Urine soluble CD163 (sCD163) as biomarker in glomerulonephritis: stability, reference interval and diagnostic performance

TY - JOUR

T1 - Urine soluble CD163 (sCD163) as biomarker in glomerulonephritis

T2 - stability, reference interval and diagnostic performance

AU - Nielsen, Anne Juhl

AU - Nielsen, Marlene Christina

AU - Birn, Henrik

AU - Ivarsen, Per

AU - Møller, Holger Jon

AU - Hviid, Claus Vinter Bødker

PY - 2021/3

Y1 - 2021/3

N2 - Soluble (s) CD163 is a well-established macrophage biomarker, and recent data suggests urine sCD163 to reflect disease activity in crescentic glomerulonephritis (GN). Other types of GN may also be associated with glomerular inflammation but the potential usefulness of urine sCD163 as a general biomarker of GN remains unaddressed. An in-house sCD163 enzyme-linked immunosorbent assay (ELISA) was validated for urinary use and compared to a frequently used commercial ELISA. The pre-analytical stability of urine sCD163 was assessed and a reference interval was established according to the CLSI guidelines using specimens from 253 healthy individuals. Urine samples from 64 patients with different types of renal disorders were also analysed. Urine sCD163 was highly stable during storage. An upper reference limit of 5.1 μg/L (1.9 μg/mmol, normalised to creatinine) was established using the in-house ELISA. Urine sCD163 was generally increased in GN patients (3.9 μg/mmol, p<0.0001, AUROC=0.97) and decreased upon treatment, but did not perform better than urine albumin (AUROC=1.00). Patients with proliferative GN had higher urine sCD163/albumin (p=0.0001) ratio. The commercial assay had a higher detection limit, and patient levels were 4-6 times lower than in the in-house assay. Urine sCD163 is a stable biomarker that can be measured with acceptable accuracy using our in-house ELISA. Its pre-analytical characteristics makes it a reliable biomarker and our findings point towards the use of urine sCD163 as a biomarker of specific subtypes of GN.

AB - Soluble (s) CD163 is a well-established macrophage biomarker, and recent data suggests urine sCD163 to reflect disease activity in crescentic glomerulonephritis (GN). Other types of GN may also be associated with glomerular inflammation but the potential usefulness of urine sCD163 as a general biomarker of GN remains unaddressed. An in-house sCD163 enzyme-linked immunosorbent assay (ELISA) was validated for urinary use and compared to a frequently used commercial ELISA. The pre-analytical stability of urine sCD163 was assessed and a reference interval was established according to the CLSI guidelines using specimens from 253 healthy individuals. Urine samples from 64 patients with different types of renal disorders were also analysed. Urine sCD163 was highly stable during storage. An upper reference limit of 5.1 μg/L (1.9 μg/mmol, normalised to creatinine) was established using the in-house ELISA. Urine sCD163 was generally increased in GN patients (3.9 μg/mmol, p<0.0001, AUROC=0.97) and decreased upon treatment, but did not perform better than urine albumin (AUROC=1.00). Patients with proliferative GN had higher urine sCD163/albumin (p=0.0001) ratio. The commercial assay had a higher detection limit, and patient levels were 4-6 times lower than in the in-house assay. Urine sCD163 is a stable biomarker that can be measured with acceptable accuracy using our in-house ELISA. Its pre-analytical characteristics makes it a reliable biomarker and our findings point towards the use of urine sCD163 as a biomarker of specific subtypes of GN.

KW - ELISA

KW - biomarker

KW - glomerulonephritis

KW - inflammation

KW - macrophages

KW - reference values

KW - soluble CD163

KW - urine albumin

UR - http://www.scopus.com/inward/record.url?scp=85094951879&partnerID=8YFLogxK

U2 - 10.1515/cclm-2020-0466

DO - 10.1515/cclm-2020-0466

M3 - Journal article

C2 - 33068375

SN - 1434-6621

VL - 59

SP - 701

EP - 709

JO - Clinical Chemistry and Laboratory Medicine

JF - Clinical Chemistry and Laboratory Medicine

IS - 4

ER -