Cumulative Subject proteins

It is not known whether these changes are the result of a normal aging process (i.e., involutional) or the result of the interplay of pathology and age. Cumulative exposure to common causes of chronic kidney disease (CKD), such as (1) atherosclerosis, (2) hypertension, (3) heart failure, (4) diabetes,(5) obstructive nephropathy, (5) infection, (6) immune insult, (7) nephrotoxins such as lead, and (8) dietary protein increases with age and it is difficult to separate these effects from those of healthy aging. The decline in GFR with increasing age may be largely attributable to hypertension, atherosclerosis, or heart failure. In the absence of these or other identifiable causes of kidney disease, many older subjects have stable GFR over time. 

Regulation of HMG-CoA reductase protein levels is mechanistically complex and subject to multivalent feedback control [141]. The following lines of evidence indicate that HMG-CoA reductase responds to multiple regulatory signals which exert independent, cumulative effects ... 

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