Abstract

BackgroundPlacental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), soluble receptor for advanced glycation end products (sRAGE), extracellular newly identified receptor for RAGE binding protein (EN-RAGE) and high mobility group box 1 (HMGB-1) are novel biomarkers in chronic kidney disease (CKD). However, their clinical significance in acute kidney injury (AKI) is unknown. The aim of this cross-sectional study was to determine whether selected biomarkers are changed in AKI patients.MethodsSerum PlGF, PAPP-A, sRAGE, EN-RAGE and HMGB-1 levels were assessed in 40 patients with AKI, 42 CKD 5 patients, 31 haemodialysis patients (HD) and 39 age-matched healthy controls.ResultsPAPP-A was elevated in AKI (20.6 ± 16.9 mIU/L) compared with controls (9.1 ± 2.3 mIU/L, p < 0.001). PlGF was not increased in AKI (11.7 ± 7.4 pg/mL) versus controls (8.5 ± 2.4 pg/mL, n.s.), as well as sRAGE was not elevated in AKI (2400 ± 1400 pg/mL) compared with controls (1760 ± 730 pg/mL, n.s), but was lower compared with CKD 5 (3200 ± 1500 pg/mL, p < 0.05); EN-RAGE was elevated in AKI 480 ± 450 ng/mL in comparison with controls (60 ± 62 ng/mL), CKD 5 (190 ± 120 ng/mL), and HD (120 ± 100 ng/mL), all p < 0.001. Similarly, HMGB-1 was increased in AKI (5.8 ± 7.5 ng/mL) versus controls (1.7 ± 1.4 ng/mL), CKD 5 (3.2 ± 3.1 ng/mL) and HD (2.5 ±2.1 ng/mL), all p < 0.001.In AKI group, in multivariate regression analysis: PAPP–A levels were associated with transferrin (p <0.001), negatively with albumin (p < 0.01) and prealbumin (p < 0.05); PlGF levels were associated with C - reactive protein (p < 0.001). EN-RAGE levels were associated with ferritin (p < 0.01) and orosomucoid (p = 0.02), and HMGB-1 levels with leukocyte count (p < 0.01) and negatively with proteinuria (p = 0.02).ConclusionsIn AKI patients, PAPP-A, EN-RAGE and HMGB1 are elevated, but sRAGE and PlGF are not increased. Whereas PAPP-A correlates with markers of nutrition; PlGF, EN-RAGE and HMGB-1 are related to inflammatory parameters.

Highlights

  • Placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), soluble receptor for advanced glycation end products, extracellular newly identified receptor for RAGE binding protein (EN-RAGE) and high mobility group box 1 (HMGB-1) are novel biomarkers in chronic kidney disease (CKD)

  • PlGF was not increased in acute kidney injury (AKI) (11.7 ± 7.4 pg/mL) versus controls (8.5 ± 2.4 pg/mL, n.s.), as well as soluble receptor for advanced glycation end products (sRAGE) was not elevated in AKI (2400 ± 1400 pg/mL) compared with controls (1760 ± 730 pg/mL, n.s), but was lower compared with CKD 5 (3200 ± 1500 pg/mL, p < 0.05); EN-RAGE was elevated in AKI 480 ± 450 nanograms per milliliter (ng/mL) in comparison with controls (60 ± 62 ng/mL), CKD 5 (190 ± 120 ng/mL), and haemodialysis patients (HD) (120 ± 100 ng/mL), all p < 0.001

  • Whereas PAPP-A correlates with markers of nutrition; PlGF, EN-RAGE and HMGB-1 are related to inflammatory parameters

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Summary

Introduction

Placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), soluble receptor for advanced glycation end products (sRAGE), extracellular newly identified receptor for RAGE binding protein (EN-RAGE) and high mobility group box 1 (HMGB-1) are novel biomarkers in chronic kidney disease (CKD). Their clinical significance in acute kidney injury (AKI) is unknown. Recent studies have reported that elevated levels of circulating PlGF might be associated with worsening atherosclerosis in patients with decreased renal function [6,7]. These findings have suggested that PlGF might act as an inflammatory instigator of atherosclerotic process in patients with renal impairment

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