Circulating Testican-2 and MGT5A are Markers of Membranous Nephropathy

Membranous nephropathy (MN) is a common cause of nephrotic syndrome usually diagnosed using kidney biopsy.

We examined the association of 6592 plasma proteins with a diagnosis of MN in the Boston Kidney Biopsy Cohort (BKBC, n = 434), with replication of the top hits in the Nephrotic Syndrome Study Network (NEPTUNE, n = 132).

In BKBC, 2 proteins, testican-2 and alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase (MGT5A), were associated with MN when compared with the reference diagnosis (normal or thin basement membrane [TBM] disease) as well as when compared with all other diagnoses among individuals who had undergone kidney biopsy for the indication of proteinuria or nephrotic syndrome. In NEPTUNE, plasma levels of both proteins, as well as glomerular expression of their cognate genes, were increased in MN compared with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). In receiver operating characteristic curve analyses, the addition of plasma testican-2 and MGT5A levels significantly improved discrimination of MN from other diagnoses in BKBC and NEPTUNE compared with models incorporating age, sex, race, estimated glomerular filtration rate (eGFR), and proteinuria.

Together, these findings motivate interest in testican-2 and MGT5A as markers and potential functional participants in MN. More work is required to understand the biological role of these proteins in the glomerular basement membrane in relation to immune complex deposition as well as to assess their performance as biomarkers alongside circulating autoantibodies in patients with MN.