Journal Article

Biomarkers of inflammation and progression of chronic kidney disease

TONELLI, Marcello, JHANGRI, Gian S, PFEFFER, Marc, SACKS, Frank, CURHAN, Gary

2005

Overview

Chronic kidney disease is associated with higher levels of inflammatory biomarkers. Statins have anti-inflammatory properties and may attenuate loss of kidney function. Although inflammation may mediate progressive renal injury, the relation between statin use, markers of inflammation, and the rate of kidney function loss has not been elucidated. We examined the association between pravastatin use, levels of C-reactive protein (CRP), soluble tumor necrosis factor receptor II (sTNFrii), and the rate of kidney function loss. We performed a post hoc analysis of data from a randomized placebo controlled trial of pravastatin 40 mg daily in people with previous myocardial infarction. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease Study (MDRD) GFR equation. We studied 687 subjects with chronic kidney disease (GFR < 60 mL/min/1.73 m(2)) who did not experience a cardiovascular event during follow-up. Multivariate linear regression was used to study the relation between baseline CRP and sTNFrii and the rate of kidney function loss in mL/min/1.73 m(2)/year. Cross-product interaction terms were used to determine if these relations varied with pravastatin use. Median baseline GFR was 54.5 mL/min/1.73 m(2) (interquartile range 49.7, 57.8) and median duration of follow-up was 58 months. Higher baseline CRP level was independently associated with more rapid kidney function loss (highest tertile 0.6 mL/min/1.73 m(2) per year faster than lowest tertile) (P= 0.001). A similar independent relation was observed between tertile of sTNFrii and rate of kidney function loss (highest tertile 0.5 mL/min/1.73 m(2) per year faster than lowest tertile) (P= 0.006). Subjects with both CRP and sTNFrii in the highest tertile (\"inflamed\" status) appeared to derive more renal benefit from pravastatin than those without (P for interaction 0.047). In these 108 subjects, renal function loss in pravastatin recipients was 0.8 mL/min/1.73 m(2)/year slower than placebo (95% CI 0 to 1.5 mL/min/1.73 m(2)/year slower) (P= 0.039). Higher CRP and sTNFrii are independently associated with faster rates of kidney function loss in chronic kidney disease. Pravastatin appears to prevent loss of kidney function to a greater extent in individuals with greater evidence of inflammation, although this was of borderline significance. These data suggest that inflammation may mediate the loss of kidney function among subjects with chronic kidney disease and concomitant coronary disease.

• Publisher: Nature Publishing,Elsevier Limited
• Subject: Adult / Aged / Anticholesteremic Agents - administration & dosage / Biological and medical sciences / Biomarkers - blood / C-Reactive Protein - metabolism / Disease Progression / Etanercept / Female / Humans / Hyperlipidemias - drug therapy / Immunoglobulin G - blood / Kidney Failure, Chronic - blood / Kidney Failure, Chronic - immunology / Kidney Failure, Chronic - prevention & control / Kidney Function Tests / Male / Medical sciences / Middle Aged / Myocardial Infarction / Nephrology. Urinary tract diseases / Nephropathies. Renovascular diseases. Renal failure / Pravastatin - administration & dosage / Receptors, Tumor Necrosis Factor - blood / Renal failure