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

Eur J Clin Invest. 1999 Feb;29(2):109-15. doi: 10.1046/j.1365-2362.1999.00422.x.

Abstract

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.

Patients and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / etiology*
  • Arginine / pharmacology
  • Atrial Natriuretic Factor / pharmacology*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / urine
  • Electrolytes / urine
  • Glomerular Filtration Rate / drug effects
  • Hemodynamics / drug effects
  • Humans
  • Immunoglobulin Light Chains / urine
  • Kidney Tubules / drug effects*
  • Kidney Tubules / metabolism
  • Lithium / urine
  • Middle Aged
  • Regional Blood Flow / drug effects
  • Sodium / metabolism
  • beta 2-Microglobulin / urine

Substances

  • Electrolytes
  • Immunoglobulin Light Chains
  • beta 2-Microglobulin
  • Atrial Natriuretic Factor
  • Arginine
  • Lithium
  • Sodium