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Clin J Am Soc Nephrol. 2009 Jan;4(1):62-70. doi: 10.2215/CJN.03010608. Epub 2008 Dec 10.

Serum concentrations of markers of TNFalpha and Fas-mediated pathways and renal function in nonproteinuric patients with type 1 diabetes.

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  • 1Research Division of Joslin Diabetes Center, Boston, MA 02215, USA.

Abstract

BACKGROUND AND OBJECTIVES:

The aim of our study was to examine serum markers of the TNF and Fas pathways for association with cystatin-C based estimated glomerular filtration rate (cC-GFR) in subjects with type 1 diabetes (T1DM) and no proteinuria.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

The study group (the 2nd Joslin Kidney Study) comprised patients with T1DM and normoalbuminuria (NA) (n = 363) or microalbuminuria (MA) (n = 304). Impaired renal function (cC-GFR <90 ml/min) was present in only 10% of patients with NA and 36% of those with MA. We measured markers of the tumor necrosis factor alpha (TNFalpha) pathway [TNFalpha, soluble TNF receptor 1 (sTNFR1), and 2 (sTNFR2)], its downstream effectors [soluble intercellular and soluble vascular adhesion molecules (sICAM-1 and sVCAM-1), interleukin 8 (IL8/CXCL8), monocytes chemoattractant protein-1 (MCP1), and IFNgamma inducible protein-10 (IP10/CXCL10)], the Fas pathway [soluble Fas (sFas) and Fas ligand (sFasL)], CRP, and IL6.

RESULTS:

Of these, TNFalpha, sTNFRs, sFas, sICAM-1, and sIP10 were associated with cC-GFR. However, only the TNF receptors and sFas were associated with cC-GFR in multivariate analysis. Variation in the concentration of the TNF receptors had a much stronger impact on GFR than clinical covariates such as age and albumin excretion.

CONCLUSIONS:

Elevated concentrations of serum markers of the TNFalpha and Fas-pathways are strongly associated with decreased renal function in nonproteinuric type 1 diabetic patients. These effects are independent of those of urinary albumin excretion. Follow-up studies are needed to characterize the role of these markers in early progressive renal function decline.

PMID:
19073786
PMCID:
PMC2615709
DOI:
10.2215/CJN.03010608
[PubMed - indexed for MEDLINE]
Free PMC Article
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