Tricuspid atresia (TA) is a common form of congenital heart disease, accounting for 1-3% of congenital cardiac disorders. TA is characterized by the congenital agenesis of the tricuspid valve connecting the right atrium to the right ventricle and both an atrial septal defect (ASD) and a ventricular septal defect (VSD). Some patients also have pulmonic stenosis, persistence of a left-sided superior vena cava or transposition of the great arteries. Most cases of TA are sporadic, but familial occurrences with disease in multiple siblings have been reported. Gata4 is a zinc-finger transcription factor with a role in early cardiac development. Gata4-deficient mice fail to form a ventral heart tube and die of circulatory failure at embryonic day (E) 8.5 (refs 6,7). Zfpm2 (also known as Fog-2) is a multi-zinc-finger protein that is co-expressed with Gata4 in the developing heart beginning at E8.5 (refs 8-10). Zfpm2 interacts specifically with the N-terminal zinc finger of Gata4 and represses Gata4-dependent transcription. Here we use targeted mutagenesis to explore the role of Zfpm2 in normal cardiac development. Zfpm2-deficient mice died of congestive heart failure at E13 with a syndrome of tricuspid atresia that includes an absent tricuspid valve, a large ASD, a VSD, an elongated left ventricular outflow tract, rightward displacement of the aortic valve and pulmonic stenosis. These mice also display hypoplasia of the compact zone of the left ventricle. Our findings indicate the importance of Zfpm2 in the normal looping and septation of the heart and suggest a genetic basis for the syndrome of tricuspid atresia.

ObjectiveTo compare the measurements of glomerular filtration rate (GFR) determined by 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) renal dynamic imaging with those estimated by Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) equation and to identify a more accurate measurement of GFR of chronic kidney disease (CKD) patients in clinical practice.MethodsThe GFR was determined simultaneously by 3 methods: (a) dual plasma sample clearance method (tGFR); (b) renal dynamic imaging method (dGFR); (c) CDK-EPI equation (eGFR). The tGFR was employed as the reference method. The correlation, regression, and limit of agreement of dGFR and eGFR were used to demonstrate the validity of the two methods. The comparison of bias, precision, and accuracy between dGFR and eGFR was analyzed to identify the most suitable method. The analysis of bias, precision and accuracy was repeated after stratifying patients by a measured tGFR cutpoint of 60 ml·min−1·(1.73 m2)−1.ResultsA total of 149 patients were enrolled. Both dGFR and eGFR correlated well with tGFR and the regression equation of dGFR and eGFR against tGFR was respectively Y = −4.289+0.962X (r = 0.919; RMSE = 14.323 ml.min−1. (1.73 m2)−1; P<0.001) and Y = 2.462+0.914X (r = 0.909; RMSE = 15.123 ml.min−1. (1.73 m2)−1; P<0.001). In addition, Bland-Altman analysis showed preferable agreement between the two methods and the reference method. The comparison revealed that eGFR, compared with dGFR, showed better performance on bias and 50% accuracy and similar performance on other indexes in the whole cohort and the lower-GFR subgroup, whereas in the higher-GFR subgroup the difference of the two methods was not significant in all parameters.ConclusionsAlthough both CDK-EPI equation and renal dynamic imaging can be used to determine the GFR of CKD patients, CDK-EPI equation is more accurate than renal dynamic imaging. As a result, 99mTc-DTPA renal dynamic imaging may be unsuitable to be used as the reference method in investigating the validity of CDK-EPI equation.

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