22. Nakao N et al. Lancet 2003; 361: 117 - 24
COOPERATE Study
Combination treatment with losartan and trandolapril
Combination n = 88
Losartan n = 89
Trandolapril n = 86
Months after randomisation
0
1
2
3
Median
U
protein
excretion
(
g
/
day
)
0 5 20 25 30 35 40
15
10
P = 0.01
23. Renoprotection: ACE inhibitors vs.
other antihypertensives
Calcium antagonists ACE inhibitors Diuretics and/or b-
blockers
Urinary protein
Mean
systemic
blood
pressure
0 –10 –20 –30 –40 –50
Decrease from baseline (%)
Böhlen L et al. Am J Hypertens 1994; 7: 84S–92S
An increase in urinary albumin excretion results from a rise in its transglomerular passage. Most healthy people have urinary albumin excretion rates ranging between 5 and 30 mg/24 hrs, although excretion varies with posture, exercise and the day-to-day variation (co-efficient of variance) is 31% to 52%.1 Therefore, it has been recommended that the mean of at least three urine collections is used to determine a subject’s albumin excretion level. For screening purposes, measurement of urinary albumin concentration using the first morning specimen has been suggested, since this specimen is considered to vary the least.2 However, an important consideration is the 30% to 50% lower urinary albumin excretion values seen at night. First-void urine samples are thus more concentrated because there is little water intake and little physical activity at night.
The transition from a normal albumin excretion rate to clinical proteinuria (which is detectable by routine urinalysis) is the phase of microalbuminuria, defined as an albumin excretion rate of 30–300 mg/24 hrs.3 This is not detectable by routine urinalysis.
References
1. Mogensen CE. Microalbuminuria as a predictor of clinical diabetic nephropathy. Kidney Int 1987; 31: 673–689.
2. Howey JEA, Browning MCK, Fraser CG. Biological variation of urinary albumin: Consequences for analysis, specimen collection, interpretation of results, and screening programs. Am J Kidney Dis 1989;13: 35–37.
3. Mogensen CE, Keane WF, Bennet PH et al. Prevention of diabetic renal disease with special reference to microalbuminuria. Lancet 1995; 346: 1080–1084.
A variety of therapeutic pharmacologic agents has been developed for the control of hypertension. Long-term studies have shown that blood pressure control using thiazide diuretics and b-blockers results in a significant attenuation in the progression of renal disease; however, increasing evidence suggests that the beneficial effects on renal function seen with antihypertensive agents are not simply due to control of arterial pressure, but may also be related to their intra-renal and systemic hemodynamics as well as cellular effects.
Evidence has emerged to show agents that maintain blood pressure at similar values do not have similar effects on preservation of kidney function and suggests that ACE inhibitors may provide additional renal benefits above and beyond those induced by conventional blood pressure lowering. This has been shown in a number of studies including a meta-analysis of studies performed in a total of 1,610 patients with diabetes. This study demonstrated that ACE inhibitors had the ability to exert a specific antiproteinuric effect independent from an antihypertensive action.1 In this meta-analysis, the mean systemic blood pressure decreased by –10% with diuretics and/or b-blockers and –12% with ACE inhibitors and with calcium antagonists. ACE inhibitor therapy produced the greatest decrease in urinary albumin or protein excretion (of –45% vs. –23% with diuretics and/orb-blockers and –17% with calcium antagonists).1
Reference
1. Böhlen L, de Courten M, Weidmann P. Comparative study of the effect of ACE-inhibitors and other antihypertensive agents on proteinuria in diabetic patients. Am J Hypertens 1994; 7: 84S–92S.