We read with great interest the study by Prskalo et al. titled “Urinary CD4+ T Cells Predict Renal Relapse in ANCA-Associated Vasculitis” on the prospective investigation of the performance of urinary CD4+ T-cell count in predicting renal relapse in ANCA-associated vasculitis.1
While we recognize the need for noninvasive biomarkers to enhance the early detection of renal relapse in patients with ANCA-associated vasculitis, we respectfully question the authors' claim that CD4+ T-cell count exceeds the performance of existing standard-of-care biomarkers.
First, no statistical test to compare the area under the receiver operating characteristic curve of the different biomarkers (e.g., DeLong test2) is reported in the analyses, therefore hampering the claim of outperformance, which relies on the demonstration of statistically higher predictive performance.
Second, we suggest that the prediction of ANCA-associated vasculitis renal relapses might benefit more from a multivariable approach that integrates various biomarkers—such as ANCA titer, proteinuria or albuminuria, and hematuria—rather than relying on multiple univariable models. This approach would better reflect standard clinical practices and could potentially provide a clearer demonstration of the added value of the CD4+ T-cell count when included in such models. Similar to other investigations on the added value of biomarkers to standard of care,3,4 comparing the discriminative performances of two multivariable models, one with standard-of-care biomarkers, and another including standard-of-care biomarkers plus urinary CD4+ T-cell count, could provide a more convincing demonstration of the added value of CD4+ T-cell count, in our opinion.
Third, although the authors report a 96% negative predictive value for urinary CD4+ T-cell count in ruling out relapsing disease, further reporting of negative predictive value data for other biomarkers and a multivariable standard-of-care model would have been beneficial. Indeed, negative predictive values tend to rise in the setting of low prevalence of the event of interest.5 Given the low relapse rate of 9.8% observed in the PRE-FLARED study, this may have resulted in high negative predictive values for all tested biomarkers. Hence, presenting the negative predictive value of all the biomarkers studied could help better evaluate the added value of urinary CD4+ T-cell count as a tool to rule out relapsing disease.
Therefore, we encourage the authors to consider these perspectives, incorporating a multimodal definition of standard of care and providing a comparative analysis of models' performances to better appraise the added value of urinary CD4+ T-cell count in routine care for patients with ANCA-associated vasculitis.
Footnotes
See related reply, “Authors’ Reply: Utility of Urinary CD4+ T-Cell Count in Detecting ANCA-Associated Vasculitis Renal Relapse,” on page 1452, and original article, “Urinary CD4+ T Cells Predict Renal Relapse in ANCA-Associated Vasculitis,” in Vol. 35, Iss. 4, pages 483–494.
Disclosures
Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/E695.
Funding
None.
Author Contributions
Conceptualization: Romain Brousse.
Methodology: Romain Brousse.
Writing – original draft: Romain Brousse.
Writing – review & editing: Idris Boudhabhay, Romain Brousse, Jean Paul Duong Van Huyen, Alexandre Georges Karras.
References
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