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

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.

• Authors: Sushrut S Waikar, Venkata Sabbisetti, Johan Ärnlöv, Axel C Carlsson, Josef Coresh, Harold I Feldman, Meredith C Foster, Gudeta D Fufaa, Johanna Helmersson-Karlqvist, Chi-Yuan Hsu, Paul L Kimmel, Anders Larsson, Yumin Liu, Lars Lind, Kathleen D Liu, Theodore E Mifflin, Robert G Nelson, Ulf Risérus, Ramachandran S Vasan, Dawei Xie, Xiaoming Zhang, Joseph V Bonventre, Chronic Kidney Disease Biomarkers Consortium Investigators
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 31 Issue 9 Pg. 1460-70 (09 2016) ISSN: 1460-2385 [Electronic] England
• PMID: 27270293 (Publication Type: Journal Article, Observational Study)
• Copyright: © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Chemical References

• Biomarkers
• HAVCR1 protein, human
• Hepatitis A Virus Cellular Receptor 1

Topics

• Adult
• Aged
• Albuminuria (urine)
• Biomarkers (urine)
• Female
• Hepatitis A Virus Cellular Receptor 1 (analysis)
• Humans
• Kidney Tubules, Proximal (injuries, metabolism)
• Male
• Middle Aged
• Prospective Studies
• Renal Insufficiency, Chronic (diagnosis, urine)
• Risk Factors
• Sweden
• Young Adult