Tubulointerstitial Fibrosis of Living Donor Kidneys Associates with Urinary Monocyte Chemoattractant Protein 1.
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.



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.



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.



Urine MCP-1 may detect early tubulointerstitial fibrosis in adults with normal kidney function.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minn., USA.
Xiangling
X
Wang
John C
JC
Lieske
Mariam P
MP
Alexander
Muthuvel
M
Jayachandran
Aleksandar
A
Denic
Jerry
J
Mathew
Lilach O
LO
Lerman
Walter K
WK
Kremers
Joseph J
JJ
Larson
Andrew D
AD
Rule
D000328:Adult; D018932:Chemokine CCL2 / Q000652:urine*; D024141:Collagen Type IV / Q000652:urine*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000000981:diagnostic imaging / Q000473:pathology / Q000652:urine*
D018932:Chemokine CCL2; D024141:Collagen Type IV