The Authors Reply: We thank Pallet et al. 1 for their interest in our recent publication. They satisfactorily show urinary metabolites discriminating different chronic kidney disease (CKD) stages. 2 We concur with them on the usefulness of 1 H nuclear magnetic resonance spectroscopy for the discovery of urinary biomarkers of CKD and the need to design further studies to better understand the pathophysio- logy of CKD based on the information obtained by urine metabolomics. Their independent validation of urinary citrate and threonine as classifiers for CKD in a larger cross-sectional cohort brings the spotlight on to these two metabolites. Additional studies addressing the outcome- prediction potential as well as the causes and consequences of these changes are warranted. In this regard, we support the potential of selected reaction monitoring-based liquid chromatography–mass spectrometry/mass spectrometry and the integration of this platform in routine clinical practice. 1. Pallet N, Thervet E, Beaune P et al. The urinary metabolome of chronic kidney disease. Kidney Int 2014; 85: 1239–1240. 2. Posada-Ayala M, Zubiri I, Martin-Lorenzo M et al. Identification of a urine metabolomic signature in patients with advanced-stage chronic kidney disease. Kidney Int 2014; 85: 103–111. Gloria Alvarez-Llamas 1 , Fernando Vivanco 1,2 and Alberto Ortiz 3 1 Department of Immunology, IIS-Fundacio´n Jime ´ nez Dı´az, Madrid, Spain; 2 Department of Biochemistry and Molecular Biology I, Universidad Complutense de Madrid, Madrid, Spain and 3 Department of Nephrology, IIS-Fundacio´nJime ´ nez Dı´az-UAM/IRSIN, Madrid, Spain Correspondence: Gloria Alvarez-Llamas, Department of Immunology, IIS-Fundacio´nJime ´ nez Dı´az, Avenida Reyes Cato´licos, 2, 28040 Madrid, Spain. E-mail: galvarez@fjd.es Kidney International (2014) 85, 1240; doi:10.1038/ki.2014.39 Acceptable mortality after living kidney donation To the Editor: Mjoen et al. 1 presented mortality data for living kidney donors compared with a group of matched controls over a follow-up period far longer than that in earlier studies. The article outlines the improved validity of the control group, which incorporated matched patients from the Health Study of Nord-Trndelag (HUNT) study population, effectively excluding a number of background conditions that historically represented biases in previous studies. The article concludes that kidney donors are at a higher long-term risk of end-stage renal disease and death compared with matched controls, highlighting a relative risk of mortality of 1.3 (95% confidence interval (CI) 1.11–1.52) and 11.38 (95% CI 4.37–29.6) for end-stage renal failure. 1 The effects of diminished renal function demonstrated in the general population 2 make it unsurprising that living kidney donation increases the lifetime likelihood of end-stage renal failure or death. The major doubt in the minds of clinicians counseling potential living kidney donors has been the exact magnitude of this effect and whether it is acceptable eGFR>60 ml/min eGFR<60 ml/min eGFR>90 ml/min eGFR<30 ml/min Cit. Cit. Cit. Cit. Cit. Thr. Thr. Cit. Cit. Cit. Cit. Thr. Thr. Cross validation P =1.7 × 10 –5 Cross validation P =2.8 × 10 –6 15 4 3 2 VIP[1] 1 0 2.72 2.68 1.28 4.48 2.56 3.96 3.56 4.44 0.04 p.p.m. Buckets 2.6 2.4 3.08 2.64 3.16 1.12 3.2 3.04 1.28 2.68 2.72 2.6 4.48 3.96 2.56 2.48 0.04 p.p.m. Buckets 3.08 8.32 8.28 3.56 8.24 4.44 3.04 2.4 –1 4 3 2 VIP[1] 1 0 –1 5 1,30543* to[1] 0 –5 –10 –15 –20 –10 –8 –6 –4 –2 0 1,19583* t[1] 2 4 6 8 10 15 5 1,08573* to[1] 0 –5 –10 –15 –20 –8 –6 –4 –2 0 1,04141* t[1] 2 4 6 10 Figure 1 | Proton nuclear magnetic resonance ( 1 H-NMR)-based chronic kidney disease (CKD) urinary metabolome. (a) Orthogonal partial least square discriminant analysis. Discrimination between urine samples from 77 CKD patients with estimated glomerular filtration rate (eGFR) o60 ml/min (stages 3–5, red dots) and 24 CKD patient urine samples with eGFR 460 ml/min (stages 1 and 2, blue dots). (b) Variables of influence in the projection. (c) Orthogonal partial least square discriminant analysis. Discrimination between urine samples from 43 CKD patients with eGFR o30 ml/min (stages 4 and 5, red dots) and 14 CKD patient urine samples with eGFR 490 ml/min (stage 1, blue dots). (d) Variables of influence in the projection. The 16 variables (buckets), which contribute the most to the discrimination are identified and listed in the rank of influence. Among the most influential, citrate (Cit.) in red and threonine (Thr.) in green are present. Blue mark denotes unidentified variables. letter to the editor 1240 Kidney International (2014) 85, 1238–1244