Activin A: a novel urinary biomarker of renal impairment in multiple myeloma

Abstract

Renal impairment (RI) is a common complication of multiple myeloma (MM) that significantly affects treatment efficacy and mortality. However, no useful biomarkers for early detection of renal damage in MM exist. Reports indicate that activin A, a multifunctional cytokine of the TGF-β superfamily, is involved in the development and progression of various kidney diseases. In the present study, we measured urinary activin A levels in patients with newly diagnosed MM (NDMM) (n=41), smoldering MM (SMM) (n=10), and monoclonal gammopathy of undetermined significance (MGUS) (n=28), including monoclonal gammopathy of renal significance (MGRS), and assessed the correlation between urinary activin A and several clinical parameters. Urinary activin A, undetectable in healthy volunteers, was significantly increased in NDMM patients but not in patients with SMM and MGUS (97.3, 25.0, and 6.61 mg/gCr, respectively, P<0.05). In all patients with NDMM, urinary activin A levels were significantly reduced after initial treatment regardless of the therapy regimen. There was a significant correlation of urinary activin A with spot urinary protein level (P<0.001) and serum M-protein (P=0.029) but not with estimated glomerular filtration rate (eGFR), serum creatinine (Cr), N-acetyl-glucosaminidase (NAG), and serum activin A level. Histological analysis using renal biopsy samples revealed that activin A, which was absent from normal kidneys, was detected in the renal tubular cells of patients with MGRS. These data suggest that urinary activin A reflects tubular injury in MM and might aid the early detection of RI in plasma cell neoplasms.

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies

“…The authors also observed a relationship with FLC concentrations, which might reflect a mechanism of paraprotein deposition with subsequent expression of tubular activin A. On the other hand, it has been proposed that as a 25-kDa molecule, its filtration and subsequent reabsorption might reflect its undetectable concentrations under physiological conditions, with a subsequent rise following tubular insult [ 88 ]. Further evaluation is necessary to clarify the potential of this marker.…”

“…Urinary activin A is not present or present at very low levels in healthy controls and patients presenting with pre-renal causes of AKI [ 87 ]. Recently, data from patients with MM, MGRS, and MGUS have been reported, implicating the potential of activin A as a biomarker of RI [ 88 ]. Activin A was observed to be absent in healthy kidneys, while identified in a tubular cell in patients with MGRS, which led to a hypothesis of its tubular origin.…”

Clinical Proteomics of Biofluids in Haematological Malignancies

“…In addition, urinary activin A was reported to be significantly increased in newly diagnosed MM patients compared to patients with pre-malignancy plasma cell dyscrasia and healthy donors. Urinary activin A levels correlated with tubular injury in MM, indicating its potential as a biomarker of renal impairment [ 159 ]. As with saliva, urine represents an ideal medium for point-of-care testing.…”