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 end-stage kidney disease. Urinary sediment podocyte (u-sed Pod) mRNA excretion and urinary supernatant podocyte (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 (minor glomerular abnormality with mild proteinuria and/or microscopic hematuria, n = 15; minimal change nephrotic syndrome [MCNS], n = 15; membranous nephropathy [MN], n = 15; IgA nephropathy [IgAN], n = 60; crescentic glomerulonephritis [Cres GN], n = 19; lupus nephritis [LN], n = 10; others, n = 38). 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 glomerulonephritis-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 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 glomerulonephritis indicating podocyte detachment and subepithelial dense deposit-type glomerulonephritis, 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.

Podocyte injury and death: New insights into lupus nephritis pathogenesis and therapy

“…These components are, therefore, potential biomarkers for LN diagnosis and monitoring (Table 2). [41][42][43][44][45][46][47] For example, variations in urinary sediment podocin and podocalyxin levels among LN patients emphasize the diagnostic value of podocyte components. 41…”

“…[41][42][43][44][45][46][47] For example, variations in urinary sediment podocin and podocalyxin levels among LN patients emphasize the diagnostic value of podocyte components. 41…”

“…Urinary sediment podocin (used Pod) mRNA Associated with severe proliferative LN [41] Urinary supernatant podocalyxin protein Associated with subepithelial dense deposit LN Neuraminidase 1 Associated with pathological CI scores and renal outcomes in patients with proliferative LN [42] Podocyte-derived microparticles Positively correlated with increased proteinuria [43] Cmaf-inducing protein Be limited to nonproliferative forms and may define a specific pattern of podocyte injury in LN [44] Podocalyxin Urinary podocalyxin level significantly predicts the pathological impact of SLE on the kidney [45] Soluble urokinase plasminogen activator receptor Urine suPAR levels raised again in patients with a relapse of LN [46] S100 proteins Higher urine S100 levels are associated with increased LN activity in childhood-onset SLE [47] Abbreviations: CI, chronicity index; LN, lupus nephritis; mRNA, messenger RNA; SLE, systemic lupus erythematosus, suPAR, soluble urokinase plasminogen activator receptor. phosphorylation of nephrin in LN.…”

Urinary Podocyte Biomarkers and Glomerular Histologic Change

“…In summary, Fukuda et al . (12) show the association between glomerular histologic lesions and urinary podocyte markers. This study provides an intriguing clue for future studies to find molecular mechanisms for renal histologic changes and urinary-specific biomarkers in patients with glomerular diseases.…”

“…In Kidney360 , Fukuda et al (12) reveal the association of urinary podocyte marker mRNA expression levels with renal histologic change in patients with glomerulonephritis (GN). They collected urine samples from 184 patients with glomerular diseases and 12 healthy volunteers during a 3-year period.…”