Value Of Early Therapy

The treatment of hypertension has long been recognized as a means for attenuating the course of overt nephropathy [18] (See Chapters 31 and 33). In recent years the particular value of ACEI or ARBs in such treatment has been established [1, 25-28]. When applied at a GFR of approximately 40 ml/min, ARBs delays ESRD by about two years compared to other antihypertensives. Probably another two years reprieve would occur for every 30 ml/min higher level of initiation [1, 25]. That is, four years would likely be gained if the drugs were started with overt proteinuria but a GFR of 70 ml/min. The earlier the treatment of overt nephropathy, the more time free of ESRD is gained.

For some observers, the major remaining point of uncertainty is the advantage of applying these drugs during the microalbumiuric phase and particularly in those who remain normotensive at that phase. Most patients with type 2 diabetes and microalbuminuria have hypertension especially if current JNC 7,

ADA, and NKF guidelines for target blood pressure of less than 130/80 are used [7, 29-32]. However, many type 1 diabetics with microalbuminuria may remain within these bounds [33]

The result of treatment with ACEIs or ARBs during microalbuminuria has been established by in randomized controlled trials and is similar in both types of diabetes though more extensive with type 2 disease. Such treatment clearly delays the appearance of overt nephropathy [1, 33, 34]. However, studies demonstrating delay to ESRD are lacking. Nevertheless, the continuous nature of albuminuria- the division between micro and overt is largely arbitrary-coupled with the clear diminution in deterioration in GFR by ACEI and ARB in the overt stage, both argue for a benefit in the earlier phase. The micro HOPE trial provides some additional support for these drugs at this phase [8]. In the final analysis though it must be admitted that formal evidence of prevention or delay of ESRD from a randomized clinical trial has not been adduced for treatment during microalbuminuria.

Current therapy applied at the stage of microalbuminuria cannot promise complete interdiction of progressive renal injury. Retrospectively identified subsets of patients do show stabilization or at least the slow declines comparable to aging alone [35]. Still, the follow-ups are not long enough to confidently consider these in remission. Thus, cure in the sense that successful surgery for cancer can cure, is not yet predictable in even early diabetic nephropathy. Substantial delay in ESRD is predictable and the earlier the application the longer the respite.

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