title: High urinary sulfate concentration is associated with reduced risk of renal disease progression in type 2 diabetes.
abstract: Diabetes is associated with a high incidence of microvascular disease, including nephropathy. Diabetic nephropathy is the most common cause of chronic kidney disease in the Western world. Sulfate in the urine is the metabolic end product of hydrogen sulfide (H2S), a recent discovered gaseous signaling molecule. Urinary sulfate has earlier shown beneficial predictive properties in renal transplant recipients. Based on the protective role of exogenous H2S in experimental models of diabetic nephropathy, we aimed to cross-sectionally investigate the association of sulfate with renal risk markers, and to prospectively investigate its predictive value for renal events in patients with diabetic nephropathy. Post-hoc analysis on data of the sulodexide macroalbuminuria (Sun-MACRO) trial and the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study was performed. A total of 1004 patients with type 2 diabetes were included. Urinary sulfate concentration was measured and cross-sectionally associated to renal risk markers by linear regression. Multivariable Cox regression analysis was performed to assess the prospective association of sulfate with renal events, which was defined as end stage renal disease or a doubling of baseline serum creatinine. Mean age was 63 ± 9 years, median sulfate concentration was 8.0 (IQR 5.8-11.4) mmol/L. Urinary sulfate positively associated with male gender, hemoglobin, and negatively associated with albuminuria at baseline. During follow-up for 12 (IQR 6-18) months, 38 renal events occurred. Each doubling of urinary sulfate was associated with a 19% (95%CI 1%-34%) lower risk of renal events, independent of adjustment for potential confounders, including age, estimated glomerular filtration rate (eGFR), and albuminuria. To conclude, higher urinary sulfate concentration is associated with a more beneficial profile of renal risk markers, and is independently associated with a reduced risk for renal events in type 2 diabetes patients with nephropathy.
authors.affiliation: Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Joost C
authors.initials: JC
authors.lastname: van den Born
authors.affiliation: Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Anne-Roos S
authors.initials: AR
authors.lastname: Frenay
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, the Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Clinical Chemistry, University Hospital Bern, Inselspital, Bern, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pasch
authors.affiliation: Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.affiliation: Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: h.van.goor@umcg.nl.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000209:etiology / Q000503:physiopathology / Q000652:urine*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology / Q000652:urine*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000503:physiopathology / Q000652:urine*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000503:physiopathology / Q000652:urine*; D012709:Serum Albumin / Q000032:analysis; D013431:Sulfates / Q000652:urine*
chemical_list: D006454:Hemoglobins; D012709:Serum Albumin; D013431:Sulfates; D003404:Creatinine
keywords: Diabetic nephropathy; End stage renal disease; Epidemiology; Hydrogen sulfide; Sulfate; Type 2 diabetes