From KDIGO 2012 towards KDIGO 2021 in idiopathic membranous nephropathy guidelines: what has changed over the last 10 years?

Abstract

The recommendations in the Kidney Disease: Improving Global Outcomes (KDIGO) 2021 guidelines regarding Idiopathic Membranous Nephropathy (IMN) management include significant changes as compared to those published in 2012. According to the recent guidelines, a biopsy is not always needed for IMN diagnosis; since diagnosis can be allowed for by the detection of circulating antibodies against the M-type transmembrane phospholipase A2 receptor (anti-PLA2R). Moreover, alterations in anti-PLA2R concentrations, along with other serum and urinary markers, may guide further follow-up. The findings of numerous recent studies which compared different immunosuppressive treatments resulted in substantial changes in treatment indications in the KDIGO 2021 guidelines, suggesting the stratification of patients into four risk categories. The definition of resistant cases and relapses was likewise modified. All the above will lead to a more granular and personalized approach, whose results need to be tested over time. In this commentary, we discuss the changes in the 2012 and 2021 guidelines, adding information from the most recent literature. Graphical abstract

Is There a Place for Apheresis in the Management of Idiopathic Membranous Nephropathy? A Report of Three Cases and Literature Review

“…As per the 2021 recommendations from KDIGO, rituximab (RTX) is advised as the initial treatment for moderate-risk patients with a normal eGFR and significant proteinuria (exceeding 3.5 g/day). For high-risk patients characterized by a decreased eGFR, cyclophosphamide is recommended as the first-line treatment [ 7 , 17 ].…”

“…The most prevalent among these is the antibody directed against the M-type phospholipase A2 receptor (PLA2R), identified in 75 to 85% of patients with primary membranous nephropathy [ 5 , 6 ]. Recent discoveries include other target molecules, such as thrombospondin-type-1-domain-containing 7A (THSD7A), neural epidermal growth factor type 1 protein (NELL-1), semaphorin 3B (SEMA3B), superoxide dismutase 2 (SOD2), and aldose reductase (AR) [ 7 ].…”

“…[ 8 , 9 ]. The recognition of the autoimmune nature of membranous nephropathy has prompted the adoption of anti-CD20-based therapies, e.g., rituximab, which are characterized by their lower toxicity and greater specificity when compared to alkylating agents and calcineurin inhibitors [ 7 ].…”

Evaluating Efficacy and Safety of Tacrolimus Treatment in Membranous Nephropathy: Results of a Retrospective Study of 182 Patients

“… 17 The 2012 KDIGO Clinical Practice Guideline for Glomerulonephritis recommends rituximab or cyclophosphamide and alternate month glucocorticoids for 6 months, or CNI-based therapy for ≥6 months for patients with MN and at least one risk factor for disease progression. 18 One clinical study showed that CNIs increased the likelihood of partial or complete remission of proteinuria compared with no treatment (72–75% vs 22%) and that the remission rate at 12 months of treatment was comparable to and numerically higher than that of cyclophosphamide (71–89% for CNIs; 65–77% for cyclophosphamide). 19 In a retrospective study, tacrolimus induced remission of membranous nephropathy in 84% of patients.…”