Effect of renin angiotensin system blockade on pentraxin 3 levels in type-2 diabetic patients with proteinuria

Clin J Am Soc Nephrol. 2009 Mar;4(3):535-41. doi: 10.2215/CJN.04330808. Epub 2009 Feb 11.

Abstract

Background and objectives: Long pentraxin 3 (PTX3) is a multimeric inflammatory mediator. Increased serum PTX3 levels have been reported among end-stage renal disease patients. Moreover, PTX3 has been suggested to represent a novel mortality risk factor, and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease (CKD).

Design, setting, participants, & measurements: We analyzed data of 49 persons with stage 1 diabetic CKD and 32 healthy subjects in a prospective controlled trial. Endothelial dysfunction was determined by flow-mediated dilation (FMD). Serum PTX3, high-sensitivity C-reactive protein (hs-CRP) levels, and FMD were studied in baseline and after 12 wk of ramipril therapy. Stepwise multivariate regression analysis evaluated the association of FMD with clinical and serologic parameters.

Results: Serum PTX3, hsCRP, and albumin levels and proteinuria were significantly decreased, and FMD levels were significantly increased, after ramipril treatment. FMD was negatively correlated with serum PTX3, 24-h proteinuria, and hsCRP levels and positively correlated to serum albumin both at baseline and after the 12-wk treatment period. Multivariate regression analysis revealed that PTX3 levels were independently related to FMD both before and after ramipril treatment.

Conclusions: Our study shows that serum PTX3 levels are associated with endothelial dysfunction in patients with stage 1 diabetic CKD, independent of CRP. In addition, short-term ACE-inhibitor treatment significantly improves FMD and normalizes PTX3, hsCRP, and urinary protein excretion. (NCT: The study was registered in clinicaltrials.gov as NCT00674596.).

Publication types

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

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / physiopathology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Proteinuria / blood
  • Proteinuria / drug therapy*
  • Proteinuria / etiology
  • Proteinuria / physiopathology
  • Ramipril / therapeutic use*
  • Renin-Angiotensin System / drug effects*
  • Serum Amyloid P-Component / metabolism*
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Vasodilation / drug effects

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein
  • Ramipril

Associated data

  • ClinicalTrials.gov/NCT00674596