Using digital whole-slide images to evaluate renal amyloid deposition and its association with clinical features and outcomes of AL amyloidosis

Abstract

Background

Few data are available quantifying the proportion of amyloid deposition in renal biopsy specimens. The aim of the study is to investigate the correlation between the proportion of amyloid deposition in renal biopsy and clinical characteristics of Chinese patients with immunoglobulin light-chain amyloidosis (AL amyloidosis).

Methods

259 patients diagnosed with renal AL amyloidosis between 2003 and 2015 were studied retrospectively. We developed a digital, automated quantification method to evaluate amyloid deposits in glomeruli, vessels and interstitium on digital whole-slide images (WSIs). The associations between the proportion of amyloid-positive area in the renal biopsy and clinical manifestations were analyzed.

Results

The proportion (%) of amyloid-positive area in glomeruli, vessels, interstitium and the whole renal tissue were 11.81 ± 11.38, 14.14 ± 14.05, 3.34 ± 5.36 and 4.25 ± 5.77, respectively. The proportion of amyloid deposition in glomeruli, vessels and interstitium was positively correlated with serum creatinine (Scr), estimated glomerular filtration rate (eGFR) and urinary retinol binding protein (RBP). The proportion of glomerular amyloid deposition, age, urinary N-acetyl-b-D-glucosaminidase (NAG) and urinary RBP could independently predict the risk for overall death. The proportion (%) of amyloid-positive area in blood vessels, interstitium and the whole renal tissue, Scr, and urinary RBP were independent risk factors associated with renal survival.

Conclusion

A novel digital analysis algorithm was firstly developed to quantify the proportion of amyloid deposits in renal tissues based on digital WSIs. The degree and localization of amyloid deposits in the kidney evaluated by digital WSIs may have predictive value in assessing risk of outcome of AL amyloidosis.

Graphical abstract

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Funding

This research was funded by National Key Research and Development Program of China (2016YFC0901202), National Natural Science Foundation of China (81570644), and Project of Invigorating Health Care through Science, Technology and Education of Jiangsu Province Medical key Talent(ZDRCA2016098).

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Contributions

Research idea and study design: YF, DL, CZ; data acquisition: YF, DL; data analysis and interpretation: YF, DL, HR, FY, FX; statistical analysis: YF, DL, HR; supervision or mentorship: CZ, DL, FX, YX, SL, FY, XZ, MZ, XH. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Caihong Zeng.

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The authors declare that they have no other relevant financial interests.

Ethics Approval

This study was approved by the local Ethics Committee (2019NZKYKS-010-01) and was performed according to the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee.

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Fan, Y., Liang, D., Rui, H. et al. Using digital whole-slide images to evaluate renal amyloid deposition and its association with clinical features and outcomes of AL amyloidosis. J Nephrol (2021). https://doi.org/10.1007/s40620-020-00948-1

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Keywords

  • AL amyloidosis
  • Amyloid-positive area
  • Digital whole-slide images
  • Prognosis