Open AccessTubulointerstitial Fibrosis of Living Donor Kidneys Associates with Urinary Monocyte Chemoattractant Protein 1
Author(s) -
Xiangling Wang,
John C. Lieske,
Mariam P. Alexander,
Muthuvel Jayachandran,
Aleksandar Denic,
Jerry Mathew,
Lilach O. Lerman,
Walter K. Kremers,
Joseph J. Larson,
Andrew D. Rule
Publication year - 2016
Publication title -
american journal of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.394
H-Index - 85
eISSN - 1421-9670
pISSN - 0250-8095
DOI - 10.1159/000446851
Subject(s) - medicine , urine , renal function , fibrosis , kidney , urinary system , creatinine , urology , kidney disease , excretion , albumin , proteinuria , endocrinology , gastroenterology
Background: Non-invasive biomarkers that detect occult pathology in patients with normal glomerular filtration rate (GFR) and normal urine albumin excretion may help identify patients at risk for chronic kidney diseases. Methods: Two promising biomarkers of interstitial fibrosis, urinary monocyte chemoattractant protein 1 (MCP-1) and collagen IV, were assayed among 634 living kidney donors from 2005 to 2011, who had both a frozen pre-donation spot urine sample and a core needle biopsy of their donated kidney at transplantation (‘time zero biopsy'). The association of urine MCP-1 and collagen IV with kidney function (GFR and urine albumin excretion), kidney volume on computed tomographic imaging and histological findings was assessed. Results: The mean ± SD age was 45 ± 12 years, 24-hour urine albumin was 4 ± 7 mg and measured GFR (mGFR) was 102 ± 18 ml/min/1.73 m2. The median (25th-75th percentile) urine level of MCP-1 was 146 (54-258) pg/ml and of collagen IV was 2.0 (1.0-3.5) µg/l. Higher urine MCP-1 associated with higher 24-hour urine albumin excretion; higher urine collagen IV associated with male gender. On kidney biopsy, any interstitial fibrosis was present in 22% and fibrosis >5% in 4% of donors. The mean MCP-1/Cr ratio was 1.49 pg/mg for 0% fibrosis, 1.80 pg/mg for 1-5% fibrosis, 2.33 pg/mg for 6-10% fibrosis and 4.33 pg/mg for >10% fibrosis. After adjustment for age, sex, mGFR and 24-hour urine albumin, higher urine MCP-1 but not collagen IV associated with interstitial fibrosis and tubular atrophy. Conclusion: Urine MCP-1 may detect early tubulointerstitial fibrosis in adults with normal kidney function.