Inflammation and Renal Function after a Four-Year Follow-Up in Subjects with Unimpaired Glomerular Filtration Rate: Results from the Observational, Population-Based CARLA Cohort

<div><p>Background</p><p>There is evidence that chronic inflammation is associated with the progression/development of chronic renal failure; however, relations in subjects with preserved renal function remain insufficiently understood.</p><p>Objective</p><p>To examine the association of inflammation with the development of renal failure in a cohort of the elderly general population.</p><p>Methods</p><p>After excluding subjects with reduced estimated glomerular filtration rate (eGFR<60 mL/min/1.73 m²) and missing data, the cohort incorporated 785 men and 659 women (aged 45–83 years). Follow-up was performed four years after baseline. Covariate adjusted linear and logistic regression models were used to assess the association of plasma/serum concentrations of soluble tumour necrosis factor receptor 1 (sTNF-R1), C-reactive protein (CRP), and interleukin 6 (IL-6) with change in eGFR/creatinine. The areas under the curve (AUCs) from receiver operating characteristics (ROCs) were estimated.</p><p>Results</p><p>In adjusted models sTNF-R1 was distinctively associated with a decline in eGFR in men (0.6 mL/min/1.73 m² per 100 pg/mL sTNF-R1; 95% CI: 0.4–0.8), but not in women. A similar association could not be found for CRP or IL-6. Estimates of sTNF-R1 in the cross-sectional analyses were similar between sexes, while CRP and IL-6 were not relevantly associated with eGFR/creatinine.</p><p>Conclusion</p><p>In the elderly male general population with preserved renal function sTNF-R1 predicts the development of renal failure.</p></div

Cross-sectional and longitudinal regression analyses in women: association of inflammation parameters with GFR/creatinine.

<p>unadj. = unadjusted estimates; CI = confidence limit; adj. = estimates adjusted for age, body mass index (BMI), HbA1c, low-density lipoprotein (LDL), high-density lipoprotein (HDL), baseline diastolic and systolic blood pressure and baseline to follow-up change in the longitudinal analyses, number of cigarettes/cigars/pipes smoked, presence of cardio-vascular diseases, regular intake of anti-diabetic (Anatomical Therapeutic Chemical Classification [ATC]: A10) and anti-hypertensive medication (ATC: C02/C03/C07/C08/C09); users coded as “1”, non-users coded as “0”. GFR estimated by means of CKD-EPI formula¹⁰. Effect estimates with 95% confidence intervals are displayed.</p><p>*Effect estimates refer to an increase of one standard deviation in the log-transformed inflammation parameter.</p><p>Abbreviations: sTNF-R1: Soluble tumour necrosis factor-α receptor 1; hsCRP: High-sensitivity C-reactive protein; IL-6: Interleukin 6; eGFR: estimated glomerular filtration rate.</p><p>Cross-sectional and longitudinal regression analyses in women: association of inflammation parameters with GFR/creatinine.</p

ROC curves and respective AUCs [95% confidence intervals].

<p>Abbreviations: sTNF-R1: Soluble tumour necrosis factor-α receptor 1; hsCRP: High- sensitivity C-reactive protein; IL-6: Interleukin 6; CI: confidence interval.</p

Subject characteristics.

<p>Baseline and follow-up means, displayed as geometric means with respective 95% confidence limits.</p><p>Abbreviations: sTNF-R1: Soluble tumour necrosis factor-α receptor 1; hsCRP: High-sensitivity C-reactive protein; IL-6: Interleukin 6; eGFR: estimated glomerular filtration rate; BMI: Body mass index; Dia. BP: Diastolic blood pressure; Sys. BP: Systolic blood pressure; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; PAD: Peripheral arterial disease.</p>†<p>p-values for mean differences between men and women (using T-test) or differences in numbers between men and women (using Fisher’s exact test); ** indicates p-values <0.0001 for baseline to follow-up change; * indicates p-values <0.05 for baseline to follow-up change.</p><p>Subject characteristics.</p

Change in mean eGFR/creatinine plasma level in subjects with the 50% lowest and 50% highest sTNF-R1 plasma levels at baseline.

<p>Abbreviations: sTNF-R1: Soluble tumour necrosis factor-α receptor 1, eGFR: estimated glomerular filtration rate.</p