Effectiveness of steroid therapy in different stages of membranous nephropathy

The published studies on histological staging and response to steroid therapy of membranous glomerulonephritis are not consistent. We analysed data from 25 adult patients with stage I (group 1, n = 7) and stage II (group 2, n = 18) disease. The interval between clinical onset and admission was similar in the two groups. At admission all patients had normal creatinine clearance; proteinuria averaged 5.4 +/- 4.0 in group 1 and 9.0 +/- 4.0 in group 2 (g/day per 100 ml GFR). All patients received 6 months steroid therapy (months 1-2, 1 mg/kg b.w. per day; month 3-5: 0.65 mg/kg b.w. e.o.d.; month 6, tapering). After this cycle of steroid therapy, proteinuria declined by 84% in group 1 (five patients being in partial remission, i.e. 0.4-2 g/day, and two patients in complete remission, i.e. less than or equal to 0.3 g/day) and by 47% in group 2 (two patients being in complete remission and six in partial remission). Only 1 patient in group 1 relapsed with nephrotic proteinuria after 36 months, and renal function was still normal in all patients at the most recent follow-up (59 +/- 32 months). In contrast, 14 patients in group 2 had nephrotic syndrome and seven renal insufficiency at the most recent follow-up. We conclude that short-term steroid therapy is effective only in patients with early membranous changes.     

Nonimmunosuppressive therapy of membranous nephropathy

Idiopathic membranous nephropathy (MN) has a variable rate of progression to end-stage renal failure, with a significant number of patients going into spontaneous remission without therapy. For those who have persistent nephrotic proteinuria or manifest deterioration of renal function, steroids and immunosuppressive drugs are used. However, their long-term efficacy is challenged by a meta-analysis presented here. A different approach to reduction of proteinuria, a recognized progression promoter, is based on the notion that angiotensin II inhibition controls proteinuria and slows progression. Further, a more complex approach is required than simple administration of an angiotensin-converting enzyme (ACE) inhibitor: a multidrug approach to remission of nephrotic syndrome therefore is described here.     

Mycophenolate therapy of SLE membranous nephropathy

BACKGROUND: The immunosuppressant mycophenolic acid (MMF) has been used successfully to manage proliferative forms of systemic lupus erythematosus (SLE) glomerulonephritis (GN) World Health Organization (WHO) Classes III and IV. Less is known about MMF treatment of membranous SLE GN (WHO Class V, SLE MN). METHODS: We report our experience with MMF therapy in 13 consecutive SLE MN patients participating in a prospective study of risk factors for SLE flare. RESULTS: Baseline characteristics were: mean age 33 +/- 14 SD years, female/male ratio 11/2, Caucasians 7, African Americans 5, Oriental 1, serum creatinine 1.02 +/- 0.41, and mean 24-hour urine protein (P)/creatinine (C), ratio 5.1 +/- 4.1. Initial therapy was prednisone mean dose 31 +/- 17 mg/day, and MMF mean dose 1173 +/- 746 mg/day. Therapy also featured interventions to achieve renoprotection and proteinuria reduction. At 6 months of therapy, complete or partial remission was achieved in 10 of 13 patients. At most recent follow-up visit (mean follow-up 16 +/- 8 months), 9 of 13 patients were in complete remission, and in 11 of 13 patients, urine P/C ratio was < 0.8. During follow-up, serum creatinine either stabilized or was improved. The only serious complication during 208 patient months of follow-up was histoplasma pneumonia in 1 patient. CONCLUSION: These promising results suggest that moderate dose MMF in combination with renoprotective/antiproteinuria therapy warrants further study in the management of SLE MN.     

Mycophenolate mofetil and cyclosporine therapy in membranous nephropathy

Idiopathic membranous nephropathy (IMN) remains one of the most common causes of the nephrotic syndrome (NS) in adults. Although the natural history is extremely variable, approximately two thirds of the patients will have persistent high-grade proteinuria and/or develop renal failure over a decade of observation. On the other hand, the remaining third of patients will remit spontaneously and potentially toxic therapy should be avoided in this group. Our capacity to predict which patient will progress at an early stage of the disease has improved substantially in the past 10 years. We present the data from studies of cyclosporine (CSA) and mycophenolate mofetil (MMF) treatment of IMN with their level of evidence in support of efficacy. In addition, based on data related to predicting prognosis, we assign a risk for progression category to the trial patients at entry into these studies. The data are presented in this format so the reader will be able to better discern the risk benefit of treatment within each category and the rationale for our subsequent grade of recommendation for the use of these agents in IMN. CSA has been shown in randomized controlled trials in both the medium and high risk of progression categories of IMN patients to improve proteinuria and preserve renal function at least in the short term in up to two thirds of patients. Other studies suggest prolonged therapy beyond 6 months to 1 year may reduce the high relapse rate after CSA treatment supporting more long-term, continuous, or combination therapy in IMN treatment. The data in favor of MMF treatment of this disease is much weaker and are derived from pilot studies. Only one report applied MMF specifically to IMN patients. In these medium to high risk of progression patients, approximately one-half had a 50% reduction in their baseline proteinuria without a significant alteration in their serum creatinine level. MMF's role as a single agent or as adjunctive therapy in the treatment of IMN needs more rigorous evaluation.     

Relationship between interstitial infiltrates and steroid responsiveness of proteinuria in membranous nephropathy

Mononuclear inflammatory cells were retrospectively analysedusing monoclonal antibodies in the interstitium and glomeruliof 16 renal biopsy specimens from patients with nephrotic syndromedue to idio-pathic membranous nephropathy (IMN). The aim ofthe study was to determine the composition of the infiltrateand to assess the ability to predict the response of proteinuriato corticosteroids. All patients had received prednisolone asa sole treatment. Nine patients had shown a complete or partialremission of proteinuria (group A) and seven did not respondat all (group B). Both groups were matched for age and degreeof proteinuria; also both groups had normal renal function atthe time of biopsy. Very few intraglomerular leukocytes, mostlymonocytes/ macrophages (MM) were found. The majority of interstitialcells were T lymphocytes and MM. CD4+ve T helper/inducer cellspredominated among the interstitial T cell population and Bcells were a minor component. No significant differences werefound between the two groups regarding the types of the intraglomerularcells. However, interstitial T-cells, CD4 + ve T helper/inducercells, CD8+ve T cytotoxic/suppressor cells and MM were significantlyhigher in group A than in group B. Also HLA-DR expressing interstitialcells were much in excess in group A. In addition patients with complete remission of proteinuriahad higher numbers of interstitial cells compared to those withpartial response. There was no correlation between the numbersof types of intraglomerular and interstitial cells and the degreeof proteinuria at presentation. Also no association was foundbetween intraglomerular or interstitial cell population andsubsequent relapse of proteinuria. In conclusion, interstitial but not intraglomerular mononuclearcells seem to determine the initial response of proteinuriato corticosteroids in patients with IMN.     

Effect of mizoribine pulse therapy in adult membranous nephropathy

International Urology and Nephrology - Membraneous nephropathy (MN) is one of the complicated kidney diseases associated with proteinuria. Mizoribine (MZR) is an emerging treatment option for...     

Long-term outcomes of initial therapy for idiopathic membranous nephropathy

Background

The objective of this study is to determine whether initial steroid therapy is actually effective for the treatment of iMN, and we examined a 40% reduction in estimated glomerular filtration rate (eGFR) and remission rates.

Methods

This was a retrospective study between 1993 and 2013. First, we divided patients with iMN having a urinary protein level of ≥1 g/gCre into two groups: those who had received steroid therapy (Group S₁; n = 52) within 6 months of diagnosis and those who had received supportive therapy (Group H₁; n = 31). Second, we compared 20 cases using propensity score matching (Group S₂, Group H₂). Third, we compared patients with a urinary protein level of 1–3.5 g/gCre (Group S₃, n = 18; Group H₃, n = 19) and those with a urinary protein level ≥3.5 g/gCre (Group S₄, n = 34; Group H₄, n = 12). The primary endpoint was a 40% reduction in eGFR, and the secondary endpoint was the achievement of complete remission (CR).

Results

In Group S₁ and Group H₁, a 40% reduction in the eGFR was observed at the end of 5 years in 18 and 17% of the patients, respectively (P = 0.93); at the end of 10 years, these rates had increased to 43% and 50%, respectively (P = 0.88). The CR rates at the end of 5 years were 58% and 32%, respectively (P = 0.02), while the rates at 10 years were 65 and 39%, respectively (P = 0.02). No difference in renal outcomes was observed between Group S₁ and Group H₁. No significant differences were observed between Group S₂ and Group H₂, between Group S₃ and Group H₃, or between Group S₄ and Group H₄.

Conclusion

Initial steroid therapy is not superior to supportive care within the first 6 months after diagnosis in terms of a 40% reduction in eGFR.

     

Segmental membranous nephropathy

Clinical and Experimental Nephrology - Most cases of membranous nephropathy (MGN) present with global and diffuse distribution of subepithelial deposits. However, segmental MGN, in which there is...     

Corticosteroids,cyclophosphamide, and chlorambucil therapy of membranous nephropathy

Corticosteroids and cytotoxic agents have been studied widely in membranous nephropathy (MN). However, controlled studies with corticosteroids have not shown a clear benefit of these agents on the outcome of the disease. Some controlled trials reported that cytotoxic agents can reduce proteinuria significantly, but it was difficult to assess the efficacy of these drugs in protecting renal function because of the short follow-up period of the studies. Three randomized controlled trials showed that a 6-month treatment regimen based on corticosteroids and a cytotoxic agent, giving each for 1 month at a time in an alternating schedule, could favor remission of the nephrotic syndrome and protect renal function. Taken together, the results of these trials at the end of the follow-up period, 74% of the 174 treated patients were without nephrotic syndrome, 4 patients were on chronic dialysis, and 2 patients died. Good results with cytotoxic drugs, often associated with corticosteroids, also have been reported in progressive membranous nephropathy. However, in patients with renal insufficiency side effects were frequent and severe. Moreover, in most cases renal function improved but did not return to normal.     

Management of membranous nephropathy

SUMMARY: The Management of membranous nephropathy requires a recognition of its natural history and an ability to predict those pationts with the worst prognosis. Treatment of those at risk of progression with immunosuppressive drugs should be accompanied by additional conservative risk reduction strategies such as dietary protein restriction, blood pressure reduction, angiotensin-converting enzyme inhibitors and lipid-lowering agents. Anticoagulants should also be considered as well as medications to reduce drug toxicity.     

Combined membranous nephropathy and IgA nephropathy

IgA nephropathy (IgAN) and membranous nephropathy (MN) are both common renal biopsy findings that rarely have been described together in the same patient. The significance of this finding is not clear. We present the clinical and pathological data of four patients with combined MN-IgAN and discuss possible pathogenetic mechanisms. By definition, all cases showed immunodominant mesangial deposits of IgA (+/-C3) and subepithelial capillary wall deposits of IgG (+/-C3) by immunofluorescence microscopy, confirmed by electron microscopy. There were three men and one woman, whose ages ranged from 41 to 67 years (average, 51.7 years). All four presented with microscopic hematuria and proteinuria, three in the nephrotic range. Renal function was normal in three individuals, and one subject had mild renal insufficiency accompanied by long-standing hypertension. Two other patients had newly uncovered hypertension. Complement levels were normal in all subjects. One patient had a positive antinuclear antibody (ANA) test, but none had other serologic or clinical features diagnostic of lupus. None of the four individuals had any other predisposing factors for either MN or IgAN, including hepatitis B infection. All four patients had stable renal function at last determination (average follow-up, 24 months; range, 4 to 34 months), with markedly reduced proteinuria in three individuals and persistent heavy proteinuria in one. A review of the literature indicates that combined MN-IgAN is most often characterized by heavy proteinuria and stable renal function. Some cases may be related to hepatitis B infection, but in most instances the cause is unknown. The combination of these two pathological processes does not result in a particularly deleterious clinical outcome for patients.