Which is the most Powerful Proteinuric Marker in GN and NS for Outcome Prediction, Correlation with Functional and Histologic Parameters and Assessment of Responsiveness to Steroids and Cyclophosphamide?

Abstract

Background: In glomerulonephritis (GN) with nephrotic syndrome (NS), proteinuric and novel molecular biomarkers do not achieve 100% accuracy in predicting outcome and treatment responsiveness. Aim of study: To verify whether the combined excretion of IgG/C and α2m/C, markers of damage to the epithelial cell layer (podocytes and slit diaphragm) of the glomerular filtration barrier (GFB) can assess disease severity, and predict outcome and responsiveness to steroids and cyclophosphamide. Methods: In 151 patients with glomerulonephritis and nephrotic syndrome a new proteinuric marker was developed based on a combination of different median values of urinary excretion of IgG/C and α2m/C: IgG/C < or > than the median was classified as IgG/C0 or IgG/C1, respectively. The median of α2m/C was calculated independently in IgG/C0 and IgG1, and classified as α2m/C0 and α2m/C1 if < or > than the median. Thus 4 groups were defined: IgG/C0 & α2m/C0, IgG/C0 & a2m/C1, IgG/C1 & α2m/C0, IgG/C1 & α2m/C1. Results: The groups from 1+1 to 0+0 are characterized by increasingly severe disease, with progressively higher eGFR and progressively lower histologic (GGS%, TID and AH scores) and proteinuric parameters (TUP/C, IgG/C, α2m/C and α1m/C). In 151 patients the functional outcomes rates were: IgG/C1&α2m/C1&BP 1: “Remission and persistent NRF”, 15%; “Progression and eGFR reduction”, 85%. In IgG/C0&α2m/C0&BP 0: “Remission and persistent NRF”, 96%; “Progression and eGFR reduction”, 4%. In 84 patients treated with steroids + cyclophosphamide: IgG/C1&α2m/C 1&BP 1: “Progression and eGFR reduction”, 100%: “Remission and persistent NRF”, 0%; IgG/C0&α2m/C0& BP 0: “Remission and persistent NRF”, 100%; “Progression and eGFR reduction”, 0%. Conclusions: Combined urinary excretion of IgG/C and α2m/C in association with blood pressure offers 100% prediction of outcome and responsiveness to steroid and cyclophosphamide treatment