title: A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis.
abstract: The kidney is involved in 70% of patients with immunoglobulin light-chain (AL) amyloidosis, but little is known on progression or reversibility of renal involvement, and criteria for renal response have never been validated. Newly diagnosed patients from the Pavia (n = 461, testing cohort) and Heidelberg (n = 271, validation cohort) centers were included. Proteinuria >5 g/24 h and estimated glomerular filtration rate (eGFR) <50 mL/min predicted progression to dialysis best. Proteinuria below and eGFR above the thresholds indicated low risk (0 and 4% at 3 years in the testing and validation cohorts, respectively). High proteinuria and low eGFR indicated high risk (60% and 85% at 3 years). At 6 months, a ≥25% eGFR decrease predicted poor renal survival in both cohorts and was adopted as criterion for renal progression. A decrease in proteinuria by ≥30% or below 0.5 g/24 h without renal progression was the criterion for renal response, being associated with longer renal survival in the testing and validation populations. Hematologic very good partial or complete remission at 6 months improved renal outcome in both populations. We identified and validated a staging system for renal involvement and criteria for early assessment of renal response and progression in AL amyloidosis that should be used in clinical practice and trial design.
authors.affiliation: Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palladini
authors.affiliation: Amyloidosis Center, Division of Hematology, Oncology, and Rheumatology, Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; and.
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.affiliation: Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Milani
authors.affiliation: Amyloidosis Center, Division of Hematology, Oncology, and Rheumatology, Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kimmich
authors.affiliation: Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Foli
authors.affiliation: Amyloidosis Center, Division of Hematology, Oncology, and Rheumatology, Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; and.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy;
authors.forename: Marta
authors.initials: M
authors.lastname: Vidus Rosin
authors.affiliation: Clinical Chemistry Laboratory, and.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Albertini
authors.affiliation: Scientific Direction, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Remigio
authors.initials: R
authors.lastname: Moratti
authors.affiliation: Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy; Clinical Chemistry Laboratory, and.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.affiliation: Amyloidosis Center, Division of Hematology, Oncology, and Rheumatology, Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; and.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schönland
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000188:drug therapy* / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism*; D015331:Cohort Studies; D003956:Dialysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D000075363:Immunoglobulin Light-chain Amyloidosis; D007668:Kidney / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains