Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with CKD

Abstract

Background: Podocyte depletion causes glomerulosclerosis, and persistent podocyte loss drives progression to ESKD. Urinary sediment podocin (u-sed Pod) mRNA excretion and urinary supernatant podocalyxin (u-sup PCX) protein have been used to monitor disease activity in glomerular diseases. However, the differences in these markers among pathologies have not been investigated. We examined the roles of these markers in kidney diseases.

Methods: From January 2013 to March 2016, early morning urine samples were collected from 12 healthy controls and 172 patients with kidney disease (n=15 patients with minor glomerular abnormality with mild proteinuria and/or microscopic hematuria, n=15 with minimal change nephrotic syndrome [MCNS], n=15 with membranous nephropathy [MN], n=60 with IgA nephropathy [IgAN], n=19 with crescentic GN [Cres GN], n=10 with lupus nephritis [LN], and n=38 with other kidney diseases). We examined u-sed Pod mRNA excretion, u-sup PCX protein, and the urinary protein-creatinine ratio (u-PCR).

Results: u-sed Pod mRNA excretion was significantly correlated with u-sup PCX protein (r=0.37, P<0.001). Both u-sed Pod mRNA excretion and u-sup PCX protein were significantly correlated with u-PCR (r=0.53, P<0.001 and r=0.35, P<0.001, respectively). Interestingly, u-sed Pod mRNA excretion was significantly increased in proliferative-type GN-including IgAN with extracapillary proliferative lesions, Cres GN, and LN class IV-and significantly correlated with the rate of crescent formation, whereas u-sup PCX protein was significantly increased only in those with MN and subepithelial dense deposit-type LN compared with controls.

Conclusions: Higher u-sed Pod mRNA excretion and u-sup PCX protein were associated with proliferative-type GN, indicating podocyte detachment and subepithelial dense deposit-type GN, respectively. The results suggest that u-sed Pod mRNA excretion and u-sup PCX protein have usefulness for the diagnosis and measurement of disease activity with regard to glomerular diseases.

Keywords: chronic kidney disease; podocyte; proteinuria; urinary sediment podocyte mRNA; urinary supernatant podocyte protein.