Advanced

Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years

Schulz, Christina-Alexandra LU ; Engström, Gunnar LU ; Nilsson, Jan LU ; Almgren, Peter LU ; Petkovic, Marinka LU ; Christensson, Anders LU ; Nilsson, Peter M LU ; Melander, Olle LU and Orho-Melander, Marju LU (2019) In Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Abstract

Background: The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear.

Methods: At baseline (1991-1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine-cystatin C equation at baseline and follow-up examination (2007-2012). Incident CKD was defined as an eGFR <60 mL/min/1.73 m2 at follow-up.

Results: During a... (More)

Background: The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear.

Methods: At baseline (1991-1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine-cystatin C equation at baseline and follow-up examination (2007-2012). Incident CKD was defined as an eGFR <60 mL/min/1.73 m2 at follow-up.

Results: During a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 -1.36 versus quartile 4 -1.54 mL/min/1.73 m2; P < 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio [OR] 1.45 [95% confidence interval (CI) 1.10-1.92]} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD [OR 1.20 (95% CI 1.08-1.33) per 1 standard deviation (SD) increase in p-KIM-1] was comparable to those of age and systolic blood pressure (SBP) [OR 1.55 (95% CI 1.38-1.74) and OR 1.21 (95% CI 1.09-1.35) per 1 SD increase, respectively]. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 [hazard ratio per 1 SD 1.43; (95% CI 1.18-1.74)] during a mean follow-up time of 19.2 years.

Conclusion: Our results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
publisher
Oxford University Press
ISSN
1460-2385
DOI
10.1093/ndt/gfy382
language
English
LU publication?
yes
id
11eb797a-69b5-4a70-afeb-c5f836cca22c
date added to LUP
2019-05-16 13:33:20
date last changed
2019-05-28 14:00:55
@article{11eb797a-69b5-4a70-afeb-c5f836cca22c,
  abstract     = {<p>Background: The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear.</p><p>Methods: At baseline (1991-1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine-cystatin C equation at baseline and follow-up examination (2007-2012). Incident CKD was defined as an eGFR &lt;60 mL/min/1.73 m2 at follow-up.</p><p>Results: During a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 -1.36 versus quartile 4 -1.54 mL/min/1.73 m2; P &lt; 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio [OR] 1.45 [95% confidence interval (CI) 1.10-1.92]} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD [OR 1.20 (95% CI 1.08-1.33) per 1 standard deviation (SD) increase in p-KIM-1] was comparable to those of age and systolic blood pressure (SBP) [OR 1.55 (95% CI 1.38-1.74) and OR 1.21 (95% CI 1.09-1.35) per 1 SD increase, respectively]. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 [hazard ratio per 1 SD 1.43; (95% CI 1.18-1.74)] during a mean follow-up time of 19.2 years.</p><p>Conclusion: Our results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.</p>},
  author       = {Schulz, Christina-Alexandra and Engström, Gunnar and Nilsson, Jan and Almgren, Peter and Petkovic, Marinka and Christensson, Anders and Nilsson, Peter M and Melander, Olle and Orho-Melander, Marju},
  issn         = {1460-2385},
  language     = {eng},
  month        = {01},
  publisher    = {Oxford University Press},
  series       = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association},
  title        = {Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years},
  url          = {http://dx.doi.org/10.1093/ndt/gfy382},
  year         = {2019},
}