Background:
The urinary biomarkers of tubular injury ((urine neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1)) can indicate acute kidney injury before reductions in estimated glomerular filtration rate (eGFR) are clinically detectable. Whether elevations of these markers are associated with future risk of kidney disease has not been investigated.
Methods:
We studied the association of urinary NGAL and KIM-1 with kidney function decline in a 1:1 ratio case-control study among 686 MESA participants. NGAL and KIM-1 were measured at baseline (standardized for urinary creatinine) and expressed both as continuous and in deciles. eGFR was estimated by cystatin C. Cases were defined as persons with eGFR>60 ml/min/1.73m
2
who subsequently developed
incident CKD
(defined as eGFR<60 plus eGFR decline > 1ml/min/year) and/or had
rapid kidney function decline
(RKFD, ≥3ml/min/1.73m
2
/year) by the MESA year 5 visit. Of the 343 cases, 145 had incident CKD, 141 had RKFD and 57 had both. Controls were matched for age, gender, race, diabetes, and baseline eGFR. We adjusted for age, hypertension and presence of albuminuria (ACR ≥30 mg/g).
Results:
Higher levels of KIM-1 were significantly associated with kidney function decline, and these associations were strongest for the top decile compared to lowest decile. Presence of albuminuria only minimally attenuated the findings. NGAL levels were not associated with kidney function decline. (Table)
Model
OR (95%CI) for Incident CKD and/or Rapid Kidney Function Decline
KIM-1 (pg/ml)
*
KIM-1-Cr Ratio
*
(pg/mg)
KIM-1 ≥ 927 pg/ml (Top Decile)
NGAL (ng/ml)
*
NGAL-Cr Ratio
*
(ng/mg)
NGAL ≥ 36 ng/ml (Top Decile)
Age Adjusted
1.15 (1.02, 1.29)
1.17 (1.02, 1.34)
2.09 (1.21, 3.62)
1.04 (0.99, 1.10)
1.03 (0.98, 1.09)
1.63 (0.96, 2.78)
Age + HTN Adjusted
1.15 (1.03, 1.29)
1.16 (1.01, 1.33)
2.13 (1.22, 3.70)
1.04 (0.99, 1.10)
1.03 (0.98, 1.09)
1.58 (0.93, 2.71)
+ ACR ≥ 30mg/g
1.15 (1.02, 1.29)
1.13 (0.98, 1.30)
2.02 (1.15, 3.56)
1.04 (0.99, 1.10)
1.03 (0.97, 1.08)
1.55 (0.89, 2.70)
*
Per doubling. Top decile is compared to lowest decile
Conclusions:
KIM-1, a marker of tubular injury, is associated with future risk of kidney disease independent of albuminuria. Our findings suggest that urinary biomarkers of tubular injury are a promising tool for identifying persons at risk for CKD.
Author Correction: Longitudinal urinary biomarkers of immunological activation in covid-19 patients without clinically apparent kidney disease versus acute and chronic failure
