P0375URINARY DICKKOPF-3 PREDICTS RENAL SURVIVAL IN ANCA-ASSOCIATED VASCULITIS

Abstract

Abstract Background and Aims Urinary Dickkopf-related protein-3 (DKK3), a stress-induced renal tubular glycoprotein, has been identified as a novel biomarker for chronic kidney disease patients at risk of kidney disease progression. The aim of our study was to assess urinary DKK3 as a diagnostic biomarker for predicting GFR loss and renal survival in a cohort of patients with ANCA-associated vasculitis Method We measured baseline urinary DKK3 levels in a cohort of patients diagnosed with ANCA-associated vasculitis (AAV), and repeated measurements at 1 and 3 months of diagnosis. Urinary DKK3 levels were normalized to urinary creatinine concentrations to account for dilution of the urine. The association between baseline uDKK3/creatinine levels and the rate of GFR loss was measured. The primary composite outcome was defined as an increase of >50% in baseline serum creatinine, initiation of renal replacement therapy or death. Results We included 36 AAV patients with a mean age 71.2 ±12.0 years, 55.6% males, with baseline eGFR at diagnosis 22.3 ±14.1 ml/min. There was a correlation between baseline DKK3-creatinine levels and age (r=0.48, p=0.003) and baseline eGFR (r=-0.327, p=0.051). Ten patients (27.8%) reached the primary composite outcome. Patients were then stratified into two groups according to baseline uDKK3 levels. The group of patients with baseline uDKK3-Creatinine >16000 pg/mg were older (76±12.5 vs 66.4 years, p=0.014), presented a lower baseline eGFR (16.2±10.8 vs 28.5±14.5 ml/min, p=0.007) and had higher baseline uCD163 levels (1135.1 [312.4-2537.5] vs 397.2 [146-809.4], p=0.089]). There were no differences in baseline proteinuria, microhematuria or histological class across the groups. After a median follow-up of three years, 44.4% of the patients in the highest DKK3 group reached the primary composite outcome, whereas only 11.1% of those with lower DKK3 levels reached the endpoint at the end of follow-up (p=0.026) . The area under the time-dependent curve for predicting the primary composite outcome according to uDKK3 was 0,677, with a sensibility of 80% and specificity of 61.5% at the cutoff 16056 pg/mg. Additionally, patients who had a >30% increase in uDKK3 levels after one month reached the primary composite outcome more often (40%) than those who remained with a stable or decreasing DKK3 levels (0%, p=0.04). There were no differences in the rate of change in DKK3 and the different treatment regimens. Conclusion Elevated urinary DKK3 levels help identify those patients who are at a higher risk of kidney disease progression and dialysis dependency over the next three years in ANCA-associated vasculitis. DKK3 monitoring could be considered in the follow-up of these patients to assess the effect of treatment and predict the long-term response.