P0712TRANSGELIN AS A POTENTIAL MARKER OF RENAL IMPAIRMENT IN MULTIPLE MYELOMA PATIENTS
Authors: Woziwodzka Karolina , Malyszko Jolanta , Banaszkiewicz Małgorzata , Koc- Żorawska Ewa , Dumnicka Paulina , Jurczyszyn Artur , Batko Krzysztof , Maleszka Aleksandra , Krzanowski Marcin , Miarka P , Zorawski Marcin , Małyszko Jacek , Drozdz Ryszard , Kuznieswki Marek Jan , Krzanowska Katarzyna 
Published: June 2020

Abstract

Background and Aims
Transgelin (SM22) is a cytoskeletal actin-binding protein involved in differentiation of smooth muscle cells, osteoblasts and adipocytes. It is present in fibroblasts, some epithelium, immune cells and acts as a tumor suppressor. It was found as a marker of interstitial fibrosis and glomerulosclerosis. Transgelin upregulation depends on the etiology of the disease in various cells (glomerular parietal or visceral, or tubular interstitial cells). Elevated SM22 expression was detected in glomerular and in tubulointerstitial injury. Among patients with multiple myeloma (MM) up to 50% suffer from renal insufficiency (RI) in early stages. Free light chains (FLCs), potential nephrotoxic substances, where lambda light chains are more commonly associated with renal damage, appear to have a prognostic value in MM and indicate the stages of MM.
The aim of the study was to analyse the utility of transgelin in case of renal impairment in MM patients and investigate its relationship with acclaimed parameters of renal failure and markers of MM stages.

Method
The analysis included 126 patients (73 women and 53 men) in mean age 66 ± 10 years. Symptomatic MM was diagnosed in 119 patients, including 84 (67%) with ISS stage 1, 20 (16%) with stage 2 and 15 (12%) with stage 3; 7 (6%) patients had smoldering MM. Mean baseline eGFR (CKD-EPICr) was 74 ± 24 ml/min/1.73 m2 and 31 (25%) patients had eGFR &lt;60 ml/min/1.73 m2. The examined parameters included creatinine, urea, NGAL urine, serum and urine cystatin C, periostin, FLC kappa and lambda in serum and urine. The association between transgelin, markers of renal failure, MM were determined by the Pearson's test and multivariate stepwise regression analysis. The p-value &lt;0.05 was considered statistically significant.

Results
Median serum transgelin in the whole studied group was 84.1 (IQR: 65.4; 116.4) ng/ml. Transgelin concentrations were higher in men (median 96.2 versus 78.8 ng/ml; p=0.022) and in patients with smoldering MM (median 149.2 versus 82.4 ng/ml; p=0.003). Transgelin did not differ according to ISS stage (p=0.3) or disease state (regression, stable disease or progression) (p=0.3). Significant correlations were detected between transgelin and serum creatinine (R=0.29; p=0.001), eGFR (CKD-EPICr) (R=-0.25; p=0.007), uric acid (R=0.19; p=0.036), alanine (R=0.18; p=0.048) and aspartate (R=0.26; p=0.003) aminotransferases, ferritin (R=-0.22; p=0.049), hepcidin (R=-0.25; p=0.033), and urine cystatin C (R=0.19; p=0.042). Moreover, after exclusion of patients with smoldering MM, transgelin significantly correlated with serum FLC lambda (R=0.18; p=0.047) and serum periostin (R=-0.22; p=0.013). After median follow-up of 21 (IQR: 15; 24) months, eGFR decreased in 47 (37%) of patients and increased in 71 (56%) patients (no follow-up data were available in 8, i.e. 6% of patients). Patients in whom eGFR decreased had higher transgelin (median 106.6 versus 83.9 ng/ml), although the difference was marginally significant (p=0.05). However, baseline transgelin positively correlated with serum creatinine after follow-up (R=0.37; p&lt;0.001) and negatively correlated with eGFR after follow-up (R=-0.33; p&lt;0.001). Moreover, higher baseline serum transgelin (beta=-0.11 ± 0.05; p=0.032) significantly predicted lower eGFR values after the follow-up, independently of baseline eGFR and the duration of follow-up.

Conclusion
Transgelin may be useful in investigating renal damage because of its proven role in regulation of fibrosis, especially in kidney. As a biomarker it may indicate diagnosis and etiology of MM-related chronic kidney disease, which can lead to beginning of early therapeutic interventions and improved overall survival and quality of life in patients with MM. Moreover, elevated transgelin at the beginning of the disease may induce future development of chronic kidney disease.