Original Research: Potential of urinary nephrin as a biomarker reflecting podocyte dysfunction in various kidney disease models

Abstract

Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies.

Angiopoietin-like-3 knockout protects against glomerulosclerosis in murine adriamycin-induced nephropathy by attenuating podocyte loss

“…Podocyte detachment and apoptosis are two risk factors that cause podocyte loss [21, 22]. Podocytes adhere to the GBM principally via integrinα3β1 [28], and ILK plays a key role in integrinα3β1-mediated podocyte adhesion [29].…”

“…Urine was collected overnight (average 12 h), and the total urine pellet ribonucleic acids (RNA) was isolated using the protocol of the RNeasy Mini Kit (Qiagen, Hilden, Germany) [22]. The steady-state amount of nephrin, and podocin messenger ribonucleic acids (mRNAs) was analyzed by real-time PCR using the Stratagene Mx3000p real-Time PCR System (Santa Clara, CA, United States).The analysis was conducted as described in the instructions of the SYBR FAST qPCR Kit (KAPA).…”

Icariin improves acute kidney injury and proteinuria in a rat model of pregnancy-induced hypertension

“…The nephrin gene is specifically expressed in the kidney, brain and pancreas of rodents, and inactivation of nephrin results in proteinuria and neonatal death ( 23 ). Nephrin as a biomarker reflects podocyte dysfunction in various kidney disease models ( 24 ). The present study verified that L-NAME treatment in pregnant rats resulted in AKI, evidenced by severe proteinuria and BUN and serum creatinine elevation, which may potentially be associated with a decrease in nephrin expression in the kidney.…”

Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-Albuminuric Diabetic Kidney Disease

“…The panel of circulating cytokines and growth factors was assessed by multiplex bead array assay. Urinary concentrations of nephrin and podocin, two biomarkers of podocyte injury [ 23 , 24 , 25 ] and whey acidic protein four-disulfide core domain protein 2 (WFDC2), a biomarker of tubulointerstitial fibrosis [ 26 , 27 ], were determined by the enzyme-linked immunosorbent assay(ELISA).…”