title: Urinary kidney injury molecule 1 and incidence of heart failure in elderly men.
abstract: OBJECTIVE
  There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk.
  
  
  RESULTS
  This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001).
  
  
  CONCLUSIONS
  Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.
authors.affiliation: Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Axel C
authors.initials: AC
authors.lastname: Carlsson
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Johanna
authors.initials: J
authors.lastname: Helmersson-Karlqvist
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
authors.forename: Johan
authors.initials: J
authors.lastname: Arnlöv
mesh_terms: D000368:Aged; D000419:Albuminuria; D015415:Biomarkers / Q000652:urine*; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000453:epidemiology* / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007684:Kidney Tubules / Q000378:metabolism / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D016016:Proportional Hazards Models; D011991:Receptors, Virus; D012111:Residence Characteristics; D012307:Risk Factors; D013548:Sweden
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D003404:Creatinine