Association of TNF Receptor 2 and CRP with GFR Decline in the General Nondiabetic Population

Background and objectives Higher levels of inflammatory markers have been associated with renal outcomes in diabetic populations. We investigated whether soluble TNF receptor 2 (TNFR2) and high-sensitivity C-reactive protein (hsCRP) were associated with the age-related GFR decline in a nondiabetic population using measured GFR (mGFR). Design, setting, participants, & measurements A representative sample of 1590 middle-aged people from the general population without prevalent kidney disease, diabetes, or cardiovascular disease were enrolled in the Renal Iohexol-Clearance Survey in Tromso 6 (RENIS-T6) between 2007 and 2009. After a median of 5.6 years, 1296 persons were included in the Renal Iohexol-Clearance Survey Follow-Up Study. GFR was measured using iohexol clearance at baseline and follow-up. Results The mean decline of mGFR during the period was −0.84 ml/min per 1.73 m 2 per year. There were 133 participants with rapid mGFR decline, defined as an annual mGFR loss >3.0 ml/min per 1.73 m 2 , and 26 participants with incident CKD, defined as mGFR 2 at follow-up. In multivariable adjusted mixed models, 1 mg/L higher levels of hsCRP were associated with an accelerated decline in mGFR of −0.03 ml/min per 1.73 m 2 per year (95% confidence interval [95% CI], −0.05 to −0.01), and 1 SD higher TNFR2 was associated with a slower decline in mGFR (0.09 ml/min per 1.73 m 2 per year; 95% CI, 0.01 to 0.18). In logistic regression models adjusted for sex, age, weight, and height, 1 mg/L higher levels of hsCRP were associated with higher risk of rapid mGFR decline (odds ratio, 1.03; 95% CI, 1.01 to 1.06) and incident CKD (odds ratio, 1.04; 95% CI, 1.00 to 1.08). Conclusions Higher baseline levels of hsCRP but not TNFR2 were associated with accelerated age-related mGFR decline and incident CKD in a general nondiabetic population.