Balanced forced-diuresis compared to control as a reno-protective approach in cardiac surgery: secondary outcome of a randomized controlled trial, assessment of neutrophil gelatinase-associated lipocalin levels

Heyman Luckraz, Ramesh Giri, Benjamin Wrigley, Kumaresan Nagarajan, Eshan Senanayake, Emma Sharman, Lawrence Beare, Alan Nevill, Heyman Luckraz, Ramesh Giri, Benjamin Wrigley, Kumaresan Nagarajan, Eshan Senanayake, Emma Sharman, Lawrence Beare, Alan Nevill

Abstract

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a recognised biomarker for acute kidney injury (AKI).This study investigated the impact of balanced forced-diuresis using RenalGuard® system (RG), in reducing acute kidney injury (AKI) rates and the associated NGAL levels (6-h post-CPB plasma level) post adult cardiac surgery with cardiopulmonary bypass (CPB).

Methods: Patients included in the study were at high-risk for AKI post cardiac surgery, namely history of diabetes and/or anaemia, e-GFR 20-60 ml/min/1.73 m2, Logistic EuroScore > 5, anticipated CPB time > 120 min. Patients were randomized to either RG (n = 110) or managed as per current practice (control = 110). RIFLE-defined AKI rate (based on serum creatinine level increase) within first 3 days of surgery and 6-h post CPB NGAL levels were the primary and secondary end-points.

Results: Pre and intra-operative characteristics between the two groups were similar (p > 0.05) including the pre-op NGAL levels, the oxygen delivery (ecDO2i) and the carbon dioxide production (ecVCO2i) during CPB. Patients in the RG group had a significantly lower post-operative RIFLE-defined AKI rate compared to control (10% (11/110) v/s 20.9% (23/110), p = 0.03). Overall, median 6-h post CPB NGAL levels in patients with AKI were significantly higher than those who did not develop AKI (211 vs 150 ng/ml, p < 0.001). Patients managed by balanced forced-diuresis had lower post-operative NGAL levels (146 vs 178 ng/ml, p = 0.09). Using previously reported NGAL cut-off level for AKI (142 ng/ml), binary logistic regression analysis confirmed a beneficial effect of the RG system, with an increased risk of AKI of 2.2 times in the control group (OR 2.2, 95% CI 1.14-4.27, p = 0.02).

Conclusions: Overall, the 6-h post-CPB plasma NGAL levels were significantly higher in patients who developed AKI. Patients managed with the novel approach of balanced forced-diuresis, provided by the RenalGuard® system, had a lower AKI rate and lower NGAL levels indicating a lesser degree of renal tissue injury. Trial registration ClinicalTrials.gov website, NCT02974946, https://ichgcp.net/clinical-trials-registry/NCT02974946 .

Keywords: Acute kidney injury; Balanced forced-diuresis; Cardiac surgery; Neutrophil gelatinase-associated lipocalin; RenalGuard® system.

Conflict of interest statement

This study was funded by a research grant from RenalGuard Solutions and there are no other competing interests to declare.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT flow diagram for recruitment

References

    1. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14:2534. doi: 10.1097/01.ASN.0000088027.54400.C6.
    1. Kjeldsen L, Cowland JB, Borregaard N. Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse. Biochim Biophys Acta. 2000;1482:272. doi: 10.1016/S0167-4838(00)00152-7.
    1. Uttenthal LO. NGAL: a marker molecule for the distressed kidney? . Accessed 27 Sept 2020.
    1. Luckraz H, Gravenor MB, George R, Taylor S, Williams A, Ashraf S, et al. Long and short-term outcomes in patients requiring continuous renal replacement therapy post cardiopulmonary bypass. Eur J Cardiothorac Surg. 2005;27:906. doi: 10.1016/j.ejcts.2005.01.057.
    1. Joannidis M, Druml W, Forni LG, Groeneveld ABJ, Honore PM, Hoste E, et al. Prevention of acute kidney injury and protection of renal function in the intensive care unit: update 2017: Expert opinion of the Working Group on Prevention, AKI section, European Society of Intensive Care Medicine. Intensive Care Med. 2017;43:730. doi: 10.1007/s00134-017-4832-y.
    1. Mishra PK, Luckraz H, Nandi J, Nevill A, Giri R, Panayiotou A, et al. Long-term quality of life post acute kidney injury in cardiac surgery patients. Ann Card Anaesth. 2018;2:41.
    1. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005;365:1231. doi: 10.1016/S0140-6736(05)74811-X.
    1. Ho J, Tangri N, Komenda P, Kaushal A, Sood M, Brar R, et al. Urinary, plasma, and serum biomarkers' utility for predicting acute kidney injury associated with cardiac surgery in adults: a meta-analysis. Am J Kidney Dis. 2015;66:993. doi: 10.1053/j.ajkd.2015.06.018.
    1. Luckraz H, Giri R, Wrigley HAM, Nicholas J, Nevill AM. The use of the RenalGuard system in cardiac surgery with cardiopulmonary-bypass: a first in man prospective, observational, feasibility pilot study. Open Heart BMJ. 2017;4:e000669. doi: 10.1136/openhrt-2017-000669.
    1. Luckraz H, Giri R, Wrigley B, Nagarajan K, Senanyake E, Sharman E, et al. Reduction in acute kidney injury post cardiac surgery using balanced forced diuresis: a randomized, controlled trial. Eur J Cardiothorac Surg. 2020 doi: 10.1093/ejcts/ezaa395.
    1. Tecson KM, Erhardtsen E, Eriksen PM, Gaber AO, Germain M, Golestaneh L, et al. Optimal cut points of plasma and urine neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury among critically ill adults: retrospective determination and clinical validation of a prospective multicentre study. BMJ Open. 2017;7:e016028. doi: 10.1136/bmjopen-2017-016028.
    1. de Geus HR, Ronco C, Haase M, Jacob L, Lewington A, Vincent JL. The cardiac surgery-associated neutrophil gelatinase-associated lipocalin (CSA-NGAL) score: a potential tool to monitor acute tubular damage. J Thorac Cardiovasc Surg. 2016;151:1476. doi: 10.1016/j.jtcvs.2016.01.037.
    1. Fanning N, Galvin S, Parke R, Gilroy J, Bellomo R, McGuinness S. A prospective study of the timing and accuracy of neutrophil gelatinase-associated lipocalin levels in predicting acute kidney injury in high-risk cardiac surgery patients. J Cardiothorac Vasc Anesth. 2016;30:76. doi: 10.1053/j.jvca.2015.07.034.
    1. Friedrich MG, Bougioukas I, Kolle J, Bireta C, Jebran FA, Placzek M, et al. NGAL expression during cardiopulmonary bypass does not predict severity of postoperative acute kidney injury. BMC Nephrol. 2017;18:73. doi: 10.1186/s12882-017-0479-8.
    1. Lannemyr L, Bragadottir G, Krumbholz V, Redfors B, Sellgren J, Ricksten SE. Effects of cardiopulmonary bypass on renal perfusion, filtration, and oxygenation in patients undergoing cardiac surgery. Anesthesiology. 2017;126:205. doi: 10.1097/ALN.0000000000001461.
    1. Ranucci M, Romitti F, Isgrò G, Cotza M, Brozzi S, Boncilli A, et al. Oxygen delivery during cardiopulmonary bypass and acute renal failure after coronary operations. Ann Thorac Surg. 2005;80:2213. doi: 10.1016/j.athoracsur.2005.05.069.
    1. Rasmussen SR, Kandler K, Nielsen RV, Cornelius-Jakobsen P, Knudsen NN, Ranucci M, et al. Duration of critically low oxygen delivery is associated with acute kidney injury after cardiac surgery. Acta Anaesthesiol Scand. 2019;63:1290. doi: 10.1111/aas.13457.
    1. Ranucci M, Carboni G, Cotza M, de Somer F. Carbon dioxide production during cardiopulmonary bypass: pathophysiology, measure and clinical relevance. Perfusion. 2017;32:4. doi: 10.1177/0267659116659919.
    1. Arumugham VB, Shahin MH. Therapeutic uses of diuretic agents. 2020 Jun 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. Accessed 1st Oct 2020.
    1. Desanti De Oliveira B, Xu K, Shen TH, Callahan M, Kiryluk K, D'Agati VD, et al. Molecular nephrology: types of acute tubular injury. Nat Rev Nephrol. 2019;15:599. doi: 10.1038/s41581-019-0184-x.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir