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

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 m 2 . 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) ?g/l. Higher urine MCP-1 associated with higher 24- hour urine albumin excretion; higher urine collagen IV asso- ciated 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.

Original languageEnglish (US)
Pages (from-to)454-459
Number of pages6
JournalAmerican Journal of Nephrology
Volume43
Issue number6
DOIs
StatePublished - Jul 1 2016

Fingerprint

Chemokine CCL2
Living Donors
Fibrosis
Urine
Kidney
Albumins
Collagen
Glomerular Filtration Rate
Biomarkers
Large-Core Needle Biopsy
Biopsy
Chronic Renal Insufficiency
Kidney Transplantation
Atrophy
Tissue Donors
Pathology

Keywords

  • Collagen type IV Tubulointerstitial fibrosis
  • Implantation biopsies
  • Living kidney donors
  • Monocyte chemoattractant protein 1

ASJC Scopus subject areas

  • Nephrology

Cite this

Tubulointerstitial Fibrosis of Living Donor Kidneys Associates with Urinary Monocyte Chemoattractant Protein 1. / Wang, Xiangling; Lieske, John C; Alexander, Mariam P; Jayachandran, Muthuvel; Denic, Aleksandar; Mathew, Jerry; Lerman, Lilach O; Kremers, Walter K; Larson, Joseph J.; Rule, Andrew D.

In: American Journal of Nephrology, Vol. 43, No. 6, 01.07.2016, p. 454-459.

Research output: Contribution to journalArticle

@article{c1b935608b0e4fcca90f234ccb706653,
title = "Tubulointerstitial Fibrosis of Living Donor Kidneys Associates with Urinary Monocyte Chemoattractant Protein 1",
abstract = "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 m 2 . 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) ?g/l. Higher urine MCP-1 associated with higher 24- hour urine albumin excretion; higher urine collagen IV asso- ciated 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.",
keywords = "Collagen type IV Tubulointerstitial fibrosis, Implantation biopsies, Living kidney donors, Monocyte chemoattractant protein 1",
author = "Xiangling Wang and Lieske, {John C} and Alexander, {Mariam P} and Muthuvel Jayachandran and Aleksandar Denic and Jerry Mathew and Lerman, {Lilach O} and Kremers, {Walter K} and Larson, {Joseph J.} and Rule, {Andrew D}",
year = "2016",
month = "7",
day = "1",
doi = "10.1159/000446851",
language = "English (US)",
volume = "43",
pages = "454--459",
journal = "American Journal of Nephrology",
issn = "0250-8095",
publisher = "S. Karger AG",
number = "6",

}

TY - JOUR

T1 - Tubulointerstitial Fibrosis of Living Donor Kidneys Associates with Urinary Monocyte Chemoattractant Protein 1

AU - Wang, Xiangling

AU - Lieske, John C

AU - Alexander, Mariam P

AU - Jayachandran, Muthuvel

AU - Denic, Aleksandar

AU - Mathew, Jerry

AU - Lerman, Lilach O

AU - Kremers, Walter K

AU - Larson, Joseph J.

AU - Rule, Andrew D

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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 m 2 . 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) ?g/l. Higher urine MCP-1 associated with higher 24- hour urine albumin excretion; higher urine collagen IV asso- ciated 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.

AB - 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 m 2 . 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) ?g/l. Higher urine MCP-1 associated with higher 24- hour urine albumin excretion; higher urine collagen IV asso- ciated 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.

KW - Collagen type IV Tubulointerstitial fibrosis

KW - Implantation biopsies

KW - Living kidney donors

KW - Monocyte chemoattractant protein 1

UR - http://www.scopus.com/inward/record.url?scp=84975109096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975109096&partnerID=8YFLogxK

U2 - 10.1159/000446851

DO - 10.1159/000446851

M3 - Article

VL - 43

SP - 454

EP - 459

JO - American Journal of Nephrology

JF - American Journal of Nephrology

SN - 0250-8095

IS - 6

ER -