Kidney injury molecule (KIM)-1 is associated with insulin resistance: results from two community-based studies of elderly individuals.
OBJECTIVE
Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.


METHODS
Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).


RESULTS
Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.


CONCLUSIONS
Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.
Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Electronic address: axelcefam@hotmail.com.
Axel C
AC
Carlsson
Landstinget Dalarna, Falun, Sweden.
Michael
M
Calamia
Department of Public Health and Caring Sciences/Section of Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
Ulf
U
Risérus
Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Anders
A
Larsson
Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Johanna
J
Helmersson-Karlqvist
Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Lars
L
Lind
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. Electronic address: johan.arnlov@pubcare.uu.se.
Johan
J
Arnlöv
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood; D000959:Antihypertensive Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000652:urine*; D001794:Blood Pressure; D055812:Community-Based Participatory Research; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007333:Insulin Resistance; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011446:Prospective Studies; D011991:Receptors, Virus; D012111:Residence Characteristics
D000959:Antihypertensive Agents; D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus
Blood glucose; Diabetes; Glomerular filtration; Kidney injury; Microalbuminuria