Abstract
AimsDiagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment.Methods and resultsHistological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re‐evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow‐up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow‐up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation.ConclusionsThe presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long‐term follow‐up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.
Highlights
Primary membranous nephropathy (PMN) remains the most common cause of nephrotic syndrome in white adults, representing 20–30% of cases in 50– 60-year-old patients, rising to 40% in ages greater than 60 years.[1–3]Diagnosis of MN is based on optical microscopy and immunohistochemistry and/or immunofluoresence findings, showing thickening of glomerular basement membrane with or without spikes and granular deposition of immunoglobulin (Ig)G and C3 along the glomerular capillary walls
Multiple regression analysis was performed to assess independent factors associated by renal function outcome, defined by eGFR, slope-eGFR and response to treatment, and binary logistic regression was used when outcome was defined by the 50% reduction in eGFR
We evaluated the impact of focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH) in the response to immunosuppression
Summary
Primary membranous nephropathy (PMN) remains the most common cause of nephrotic syndrome in white adults, representing 20–30% of cases in 50– 60-year-old patients, rising to 40% in ages greater than 60 years.[1–3]. Diagnosis of MN is based on optical microscopy and immunohistochemistry and/or immunofluoresence findings, showing thickening of glomerular basement membrane with or without spikes and granular deposition of immunoglobulin (Ig)G and C3 along the glomerular capillary walls. Classification of the disease on a scale of 0–IV, based on electron microscopy findings, was an attempt to estimate disease severity and categorise patients according to renal lesions, it has not always been proved to be of clinical significance.[14]. There is a need to evaluate optical microscopy and define specific features which can be assessed in clinical everyday practice, and have the capacity to estimate severity of the disease and guide treatment. We defined specific histological findings which, in combination with clinical symptoms at presentation, may identify the profile of patients who are likely to benefit from immunosuppressive treatment
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