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.

There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage (in terms of treatment tolerance, nutritional parameters and pre-treatment beta-microglobulin levels) over a traditional membrane (Cuprophan). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan hemodialysis (Cu-HD), low-flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 +/- 10.46 mg/liter (23%) and in hemodiafiltration of 6.35 +/- 12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes (P = 0.032). The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications.

We conducted a controlled trial to investigate the long-term effects of treatment with methylprednisolone and chlorambucil in patients with idiopathic membranous nephropathy. We have previously reported that after a mean of 31 months, treated patients did better. We now report the results of a longer follow-up. Eighty-one patients with proteinuria (greater than or equal to 3.5 g per day) and biopsy-proved membranous nephropathy were randomly assigned to receive either supportive therapy alone or a six-month course of corticosteroids alternated with chlorambucil (0.2 mg per kilogram of body weight per day) every other month. Methylprednisolone was first given intravenously in three pulses (1 g per day) and was then given orally (0.4 mg per kilogram per day) for 27 days. The patients were followed for 2 to 11 years (median, 5). Two patients in the control group and one in the treatment group died. At the last follow-up visit, 9 of 39 patients assigned to the control group (23 percent) and 28 of 42 patients assigned to the treatment group (67 percent) did not have the nephrotic syndrome. At five years there were more remissions of the nephrotic syndrome in treated patients than in controls (22 of 30 vs. 10 of 25; P = 0.026). Compared with base-line values, the mean reciprocal of the plasma creatinine level declined significantly in the control group (33 percent; P = 0.0002) but not in the treatment group (6 percent; P not significant). Plasma creatinine increased by 50 percent or more in 19 controls (49 percent) and in 4 treated patients (10 percent). We conclude that a six-month course of methylprednisolone and chlorambucil can bring about sustained remission of the nephrotic syndrome and help to preserve renal function in patients with idiopathic membranous nephropathy.

Sixty-seven adults with idiopathic membranous nephropathy and the nephrotic syndrome were randomly assigned to symptomatic treatment only or to a six-month course of methylprednisolone alternated with chlorambucil every other month. Patients were followed for one to seven years. At the end of follow-up (mean of 31.4 +/- 18.2 months for the treated group and 37.0 +/- 22.0 for the control group) 23 of 32 treated patients were in complete or partial remission, as compared with 9 of 30 control patients (P = 0.001). Twelve of the treated patients were in complete remission, as compared with only two of the controls. In the treated group there were no changes in renal function during follow-up, whereas in the control group the reciprocal of the plasma creatinin level, which is proportional to the creatinine clearance, decreased significantly (P = 0.00017) after two years of follow-up. Side effects were minimal in all treated patients except two, who were dropped from the study because of peptic ulcer and gastric intolerance to chlorambucil. We conclude that steroid and chlorambucil treatment for six months favors remission of the nephrotic syndrome in adults with idiopathic membranous nephropathy and can preserve renal function for at least some years.