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Aim: Our previous study demonstrated that the cystatin C-based chronic kidney disease (CKD)-EPI equation and combined by serum creatinine (CKD-EPIscr-cys) had better capability to accurately evaluate glomerular filtration rate in the CKD participants. Considering that the accuracy of estimated glomerular filtration rate (eGFR) remains less ideally, it is essential to modify the equation by including the Chinese eGFR racial factor in order to improve its performance. Methods: Two prospective cohorts were enrolled in 2 medical centers. New equations were developed in 529 participants and validated in 313 participants. Reference glomerular filtration rate (rGFR) was taken by 99mTc-DTPA renal dynamic imaging method (Gates method). The primary outcomes of this study were bias, precision (interquartile range of difference [IQR]), and accuracy (the proportion of eGFR within 30% of rGFR [P30] and root mean square error [RMSE]) of eGFR versus rGFR. Results: In a development data set, Chinese coefficients for CKD-EPIscr (C-CKD-EPIscr), CKD-EPIcys (C-CKD-EPIcys), and CKD-EPIscr-cys (C-CKD-EPIscr-cys) were 0.871, 0.879, and 0.891, respectively. In a validation data set, C-CKD-EPIcys was the most accurate with highest P30 value (62.3%), relative lowest IQR (15.45), and RMSE (0.80) among 6 equations, though the bias of C-CKD-EPIcys was not better than CKD-EPIcys. C-CKD-EPIscr and C-CKD-EPIscr-cys equations were improved in bias (p < 0.001), -precision, and accuracy (p = 0.004 and <0.001 for P30) compared with CKD-EPIscr and CKD-EPIscr-cys. Conclusion: C-CKD-EPIcys was the most accurate with the highest P30 value, relative lowest IQR, and RMSE among 6 equations. C-CKD-EPIscr and C-CKD-EPIscr-cys equations were improved in bias, precision, and accuracy. Other external validation of these equations is needed. [ABSTRACT FROM AUTHOR]

Background/Aims: Angiotensin II type I receptor agonistic autoantibody (AT1-AA) is closely related to pre-eclampsia, which is characterized by proteinuria and hypertension. AT1-AA has been shown to enhance the effect of AngII in pre-eclampsia, such as production of endothelin-1, activation of ROS, and vasoconstriction, which are considered to be associated with hypertension; however, whether or not AT1-AA participates in podocyte damage leading to the generation of proteinuria has not been reported. In this study we investigated the role of pre-eclamptic serum AT1-AA on podocytes and the mechanism underlying the generation of proteinuria. Methods: The levels of AT1-AA isolated from pre-eclamptic sera were determined by an enzyme-linked immunosorbent assay. Human podocytes were cultured in vitro and treated with various concentrations of AT1-AA. Whether or not an ERK1/2 inhibitor and TRPC6 siRNA inhibit the effect of AT1-AA on podocytes was determined. Western blot was used to detect the expression of podocyte-specific proteins (nephrin, synaptopodin, and podocin) and the phosphorylation of ERK1/2 and TRPC6. The arrangement of F-actin was observed by immunofluorescence. A Calcineurin Cellular Activity Assay Kit was used to detect calcineurin activity. Changes in the intracellular Ca2+ concentration was determined by confocal laser. Results: AT1-AA induced a decrease in podocyte-specific protein expression and calcineurin activity and increased expression of p-ERK1/2 and TRPC6 protein and the intracellular Ca2+ concentration. Immunofluorescence revealed rearrangement of F-actin. PD98059, an inhibitor of ERK1/2, and TRPC6 siRNA attenuated the decreased expression of podocyte-specific proteins and decreased intracellular Ca2+ concentration. The expression of TRPC6 was reduced following the addition of ERK1/2 inhibitor. Conclusion: AT1-AA induced podocyte damage in a dose-dependent manner. The underlying mechanism might involve activation of the TRPC6 –calcium/calcineurin pathway. This study provides new details regarding podocyte injury and the mechanism underlying the generation of proteinuria in pre-eclampsia. [ABSTRACT FROM AUTHOR]