Nephrin – a biomarker of early glomerular injury

Abstract

Nephrin is a 180 KD trans-membrane protein expressed in glomerular podocytes. It was first identified in children with congenital nephrotic syndrome of the Finnish type (NPHS1). Nephrin forms an integral part of podocytes, which—together with endothelial cells and the basement—form the glomerular filtration barrier. Podocytopathies result in the detection of nephrin in the urine. We reviewed the literature to determine if urine nephrin measurements could become useful as a biomarker to detect early podocyte injury. Our search identified a total of 19 studies that have been published to date. The most common clinical conditions for which urine nephrin analyses were carried out included diabetic nephropathy, glomerulonephritis and pre-eclampsia. Nephrin measurement was carried out using commercially available ELISA kits, the messenger ribonucleic acid real-time polymerase chain Reaction, or electrophoresis. Nephrinuria showed positive correlation with proteinuria and severity of podocyte injury. In two studies, the level of nephrinuria declined in conjunction with clinical improvement in the patient following immunosuppressive treatment. Currently, there is no published data on the value of measuring urinary nephrin in pediatric patients.

Association between nephrinuria, podocyturia, and proteinuria in women with pre‐eclampsia

“…The podocytes are glomerular epithelial cells, located at the outermost layer of the glomerular basement membrane, the foot processes of which form tight interdigitating networks that regulate the filtration of circulating plasma proteins from the capillary lumen into Bowman's space . Several diseases with proteinuria, including PE, show increased podocyturia . Nephrin is a podocyte‐specific transmembrane protein that is predominantly localized at the glomerular slit diaphragm of podocytes .…”

Bone marrow mononuclear cell transplantation rescues the glomerular filtration barrier and epithelial cellular junctions in a renovascular hypertension model

“…Therefore, SD dysfunction results in GFB injury, leading to proteinuria and progressive renal injury (Zha et al., ; Kandasamy et al., ; Scott & Quaggin, ). Nephrin may be a new effective therapeutic target for podocyte injury in glomerulopathies (Grahammer, Schell, & Huber, ; Kandasamy, Smith, Lumbers, & Rudd, ). A previous study demonstrated a significant reduction of nephrin and podocin in the glomeruli of 2K1C rats (Finne et al., ).…”

“…Podocyte injury directly causes proteinuria and albuminuria, because podocytes have a key role in maintaining the integrity of the GFB, a highly dynamic stable filter which selects blood components, generating the primary urinary ultrafiltrate (Scott & Quaggin, 2015). Therefore, SD dysfunction results in GFB injury, leading to proteinuria and progressive renal injury (Zha et al, 2013;Kandasamy et al, 2014;Scott & Quaggin, 2015). Nephrin may be a new effective therapeutic target for podocyte injury in glomerulopathies (Grahammer, Schell, & Huber, 2013;Kandasamy, Smith, Lumbers, & Rudd, 2014).…”

Urinary Nephrin as a Biomarker of Glomerular Maturation and Injury Is Associated with Acute Kidney Injury and Mortality in Critically Ill Neonates

“…The protein markers in podocytes can be excreted in urine in the presence of podocyte injury, and the increased concentrations of nephrin in urine may reflect early glomerular injury [11-13]. To date, most studies of urinary nephrin (uNep) have been conducted in patients who have kidney disease with podocyte dysfunction, such as lupus nephritis, and have investigated the association of uNep with various renal traits [14-17].…”

“…Nephrin, identified as a transmembrane protein of the immunoglobulin family, is a key component of the slit diaphragm of the glomerular podocyte and is involved in several aspects of podocyte biology [11-13]. The protein markers in podocytes can be excreted in urine in the presence of podocyte injury, and the increased concentrations of nephrin in urine may reflect early glomerular injury [11-13].…”