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) contributes to the glomerular hyperfiltration of diabetes mellitus. Infusion of ANP increases the urinary excretion of albumin in patients with type I diabetes mellitus (IDDM). Although the increased albuminuria is attributed to a rise in glomerular pressure, alterations in tubular protein handling might be involved.


METHODS
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 microgram kg-1, infusion rate 0.01 microgram kg-1 min-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 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 1.73 m-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 micrograms min-1 (P < 0.01). Changes in the urinary excretion of beta 2-microglobulin 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 micrograms min-1 (P < 0.01), and of free kappa-light chains from 4.73 +/- 1.74 to 46.14 +/- 6.19 micrograms min-1 (P < 0.01).


CONCLUSIONS
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.
Jacobs
E M
EM
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Vervoort
G
G
Branten
A J
AJ
Klasen
I
I
Smits
P
P
Wetzels
J F
JF
D000328:Adult; D000419:Albuminuria / Q000209:etiology*; D001120:Arginine / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism* / Q000652:urine; D004573:Electrolytes / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000652:urine; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000652:urine; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000652:urine
D004573:Electrolytes; D007147:Immunoglobulin Light Chains; D001613:beta 2-Microglobulin; D009320:Atrial Natriuretic Factor; D001120:Arginine; D008094:Lithium; D012964:Sodium