Brain natriuretic peptide increases urinary albumin and alpha-1 microglobulin excretion in Type 1 diabetes mellitus

Diabet Med. 2001 Dec;18(12):973-8. doi: 10.1046/j.0742-3071.2001.00569.x.

Abstract

Atrial natriuretic peptide (ANP) increases urinary albumin excretion in Type 1 diabetes mellitus (DM). Brain natriuretic peptide (BNP) is structurally and functionally related to ANP, but its effect on urine albumin excretion rate (UAER) is unknown.

Aims: To compare the albuminuric effects of intravenous infusion of ANP and BNP, and to assess the effect of both peptides on tubular protein excretion.

Methods: Eight subjects with Type 1 DM were randomised to a three leg, double blind, and placebo controlled study. On each study day, subjects were euglycaemic clamped and subsequently water loaded (20 mL/kg orally, plus urine losses) to steady state diuresis. When in steady state, creatinine clearance was estimated in three separate 1 hour periods. At the end of the first period, a 1 hour intravenous infusion of either placebo, ANP 0.025 microg/kg/min, or BNP 0.025 microg/kg/min was administered. There followed a 1 hour recovery period. Urine was collected at 15 min intervals for estimation of urine albumin (ACR) and alpha1 microglobulin creatinine ratio (MCR). Results were analysed by anova.

Results: Creatinine clearance was similar on the three study days, and was unaltered by any infusion. ACR was unaltered by placebo (1.3 +/- 0.5-1.2 +/- 0.4 mg/mmol, mean +/- SD, p = 0.81), but increased compared to placebo with infusion of both ANP (1.2 +/- 0.4-9.8 +/- 8.4 mg/mmol, P = 0.0004), and BNP (1.1 +/- 0.4-13.4 +/- 8.6 mg/mmol, P = 0.0001). The MCR was unaltered by placebo infusion (P = 0.89), but increased compared with placebo after infusion of ANP (5.4 +/- 0.9-12.3 +/- 4.2 mg/mmol, P < 0.0001), and BNP (5.4 +/- 0.8-12.1 +/- 2.5 mg/mmol, P < 0.0001).

Conclusions: Intravenous infusion of BNP and ANP both increase the urine excretion of albumin and the tubular protein alpha1 microglobulin, independent of creatinine clearance.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria* / chemically induced
  • Alpha-Globulins / urine*
  • Atrial Natriuretic Factor / administration & dosage
  • Atrial Natriuretic Factor / pharmacology*
  • Creatinine / metabolism
  • Creatinine / urine
  • Diabetes Mellitus, Type 1 / urine*
  • Double-Blind Method
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Natriuretic Peptide, Brain / administration & dosage
  • Natriuretic Peptide, Brain / pharmacology*
  • Placebos

Substances

  • Alpha-Globulins
  • Placebos
  • alpha-1-microglobulin
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor
  • Creatinine