Relationship of proximal tubular injury to chronic kidney disease as assessed by urinary kidney injury molecule-1 in five cohort studies.
The primary biomarkers used to define CKD are serum creatinine and albuminuria. These biomarkers have directed focus on the filtration and barrier functions of the kidney glomerulus even though albuminuria results from tubule dysfunction as well. Given that proximal tubules make up ∼90% of kidney cortical mass, we evaluated whether a sensitive and specific marker of proximal tubule injury, urinary kidney injury molecule-1 (KIM-1), is elevated in individuals with CKD or with risk factors for CKD.



We measured urinary KIM-1 in participants of five cohort studies from the USA and Sweden. Participants had a wide range of kidney function and were racially and ethnically diverse. Multivariable linear regression models were used to test the association of urinary KIM-1 with demographic, clinical and laboratory values.



In pooled, multivariable-adjusted analyses, log-transformed, creatinine-normalized urinary KIM-1 levels were higher in those with lower eGFR {β = -0.03 per 10 mL/min/1.73 m(2) [95% confidence interval (CI) -0.05 to -0.02]} and greater albuminuria [β = 0.16 per unit of log albumin:creatinine ratio (95% CI 0.15-0.17)]. Urinary KIM-1 levels were higher in current smokers, lower in blacks than nonblacks and lower in users versus nonusers of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.



Proximal tubule injury appears to be an integral and measurable element of multiple stages of CKD.
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sushrut S
SS
Waikar
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Venkata
V
Sabbisetti
Uppsala University, Uppsala, Sweden Dalarna University, Falun, Sweden.
Johan
J
Ärnlöv
Uppsala University, Uppsala, Sweden Karolinska Institutet, Huddinge, Sweden.
Axel C
AC
Carlsson
Johns Hopkins University, Baltimore, MD, USA.
Josef
J
Coresh
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Harold I
HI
Feldman
Tufts Medical Center, Boston, MA, USA.
Meredith C
MC
Foster
National Institute of Diabetes and Digestive and Kidney Diseases.
Gudeta D
GD
Fufaa
Uppsala University, Uppsala, Sweden.
Johanna
J
Helmersson-Karlqvist
University of California, San Francisco, San Francisco, CA, USA Kaiser Permanente Northern California, Oakland, CA, USA.
Chi-Yuan
CY
Hsu
National Institute of Diabetes and Digestive and Kidney Diseases.
Paul L
PL
Kimmel
Uppsala University, Uppsala, Sweden.
Anders
A
Larsson
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Yumin
Y
Liu
Uppsala University, Uppsala, Sweden.
Lars
L
Lind
University of California, San Francisco, San Francisco, CA, USA.
Kathleen D
KD
Liu
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Theodore E
TE
Mifflin
National Institute of Diabetes and Digestive and Kidney Diseases.
Robert G
RG
Nelson
Uppsala University, Uppsala, Sweden.
Ulf
U
Risérus
Boston University, Boston, MA, USA.
Ramachandran S
RS
Vasan
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Dawei
D
Xie
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Xiaoming
X
Zhang
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Joseph V
JV
Bonventre
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000032:analysis*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000293:injuries / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000652:urine*; D012307:Risk Factors; D013548:Sweden; D055815:Young Adult
D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1
KIM-1; albuminuria; chronic kidney disease