Vascular health, systemic inflammation and progressive reduction in kidney function; clinical determinants and impact on cardiovascular outcomes

Nephrol Dial Transplant. 2011 Nov;26(11):3537-43. doi: 10.1093/ndt/gfr081. Epub 2011 Mar 4.

Abstract

Introduction: Systemic inflammation, endothelial dysfunction and arterial thickening contribute to the elevated cardiovascular risk of dialysis patients. However, the course of these derangements and their relative contribution to the cardiovascular risk of nondialysed chronic kidney disease (CKD) are scarcely investigated.

Methods: Flow-mediated dilatation (FMD) and intima-media thickness (IMT) were assessed in 304 nondialysed CKD patients Stages 1-5 (mean age 46 ± 12 years, 158 men), together with routine biochemical measurements, C-reactive protein (CRP) and insulin resistance. Patients were then followed for time-to-event analysis of cardiovascular outcomes (fatal and nonfatal).

Results: CRP and IMT increased, while FMD decreased in parallel with estimated glomerular filtration rate (eGFR) decline (P < 0.001 for all). CRP and intact parathormone, as well as eGFR, appeared as strong determinants of FMD and IMT in multivariate analyses. After a median follow-up of 41 (range 6-46) months, 30 fatal and 59 nonfatal cardiovascular events occurred. In univariate analysis, FMD, IMT and CRP were significant predictors of outcome. In a multivariate Cox model excluding IMT, both FMD [hazard ratios 0.52 (95% confidence intervals 0.37-0.73) per %] and CRP [1.07 (1.03-1.11) per mg/L] predicted cardiovascular outcomes independently of confounders. In a model excluding FMD, only CRP (and not IMT) was a significant predictor.

Conclusions: Endothelial dysfunction, arterial thickening and inflammation occur in parallel with the decline in eGFR, contributing to the increased cardiovascular risk of nondialysed CKD. Our results support the use of FMD over IMT measurements to monitor nondialysed CKD patients at risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / mortality*
  • Cohort Studies
  • Endothelium, Vascular / physiopathology*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Humans
  • Inflammation / physiopathology*
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Prognosis
  • Renal Dialysis / adverse effects*
  • Risk Factors
  • Survival Rate
  • Tunica Media / physiopathology*

Substances

  • C-Reactive Protein