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

Abstract

Aim Podocyte depletion in the kidney is associated with end‐stage kidney disease (ESKD). Pre‐eclampsia (PE) increases the risk of ESKD in later life. This study was performed to determine whether nephrinuria (soluble nephrin in the urine) is correlated with proteinuria and/or podocyturia (podocytes in the urine) in PE women. Methods Eighty‐three urine samples, consisting of 45 and 38 samples from 27 normotensive and nine PE women, respectively, underwent simultaneous determination of nephrin, protein, and creatinine concentrations in the urine supernatant and quantitative analysis of podocyte‐specific protein mRNA expression. This included podocin (Pod‐mRNA) and nephrin (Nep‐mRNA), using real‐time polymerase chain reaction in the pelleted urine. Nephrinuria and proteinuria were corrected by creatinine concentration. Pod‐ and Nep‐mRNA expression levels were corrected by GAPDH. Results Nephrinuria, proteinuria, Pod‐mRNA expression, and Nep‐mRNA expression all increased with advancing gestation in PE women, while not in normotensive women. The nephrinuria was strongly correlated with proteinuria (R = 0.901, P < 0.001), Pod‐mRNA expression level (R = 0.824, P < 0.001), and Nep‐mRNA expression level (R = 0.724, P < 0.001) in urine samples from PE women, while the nephrinuria was significantly correlated with proteinuria alone (R = 0.419, P < 0.005) in urine samples from normotensive women. Conclusion Nephrinuria reflected well the degrees of proteinuria and podocyturia in PE women. This suggested that increased nephrinuria/proteinuria was associated with podocyte loss in the kidneys of PE women.

Second-trimester urine nephrin:creatinine ratio versus soluble fms-like tyrosine kinase-1:placental growth factor ratio for prediction of preeclampsia among asymptomatic women

“…As FPR was consistently predictive of later PE in most studies6789101112131415161718192021222324, FPR has been accepted as a diagnostic aid for PE in conjunction with other clinical findings26. This was also confirmed in the present study; women with FPR >90 th percentile value had RR of PE = 4.98 (1.91–13.0) compared to women with FPR <90 th percentile value.…”

“…The podocytes are glomerular epithelial cells located at the outermost layer of the glomerular basement membrane (GBM)7 and form the final barrier to protein loss8. Glomerular podocytes with reduced nephrin expression are likely to detach from the GBM, and podocyturia as a result from podocytes detachment from the GBM is associated with increased nephrinuria and proteinuria in women with PE910. These suggested that glomerular podocytes that had shed nephrin were impending detachment from the GBM and the shed nephrin became nephrinuria.…”

Post‐partum podocyturia following pre‐eclamptic pregnancy

“…Podocyturia can be monitored via mRNA expression of podocyte‐specific proteins, such as podocin and nephrin, and increases with increasing proteinuria in pregnancy complicated with PE . Certain stimuli, however, cause alteration of the phenotype of glomerular podocytes, that is, reduced nephrin mRNA expression in the glomerular podocytes (i.e.…”

“…[2][3][4][5][6][7] Given that podocytes are terminally differentiated cells 1 and their turnover rate is very low, 8,9 the detachment of glomerular podocytes from the GBM contributes to a decrease in the number of glomerular podocytes in the kidneys. 1,10 Podocyturia can be monitored via mRNA expression of podocyte-specific proteins, such as podocin and nephrin, 7,11,12 and increases with increasing proteinuria in pregnancy complicated with PE. 7,11,12 Certain stimuli, however, cause alteration of the phenotype of glomerular podocytes, that is, reduced nephrin mRNA expression in the glomerular podocytes (i.e.…”

“…1,10 Podocyturia can be monitored via mRNA expression of podocyte-specific proteins, such as podocin and nephrin, 7,11,12 and increases with increasing proteinuria in pregnancy complicated with PE. 7,11,12 Certain stimuli, however, cause alteration of the phenotype of glomerular podocytes, that is, reduced nephrin mRNA expression in the glomerular podocytes (i.e. in animal models), and such glomerular podocytes with reduced nephrin mRNA expression are likely to detach from the GBM, resulting in increases in urine podocin : nephrin mRNA ratio (PNR).…”