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Urinary isomorphic red blood cells for the prediction of disease severity and renal outcomes in MPO-ANCA-associated vasculitis: a retrospective cohort study

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Abstract

Background

Hematuria is common in myeloperoxidase anti-neutrophil cytoplasmic antibody associated vasculitis (ANCA-MPO). Previous studies have mainly focused on urinary dysmorphic red blood cells and few have reported the clinical significance of isomorphic urinary red blood cells. Therefore, the main aim of this study was to assess the predictive yield  of urinary isomorphic red blood cells for disease severity and renal outcomes in patients with ANCA-MPO associated vasculitis.

Methods

A total of 191 patients with ANCA-MPO associated vasculitis with hematuria were retrospectively selected and were divided into two groups (with isomorphic red blood cells versus dysmorphic red blood cells) according to the percentage of isomorphic red blood cells on urinary sediment analysis. Clinical, biological and pathological data at diagnosis were compared. Patients were followed up for a median of 25 months and progression to end-stage kidney disease and death were regarded as main outcome events. Additionally, univariate and multivariate Cox regression models were used to estimate the risk factors for end-stage kidney disease.

Results

Out of 191 patients, 115 (60%) had ≥ 70% and 76 (40%) had < 30% urine isomorphic red blood cells. Compared with patients in the dysmorphic red blood cell group, patients in the isomorphic red blood cell group had a significantly lower estimated glomerular filtration rate (eGFR) [10.41 mL/min (IQR 5.84–17.06) versus 12.53 (6.81–29.26); P = 0.026], higher Birmingham Vasculitis Activity Score [16 (IQR 12–18) versus 14 (10–18); P = 0.005] and more often received plasma exchange [40.0% versus 23.7% (P = 0.019)] at diagnosis. Kidney biopsies revealed a higher proportion of patients with glomerular basement membrane fracture in the isomorphic red blood cell group [46.3% versus 22.9% (P = 0.033)]. Furthermore, patients with predominant urinary isomorphic red blood cells were more likely to progress to end-stage kidney disease [63.5% versus 47.4% (P = 0.028)] and had a higher risk of death [31.3% versus 19.7% (P = 0.077)]. The end-stage kidney disease-free survival was lower in patients in the isomorphic red blood cell group (P = 0.024). However, urine isomorphic red blood cells ≥ 70% could not predict the presence of end-stage kidney disease in multivariate Cox analysis.

Conclusion

Myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis patients with predominant urinary isomorphic red blood cells at diagnosis had more severe clinical manifestations and a higher risk of poor renal outcomes. In this respect, urinary isomorphic red blood cells could be viewed as a promising biomarker of ANCA_MPO vasculitis severity and progression.

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Data availability

The datasets used during the current study are available from the corresponding author on reasonable request.

Abbreviations

AAV:

Antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis

MPO:

Myeloperoxidase

PR3:

Proteinase 3

iRBCs:

Isomorphic red blood cells

dRBCs:

Dysmorphic red blood cells

IF:

Immunofluorescence

ELISA:

Enzyme-linked immunosorbent assay

HPF:

High-power field

WBC:

White blood cell

RBC:

Red blood cell

HB:

Hemoglobin

sC3:

Serum C3 levels

sC4:

Serum C4 levels

sIgA:

Serum IgA levels

sIgG:

Serum IgG levels

sIgM:

Serum IgM levels

CRP:

C-reactive protein

ESR:

Erythrocyte sedimentation rate

UACR:

Urinary albumin to creatinine ratio

eGFR:

Estimated glomerular filtration rate

BVAS:

Birmingham vasculitis activity score

GBM:

Glomerular basement membrane

IC:

Immune-complex

PE:

Plasma exchange

ESRD:

End-stage renal disease

KRT:

Kidney replacement therapy

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Funding

This research was supported by the National Natural Science Foundation of China (81270786), Natural Science Foundation of Hunan Province (2020JJ4887), and Clinical Medical Technology Innovation Guidance Program of Hunan Province (2020SK53701).

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Authors and Affiliations

  1. Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China

    Fangyuan Wang, Yanli Jin, Fangyu Zhou, Liying Luo, Lingyu Huang, Zhonghua Liao, Danni Sun, Gong Xiao & Xiaozhao Li

  2. Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China

    Jiale Tang, Xinyue Hu, Linzi Dengshuang, Huan Ge & Juntao Feng

  3. Department of Laboratory Medicine, Xiangya Hospital, Central South University, Changsha, China

    Yuanyuan Jiang

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  1. Fangyuan Wang
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Contributions

All authors have made substantial contributions to the completion of the work. Research idea and study design: FW, XL; Data acquisition: FW, YJ, FZ, LL, JT, LH, ZL, YJ, LD, HG, DS, GX; Statistical analysis and manuscript writing: FW, LL; Supervision: XL, JF, XH. All authors reviewed and approved the article.

Corresponding author

Correspondence to Xiaozhao Li.

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The authors have no potential or apparent conflicts of interest with regard to this work.

Ethical approval

This study was approved by the medical ethics committee of Xiangya Hospital of Central South University (2019030598).

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Informed written consent was obtained from all participants involved in the study for the use of their clinical data for research purposes.

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Wang, F., Jin, Y., Zhou, F. et al. Urinary isomorphic red blood cells for the prediction of disease severity and renal outcomes in MPO-ANCA-associated vasculitis: a retrospective cohort study. J Nephrol 36, 2295–2304 (2023). https://doi.org/10.1007/s40620-023-01663-3

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