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Abstract: FR-OR54

Urinary CD4+ T Cell Quantification Identifies ANCA Patients at Risk for Subsequent Renal Flares: Results of the Prospective, Multicenter Pre-Flared Study

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Prskalo, Luka, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Skopnik, Christopher, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Sonnemann, Janis, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Grothgar, Emil, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Klocke, Jan, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Schneider, Udo, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Salama, Alan D., University College London Medical School, London, London, United Kingdom
  • Bieringer, Markus, Helios Kliniken GmbH, Berlin, Germany
  • Schreiber, Adrian, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Enghard, Philipp, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
Background

Patients with ANCA-associated vasculitis (AAV) are at risk for recurrent renal flares. Presently, there are no reliable biomarkers for flare prediction. Urinary CD4+ T cells have previously been reported to distinguish active renal involvement in AAV from AAV in stable remission, but it is currently unknown if they may predict future flares in quiescent disease.

Methods

We prospectively collected urine samples from 112 AAV patients in remission (BVAS=0) at three AAV clinics in two hospitals (NCT04428398). 10 patients met the exclusion criteria; 102 patient samples were analyzed. Renal flares were defined as an increase in BVAS >0 and at least one element of the renal BVAS or alternatively as new initiation of induction treatment. Using flow cytometry, urinary CD4+ and CD8+ T cell subsets were quantified. The primary end point was the prediction of renal relapse after six months using the initial CD4+ count.

Results

Of the 102 analyzed patients 10 developed a renal flare, 2 developed a non-renal flare and 90 remained in stable remission. The number of urinary CD4+ T cells predicted renal flares with an Receiver-Operator Characteristic (ROC) area under the curve (AUC) of 0.88. Urinary CD4+ T cells outperformed traditional biomarkers such as ANCA titers, hematuria, and proteinuria in renal flare prediction. Applying a cut-off of 490 CD4+ T cells per 100ml urine yielded a sensitivity of 60% and specificity of 97.8% in identifying patients with future renal flares. A combination of urinary CD4+ T cells (>50/100ml) and PR3 ANCA levels (>40IU/ml) increased the predictive value to the sensitivity of 100% and specificity of 92%. Furthermore, in the complete patient cohort (n=102), the number of urinary CD4+ T cells correlated with loss of GFR (p<0.01) and increase in proteinuria (p<0.05) in the subsequent 6 months.

Conclusion

Urinary CD4+ T cell numbers identify AAV patients at risk for renal flares. Combining urinary CD4+ T cell numbers with ANCA levels may further improve flare prediction.