Treatment of Membranous Nephropathy

Initial Management

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend that all patients with primary membranous nephropathy and proteinuria receive optimal supportive care, including RAS blockade, statin therapy, diuretics, and anticoagulation assessment based on albumin levels and thromboembolism risk 1, 2, 3
The American College of Physicians recommends targeting blood pressure <130/80 mmHg using RAS blockade (ACE inhibitors or ARBs) 1, 4
The National Kidney Foundation recommends statin therapy for dyslipidemia management and diuretics for edema control 5

The KDIGO guidelines recommend that immunosuppressive therapy is not required for low-risk patients with proteinuria <3.5 g/day, serum albumin >30 g/L, and eGFR >60 mL/min per 1.73 m² 1, 2, 3
The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) recommends that immunosuppressive therapy should be initiated when any of the following risk factors are present: proteinuria ≥3.5 g/day with serum albumin ≤30 g/L, eGFR ≤60 mL/min per 1.73 m², or serious nephrotic syndrome complications (AKI, infections, thromboembolic events) 1, 2, 3

The KDIGO guidelines recommend three equivalent first-line options for patients requiring immunosuppression: rituximab, cyclophosphamide + alternating glucocorticoids, and tacrolimus-based therapy (Grade 1B) 1, 2, 3
The American Society of Nephrology recommends rituximab as first-line therapy with equivalent efficacy to cyclophosphamide-based regimens and superior safety profile 4
The European Society of Nephrology recommends cyclophosphamide + glucocorticoids for high-risk patients with rapidly declining eGFR or very high-risk disease (proteinuria >8 g/day with declining function) 1, 2, 6

The KDIGO guidelines recommend that the initial therapy can be repeated, or switch to rituximab if initially treated with CNIs or cyclophosphamide, for initial relapse after successful treatment 1, 2, 3, 6
The American College of Physicians recommends verifying true resistance to treatment by checking compliance, monitoring drug efficacy markers, and considering repeat biopsy if proteinuria persists despite normalized albumin or loss of anti-PLA2R antibodies 1, 2, 3, 6

The KDIGO guidelines recommend longitudinal monitoring of anti-PLA2R antibody levels for treatment response evaluation and therapy adjustments 1, 2, 3
The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) recommends using anti-PLA2R antibody levels to predict remission, relapse, and treatment response 1, 2, 6

The KDIGO guidelines recommend referring all cases of membranous nephropathy in children to expert centers 1, 2, 3
The American Society of Nephrology recommends monitoring anti-PLA2R antibody levels every 1-3 months post-transplant in kidney transplant recipients with PLA2R-associated disease 2, 4

The Kidney International guideline recommends assessing anticoagulation needs, strongly considering prophylactic anticoagulation when serum albumin is low due to high thromboembolism risk 7

The American Journal of Kidney Diseases guideline suggests that immunosuppressive therapy should be initiated only in patients with nephrotic syndrome who meet specific high-risk criteria after at least 6 months of conservative management 8, 9, 10, 11
The American Journal of Kidney Diseases guideline recommends starting immunosuppressive therapy when any of the following criteria are met: persistent severe proteinuria, declining kidney function, or severe nephrotic complications 8, 9, 10, 11

The American Journal of Kidney Diseases guideline suggests that three regimens are considered equivalent first-line options: rituximab, cyclophosphamide plus alternating corticosteroids, or tacrolimus-based therapy 8, 9, 10, 11
The Kidney International guideline recommends using calcineurin inhibitor (tacrolimus or cyclosporine) based therapy as initial treatment, with CNI blood levels monitored regularly during initial treatment and whenever unexplained rise in creatinine occurs 7

The Kidney International guideline recommends switching to a CNI-based regimen if resistant to alkylating agent/steroid-based therapy, and switching to alkylating agent/steroid-based therapy or rituximab if resistant to CNI-based therapy 7
The Kidney International guideline suggests reinstituting the same therapy that resulted in initial remission for relapse treatment, with a critical limitation of only repeating a 6-month cyclical corticosteroid/alkylating-agent regimen once for relapse treatment 7

The Kidney International guideline recommends following adult treatment recommendations for children, giving no more than one course of cyclical corticosteroid/alkylating-agent regimen, and referring all pediatric cases to expert centers 7