Although the most important events are the requirement for renal replacement therapy or death due to kidney failure, many studies have used surrogates such as changes in GFR or the percentage of patients in whom the serum creatinine (SCr) level doubles. Such numerical end points may be particularly relevant in trials that include patients with early-stage CKD, among whom kidney failure and death are uncommon events. One problem with the assessment of such surrogates is that the therapeutic agent used to modify BP may also directly alter kidney function. For example, ACE-Is are known to reduce GFR through a vasodilator effect on the efferent arteriole. This effect may be beneficial in the early stages of CKD when a reduced intra-glomerular pressure is protective, but might be detrimental at a later stage when kidney function is severely compromised and dialysis may be imminent, at which time GFR may increase if ACE-Is are Thus, a drug may modify GFR via a mechanism that does not directly involve changes in systemic BP and the impact of this effect on the patient may vary according to CKD stage. The Work Group bore such considerations in mind when assessing the evidence and viewed consistency in the change of GFR outcomes across various CKD stages as a strong indicator of the benefits of a particular agent on kidney function. Albuminuria. The level of albuminuria in CKD predicts not only the prognosis with respect to kidney function but also morbidity and mortality from CVD events including Urinary albumin excretion is influenced by BP and by many of the agents used to reduce BP, particularly ACE-Is and ARBs. 