Blood and urinary cytokine balance and renal outcomes at cardiac surgery

William T Mcbride,Joanne Watt,Mary Jo Kurth,Mark W Ruddock,Jijin Joseph,Gavin Mclean,Peter Fitzgerald,John V Lamont,Anna Domanska

doi:10.1186/s12882-021-02621-6

William T Mcbride, Joanne Watt + Show 7 more

Open Access

https://doi.org/10.1186/s12882-021-02621-6

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Abstract

BackgroundIncreased perioperative pro-inflammatory biomarkers, renal hypoperfusion and ischemia reperfusion injury (IRI) heighten cardiac surgery acute kidney injury (CS-AKI) risk. Increased urinary anti-inflammatory cytokines attenuate risk. We evaluated whether blood and urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation, hypoperfusion and IRI are increased in CS-AKI patients.MethodsPreoperative and 24-h postoperative blood and urinary pro-inflammatory and anti-inflammatory cytokines, blood VEGF and H-FABP (hypoperfusion biomarkers), and MK, a biomarker for IRI, were measured in 401 cardiac surgery patients. Pre- and postoperative concentrations of biomarkers and selected ratios thereof, were compared between non-CS-AKI and CS-AKI patients.ResultsCompared with non-CS-AKI, blood pro-inflammatory (pre- and post-op TNFα, IP-10, IL-12p40, MIP-1α, NGAL; pre-op IL-6; post-op IL-8, MK) and anti-inflammatory (pre- and post-op sTNFsr1, sTNFsr2, IL-1RA) biomarkers together with urinary pro-inflammatory (pre- and post-op uIL-12p40; post-op uIP-10, uNGAL) and anti-inflammatory (pre- and post-op usTNFsr1, usTNFsr2, uIL-1RA) biomarkers, were significantly higher in CS-AKI patients. Urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation (blood and urine), hypoperfusion (blood H-FABP and VEGF) and IRI (blood MK) were decreased in CS-AKI. In contrast, blood anti-inflammatory biomarkers expressed as similar ratios with blood biomarkers were increased in CS-AKI.ConclusionsThe urinary anti-inflammatory response may protect against the injurious effects of perioperative inflammation, hypoperfusion and IRI. These finding may have clinical utility in bioprediction and earlier diagnosis of CS-AKI and informing future therapeutic strategies for CS-AKI patients.

Highlights

Increased perioperative pro-inflammatory biomarkers, renal hypoperfusion and ischemia reperfusion injury (IRI) heighten cardiac surgery acute kidney injury (CS-AKI) risk
In preliminary analysis of serum samples of 401 patients undergoing elective cardiac surgery, logistic regression analyses confirmed that biomarkers predictive of postoperative renal dysfunction represented the three underlying processes: hypoperfusion (H-FABP), IRI (MK) and pro-inflammation (serum tumor necrosis factor soluble receptor 1 and serum tumor necrosis factor soluble receptor 2) [9]
Mechanisms protecting against CS‐AKI In contrast to the three major injurious processes identified in blood samples, a possible protective role against CS-AKI has been attributed to an intra renal anti-inflammatory cytokine response at cardiac surgery, characterized by perioperative increases in urinary tumor necrosis factor soluble receptor 2 and urinary interleukin-1 receptor antagonist [7, 10,11,12]

Summary

Introduction

Increased perioperative pro-inflammatory biomarkers, renal hypoperfusion and ischemia reperfusion injury (IRI) heighten cardiac surgery acute kidney injury (CS-AKI) risk. Mechanisms protecting against CS‐AKI In contrast to the three major injurious processes identified in blood samples, a possible protective role against CS-AKI has been attributed to an intra renal anti-inflammatory cytokine response at cardiac surgery, characterized by perioperative increases in urinary tumor necrosis factor soluble receptor 2 (uTNFsr2) and urinary interleukin-1 receptor antagonist (uIL-1RA) [7, 10,11,12]. The molecular weights of uIL-1RA, urinary tumor necrosis factor soluble receptor 1 (uTNFsr1) and uTNFsr, are greater than 20 kDa and their glomerular filtration is lower than their smaller pro-inflammatory counterparts [13] These considerations point to urinary anti-inflammatory biomarkers being mainly generated within the kidney with a smaller additional contribution from glomerular filtration [10, 11]. Urinary pro-inflammatory biomarkers are measurable e.g., interferon gamma-induced protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1δ (MIP-1δ) in diabetic nephropathy patients [15]; neutrophil gelatinase-associated lipocalin (NGAL), macrophage inflammatory protein–1α (MIP-1α) and IP-10 in CS-AKI patients [1, 3, 17]; MCP-1 in mice with

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