Alteration of podocyte phenotype in the urine of women with preeclampsia

Abstract

Podocyte injury has been suggested to induce phenotypic alteration of glomerular podocytes and accelerate the detachment of podocytes from the glomeruli resulting in podocyturia. However, it is not clear whether podocyte phenotypic alteration occurs in the urine of women with preeclampsia (PE). Seventy-seven and 116 pelleted urine samples from 38 and 18 women at various stages of normal and PE pregnancies, respectively underwent quantitative analysis of podocyte-specific or associated protein mRNA expression, including podocin, nephrin, and synaptopodin using RT-PCR. Significant proteinuria in pregnancy (SPIP) is defined as protein:creatinine ratio (P/Cr, mg/mg) ≥0.27 in the urine supernatant. All three urine-pellet mRNAs expression levels were significantly positively correlated with P/Cr levels, suggesting that podocyturia increased with proteinuria. The podocin:nephrin mRNA ratio (PNR) and synaptopodin:nephrin mRNA ratio (SNR) increased significantly with increasing P/Cr, while the podocin:synaptopodin mRNA ratio (PSR) did not change significantly according to P/Cr, resulting in significantly higher PNR and SNR, but not PSR levels, in urine from PE women with than without SPIP. The PNR, SNR, and PSR in urine from PE women before onset of SPIP were comparable to those from controls. Thus, nephrin mRNA expression was reduced in the podocytes recovered from 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.…”

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 .…”

“…Podocin is another podocyte‐specific protein that contributes to the integrity of the filtration barrier. Thus, the degree of podocyturia can be monitored by quantification of podocin and nephrin mRNA expression in pelleted urine samples …”

“…Nephrin expression is reduced in kidney biopsy specimens from PE women and in autopsy specimens from women who have died from PE, and PE women show increased nephrinuria . In humans and animal models, podocyte loss in the kidney is associated with reduced nephrin (but not podocin) mRNA expression in urine podocytes, suggesting that glomerular podocytes that have shed nephrin are likely to detach from the glomerular basement membrane and be excreted in the urine . Under such conditions, the shedding of nephrin from glomerular podocytes would lead to increased nephrinuria.…”