nephrin and Hypertension--Pregnancy-Induced

Topics: Actins; Adult; Angiotensin I; Animals; Blood Pressure; Cell Line; Down-Regulation; Female; Humans; Hypertension, Pregnancy-Induced; Membrane Proteins; Mice; Peptide Fragments; Podocytes; Pre-Eclampsia; Pregnancy; Proteinuria; Proto-Oncogene Mas; Proto-Oncogene Proteins; Receptors, G-Protein-Coupled; Renin-Angiotensin System; Zonula Occludens-1 Protein

Icariin has previously been demonstrated to attenuate hyperglycemia‑induced renal injury, however the renoprotective effects of icariin in a rat model of pregnancy‑induced hypertension (PIH) remain to be elucidated. The present study aimed to investigate the effect of icariin on PIH‑induced acute kidney injury (AKI) and proteinuria. Following 18 days of icariin treatment between day 1 and day 18 of gestation, which was combined with NG‑nitro‑L‑arginine methyl ester (L‑NAME) treatment between day 12 and day 18 of gestation to induce PIH, the 24 h urine protein level, blood urea nitrogen and serum creatinine were measured by using the Coomassie Brilliant Blue method, a commercial enzymatic kit and the picric acid method, respectively. Renal tissues were collected at day 18 of gestation for hematoxylin and eosin staining and immunohistochemistry. The mRNA expression of AGT and protein expression of angiotensin II (Ang II) in the kidneys of control and PIH rats was investigated by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively, to determine the effect of icariin on components of the renin‑angiotensin system. The results demonstrated that L‑NAME treatment in pregnant rats resulted in significant increases in systolic blood pressure (SBP) and diastolic blood pressure, in addition to the induction of severe proteinuria. The significant increase in SBP and proteinuria in PIH rats was prevented by icariin. L‑NAME‑induced AKI resulted in profound renal histological alterations, including mesangial expansion and glomerular lesions. L‑NAME administration exerted a marked decrease in the mRNA and protein expression levels of nephrin in the kidneys from PIH rats compared with control group. Furthermore, upregulation of circulating and renal Ang II levels in PIH rats was observed. However, icariin treatment significantly reversed the L‑NAME‑induced downregulation of nephrin and upregulation of circulating and renal Ang II levels in PIH rats. These results demonstrated that icariin administration improved urinary protein excretion levels and renal tissue damage in PIH rats, and the underlying mechanism was mediated in part, via upregulation of nephrin expression and downregulation of Ang II.

Topics: Acute Kidney Injury; Angiotensin II; Animals; Blood Pressure; Blood Urea Nitrogen; Creatinine; Disease Models, Animal; Down-Regulation; Female; Flavonoids; Gestational Age; Hypertension, Pregnancy-Induced; Kidney; Membrane Proteins; NG-Nitroarginine Methyl Ester; Pregnancy; Proteinuria; Rats; Rats, Wistar; Renin-Angiotensin System; Reproduction; Up-Regulation

To investigate the possibility of nephrinuria as a screening tool for the risk of pre-eclampsia (PE).. Prospective observational study.. A single university hospital. Changes in urinary nephrin:creatinine ratio (NCR, ng/mg) and protein:creatinine ratio (PCR, mg/mg) in pregnancy were determined. Significant proteinuria in pregnancy (SPIP) was defined as PCR>0.27. PE was diagnosed in women with both SPIP and hypertension.. 89 pregnant women in whom neither hypertension nor SPIP was present at enrolment, providing 31, 125 and 93 random urine samples during first, second and third trimesters, respectively.. PE developed in 14 of the 89 women. NCR increased with increasing PCR in 14 women with PE (correlation coefficient, 0.862; p<0.0001). In contrast, NCR did not change significantly despite significant increases in PCR in 75 women with normotensive pregnancies defined as neither SPIP nor hypertension, indicating that there was little increase in nephrinuria over the physiological range of proteinuria in pregnancy. Relative risk of later development of PE among asymptomatic second and third trimester women with NCR (ng/mg) >122 (95th centile value for 75 women with normotensive pregnancies) was 5.93 (95% CI 2.59 to 13.6; 60% (6/10) vs 10% (8/79)) and 13.5 (95% CI 3.31 to 55.0; 75% (6/8) vs 5.5% (2/36)), respectively, compared with women with NCR≤122 at that time.. Nephrinuria was unlikely to increase in normal pregnancy. A certain NCR cut-off may efficiently differentiate women at higher risk of PE.

Topics: Adult; Biomarkers; Creatinine; Feasibility Studies; Female; Humans; Hypertension, Pregnancy-Induced; Membrane Proteins; Parity; Pre-Eclampsia; Pregnancy; Pregnancy Trimesters; Prenatal Diagnosis; Prospective Studies; Proteinuria; Risk Assessment; Young Adult

Preeclampsia is a significant cause of maternal and fetal morbidity and mortality worldwide. A clinically useful screening test that can predict development of preeclampsia at an early stage is urgently needed. The detection of podocyturia by immunohistochemistry after cell culture has been noted as a reliable marker for preeclampsia. However, this method is laborious and carries the risk of cell culture contamination. The aim of this study was to investigate the diagnostic value of quantitative polymerase chain reaction as a rapid method to detect preeclampsia. Clean-catch urine samples were collected from preeclamptic (n=35), healthy pregnant (n=34), and healthy nonpregnant (n=12) women. Furthermore, a control group of women with gestational hypertension (n=5) was included. Quantitative polymerase chain reaction analysis was performed for podocyte-specific markers. Receiver operating characteristic curve analyses were performed. Significantly elevated mRNA levels of nephrin, podocin, and vascular endothelial growth factor were detected in preeclamptic women compared with healthy pregnant and healthy nonpregnant controls. In addition, significantly elevated levels of nephrin mRNA were detected in urine of preeclamptic women compared with women with gestational hypertension. A positive correlation (ρ=0.82; P<0.0001) was observed between nephrin and vascular endothelial growth factor mRNA levels in preeclamptic women. Receiver operating characteristic curve analyses demonstrated a strong ability of this method to discriminate between the different study groups. Quantitative polymerase chain reaction analysis of podocyte-specific molecules in urine samples is a rapid and reliable method to quantify podocyturia. We demonstrate that this method distinguishes preeclamptic patients from healthy controls and women with gestational hypertension. This method may be a tool for the detection of preeclampsia at an earlier stage, thereby preventing maternal and fetal morbidity and mortality.

Topics: Adult; Case-Control Studies; Female; Humans; Hypertension, Pregnancy-Induced; Membrane Proteins; Podocytes; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Vascular Endothelial Growth Factor A