Is Serum Phosphate Concentration a Biomarker for Renal Injury and Recovery in Cardiac Surgery?

Abstract

ACUTE KIDNEY INJURY (AKI) after cardiac surgery on cardiopulmonary bypass (CPB) is associated with increased hospital length of stay and perioperative morbidity and mortality. Preoperative risk factors include chronic kidney disease (CKD), heart failure with reduced ejection fraction, diabetes, hypertension, anemia, nephrotoxic drugs, and a higher Euroscore II. Perioperative risk factors include prolonged CPB and aortic cross-clamp time, hypotension, low- cardiac- output state, and hemorrhage.1Chew STH Acute kidney injury after cardiac surgery: A narrative review of the literature.J Cardiothorac Vasc Anesth. 2019; 33: 1122-1138Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar,2Coulson DT Bailey M Pilcher D et al.Predicting acute kidney injury after cardiac surgery using a simpler model [e-pub ahead of print].J Cardiothorac Vasc Anesth. 2020; (Accessed July 29, 2020)https://doi.org/10.1053/j.jvca.2020.06.072Abstract Full Text Full Text PDF Scopus (2) Google Scholar AKI is diagnosed using the Kidney Disease: Improving Global Outcome (KDIGO) criteria based on oliguria and elevation in serum creatinine (SCr) concentration relative to baseline.3Machado MN Nakazone MA Maia LN Acute kidney injury based on KDIGO (kidney disease improving global outcomes) criteria in patients with elevated baseline serum creatinine undergoing cardiac surgery.Rev Bras Cir Cardiovasc. 2014; 29: 299-307PubMed Google Scholar As creatinine is freely filtered at the glomerulus, and neither secreted nor reabsorbed, an increasing SCr concentration represents a reduction in glomerular filtration rate (GFR). However, SCr concentration is considered a lagging indicator in AKI as it peaks at 48- to- 72 hours after the insult.4Mohsenin V. Practical approach to detection and management of acute kidney injury in critically ill patient.J Intensive Care Med. 2017; 5: 57Crossref Scopus (17) Google Scholar Several biomarkers have been investigated as alternatives to SCr concentration for the diagnosis of AKI; however, to date, none has shown superior prognostic value compared with SCr.5Wu B Chen J Yang Y Biomarkers of acute kidney injury after cardiac surgery: A narrative review.Biomed Res Int. 2019; 20197298635Crossref PubMed Scopus (18) Google Scholar Phosphate is also freely filtered at the glomerulus, and approximately 80% is reabsorbed in the tubules, with the balance being excreted. In CKD, hyperphosphatemia results from the reduction in GFR, as well as the effects of parathyroid hormone and vitamin D on bone, intestinal, and renal tubular phosphate reabsorption. In AKI, an increasing serum phosphate (SPh) concentration is thought to be a more direct measure of reduced GFR.6Blaine J Chonchol M Levi M Renal control of calcium, phosphate, and magnesium homeostasis.Clin J Am Soc Nephrol. 2015; 10: 1257-1272Crossref PubMed Scopus (339) Google Scholar Development of hypophosphatemia is associated with increased requirements for hemodynamic support, duration of mechanical ventilation, and intensive care unit (ICU) length of stay after CPB.7Grobbelaar L Joubert G Diedericks J Hypophosphatemia after cardiopulmonary bypass—Incidence and clinical significance.J Cardiothorac Vasc Anesth. 2018; 32: S23Abstract Full Text Full Text PDF Google Scholar Hence, the use of SPh concentration as a renal biomarker is an attractive concept in that it is a widely available, routinely performed, and cost-effective assay after cardiac surgery. Saour et al. presented a prospective, single-center observational study describing the relationship between perioperative SPh concentrations and AKI in a cohort of 260 consecutive adult patients undergoing cardiac surgery on CPB.8Saour M Zeroual N Ridolfo J et al.Serum phosphate kinetics in acute kidney injury after cardiac surgery: An observational study.J Cardiothorac Vasc Anesth. 2020; 34: 2964-2972Abstract Full Text Full Text PDF Scopus (3) Google Scholar Patients with severely reduced CKD epidemiology collaboration (CKD-EPI) estimated GFR <15 mL/min/1.73 m2, prior renal transplant, prior nephrectomy or single kidney, preoperative AKI, mechanical circulatory support, surgical reopening within 48 hours, or perioperative hemofiltration were excluded. Cardiopulmonary bypass management was standard, and perioperative hemodynamic management was guided by monitoring of pulmonary artery pressures or echocardiography and included dobutamine infusion for a refractory cardiac index <2.2 L/min/m2 despite an adequate left atrial pressure, and norepinephrine infusion for refractory hypotension if cardiac index was preserved. Blood assays for SCr and SPh concentrations were performed 1 day prior to surgery, at admission to the postoperative ICU, every 12 hours during ICU stay, and every morning up to postoperative day 5. AKI was diagnosed according KDIGO SCr concentration criteria, but not urine output criteria. In view of the lack of a consensus definition, renal recovery was defined as an SCr concentration at hospital discharge less than or equal to preoperative SCr concentration + 26.5 µmol/l, similar to the definition of KDIGO stage 1.9Xu J Xu X Shen B et al.Evaluation of five different renal recovery definitions for estimation of long-term outcomes of cardiac surgery associated acute kidney injury.BMC Nephrol. 2019; 20: 427Crossref PubMed Scopus (9) Google Scholar AKI was diagnosed in 86 patients, of whom approximately two-thirds of cases were mild (KDIGO 1), and the remainder moderate- to- severe (KDIGO 2 and 3). Changes in SPh concentration mirrored SCr concentration elevations in patients who developed AKI, peaking at 48 hours. However, changes in SPh concentrations were more exaggerated than changes in SCr concentration. A SPh concentration <1.33 µmol/L at 48 hours was associated with a 98% negative predictive value for the development of moderate- to- severe AKI (KDIGO 2 or 3). Renal replacement therapy (RRT) was not required in 72/86 patients, and renal recovery was observed in 60/86 patients, the majority of whom had less severe AKI (KDIGO 1). A 25% or more decrease in SPh concentration between 48 and 72 hours was associated with 100% positive predictive value for renal recovery. Patients who did not recover renal function had a higher mortality (33%, p = 0.01). A similar observational study in postcardiac surgery patients previously served as the power calculation for the current study.10Saour M Ridolfo J Zéroual N et al.Serum phosphorus, a simple biomarker of acute kidney injury severity and renal recovery after cardiac surgery.J Cardiothorac Vasc Anesth. 2017; 31: S26-S27Abstract Full Text Full Text PDF PubMed Google Scholar This previous study established that a maximum postoperative SPh concentration elevation of ≥54% relative to baseline predicted moderate- to- severe AKI (KDIGO 2 or 3), and ≥59% predicted the requirement for RRT. A prior retrospective study by the same research group identified that the maximal elevation in SPh concentration relative to baseline, and 48-hour SPh concentration, correlated with the severity of AKI and identified patients who did not require RRT after cardiac surgery.11Ridolfo J Saour M Culas G et al.Elevation of serum phosphorus, an early biomarker of acute kidney injury after cardiac surgery?.Intensive Care Med Exp. 2015; 3: A465Crossref Google Scholar Burra et al. documented similar findings in a pediatric cardiac surgical population and found that SPh concentration elevation predicted postoperative AKI as early as 24 hours postoperatively.12Burra V Nagaraja PS Singh NG et al.Early prediction of acute kidney injury using serum phosphorus as a biomarker in pediatric cardiac surgical patients.Ann Card Anaesth. 2018; 21: 455-459Crossref PubMed Scopus (8) Google Scholar Taken in their entirety, these studies collectively suggested that SPh and SCr concentrations should be measured at baseline preoperatively, and then daily for 72 hours postoperatively after cardiac surgery. A tandem increase in SPh with SCr concentrations relative to baseline within the first 48 hours predicts more severe AKI (KDIGO 2 and 3), and a reduction in SPh concentration between 48 and 72 hours identifies patients who are likely to recover renal function. Further prospective studies are required to confirm these findings. None. Serum Phosphate Kinetics in Acute Kidney Injury After Cardiac Surgery: An Observational StudyJournal of Cardiothoracic and Vascular AnesthesiaVol. 34Issue 11PreviewAcute kidney injury (AKI) is a common complication after cardiac surgery and may affect prognosis. Serum phosphate (SPh) elevation is well-known to occur after AKI but not well-documented. The aim of the present study was to describe SPh changes during AKI after cardiac surgery and to assess the accuracy for the diagnosis of AKI severity and recovery. Full-Text PDF