risk of progression to ESRD. Two large controlled trials demonstrated improved renal survival with alkylating agents in combination with steroids (10,11). Additionally, cohort studies confirmed the benefits of cytotoxic therapies, with cyclophosphamide being the preferred agent (12)(13)(14).…”