title: Homoarginine and Clinical Outcomes in Renal Transplant Recipients: Results From the Assessment of Lescol in Renal Transplantation Study.
abstract: BACKGROUND
  Despite improvements in kidney transplantation, complications, including cardiovascular morbidity and graft loss, contribute to reduced graft and patient survival. The amino acid homoarginine exerts a variety of beneficial effects that may be relevant for cardiovascular and graft outcomes, which is investigated in the present study.
  
  
  METHODS
  Homoarginine was measured in 829 renal transplant recipients participating in the placebo group of the Assessment of Lescol in Renal Transplantation study. Mean follow-up was 6.7 years. By Cox regression analyses, we determined hazard ratios (HRs) to reach prespecified, adjudicated endpoints according to baseline homoarginine levels: major adverse cardiovascular events (n = 103), cerebrovascular events (n = 53), graft failure or doubling of serum creatinine (n = 140), noncardiovascular mortality (n = 51), and all-cause mortality (n = 107).
  
  
  RESULTS
  Patients mean age was 50 ± 11 years, homoarginine concentration was 1.96 ± 0.76 μmol/L, and 65% were men. Patients in the lowest homoarginine quartile (<1.40 μmol/L) had an adjusted 2.6-fold higher risk of cerebrovascular events compared to those in the highest quartile (>2.34 μmol/L) (HR, 2.56; 95% confidence interval [95% CI], 1.13-5.82). Similarly, the renal endpoint occurred at a significantly increased rate in the lowest homoarginine quartile (HR, 2.34; 95% CI, 1.36-4.02). For noncardiovascular and all-cause mortality, there was also increased risk associated with the lowest levels of homoarginine, with HRs of 4.34 (95% CI, 1.63-10.69) and 2.50 (95% CI, 1.38-4.55), respectively.
  
  
  CONCLUSIONS
  Low homoarginine is strongly associated with cerebrovascular events, graft loss and progression of kidney failure and mortality in renal transplant recipients. Whether interventions with homoarginine supplementation improve clinical outcomes requires further evaluation.
authors: 1 Division of Nephrology, Department of Medicine, University Hospital Würzburg, Würzburg, Germany. 2 Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany. 3 Department of Organ Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 4 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 5 Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care, Research, VU University Medical Centre, Amsterdam, the Netherlands. 6 Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical, University of Graz, Graz, Austria. 7 Department of Cardiology, Medical University of Graz, Graz, Austria. 8 Specialist Clinic for Rehabilitation Bad Aussee, Bad Aussee, Austria. 9 Division of Nephrology, Department of Medicine, Sykehuset i Vestfold, Tønsberg, Norway. 10 Division of Nephrology, Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden. 11 Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. 12 Department of Medicine V (Nephrology, Hypertensiology, Endocrinology, Rheumatologie) Mannheim Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. 13 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 14 Synlab Academy, Synlab Services, Mannheim, Germany.
authors: Christiane
authors: C
authors: Drechsler
authors: Hege
authors: H
authors: Pihlstrøm
authors: Andreas
authors: A
authors: Meinitzer
authors: Stefan
authors: S
authors: Pilz
authors: Andreas
authors: A
authors: Tomaschitz
authors: Sadollah
authors: S
authors: Abedini
authors: Bengt
authors: B
authors: Fellstrom
authors: Alan G
authors: AG
authors: Jardine
authors: Christoph
authors: C
authors: Wanner
authors: Winfried
authors: W
authors: März
authors: Hallvard
authors: H
authors: Holdaas
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D016009:Chi-Square Distribution; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005060:Europe; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D006085:Graft Survival; D006709:Homoarginine / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009656:North America; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D006709:Homoarginine; D000077340:Fluvastatin; D003404:Creatinine