Adult-onset Nephrotic Syndrome Research Articles

Idiopathic membranous nephropathy: Definition and relevance of a partial remission

Membranous nephropathy (MGN) remains the most common cause of adult onset nephrotic syndrome, and within the primary glomerulonephritis group is a leading cause of renal failure. A complete remission (CR) confers an excellent long-term prognosis, but the quantitative benefits of partial remissions (PR) have not been defined. This study evaluated the rate of renal function decline (slope), relapse, and renal survival in nephrotic MGN patients with CR, PR, or no remission (NR). Multivariate analysis included clinical and laboratory data at presentation and over follow-up, blood pressure control and agents employed, and immunosuppressive therapy. The study cohort consisted of 348 nephrotic MGN patients with a minimum of 12 months follow-up identified from the Toronto Glomerulonephritis Registry. Over a median follow-up of 60 months, 102 experienced a CR, 136 had a PR, and 110 had no remission. A PR was independently predictive of slope and survival from renal failure by multivariate analysis (hazard ratio 0.08, 95% CI 0.03-0.19, P < 0.001). Benefit from immunosuppression could only be shown in a subset of high-risk patients. Treatment-related PR had the same long-term implication as spontaneous ones. Relapses from PR were high (47%) but often reversible. A partial remission is an important therapeutic target with implications for both progression rate and renal survival.

Hyperlipidemia and thrombotic complications in patients with membranous nephropathy

Membranous nephropathy (MN), the most common cause of adult-onset nephrotic syndrome (NS) in Caucasians, is associated commonly with the secondary complications of hyperlipidemia and hypercoagulability. These may increase the risk for cardiovascular disease, alter the rate of progression of renal disease, and raise the risk for thromboembolic events. The treatment of these secondary effects remains controversial. Although no clear practice guidelines are available to assist the clinician in deciding how and when to start disease-modifying therapies, the literature provides enough information to make reasonable decisions in most clinical scenarios. Prospective trials in the future will provide definitive information on how to best treat these abnormalities.

Cyclosporine in patients with steroid-resistant membranous nephropathy: A randomized trial

A clinical trial of cyclosporine in patients with steroid-resistant membranous nephropathy (MGN) was conducted. Although MGN remains the most common cause of adult-onset nephrotic syndrome, its management is still controversial. Cyclosporine has been shown to be effective in cases of progressive MGN, but it has not been used in controlled studies at an early stage of the disease. We conducted a randomized trial in 51 biopsy-proven idiopathic MGN patients with nephrotic-range proteinuria comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone. All patients were followed for an average of 78 weeks, and the short- and long-term effects on renal function were assessed. Seventy-five percent of the treatment group versus 22% of the control group (P < 0.001) had a partial or complete remission of their proteinuria by 26 weeks. Relapse occurred in 43% (N = 9) of the cyclosporine remission group and 40% (N = 2) of the placebo group by week 52. The fraction of the total population in remission then remained almost unchanged and significant different between the groups until the end of the study (cyclosporine 39%, placebo 13%, P = 0.007). Renal function was unchanged and equal in the two groups over the test medication period. In the subsequent follow-up, renal insufficiency, defined as doubling of baseline creatinine, was seen in two patients in each group, but remained equal and stable in all of the other patients. This study suggests that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of MGN. Although a high relapse does occur, 39% of the treated patients remained in remission and were subnephrotic for at least one-year post-treatment, with no adverse effect on filtration function.

Cytotoxics, cyclosporine and membranous nephropathy.

Membranous nephropathy remains the most common underlying cause of adult-onset nephrotic syndrome. Most patients with the idiopathic variant do well, with 10-year renal survival in a quite tight range of 70-90%. This indolence in the disease process and the spontaneous remission rate of 15-30% are the major factors that have prevented a uniform opinion from developing regarding therapy. The best long-term results come from the studies of an Italian group which used a regimen of chlorambucil and prednisone. Their most recent publication showed an impressive improvement in renal survival at 10 years from 62% in their untreated group to 90% in their treated group. The perceived risk: benefit ratio in the asymptomatic patient, however, has prevented the application of this approach to the average patient with idiopathic membranous nephropathy. The only randomized controlled study to use pulsed cyclophosphamide plus prednisone showed no benefit compared with the use of steroids alone. In contrast to the best cytotoxic trials, the application of cyclosporine treatment has been largely limited to patients at high risk of progression. Cyclosporine's efficacy in the short term is unquestioned, and a recent randomized controlled trial suggests an improved long-term preservation of renal function. Its costs, risks and long-term benefits require continuing assessment.

NIH conference. Membranous nephropathy.

Membranous nephropathy is a worldwide problem that accounts for about 20% of the cases of the adult-onset nephrotic syndrome. This disease places many patients at risk for both end-stage renal failure and the complications of hyperlipidemia. Immune-mediated injury to the glomerular capillary wall in patients with membranous nephropathy is characterized by subepithelial immune complex formation and generation of the membrane attack complex of complement. Glomerular capillary hypertension, hyperlipidemia, and possibly cytokines could contribute to the glomerular sclerosis seen in the advanced stages of the disorder. In some cases, production of pathogenic antibody can be suppressed by treating the underlying condition. The mechanisms of action of immunosuppressive agents are being investigated and treatments are being tested in clinical trials to optimize the balance of efficacy and toxicity. Alternate-day treatment with corticosteroids is often recommended for nephrotic patients with idiopathic membranous nephropathy, but this approach has not been proved beneficial. Ongoing studies are evaluating whether cytotoxic drugs or cyclosporin A combined with prednisone is more effective than treatment with corticosteroids alone. Lipid-lowering drug therapy is warranted in cases of the persistent nephrotic syndrome to avert the cardiovascular sequelae of hyperlipidemia.

Association of HLA-DRw8 and DQw3 with minimal change nephrotic syndrome in Japanese adults

The HLA systems of forty Japanese patients with adult-onset nephrotic syndrome and biopsy-proven minimal change were investigated. HLA-DRw8 was found in 35% of the patients and HLA-DQw3 in 95%, compared to 12.6 and 63.1% of the control, respectively (DRw8: and Pc less than 0.01, RR = 3.74; DQw3: Pc less than 0.02, RR = 11.1). The phenotype frequencies of all but one HLA-DR antigens, DR4, DR5, DRw8, and DRw9 associating with DQw3, were observed to increase (patient vs. control: DR4, 65 vs. 41.4%; DR5, 10 vs. 4.3%; DRw9, 20 vs. 23%). These results suggest that HLA-DQw3 may be a primary genetic marker associated with a major susceptibility gene to adult-onset minimal change nephrotic syndrome in the Japanese population.

Spontaneous remission of nephrotic syndrome in IgA glomerular disease.

We report two cases of adult onset nephrotic syndrome with pathologic features of minimal change disease but a predominance of IgA in mesangial regions. Both cases underwent spontaneous remission despite an episode of recurrent nephrotic syndrome in one patient. The relationship of the glomerular disease to minimal change and IgA nephritis is discussed.