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

Background It has been suggested that atrial natriuretic peptide (ANP) cont ributes to the glomerular hyperfiltration of diabetes mellitus. Infusion of ANP increases the urinary excretion of albumin in patients with type 1 dia betes mellitus (IDDM). Although the increased albuminuria is attributed to a rise in glomerular pressure, alterations in tubular protein handling migh t be involved. Patients and methods We have studied the effects of ANP in nine microalbumi nuric IDDM patients. After obtaining baseline parameters, ANP was infused o ver a 1-h period (bolus 0.05 mu g kg(-1), infusion rate 0.01 mu g kg(-1) mi n(-1)). Renal haemodynamics, sodium and water clearance and tubular protein handling were studied. Results The glomerular filtration rate (GFR) increased from 116.4 +/- 8.9 t o 128.3 +/- 8.8 mL min(-1) 1.73 m(-2), whereas the effective renal plasma f low (ERPF) decreased from 534.3 +/- 44.3 to 484.9 +/- 33.3 mL min(-1) 1.73 m(-2) (P < 0.05). As a result, the filtration fraction was significantly hi gher during infusion of ANP. ANP attenuated proximal tubular sodium reabsor ption. Urinary albumin excretion rose from 87.57 +/- 21.03 to 291.40 +/- 67 .86 mu g min(-1) (P < 0.01). Changes in the urinary excretion of beta(2)-mi croglobulin and free kappa-light chains were more marked, the excretion of beta(2)-microglobulin increasing from 0.28 +/- 0.21 to 51.87 +/- 10.51 mu g min(-1) (P < 0.01), and of free kappa-light chains from 4.73 +/- 1.74 to 4 6.14 +/- 6.19 mu g min(-1) (P < 0.01). Conclusions The observed rise in albuminuria during infusion of ANP does no t simply reflect a change in glomerular pressure, but might at least partly result from an attenuation of tubular protein reabsorption.