Prospective urinary albumin/creatinine ratio for diagnosis, staging, and organ response assessment in renal AL amyloidosis: results from a large cohort of patients.

Marco Basset,Riccardo Albertini,Catherine Klersy,Virginia Valeria Ferretti,Francesca Benigna,Tiziana Bosoni,Francesca Russo,Giampaolo Merlini,Jessica Ripepi,Martina Nanci,Giovanni Palladini,Mario Nuvolone,Andrea Foli,Margherita Bozzola,Melania Sesta,Paolo Milani

doi:10.1515/cclm-2021-0912

Abstract

Quantification of 24h-proteinuria is the gold standard for diagnosing, staging, and monitoring of patients with renal AL amyloidosis. However, 24h-urine collection is cumbersome and may result in preanalytical error. In this prospective study, we investigated the role of urinary albumin/creatinine ratio (UACR) (cut-off: 300mg/g) identifying renal involvement, evaluated a UACR-based staging system (UACR cut-off: 3,600mg/g) and assessed whether UACR response (UACR decrease >30% without worsening in eGFR >25%) predicts renal outcome in 531 patients with newly-diagnosed AL amyloidosis. From October 2013 paired 24h-proteinuria and UACR (on first morning void) were measured in all newly-diagnosed patients with AL amyloidosis. Correlation between 24h-proteinuria and UACR at baseline was assessed by Pearson's r test. Impact of UACR response on renal outcome was assessed in randomly created testing (n=354) and validation (n=177) cohorts. A strong linear correlation was found between 24h-proteinuria and UACR at baseline (r=0.90; p<0.001). After a median follow-up of 31months, 57 (11%) patients required dialysis. A UACR-based renal staging system identified three stages with significantly higher dialysis rate at 36months comparing stage I with stage II and stage II with stage III. Achieving a renal response, according to a UACR-based criterion, resulted in lower dialysis rate in both testing and validation cohorts. UACR is a reliable marker for diagnosis, prognosis, and organ response assessment in renal AL amyloidosis and can reliably replace 24h-proteinuria in clinical trials and individual patients' management.

Highlights

Immunoglobulin light chain (AL) amyloidosis, is caused by a misfolded monoclonal free light chain (FLC), that deposits as amyloid fibrils causing dysfunction and damage in target organs [1]
We investigated the role of urinary albumin/creatinine ratio (UACR) identifying renal involvement, evaluated a UACR-based staging system (UACR cut-off: 3,600 mg/g) and assessed whether UACR response (UACR decrease >30% without worsening in eGFR >25%) predicts renal outcome in 531 patients with newly-diagnosed AL amyloidosis
Concordance between UACR-based renal response and 24 hproteinuria-based renal response was 85%

Summary

Introduction

Immunoglobulin light chain (AL) amyloidosis, is caused by a misfolded monoclonal free light chain (FLC), that deposits as amyloid fibrils causing dysfunction and damage in target organs [1]. The use of this biomarker in AL amyloidosis was largely discussed and recently the Mayo Clinic group proposed UACR cut-offs for identification of renal involvement, prognostication of renal survival at diagnosis and definition of renal response [13] In this large study (575 patients included) UACR and 24 h-proteinuria samples were collected on the same day only in a half of cases and paired samples at diagnosis were available only in 155 patients (of whom 109 with renal involvement). We present a large prospective study on 531 patients with newlydiagnosed AL amyloidosis and paired 24 h-proteinuria and UACR (first morning void) samples at baseline and at response assessment in order to define and validate the possibility to replace the 24 h-urine collection with a simpler test in the diagnosis, staging, and response assessment of renal AL amyloidosis

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