Blood Pressure Lowering Alone May Not Reduce Macroalbuminuria in Type 2 Diabetes

Blood pressure (BP) lowering is not sufficient to reduce macroalbuminuria in hypertensive patients with type 2 diabetes mellitus (DM2) and overt nephropathy, because losartan is effective but amlodipine is not.

"In hypertensive patients with advanced type 2 diabetic nephropathy, it is important to clarify whether 24-hour blood pressure control, especially nocturnal blood pressure reduction, induced by antihypertensive agents improves macroalbuminuria, a well-established predictor of end-stage renal disease," write Gen Yasuda, MD, from the Yokohama City University School of Medicine in Japan, and colleagues. "The aim of the present prospective study was to compare the effects of losartan, an angiotensin II receptor blocker, with those of amlodipine, a long-acting dihydropyridine calcium channel blocker, on the 24-hour blood pressure profile and the circadian autonomic nervous balance in hypertensive type 2 diabetic patients with overt nephropathy."

In this open-label, parallel study, patients were randomized to treatment with losartan (n = 44) or amlodipine (n = 43) for a 12-week titration phase and a maintenance phase for a maximum of 12 weeks. Urinary albumin excretion and 24-hour BP were measured before and during treatment, with simultaneous power spectral analysis of heart rate to evaluate low-frequency (LF) and high-frequency (HF) components and LF-to-HF ratios as an index of sympathovagal balance.

Losartan decreased mean systolic/diastolic BP from 162/91 to 150/82 mmHg during the day and from 146/82 to 137/74 mmHg during the night (P < .001). The corresponding decreases with amlodipine were from 159/90 to 147/82 mmHg and from 143/81 to 131/72 mmHg, respectively. The two groups did not differ during treatment in LF and HF components or in nighttime-to-daytime ratios for the LF-to-HF ratios, reflecting no changes in the diurnal autonomic nervous rhythm.

Losartan decreased 24-hour urinary albumin excretion from 810 mg/day (95% confidence interval [CI], 780 - 1,140) to 570 mg/day (95% CI, 510 - 910; P < .001), whereas amlodipine did not decrease albuminuria (790 mg/day [95% CI, 780 - 1,170] vs 790 mg/day [95% CI, 710 - 1,260]).

"Although both losartan and amlodipine decrease daytime and nighttime blood pressure equally without affecting the autonomic nervous activity, only losartan decreases urinary albumin excretion in type 2 diabetes with macroalbuminuria," the authors write. "These findings suggest that 24-hour blood pressure regulation alone is not enough to improve overt nephropathy, and additional beneficial effects of losartan on intraglomerular mechanism are crucial for an antiproteinuric effect."
Diabetes Care July 2005
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DID YOU KNOW:
More than 18 million Americans suffer from diabetes, which kills someone every three minutes. What's more, at least 35 children nationwide are diagnosed daily with this deadly illness.