A longitudinal study of inflammation, CKD-mineral bone disorder, and carotid atherosclerosis after renal transplantation

Clin J Am Soc Nephrol. 2015 Mar 6;10(3):471-9. doi: 10.2215/CJN.07860814. Epub 2014 Dec 26.

Abstract

Background and objectives: The role of reversibility of nontraditional risk factors, like inflammation and CKD-mineral bone disorder, in the reduction of cardiovascular risk after renal transplantation is still scarcely defined.

Design, setting, participants, and measurements: The longitudinal relationship between C-reactive protein, CKD-mineral bone disorder biomarkers, and intima media thickness was investigated in a series of 178 patients (age=32±10 years) with stage 5 CKD maintained on chronic dialysis who underwent echo-color Doppler studies of the carotid arteries before and after renal transplantation. Smokers and patients with diabetes were excluded from the study. In all patients, immunosuppression was performed by a standard regimen on the basis of calcineurin inhibitors. Healthy controls were specifically selected to match the age and sex distribution of the patients. Biochemical and intima media thickness assessments were repeated 6 months after transplantation.

Results: Before transplantation, intima media thickness in patients with stage 5 CKD on dialysis (average=0.9±0.2 mm) was higher (P<0.001) than in well matched healthy controls (0.6±0.1 mm) and reduced substantially (-22%; 95% confidence interval, -24% to -20%) after transplantation (P=0.001). GFR (multivariable-adjusted β=0.23; P<0.001), C-reactive protein (β=0.15; P<0.001), and fibroblast growth factor 23 (β=0.28; P<0.001) were the strongest independent correlates of intima media thickness before transplantation. Similarly, longitudinal changes in the same biomarkers were the sole independent correlates of simultaneous changes in intima media thickness (C-reactive protein: β=0.25; fibroblast growth factor 23: β=0.26; P<0.001 for both) after renal transplantation. The evolution of intima media thickness after transplantation was largely independent of classic risk factors, including BP, LDL cholesterol, and insulin resistance, as measured by homeostatic model assessment.

Conclusions: Intima media thickness improves after renal transplantation. Such an improvement associates with parallel changes in serum C-reactive protein and fibroblast growth factor 23. These observations are in keeping with the hypothesis that the decline in cardiovascular risk after transplantation, in part, depends on partial resolution of nontraditional cardiovascular risk factors, like inflammation and CKD-mineral bone disorder.

Keywords: arteriosclerosis; chronic inflammation; renal transplantation.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Pressure
  • Bone Diseases, Metabolic / blood
  • Bone Diseases, Metabolic / complications
  • C-Reactive Protein / metabolism*
  • Calcium / blood
  • Carotid Artery Diseases / blood*
  • Carotid Artery Diseases / complications
  • Carotid Artery Diseases / diagnostic imaging*
  • Carotid Intima-Media Thickness
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood
  • Glomerular Filtration Rate
  • Humans
  • Inflammation / blood
  • Inflammation / complications
  • Insulin Resistance
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation
  • Longitudinal Studies
  • Male
  • Parathyroid Hormone / blood
  • Phosphates / blood
  • Postoperative Period
  • Preoperative Period
  • Young Adult

Substances

  • Biomarkers
  • Parathyroid Hormone
  • Phosphates
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • C-Reactive Protein
  • Calcium