title: Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men.
abstract: OBJECTIVE
  Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.
  
  
  METHODS
  This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008).
  
  
  RESULTS
  During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).
  
  
  CONCLUSIONS
  These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.
authors.affiliation: Centre for Family Medicine, Department of Neurobiology, Care Sciences, and Society, Karolinska Institute, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors.forename: Axel C
authors.initials: AC
authors.lastname: Carlsson
authors.affiliation: Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden;
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden;
authors.forename: Johanna
authors.initials: J
authors.lastname: Helmersson-Karlqvist
authors.affiliation: Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden;
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.affiliation: Department of Clinical Science, Intervention, and Technology, and.
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
authors.affiliation: Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; and.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden johan.arnlov@medsci.uu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Ärnlöv
mesh_terms: D000367:Age Factors; D000368:Aged; D000419:Albuminuria / Q000401:mortality / Q000652:urine; D015415:Biomarkers / Q000652:urine; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000401:mortality* / Q000652:urine*; D002423:Cause of Death; D003401:Creatine / Q000652:urine; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology / Q000652:urine*; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011991:Receptors, Virus; D012307:Risk Factors; D012737:Sex Factors; D013548:Sweden; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D003401:Creatine
keywords: albuminuria; epidemiology; outcomes; tubule cells