title: Urinary sulfur metabolites associate with a favorable cardiovascular risk profile and survival benefit in renal transplant recipients.
abstract: In post-transplant conditions, sulfur may be protective by intermediate conversion to hydrogen sulfide and thiosulfate. However, sulfate, the end product of sulfur-containing amino acids (SAAs), contributes to metabolic acid load and may adversely influence acid-base homeostasis. We investigated the association of urinary sulfur metabolites with cardiometabolic parameters in renal transplant recipients (RTRs) and analyzed their predictive capacity for mortality. We studied urinary sulfate and thiosulfate excretion in 24-hour urine samples from 707 RTRs at a median 5.4 years (interquartile range, 1.9 to 12.2) after transplantation as well as from 110 controls. Diet was assessed for SAA content and various risk factors were measured. Urinary sulfate was similar, whereas thiosulfate was higher in RTRs versus controls. SAA intake was lower in RTRs compared with controls and correlated with sulfate but not thiosulfate excretion. Sulfate beneficially associated with eGFR, net acid excretion, systolic BP, high-sensitivity C-reactive protein, N-terminal probrain natriuretic peptide, and proteinuria (all P≤0.01). Thiosulfate beneficially associated with eGFR, serum acidity, high-sensitivity C-reactive protein, and N-terminal probrain natriuretic peptide (all P≤0.001). During a median 27 months (interquartile range, 22-36) of follow-up, 47 RTRs died. After adjustment for age, sex, and eGFR, hazard ratios for mortality were 0.87 (95% confidence interval, 0.82 to 0.92; P<0.001) for urinary sulfate and 0.60 (95% confidence interval, 0.41 to 0.59; P=0.01) for thiosulfate. Thus, despite the association of urinary sulfate with metabolic acid load, urinary sulfate and thiosulfate beneficially associated with survival in RTRs, possibly by influencing cardiovascular parameters. Intervention studies with exogenous sulfur are warranted to elucidate mechanisms underlying these promising associations in RTRs.
authors: Top Institute Food and Nutrition, Wageningen, The Netherlands; Kidney Center Groningen, University Medical Center Groningen, University of Groningen, The Netherlands; e.van.den.berg@umcg.nl.
authors: Else
authors: E
authors: van den Berg
authors: Department of Nephrology and Hypertension, University Hospital and University of Bern, Inselspital, Bern, Switzerland; and.
authors: Andreas
authors: A
authors: Pasch
authors: Departments of Pathology and Medical Biology and.
authors: Welmoet H
authors: WH
authors: Westendorp
authors: Kidney Center Groningen, University Medical Center Groningen, University of Groningen, The Netherlands;
authors: Gerjan
authors: G
authors: Navis
authors: Top Institute Food and Nutrition, Wageningen, The Netherlands;
authors: Elizabeth J
authors: EJ
authors: Brink
authors: Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands.
authors: Reinold O B
authors: RO
authors: Gans
authors: Departments of Pathology and Medical Biology and.
authors: Harry
authors: H
authors: van Goor
authors: Top Institute Food and Nutrition, Wageningen, The Netherlands; Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands.
authors: Stephan J L
authors: SJ
authors: Bakker
mesh_terms: D000328:Adult; D000368:Aged; D000603:Amino Acids, Sulfur / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000652:urine*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000601:surgery / Q000652:urine; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012307:Risk Factors; D013431:Sulfates / Q000652:urine*; D013885:Thiosulfates / Q000652:urine*
chemical_list: D000603:Amino Acids, Sulfur; D013431:Sulfates; D013885:Thiosulfates