ABSTRACT
BACKGROUND: Echocardiography is commonly used to assess hydratation status and cardiac function in kidney failure patients, but the impact of structural or functional abnormalities on the prognosis of kidney failure patients was yet to be investigated. This study aimed to investigate the prevalence and clinical significance of echocardiographic abnormalities in kidney failure patients. METHODS: This study included 857 kidney failure patients who underwent echocardiography at dialysis initiation. Patients were followed up for a median of 4.2 years for the occurrence of major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: Among the 857 patients studied, 77% exhibited at least one echocardiographic abnormality. The most common abnormalities were left ventricular hypertrophy and left atrial enlargement, but they were not significantly correlated with poor outcomes. Instead, the primary predictors of both major adverse cardiovascular events and mortality in kidney failure patients were left ventricular systolic function, right ventricular systolic function, left ventricular volume index, and valvular abnormalities. Although diastolic dysfunction was linked to major adverse cardiovascular events, it was not associated with mortality. Furthermore, the study revealed that increased left ventricular volume index and left ventricular systolic dysfunction had a more significant impact on peritoneal dialysis (PD) patients than on hemodialysis (HD) patients. CONCLUSION: This study provides insights into the echocardiographic abnormalities and their association with adverse outcomes in kidney failure patients, which can help clinicians optimize the management of patients and closely monitor possible high-risk populations.
ABSTRACT
The type 2 transmembrane serine protease matriptase is broadly expressed in human carcinomas and hematological cancers. The proteolytic activity of matriptase is a potential target of drugs and imaging probes. We assessed the fate of active matriptase following the induction of matriptase zymogen activation. Exposing eight human carcinoma cells to pH 6.0 buffer induced robust matriptase zymogen activation followed by rapid inhibition of the nascent active matriptase by hepatocyte growth factor activator inhibitor (HAI)-1. Consequently, no enzymatically active matriptase was detected in these cells. Some active matriptase is, however, rapidly shed to the extracellular milieu by these carcinoma cells. The lack of cell-associated active matriptase and the shedding of active matriptase were also observed in two hematological cancer lines. Matriptase shedding is correlated closely with the induction of matriptase activation, suggesting that matriptase activation and shedding are kinetically coupled. The coupling allows a proportion of active matriptase to survive HAI-1 inhibition by rapid shedding from cell surface. Our study suggests that cellular free, active matriptase is scarce and might not be an effective target for in vivo imaging and drug development.
