Renal amyloidosis: validation of a proposed histological scoring system in an independent cohort

Abstract

Background In systemic amyloidosis, the kidney is frequently affected and renal involvement has a major impact on survival. Renal involvement is clinically characterized by decreased estimated glomerular filtration rate (eGFR) and proteinuria. The two most common renal amyloidosis types are light chain-related amyloidosis (AL) and serum amyloid A (AA) amyloidosis. Standardized histopathological scoring of amyloid deposits is crucial to assess disease progression. Therefore, we aimed to validate the proposed scoring system from Rubinstein et al. (Novel pathologic scoring tools predict end-stage kidney disease in light chain (AL) amyloidosis. Amyloid 2017; 24: 205–211) in an independent patient cohort. Methods We attempt to reproduce the scoring system, consisting of an amyloid score (AS) and a composite scarring injury score (CSIS), in a multicentre AL and AA case series. Additionally, we analysed all renal amyloidosis kidney biopsies performed in the Netherlands between 1993 and 2012. Results Similar to the original study, AS and CSIS correlated to eGFR (r = −0.45, P = 0.0061 and r = −0.60, P < 0.0001, respectively) but not to proteinuria at diagnosis. Furthermore, AS, but not CSIS, was associated with renal outcome. The scoring system was not reproducible in AA patients. The median incidence rate for renal amyloidosis in the Netherlands was 2.3 per million population per year, and increased during the study period. Conclusions In our AL case series and the original study, AS and CSIS were correlated to eGFR but not to proteinuria, and AS correlated with renal outcome. Overall, we regard this scoring system as competent for standardized histopathological assessment of amyloid deposits burden and thereby disease advancement in renal biopsies.

Spatial resolution of renal amyloid deposits through MALDI-MSI: a combined digital and molecular approach to monoclonal gammopathies

“…For all cases, a composite scarring injury score (CSIS) was calculated jointly by two experienced renal pathologists (VL’I and FP) based on the percentage of globally sclerosed (GS) glomeruli and interstitial fibrosis and tubular atrophy (IFTA). In amyloidosis cases, this score was complemented by a previously proposed and validated system consisting in the quantification and localisation of the deposits, the amyloid score (AS) 15 16. Clinical data (sex, age, serum creatinine at diagnosis, proteinuria and serum/urine monoclonal component M-pike) were also collected.…”

Amyloidosis: What does pathology offer? The evolving field of tissue biopsy

“…In 2017 Rubinstein et al ( 56 ) proposed another score, validated in an AL cohort including glomerular, interstitial and vascular deposits, which was found to be predictive of end stage renal disease. More recently this score was also validated in an AA cohort ( 57 ).…”

Clinical Correlation of Histopathological Classification, Scoring, and Grading in Amyloid Nephropathies: Single-Center Experience

“…It can result in renal disease in final stages if neglected. 7 According to a recent study, the dialysis reliance after the diagnosis and median patient survival for AL were 36.3 months and 50 months, respectively, those were 52.9 months and 18 months for AA. 7 AA and AL types of renal amyloidosis can be defined immunohistochemistry (IHC) and immunofluorescence (IF) examinations.…”

“…7 According to a recent study, the dialysis reliance after the diagnosis and median patient survival for AL were 36.3 months and 50 months, respectively, those were 52.9 months and 18 months for AA. 7 AA and AL types of renal amyloidosis can be defined immunohistochemistry (IHC) and immunofluorescence (IF) examinations. 8 IF is used to show the clonality of light chains for primary amyloidosis and IHC is used to determine the acute phase reactants secondary amyloidosis, typically serum amyloid A (SAA).…”