Determinants of intra-individual variation in kidney function in normoalbuminuric insulin-dependent diabetic patients: importance of atrial natriuretic peptide and glycaemic control

1. In order to investigate the modulation of kidney function in insulin-dependent diabetes mellitus, intra-individual variation in glomerular filtration rate, renal plasma flow, urinary albumin excretion rate and mean arterial blood pressure was assessed in 22 normoalbuminuric patients [age 31 ± 8 years, duration of diabetes 9 ± 5 years, mean arterial blood pressure 90 ± 5 mmHg (means ± sd), urinary albumin excretion rate 5.4 × / ÷ 1.6 μg/min]. The variation in these parameters was calculated from the results of two clearance studies (continuous infusion of [¹²⁵I]-iothalamate and ¹³¹I-hippuran as markers for glomerular filtration rate and renal plasma flow, respectively) and was subsequently analysed in relation to individual variation in plasma concentrations of atrial natriuretic peptide, arginine vasopressin, angiotensin II and aldosterone and measures of glycaemic control.

2. Simple correlation analysis showed a significant association between intra-individual variation in glomerular filtration rate and atrial natriuretic peptide (σ = 0.66, P = 0.003). Besides variation in atrial natriuretic peptide, multiple regression analysis identified variation in glycated haemoglobin (P = 0.026) and arginine vasopressin (P = 0.057) as variables having independent association with variation in glomerular filtration rate [R² with the three variables included (adjusted for degrees of freedom) = 0.50, analysis of variance: P = 0.002].

3. With respect to variation in renal plasma flow, differences in fasting blood glucose concentration and mean arterial blood pressure were suggested as determinants (R² = 0.36, analysis of variance: P = 0.009).

4. Variation in urinary albumin excretion rate (after log transformation) was statistically associated with variation in glycated haemoglobin.

5. When compared with eight healthy control subjects, atrial natriuretic peptide was moderately increased in the diabetic patients [4.7(4.2–6.2) versus 3.9 (3.4–4.6) pmol/l, median (first and third quartile), 2P<0.05].

6. In conclusion, the study identified individual changes in atrial natriuretic peptide, arginine vasopressin and long-term glycaemic control as factors associated with intra-individual variation in glomerular filtration rate. It is suggested that atrial natriuretic peptide is involved in the regulation of glomerular filtration rate and possibly specifically in diabetic hyperfiltration.