INNATE IMMUNITY AND CKD PROGRESSION

Abstract

Alterations in innate immunity play a role in renal damage in experimental models but the role of these alterations in the progression of CKD in humans is still poorly defined. Procalcitonin (PCT), is a biomarker of innate immunity produced by C-cells of the thyroid and by the adipose tissue. Objectives: We measured serum plasma PCT levels in a cohort of 670 patients with stage 3–5 CKD and tested the relationship between this biomarker metrics of adiposity, proteinuria, GFR and progression to kidney failure over a 3 year follow-up. None of the patients had intercurrent infectious or acute inflammatory processes. Methods: PCT was measured by an ultrasensitive immunoluminometric assay. The GFR was estimated by a Cystatin-C based equation. The relationship between PCT and renal events was tested by multivariate Cox’s regression and interaction analysis. Results: Procalcitonin exceeded the upper limit of the normal range (>0.064 ng/mL) in 492 patients (67 %) while the corresponding figure for high sensitivity CRP (>1 mg/L) was 170 (%). PCT was higher (P<0.001) in males and strongly associated with the GFR (r=) as well as diabetes (P=0.004) and a history of cardiovascular (CV) events (P=0.007). Furthermore PCT was inversely related with Hb (r=−0.16, P<0.001) and with serum albumin (r=−0.10, P=0.009) and directly associated with CRP (r=0.23, P<0.001) and with white blood cells count (r=0.12, P=0.002). Of note, PCT was higher (P<0.001) in patients with large waist hip ratio (IVth quartile) than in those normal or high normal WHR (1st to 3rd quartiles). During the follow up, PCT predicted the combined renal end-point (30% GFR loss, dialysis or transplantation) (HR for 1 ng/ml increase: 2.37, 95%CI:1.25–4.48, P=0.009) in a model adjusting for age, sex, diabetes, BP, smoking, cholesterol, background cardiovascular events and PCT interacted with baseline GFR in predicting renal outcomes. Indeed the risk of for the combined end-point was minimal in patients with low PCT and high GFR and maximal in those with low GFR and high PCT. Conclusions: Plasma procalcitonin is a more sensitive biomarker of innate immunity than CRP in CKD patients and in part reflects excessive adiposity. High PCT in CKD patients predicts progression toward kidney failure. These results are compatible with the hypothesis that alterations in innate immunity play a role in the progression of CKD in humans.