Considerations about the threshold value of microalbuminuria in patients with diabetes mellitus: lessons from an 8-year follow-up study of 599 patients
Introduction
The predictive value of microalbuminuria for the subsequent development of nephropathy as well as cardiovascular disease in diabetic patients is now well established [1], [2], [3], [4]. Whether microalbuminuria and cardiovascular disease are causally related or reflect a common derangement (e.g. endothelial dysfunction) has not been hitherto settled [5]. Microalbuminuria is defined as albumin excretion rate (AER) of 30–299 mg/24 h or urinary albumin–creatinine ratio of 3–30 μg/mg [6], [7], [8]. This definition is arbitrary however, AER being indeed a continuous variable. Values in the high normal range were associated with accelerated progression to nephropathy in both type 1 and type 2 diabetes [6], [7], [8], [9], [10] and with increased mortality in the elderly general population [11]. Periodic screening for microalbuminuria is rapidly gaining acceptance in view of the emerging potential of intensive therapies to preserve kidney function and reduce morbidity and mortality in diabetic patients [12], [13]. Screening procedures require a well-defined threshold between normal and abnormal. Such a threshold may, however, be difficult to define in an apriori continuous variable and will, in any case, remain arbitrary. We have, therefore, chosen to try and redefine the threshold value of albumin excretion rate by examination of the correlation between three categories of AER, all within the normal range and the subsequent risk of nephropathy and cardiovascular events.
The present report analyses further the data of a prospective, long term follow-up study [14] on 599 patients with recently diagnosed type 2 diabetes mellitus, normal blood pressure values and initially ‘normal’ urinary albumin excretion rate (>30 mg/24 h). The lessons which may be learned form further subdivision of normoalbuminuria and their bearing on screening and therapeutic policies are the aim of this analysis.
Section snippets
Patients
The AER was determined during 1986 and 1987 in 850 consecutive patients with type 2 diabetes mellitus whose urine was negative for protein, using a standard dipstick test. The recruitment procedure, inclusion criteria and protocol were described in detail elsewhere [14]. In brief, patients were 40–60 years old, with diabetes diagnosed after age 40 and of <5 years duration. The blood pressure values were 140/90 mmHg or lower, serum creatinin was ≤124 μmol/l (1.4 mg/dl), body mass index (BMI) was
Results
Four patients discontinued the follow-up during the first 2 years and could not be traced. The data of 18 patients were incomplete. Thus, the analysis of renal outcome and of cardiovascular end-points and death was performed on 599 patients.
Twenty-four patients died during the follow-up period. The cause of death was related to coronary heart disease in 15 patients, cerebrovascular disease in two, malignancy in three, motor-vehicle crash in one and unknown in three.
The baseline characteristics
Discussion
The results of this 8-year follow-up study indicate that the subdivision of the initially normoalbuminuric patients into three groups delineated by their baseline AER was indeed valid for the prediction of a subsequent decline in renal function as well as of the risk of mortality and major manifestations of cardiovascular disease.
Group III with baseline AER values between 20.1 and 30 mg/24 h comprised 18% of the study group. The subsequent outcome of these patients both in terms of renal
References (37)
- et al.
Microalbuminuria is a predictor of vascular disease in non-diabetic subjects
Lancet
(1988) - et al.
Usefulness of microalbuminuria in predicting cardiovascular mortality in treated hypertensive men with and without diabetes mellitus. Risk factor intervention study group
Am. J. Cardiol.
(1997) - et al.
Serum creatinine determination without protein precipitation
Clin. Chim. Acta
(1972) - et al.
A statistical method for determining the breakpoint of two lines
Anal. Biochem.
(1984) - et al.
Plasma lipids and the progression of nephropathy in diabetes mellitus type 2: effect of ACE inhibitors
Kidney Int.
(1995) - et al.
Current strategies for retarding progression of renal disease
Am. J. Kidney Dis.
(1998) Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas
Diabetologia
(1999)Renoprotection in diabetes:genetic and non-genetic risk factors and treatment
Diabetologia
(1998)- et al.
Microalbuminuria and coronary heart disease in NIDDM: an incidence study
Diabetes
(1998) - et al.
Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus: prospective observational study
Br. Med. J.
(1997)