Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus

Gudeta D. Fufaa, E. Jennifer Weil, Robert G. Nelson, Robert L. Hanson, William C. Knowler, Brad H. Rovin, Haifeng Wu, Jon B. Klein, Theodore E. Mifflin, Harold I. Feldman, Ramachandran S. Vasan, Paul L. Kimmel, John W. Kusek, Michael Mauer, Bernard Zinman, Sandra Donnelly, Robert Gardiner, Samy Suissa, Keith Drummond, Paul Goodyer & 8 others Alan Sinaiko, Trudy Strand, Marie Claire Gubler, Ronald Klein, CKD Biomarkers Consortium and the RASS Investigators, CKD Biomarkers Consortium and the RASS Investigators, CKD Biomarkers Consortium and the RASS Investigators, CKD Biomarkers Consortium and the RASS Investigators

Research output: Contribution to journalArticle

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Abstract

Background Urinary monocyte chemoattractant protein-1 (MCP-1) and hepcidin are potential biomarkers of renal inflammation. We examined their association with development of diabetic nephropathy (DN) lesions in normotensive normoalbuminuric subjects with type 1 diabetes (T1D) from the Renin-Angiotensin System Study. Methods Biomarker concentrations were measured in baseline urine samples from 224 subjects who underwent kidney biopsies at baseline and after 5 years. Fifty-eight urine samples below the limit of quantitation (LOQ, 28.8 pg/mL) of the MCP-1 assay were assigned concentrations of LOQ/2 for analysis. Relationships between ln(MCP-1/Cr) or ln(hepcidin/Cr) and morphometric variables were assessed by sex using multiple linear regression after adjustment for age, T1D duration, HbA1c, mean arterial pressure, albumin excretion rate (AER) and glomerular filtration rate (GFR). In models that examined changes in morphometric variables, the baseline morphometric value was also included. Results Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 μg/min and mean iohexol GFR 129 mL/min/1.73 m2. No associations were found between hepcidin/Cr and morphometric variables. Higher MCP-1/Cr was associated with higher interstitial fractional volume at baseline and after 5 years in women (baseline partial r = 0.244, P = 0.024; 5-year partial r = 0.299, P = 0.005), but not in men (baseline partial r = -0.049, P = 0.678; 5-year partial r = 0.026, P = 0.830). MCP-1 was not associated with glomerular lesions in either sex. Conclusions Elevated urinary MCP-1 concentration measured before clinical findings of DN in women with T1D was associated with changes in kidney interstitial volume, suggesting that inflammatory processes may be involved in the pathogenesis of early interstitial changes in DN.

Original languageEnglish (US)
Pages (from-to)599-606
Number of pages8
JournalNephrology Dialysis Transplantation
Volume30
Issue number4
DOIs
StatePublished - Apr 1 2015

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Hepcidins
Chemokine CCL2
Diabetic Nephropathies
Type 1 Diabetes Mellitus
Glomerular Filtration Rate
Kidney
Albumins
Biomarkers
Urine
Iohexol
Renin-Angiotensin System
Linear Models
Arterial Pressure
Inflammation
Biopsy

Keywords

  • biomarkers
  • diabetic nephropathy
  • hepcidin
  • interstitial fibrosis
  • monocyte chemoattractant protein-1

Cite this

Fufaa, G. D., Weil, E. J., Nelson, R. G., Hanson, R. L., Knowler, W. C., Rovin, B. H., ... CKD Biomarkers Consortium and the RASS Investigators (2015). Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus. Nephrology Dialysis Transplantation, 30(4), 599-606. https://doi.org/10.1093/ndt/gfv012

Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus. / Fufaa, Gudeta D.; Weil, E. Jennifer; Nelson, Robert G.; Hanson, Robert L.; Knowler, William C.; Rovin, Brad H.; Wu, Haifeng; Klein, Jon B.; Mifflin, Theodore E.; Feldman, Harold I.; Vasan, Ramachandran S.; Kimmel, Paul L.; Kusek, John W.; Mauer, Michael; Zinman, Bernard; Donnelly, Sandra; Gardiner, Robert; Suissa, Samy; Drummond, Keith; Goodyer, Paul; Sinaiko, Alan; Strand, Trudy; Gubler, Marie Claire; Klein, Ronald; CKD Biomarkers Consortium and the RASS Investigators; CKD Biomarkers Consortium and the RASS Investigators; CKD Biomarkers Consortium and the RASS Investigators; CKD Biomarkers Consortium and the RASS Investigators.

In: Nephrology Dialysis Transplantation, Vol. 30, No. 4, 01.04.2015, p. 599-606.

Research output: Contribution to journalArticle

Fufaa, GD, Weil, EJ, Nelson, RG, Hanson, RL, Knowler, WC, Rovin, BH, Wu, H, Klein, JB, Mifflin, TE, Feldman, HI, Vasan, RS, Kimmel, PL, Kusek, JW, Mauer, M, Zinman, B, Donnelly, S, Gardiner, R, Suissa, S, Drummond, K, Goodyer, P, Sinaiko, A, Strand, T, Gubler, MC, Klein, R, CKD Biomarkers Consortium and the RASS Investigators, CKD Biomarkers Consortium and the RASS Investigators, CKD Biomarkers Consortium and the RASS Investigators & CKD Biomarkers Consortium and the RASS Investigators 2015, 'Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus', Nephrology Dialysis Transplantation, vol. 30, no. 4, pp. 599-606. https://doi.org/10.1093/ndt/gfv012
Fufaa, Gudeta D. ; Weil, E. Jennifer ; Nelson, Robert G. ; Hanson, Robert L. ; Knowler, William C. ; Rovin, Brad H. ; Wu, Haifeng ; Klein, Jon B. ; Mifflin, Theodore E. ; Feldman, Harold I. ; Vasan, Ramachandran S. ; Kimmel, Paul L. ; Kusek, John W. ; Mauer, Michael ; Zinman, Bernard ; Donnelly, Sandra ; Gardiner, Robert ; Suissa, Samy ; Drummond, Keith ; Goodyer, Paul ; Sinaiko, Alan ; Strand, Trudy ; Gubler, Marie Claire ; Klein, Ronald ; CKD Biomarkers Consortium and the RASS Investigators ; CKD Biomarkers Consortium and the RASS Investigators ; CKD Biomarkers Consortium and the RASS Investigators ; CKD Biomarkers Consortium and the RASS Investigators. / Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus. In: Nephrology Dialysis Transplantation. 2015 ; Vol. 30, No. 4. pp. 599-606.
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abstract = "Background Urinary monocyte chemoattractant protein-1 (MCP-1) and hepcidin are potential biomarkers of renal inflammation. We examined their association with development of diabetic nephropathy (DN) lesions in normotensive normoalbuminuric subjects with type 1 diabetes (T1D) from the Renin-Angiotensin System Study. Methods Biomarker concentrations were measured in baseline urine samples from 224 subjects who underwent kidney biopsies at baseline and after 5 years. Fifty-eight urine samples below the limit of quantitation (LOQ, 28.8 pg/mL) of the MCP-1 assay were assigned concentrations of LOQ/2 for analysis. Relationships between ln(MCP-1/Cr) or ln(hepcidin/Cr) and morphometric variables were assessed by sex using multiple linear regression after adjustment for age, T1D duration, HbA1c, mean arterial pressure, albumin excretion rate (AER) and glomerular filtration rate (GFR). In models that examined changes in morphometric variables, the baseline morphometric value was also included. Results Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 μg/min and mean iohexol GFR 129 mL/min/1.73 m2. No associations were found between hepcidin/Cr and morphometric variables. Higher MCP-1/Cr was associated with higher interstitial fractional volume at baseline and after 5 years in women (baseline partial r = 0.244, P = 0.024; 5-year partial r = 0.299, P = 0.005), but not in men (baseline partial r = -0.049, P = 0.678; 5-year partial r = 0.026, P = 0.830). MCP-1 was not associated with glomerular lesions in either sex. Conclusions Elevated urinary MCP-1 concentration measured before clinical findings of DN in women with T1D was associated with changes in kidney interstitial volume, suggesting that inflammatory processes may be involved in the pathogenesis of early interstitial changes in DN.",
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T1 - Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus

AU - Fufaa, Gudeta D.

AU - Weil, E. Jennifer

AU - Nelson, Robert G.

AU - Hanson, Robert L.

AU - Knowler, William C.

AU - Rovin, Brad H.

AU - Wu, Haifeng

AU - Klein, Jon B.

AU - Mifflin, Theodore E.

AU - Feldman, Harold I.

AU - Vasan, Ramachandran S.

AU - Kimmel, Paul L.

AU - Kusek, John W.

AU - Mauer, Michael

AU - Zinman, Bernard

AU - Donnelly, Sandra

AU - Gardiner, Robert

AU - Suissa, Samy

AU - Drummond, Keith

AU - Goodyer, Paul

AU - Sinaiko, Alan

AU - Strand, Trudy

AU - Gubler, Marie Claire

AU - Klein, Ronald

AU - CKD Biomarkers Consortium and the RASS Investigators

AU - CKD Biomarkers Consortium and the RASS Investigators

AU - CKD Biomarkers Consortium and the RASS Investigators

AU - CKD Biomarkers Consortium and the RASS Investigators

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Background Urinary monocyte chemoattractant protein-1 (MCP-1) and hepcidin are potential biomarkers of renal inflammation. We examined their association with development of diabetic nephropathy (DN) lesions in normotensive normoalbuminuric subjects with type 1 diabetes (T1D) from the Renin-Angiotensin System Study. Methods Biomarker concentrations were measured in baseline urine samples from 224 subjects who underwent kidney biopsies at baseline and after 5 years. Fifty-eight urine samples below the limit of quantitation (LOQ, 28.8 pg/mL) of the MCP-1 assay were assigned concentrations of LOQ/2 for analysis. Relationships between ln(MCP-1/Cr) or ln(hepcidin/Cr) and morphometric variables were assessed by sex using multiple linear regression after adjustment for age, T1D duration, HbA1c, mean arterial pressure, albumin excretion rate (AER) and glomerular filtration rate (GFR). In models that examined changes in morphometric variables, the baseline morphometric value was also included. Results Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 μg/min and mean iohexol GFR 129 mL/min/1.73 m2. No associations were found between hepcidin/Cr and morphometric variables. Higher MCP-1/Cr was associated with higher interstitial fractional volume at baseline and after 5 years in women (baseline partial r = 0.244, P = 0.024; 5-year partial r = 0.299, P = 0.005), but not in men (baseline partial r = -0.049, P = 0.678; 5-year partial r = 0.026, P = 0.830). MCP-1 was not associated with glomerular lesions in either sex. Conclusions Elevated urinary MCP-1 concentration measured before clinical findings of DN in women with T1D was associated with changes in kidney interstitial volume, suggesting that inflammatory processes may be involved in the pathogenesis of early interstitial changes in DN.

AB - Background Urinary monocyte chemoattractant protein-1 (MCP-1) and hepcidin are potential biomarkers of renal inflammation. We examined their association with development of diabetic nephropathy (DN) lesions in normotensive normoalbuminuric subjects with type 1 diabetes (T1D) from the Renin-Angiotensin System Study. Methods Biomarker concentrations were measured in baseline urine samples from 224 subjects who underwent kidney biopsies at baseline and after 5 years. Fifty-eight urine samples below the limit of quantitation (LOQ, 28.8 pg/mL) of the MCP-1 assay were assigned concentrations of LOQ/2 for analysis. Relationships between ln(MCP-1/Cr) or ln(hepcidin/Cr) and morphometric variables were assessed by sex using multiple linear regression after adjustment for age, T1D duration, HbA1c, mean arterial pressure, albumin excretion rate (AER) and glomerular filtration rate (GFR). In models that examined changes in morphometric variables, the baseline morphometric value was also included. Results Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 μg/min and mean iohexol GFR 129 mL/min/1.73 m2. No associations were found between hepcidin/Cr and morphometric variables. Higher MCP-1/Cr was associated with higher interstitial fractional volume at baseline and after 5 years in women (baseline partial r = 0.244, P = 0.024; 5-year partial r = 0.299, P = 0.005), but not in men (baseline partial r = -0.049, P = 0.678; 5-year partial r = 0.026, P = 0.830). MCP-1 was not associated with glomerular lesions in either sex. Conclusions Elevated urinary MCP-1 concentration measured before clinical findings of DN in women with T1D was associated with changes in kidney interstitial volume, suggesting that inflammatory processes may be involved in the pathogenesis of early interstitial changes in DN.

KW - biomarkers

KW - diabetic nephropathy

KW - hepcidin

KW - interstitial fibrosis

KW - monocyte chemoattractant protein-1

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