tem (RAS) such as angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs). A review of 1,102 CKD patients from 12 randomized clinical trials clearly showed that in these cases the initial serum creatinine increase associated with RAS inhibitor-based antihypertensive regimens is also followed by slower disease progression [3] . Note that larger shortterm increases were associated with slower GFR decline in the long term. Thus, as originally suggested by Apperloo et al. [1] , short-term serum creatinine increases associated with BP reduction ‘should be rewarded as an evidence of efficacy rather than an unwanted effect of treatment’. Despite the above findings, however, the very authors of the above review suggested that when serum creatinine increases exceed 30% within the first 2 months of RAS inhibition, treatment should be withdrawn [3] . This recommendation was also noted in the National Kidney Foundation K/DOQI clinical guidelines [4] . However, neither the review nor the K/DOQI guidelines provided any evidence that short-term serum creatinine increases exceeding the above threshold are associated with long-term accelerated renal function loss. In this issue of the American Journal of Nephrology, Hirsch et al. [5] strongly suggest that the opposite may be true regarding initial changes in serum creatinine and In 1997, Apperloo et al. [1] reported that in 40 patients with non-diabetic chronic kidney disease (CKD), antihypertensive treatment was associated with a short-term glomerular filtration rate (GFR) fall that inversely correlated with subsequent GFR decline. Patients with a larger fall eventually had a slower decline and even a GFR stabilization in some cases, whereas those with smaller or no short-term changes had the fastest renal function loss in the long run. Since the GFR fall was associated with a reduction in filtration fraction and fully recovered after treatment withdrawal, the authors guessed that their findings could be explained by a treatment-induced reduction of glomerular intracapillary pressure. Based on previous evidence that glomerular pressure reduction limited proteinuria and glomerulosclerosis in several experimental models of diabetic and non-diabetic CKD [2] , the authors hypothesized that a similar mechanism could explain the long-term renoprotective effect of antihypertensive treatment observed in their patients. In the following years, evidence accumulated that GFR and serum creatinine changes associated with blood pressure (BP) reduction are especially prominent in subjects with a long-lasting markedly elevated BP and renal insufficiency, in particular when the antihypertensive regimen includes inhibitors of the renin-angiotensin sysPublished online: October 30, 2012 Nephrology American Journal of