Christiane Drechsler1, Hege Pihlstrøm, Andreas Meinitzer, Stefan Pilz, Andreas Tomaschitz, Sadollah Abedini, Bengt Fellstrom, Alan G Jardine, Christoph Wanner, Winfried März, Hallvard Holdaas. 1. 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.
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.
RCT Entities:
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.