Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study

Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure

The effect of losartan on hemoglobin concentration and renal outcome in diabetic nephropathy of type 2 diabetes

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can decrease hemoglobin, causing anemia and this may be an independent risk factor for chronic kidney disease progression. We studied the relationship between a decline in hemoglobin and outcome in 1513 patients with type 2 diabetes and kidney disease by a post hoc analysis of the RENAAL Study (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) with an average follow-up of 3.4 years. The relationship between baseline and year-1 hemoglobin and treatment on end-stage renal disease (ESRD) and ESRD or death was evaluated using multivariate Cox models (covariates: baseline hemoglobin, proteinuria, serum albumin, serum creatinine, and year-1 hemoglobin). Compared with placebo, losartan treatment was associated with a significant decrease of hemoglobin, with the largest between-group difference at 1 year. After adjustment, there were significant relative risk reductions for losartan compared with placebo for ESRD and for ESRD or death regardless of the baseline hemoglobin even in those patients with a baseline hemoglobin below 120 g l−1. Hence, the renoprotective properties of losartan were maintained despite a significant lowering of the hemoglobin concentration

Supplementary Material for: Change in Hemoglobin Trajectory and Darbepoetin Dose Approaching End-Stage Renal Disease: Data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy Trial

<b><i>Background:</i></b> The pathogenesis of chronic kidney disease associated anemia is multifactorial and includes decreased production of erythropoietin (EPO), iron deficiency, inflammation, and EPO resistance. To better understand the trajectory of these parameters, we described temporal trends in hemoglobin (Hb), ferritin, transferrin saturation, C-reactive protein (CRP), and darbepoetin dosing in the Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT). <b><i>Methods:</i></b> We performed a post hoc analysis of 4,038 participants in TREAT. Mixed effects linear regression models were used to determine the trajectory of parameters of interest prior to end-stage renal disease (ESRD). Likelihood ratio tests were used to determine the overall differences in biomarker values and differences in trajectories between those who did and did not develop ESRD. <b><i>Results:</i></b> Hb declined precipitously in the year prior to the development of ESRD (irrespective of treatment assignment), and was on average 1.15 g/dL (95% CI –1.26 to –1.04) lower in those who developed ESRD versus those who did not, at the time of ESRD/end of follow-up. Simultaneously, the mean darbepoetin dose and CRP concentration increased, while serum ferritin and transferrin saturations were >140 μg/L and 20%, respectively. <b><i>Conclusions:</i></b> Our analyses provide descriptive insights regarding the temporal changes of Hb, darbepoetin dose, and related parameters as ESRD approaches in participants of TREAT. Hb declined as much as 1–2 years prior to the development of ESRD, without biochemical evidence of iron deficiency. The most precipitous decline occurred in the months immediately prior to ESRD, despite administration of escalating doses of darbepoetin and in parallel with an increase in CRP

Supplementary Material for: Change in Hemoglobin Trajectory and Darbepoetin Dose Approaching End-Stage Renal Disease: Data from the Trial to Reduce Cardiovascular Events with Aranesp Therapy Trial

<b><i>Background:</i></b> The pathogenesis of chronic kidney disease associated anemia is multifactorial and includes decreased production of erythropoietin (EPO), iron deficiency, inflammation, and EPO resistance. To better understand the trajectory of these parameters, we described temporal trends in hemoglobin (Hb), ferritin, transferrin saturation, C-reactive protein (CRP), and darbepoetin dosing in the Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT). <b><i>Methods:</i></b> We performed a post hoc analysis of 4,038 participants in TREAT. Mixed effects linear regression models were used to determine the trajectory of parameters of interest prior to end-stage renal disease (ESRD). Likelihood ratio tests were used to determine the overall differences in biomarker values and differences in trajectories between those who did and did not develop ESRD. <b><i>Results:</i></b> Hb declined precipitously in the year prior to the development of ESRD (irrespective of treatment assignment), and was on average 1.15 g/dL (95% CI –1.26 to –1.04) lower in those who developed ESRD versus those who did not, at the time of ESRD/end of follow-up. Simultaneously, the mean darbepoetin dose and CRP concentration increased, while serum ferritin and transferrin saturations were >140 μg/L and 20%, respectively. <b><i>Conclusions:</i></b> Our analyses provide descriptive insights regarding the temporal changes of Hb, darbepoetin dose, and related parameters as ESRD approaches in participants of TREAT. Hb declined as much as 1–2 years prior to the development of ESRD, without biochemical evidence of iron deficiency. The most precipitous decline occurred in the months immediately prior to ESRD, despite administration of escalating doses of darbepoetin and in parallel with an increase in CRP