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Nephrol Dial Transplant. 2016 Sep;31(9):1460-70. doi: 10.1093/ndt/gfw203. Epub 2016 Jun 7.

Relationship of proximal tubular injury to chronic kidney disease as assessed by urinary kidney injury molecule-1 in five cohort studies.

Author information

1
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2
Uppsala University, Uppsala, Sweden Dalarna University, Falun, Sweden.
3
Uppsala University, Uppsala, Sweden Karolinska Institutet, Huddinge, Sweden.
4
Johns Hopkins University, Baltimore, MD, USA.
5
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
6
Tufts Medical Center, Boston, MA, USA.
7
National Institute of Diabetes and Digestive and Kidney Diseases.
8
Uppsala University, Uppsala, Sweden.
9
University of California, San Francisco, San Francisco, CA, USA Kaiser Permanente Northern California, Oakland, CA, USA.
10
University of California, San Francisco, San Francisco, CA, USA.
11
Boston University, Boston, MA, USA.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

Proximal tubule injury appears to be an integral and measurable element of multiple stages of CKD.

KEYWORDS:

KIM-1; albuminuria; chronic kidney disease

PMID:
27270293
PMCID:
PMC5009290
DOI:
10.1093/ndt/gfw203
[Indexed for MEDLINE]
Free PMC Article

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