Renal hypertensive target organ damage--new evidence emerges in diabetics and smokers.

TLDR: Recent data from a large-scale follow-up study of apparently healthy subjects indicate that three repeated measurements of urinary albumin–creatinine ratio are superior to predict all-cause mortality compared to one or two measurements, and current European guidelines recommend that erum creat inine, preferably with estimation of creatinine clearance, and serum urea be assessed, and urinaryalbumin excretion be measured in all hypertensive patients.

Abstract: The diagnosis of hypertension-induced renal damage is based on elevated serum creatinine, decreased creatinine clearance or elevated urinary excretion of albumin according to the 2003 Guidelines of the European Society of Hypertension and the European Society of Cardiology [1]. Thus, slight elevation of serum creatinine concentration (107–133 mol/l) is taken as sign of target organ damage. According to the same guidelines, the presence of mild renal insufficiency, defined as serum creatinine 133 mol/l (1.5 mg/dl) in men and 124 mol/l (1.4 mg/dl) in women [2, 3] or by estimated creatinine clearance values below 60–70 ml/min [4], is classified as an associated clinical condition, i.e. a very high added risk in the high normal or hypertensive blood pressure range. Increased urinary albumin excretion is a sign of a derangement in the glomerular filtration barrier [5]. Microalbuminuria [usually defined as albumin concentration 20 mg/l or albumin–creatinine ratio 2.5 mg/mmol (in men) or 3.5 mg/mmol (in women)] predicts development of overt diabetic nephropathy in subjects with type 1 as well as type 2 diabetes [6], while the presence of proteinuria or albuminuria indicate the existence of established renal parenchymatous disease [7]. Microalbuminuria and in particular overt albuminuria is associated with significant increase in cardiovascular risk [8]. In non-diabetic hypertensive patients, microalbuminuria predicts cardiovascular events, even below the threshold values currently considered pathological [9]. There is a continuous relationship between urinary albumin excretion and cardiovascular as well as noncardiovascular mortality in the general population [10]. Recent data from a large-scale follow-up study of apparently healthy subjects indicate that three repeated measurements of urinary albumin–creatinine ratio are superior to predict all-cause mortality compared to one or two measurements [11]. Such a procedure lowers the albumin–creatinine ratio cut-off level to the 60th percentile ( 0.76 mg/mmol or 6.7 g/mg) allowing improved outcome prediction [11]. The finding of an impaired renal function in a hypertensive patient, i.e. elevated serum creatinine, reduced creatinine clearance or microalbuminuria, is commonly encountered in clinical practice and constitutes a potent predictor of future cardiovascular events or death [4, 12]. Current European guidelines therefore recommend that erum creatinine, preferably with estimation of creatinine clearance, and serum urea be assessed, and urinary albumin excretion be measured in all hypertensive patients [1]. This issue of Blood Pressure contains interesting papers in this respect. Firstly, the short review by Leoo & Odar-Cederlo ̈f [13] review the importance of repeated testing for microalbuminuria in patients with diabetes [13]. The goal of treatment is to reduce urinary output of albumin as well as blood pressure. Thus, urinary albumin excretion needs to be assessed regularly as does blood pressure, in order to ensure that the therapeutic measures are effective [13]. Secondly, Reims and co-workers report from the LIFE Study [14] that hypertensive patients with left ventricular hypertrophy who smoke have higher urinary albumin excretion and serum creatinine than nonsmokers, while previous smokers have an intermediate urinary albumin excretion and serum creatinine level. Increased albumin excretion was an important predictor of cardiovascular endpoints in the LIFE study patients [15] and both elevated urinary albumin excretion and increased serum creatinine may contribute to the increased risk imposed by smoking [14]. Thirdly, Sørensen and co-workers [16] report from a Danish study of 115 hypertensive smokers and 230 hypertensive non-smokers, carefully matched for clinic blood pressure, age and gender, that smokers have higher ambulatory systolic blood pressure and urinary albumin–creatinine ratio. The authors suggest that the higher daytime blood pressure as well as microalbuminuria in smokers may contribute to their increased cardiovascular risk [16]. The overall picture, thus, is that urinary albumin excretion, a measure of altered glomerular barrier and indicative of increased risk of cardiovascular disease and mortality, should be assessed in all hypertensives. This is particularly relevant in patients with diabetes and in smokers. Furthermore, threshold levels of urinary albumin excretion associated with increased risk need to be established, and randomized clinical trials are warranted to determine whether lowering of albumin excretion confers reduced cardiovascular risk.