We sought to find a urinary
biomarker for
chronic kidney disease and tested hematopoietic
growth factor inducible neurokinin-1 (HGFIN, also known as Gpnmb/Osteoactivin) as it was found to be a kidney injury
biomarker in microarray studies. Here, we studied whether HGFIN is a marker of
kidney disease progression. Its increase in
kidney disease was confirmed by real-time PCR after 5/6
nephrectomy, in
streptozotocin-induced diabetes, and in patients with
chronic kidney disease. In the remnant kidney, HGFIN
mRNA increased over time reflecting lesion chronicity. HGFIN was identified in the
infarct portion of the remnant kidney in infiltrating hematopoietic interstitial cells, and in distal nephron tubules of the viable remnant kidney expressed de novo with increasing time. In vitro, it localized to cytoplasmic vesicles and cell membranes. Epithelial cells lining distal tubules and sloughed
luminal tubule cells of patients expressed HGFIN
protein. The urine HGFIN-to-
creatinine ratio increased over time after 5/6
nephrectomy; increased in patients with proteinuric and
polycystic kidney disease; and remained detectable in urine after prolonged freezer storage. The urine HGFIN-to-
creatinine ratio compared favorably with the urine
neutrophil gelatinase-associated lipocalin (NGAL)-to-
creatinine ratio (both measured by commercial
enzyme-linked
immunosorbent assays (ELISAs)), and correlated strongly with
proteinuria, but weakly with estimated glomerular filtration rate and serum
creatinine. Thus, HGFIN may be a
biomarker of progressive
kidney disease.