Atrial natriuretic peptide increases albuminuria in type 1 diabetic patients: evidence for blockade of tubular protein reabsorption.

Abstract

It has been suggested that atrial natriuretic peptide (ANP) contributes to the glomerular hyperfiltration of diabetes mellitus. Infusion of ANP increases the urinary excretion of albumin in patients with type 1 diabetes mellitus (IDDM). Although the increased albuminuria is attributed to a rise in glomerular pressure, alterations in tubular protein handling might be involved. We have studied the effects of ANP in nine microalbuminuric IDDM patients. After obtaining baseline parameters, ANP was infused over a 1-h period (bolus 0.05 μg kg⁻¹, infusion rate 0.01 μg kg⁻¹ min⁻¹). Renal haemodynamics, sodium and water clearance and tubular protein handling were studied. The glomerular filtration rate (GFR) increased from 116.4 ± 8.9 to 128.3 ± 8.8 mL min⁻¹ 1.73 m⁻², whereas the effective renal plasma flow (ERPF) decreased from 534.3 ± 44.3 to 484.9 ± 33.3 mL min⁻¹ 1.73m⁻² (P < 0.05). As a result, the filtration fraction was significantly higher during infusion of ANP. ANP attenuated proximal tubular sodium reabsorption. Urinary albumin excretion rose from 87.57 ± 21.03 to 291.40 ± 67.86 μg min⁻¹ (P < 0.01). Changes in the urinary excretion of β₂-microglobulin and free κ-light chains were more marked, the excretion of β₂-microglobulin increasing from 0.28 ± 0.21 to 51.87 ± 10.51 μg min⁻¹ (P < 0.01), and of free κ-light chains from 4.73 ± 1.74 to 46.14 ± 6.19 μg min⁻¹ (P < 0.01). The observed rise in albuminuria during infusion of ANP does not simply reflect a change in glomerular pressure, but might at least partly result from an attenuation of tubular protein reabsorption.