pressure reduction with and without ACE inhior, in other words, it acted as a progression promoter bition. Furthermore, the UKPDS study reported that by 2044 Nephrology Forum: Diabetic nephropathy Fig. 2. Effects of intensive versus conventional blood glucose control on progression of nephropathy (from [50]). six years a smaller proportion of patients in the group A small study in Japanese patients with type 2 diabetes under tight blood pressure control had developed micro- applied a similar design as the DCCT study and showed albuminuria and a 29% reduction in risk (P 0.009), a beneficial effect on progression from normo- to microwith a non-significant 39% reduction in the risk for pro- and 266) comparing the ef- trol on the development of microalbuminuria and overt fect of intensive versus conventional blood glucose con- proteinuria [53]. trol on the risk of progression to nephropathy in patients Secondary prevention. Several modifiable risk factors with type 1 diabetes and normoalbuminuria (80%) or and markers for progression from microalbuminuria to microalbuminuria (20%). Their results showed that the overt nephropathy (level of urinary albumin excretion risk of progression of nephropathy, defined as an incre- rate, HbA1C, blood pressure, serum cholesterol concenment in urinary albumin excretion rate, was decreased tration) have been identified in clinical trials and obserwith intensified treatment [odds ratio 0.34 (95% CI, 0.20 vational studies in patients with type 1 and type 2 diabeto 0.58); Fig. 2] [50]. Development of the categorical tes [54, 55]. A meta-analysis of 12 trials in 698 type 1 variables micro- and macroalbuminuria was not ac- diabetic patients with microalbuminuria who were folcounted for in this meta-analysis. In the Diabetes Control lowed for at least one year has revealed that ACE inhibiand Complications Trial (DCCT), however, intensified tors reduced the risk of progression to macroalbuminuria therapy in patients with type 1 diabetes reduced the by 62% compared to that of the placebo group [odds occurrence of microalbuminuria by 39% (95% CI, 21% ratio 0.38 (95% CI, 0.25 to 0.57)] [56]. Regression to to 52%), and that of albuminuria by 54% (95% CI, 19% normoalbuminuria was three times greater than in the to 74%), when the two cohorts were analyzed together patients receiving a placebo. At two years, the urinary [51]. Despite this reduction, 16% in the primary preven- albumin excretion rate was 50% lower in the patients tion cohort and 26% in the secondary prevention cohort taking ACE inhibitors than in those receiving placebo. developed microalbuminuria during the nine years of Furthermore, we showed that the beneficial effect of intensified treatment. Furthermore, the trial documented ACE inhibitors on preventing progression from microthat the beneficial effect of intensified treatment does albuminuria to overt nephropathy is long lasting (eight not occur for at least three years. The DCCT trial clearly years) and, more importantly, it is associated with preserdocuments that we need additional treatment modalities vation of normal GFR [57]. Recent data from a doubleto reduce or avoid the increasing burden of diabetic blind randomized study lasting three years show that nephropathy. long-acting dihydropyridine calcium antagonists are as Nephrology Forum: Diabetic nephropathy 2045 Table 1. Progression of microalbuminuria to nephropathy in normo- and hypertensive diabetic patients with type 2 diabetes N Observation Patients developing GFR Author [reference] patients period years nephropathy %/yr mL/min/yr Mogensen [59]a 59 9 2.4— Estacio et al [48]c 150 5 4.0 1 Gerstein et al [46]d 1140 4.5 4.5 — a Normotensive/predominantly normotensive. bRandomized controlled trials (placebo arm) cRandomized controlled trial in predominantly hypertensive subjects receiving treatment with or without an ACE inhibitor dRandomized controlled trial in hypertensive type 2 diabetic patients receiving an ACE inhibitor or long-acting dihydropyridine calcium antagonist effective as ACE inhibitors in delaying the occurrence of diabetes and microalbuminuria [51, 64–67]. Statistical macroalbuminuria in normotensive patients with type 1 analysis showed no significant impact on the distribution diabetes who have persistent microalbuminuria [58]. A of the categorical variables normo-, micro-, and macroretrospective study by Mogensen suggested that the pro- albuminuria (P 0.1). This disappointing result partly much slower in patients with type 2 compared to type 1 might be due to the relatively short length of the followdiabetes [59]. However, all prospective studies have up period, since the UKPDS study with 15 years of folclearly documented a rate of progression between 4% low-up documented a progressive beneficial effect with and 9% per year, equal to that in type 1 diabetic patients time on the development of proteinuria and a twofold (Table 1) [7, 46, 48, 55, 60, 61]. Ravid et al originally increase in plasma creatinine [53]. Furthermore, pancredescribed the beneficial effect of ACE inhibition in nor- atic transplantation can reverse glomerulopathy in pamotensive microalbuminuric patients with type 2 diabe- tients with type 1 diabetes and normo- (N