P0868ZONULIN AS A THERAPEUTIC POTENTIAL BIOMARKER OF ANEMIA IN PATIENTS WITH MULTIPLE MYELOMA AND CHRONIC KIDNEY DISEASE
Authors: Woziwodzka Karolina , Malyszko Jolanta , Banaszkiewicz Małgorzata , Koc- Żorawska Ewa , Dumnicka Paulina , Krzanowski Marcin , Batko Krzysztof , Gołasa Paulina , Tisonczyk Joanna , Zorawski Marcin , Małyszko Jacek , Drozdz Ryszard , Kuznieswki Marek Jan , Krzanowska Katarzyna 
Published: June 2020

Abstract

Background and Aims
Zonulin is a haptoglobin 2 precursor, that regulates the intestinal permeability. As a double-chain form it takes part in scavenging haemoglobin. Chronic inflammation is common complication of chronic kidney disease which affects iron metabolism. The most frequent manifestation of multiple myeloma is anaemia in up to 73% of patients. Serum concentrations of zonulin are associated with inflammation process, age, kidney failure and iron status and anaemia.
The aim of the study was to analyse zonulin as a marker of anaemia in MM patients and investigate its relationship with acclaimed parameters of renal failure, inflammation, bone metabolism and stages of MM.

Method
The studied group of seventy-three patients with MM (67 symptomatic, 6 smoldering) included 35 women and 38 man, with mean age 69 ± 10 years. Median (IQR) of time from initial MM diagnosis was 36 (17; 69) months. Forty patients were in ISS stage 1, 15 in stage 2, and 12 in stage 3 at the time of blood collection. Remission of MM was diagnosed in 52 patients and stable or progressive disease in 21. Twenty-six patients had eGFR &lt;60 ml/min/1.73 m2. The examined parameters included creatinine, urea, serum monoclonal protein, albumin, ferritin, blood hemoglobin and NT-proBNP. The association between zonulin, markers of MM stages and renal and bone markers were determined by the Pearson's test and multivariate stepwise regression analysis. The p-value &lt;0.05 was considered statistically significant.

Results
Median (IQR) serum zonulin in the studied group was 23.9 (19.9; 27.4) ng/ml. There were no differences in zonulin concentrations between patients with smoldering versus symptomatic MM (p=0.4), with ISS 1 to 3 (p=0.7), with remission versus stable or progressive MM (p=0.9), or with eGFR &lt;60 ml/min/1.73 m2 versus those with higher eGFR (p=0.6). Also, zonulin did not differ between subjects with and without anemia (Hb&lt; the lower reference limit) (p=0.4). In whole studied group, significant correlations were observed between zonulin and serum albumin (R=0.30; p=0.009), creatinine (R=-0.28; p=0.018), eGFR (R=0.26; p=0.025), ferritin (R=0.34; p=0.013), NT-proBNP (R=-0.32; p=0.006). Moreover, in patients with symptomatic MM, zonulin correlated with monoclonal protein in serum (R=-0.29; p=0.046), blood hemoglobin (R=0.27; p=0.027), and age (R=-0.24; p=0.044). In multiple regression, serum concentrations of monoclonal protein (beta=-0.48 ± 0.16; p=0.006) and ferritin (beta=0.34 ± 0.14; p=0.023) as well as ISS stage 3 (beta=0.40 ± 0.18; p=0.034) were identified as independent predictors of zonulin concentrations.

Conclusion
Zonulin as a biomarker may promote diagnosis of etiology and management of MM-associated anaemia, which can contribute to biomarker-targeted therapeutic interventions. Early treatment may result in improved life expectancy in patients with MM and increase their quality of life.