Inflammation, kidney function and albuminuria in the Framingham Offspring cohort.
BACKGROUND
Inflammation and chronic kidney disease (CKD) are both associated with cardiovascular disease (CVD). Whether inflammatory biomarkers are associated with kidney function and albuminuria after accounting for traditional CVD risk factors is not completely understood.


METHODS
The sample comprised Framingham Offspring cohort participants (n = 3294, mean age 61, 53% women) who attended the seventh examination cycle (1998-2001). Inflammatory biomarkers [C-reactive protein (CRP), tumour necrosis factor (TNF)-alpha, interleukin-6, TNF receptor 2 (TNFR2), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), P-selectin, CD-40 ligand, osteoprotegerin, urinary isoprostanes, myeloperoxidase and fibrinogen] were measured on fasting blood samples. Serum creatinine-based estimated glomerular filtration rate (eGFR) and serum cystatin C concentration were used to assess kidney function. Urinary albumin-to-creatinine ratio (UACR) was used to assess albuminuria. Linear or logistic regression was used to test associations between biomarkers and kidney measures.


RESULTS
Chronic kidney disease (CKD), defined as eGFR < 59/64 mL/min/1.73 m(2) in women/men, was present in 8.8% (n = 291) of participants. TNF-alpha, interleukin-6, TNFR2, MCP-1, osteoprotegerin, myeloperoxidase and fibrinogen were higher among individuals with CKD; all biomarkers except for urinary isoprostanes were elevated in higher cystatin C quartiles; and TNF-alpha, interleukin-6, TNFR2, ICAM-1 and osteoprotegerin were elevated in higher UACR quartiles-all assessed after multivariable adjustment. Almost 6% and 17% of variability in TNFR2 were explained by CKD status and higher cystatin C quartiles, respectively.


CONCLUSIONS
Biomarkers of inflammation are associated with kidney function and albuminuria. In particular, substantial variability in soluble TNFR2 is explained by CKD and cystatin C.
Upadhyay
Ashish
A
Division of Nephrology, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA. aupadhyay@tuftsmedicalcenter.org
Larson
Martin G
MG
Guo
Chao-Yu
CY
Vasan
Ramachandran S
RS
Lipinska
Izabella
I
O'Donnell
Christopher J
CJ
Kathiresan
Sekar
S
Meigs
James B
JB
Keaney
John F
JF
Rong
Jian
J
Benjamin
Emelia J
EJ
Fox
Caroline S
CS
D000368:Aged; D000419:Albuminuria / Q000209:etiology*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000209:etiology / Q000652:urine; D007676:Kidney Failure, Chronic / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D015415:Biomarkers; D055316:Cystatin C; D003404:Creatinine