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10.1056/NEJMra021844 115 LehmannJ

Outcomes covered biologic/surrogate (e.g., proteinuria, estimated glomerular filtration rate [eGFR] slope) and hard endpoints (kidney failure, major cardiovascular events, fractures, mortality)

PMCID: PMC3166784

The dissociation between peak plasma concentration and clinical effects indicates acute tolerance, which may reflect rapid molecular processes such as redistribution of vesicular monoamines and internalization of monoamine receptors and transporters [6,36]