CD163 detection in immune check-point inhibitors-related acute interstitial nephritis
Thomas Perier, Yves Renaudineau, Juliette Pellegrini, Magali Colombat, Angie Arango Ramirez, Pierre Guy, Thibaut Jamme, Nathalie Van Acker, Clément Koundé, David Ribes, Antoine Huart, Audrey Casemayou, Julie BelliereAbstract
Background
Acute interstitial nephritis (AIN) is the most common renal immune-related adverse event after immune check-point inhibitors (ICI). We hypothesised that alternatively activated macrophages (CD163-M) could be involved in ICI-AIN and wished to evaluate the use of their soluble urinary form (us)CD163 as a non-invasive diagnostic marker.
Methods
CD163-M infiltrates were evaluated by both immune-histochemistry and multiplex immunofluorescence and imaging. usCD163 was detected with ELLA technology and evaluated together with urinary creatinine to be expressed as a ratio to creatinuria in ng/mmol. Clinical data were collected to perform correlations with renal function assessed by estimated glomerular filtration rate (eGFR).
Results
A retrospective cohort of 63 ICI-exposed patients with tubular AKI profile requiring a biopsy were selected. AIN patients (n = 44) were compared to acute tubular necrosis (ATN) patients (n = 19). CD163-M staining was detectable in all ICI-AIN patients, which was significantly higher than in ATN patients (18.4 vs 3.6% of area, p = 0.005). CD163-M staining was restricted to the interstitial compartment. CD163-M infiltrate inversely correlated with initial eGFR (r=-0.6, p = 0.003), and was positively correlated with delta eGFR, reflecting a renal improvement outcome (r = 0.48; p = 0.02). usCD163 was well detected in urines of patients, but did not allow us to distinguish ATN from AIN patients at diagnosis. No correlation was observed, neither between usCD163 and CD163-M staining nor with renal response after three months of glucocorticoid tapering.
Conclusion
CD163-M are detected in ICI-AIN and correlate both with severity at diagnosis and better prognosis at three months. CD163-M may help us to distinguish AIN from ATN but, it does not allow us to assess ICI imputability. Although detected in urine, usCD163 is clearly not a surrogate biomarker for AIN diagnosis.