Chronic kidney disease (CKD) is an inherently systemic disease that refers to a long-term loss of kidney function. The progression of CKD has repercussions for other organs, leading to many kinds of extrarenal complications. Intensive studies are now being undertaken to reveal the risk factors and pathophysiological mechanism of this disease. During the past 20 years, increasing evidence from clinical and basic studies has indicated that klotho, which was initially known as an anti-aging gene and is mainly expressed in the kidney, is significantly correlated with the development and progression of CKD and its complications. Here, we discuss in detail the role and pathophysiological implications of klotho in ion disorders, the inflammation response, vascular calcification, mineral bone disorders, and renal fibrosis in CKD. Based on the pathogenic mechanism of klotho deficiency and klotho decline in urine early in CKD stage 2 and even earlier in CKD stage 1, it is not difficult to understand that soluble klotho can serve as an early and sensitive marker of CKD. Moreover, the prevention of klotho decline by several mechanisms can attenuate renal injuries, retard CKD progression, ameliorate extrarenal complications, and improve renal function. In this review, we focus on the functions and pathophysiological implications of klotho in CKD and its extrarenal complications as well as its potential applications as a diagnostic and/or prognostic biomarker for CKD and as a novel treatment strategy to improve and decrease the burden of comorbidity in CKD.

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This research inspects the allocation of involvement load to the evaluation component of the involvement load hypothesis, examining how three typical approaches to evaluation (cloze-exercises, sentence-writing, and composition-writing) promote word learning. The results of this research were partially consistent with the predictions of the hypothesis: the two writing tasks with greater involvement load led to significantly better word learning than cloze-exercises with lower load, while composition-writing was significantly more effective than sentence-writing despite the same involvement load according to the matrix of the original model. Such results are explained from the perspectives of information organization and pre-task planning, based on which evaluation induced by cloze-exercises is suggested to be allocated with ‘moderate evaluation’ as it involves no use of chunking, hierarchical organization or pre-task planning, evaluation induced by sentence-writing with ‘strong evaluation’ as it involves chunking and pre-task planning at the sentence level, and evaluation induced by composition-writing with ‘very strong evaluation’ for it involves chunking, hierarchical organization and pre-task planning at the composition level.

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