Longitudinal prediction of hospital-acquired acute kidney injury in COVID-19: a two-center study

Abstract

Background: To investigate the temporal characteristics of clinical variables of hospital-acquired acute kidney injury (AKI) in COVID-19 patients and to longitudinally predict AKI onset.

Methods: There were 308 hospital-acquired AKI and 721 non-AKI (NAKI) COVID-19 patients from Stony Brook Hospital (New York, USA) data, and 72 hospital-acquired AKI and 303 NAKI COVID-19 patients from Tongji Hospital (Wuhan, China). Demographic, comorbidities, and longitudinal (3 days before and 3 days after AKI onset) clinical variables were used to compute odds ratios for and longitudinally predict hospital-acquired AKI onset.

Results: COVID-19 patients with AKI were more likely to die than NAKI patients (31.5% vs 6.9%, adjusted p < 0.001, OR = 4.67 [95% CI 3.1, 7.0], Stony Brook data). AKI developed on average 3.3 days after hospitalization. Procalcitonin was elevated prior to AKI onset (p < 0.05), peaked, and remained elevated (p < 0.05). Alanine aminotransferase, aspartate transaminase, ferritin, and lactate dehydrogenase peaked the same time as creatinine, whereas D-dimer and brain natriuretic peptide peaked a day later. C-reactive protein, white blood cell and lymphocyte showed group differences - 2 days prior (p < 0.05). Top predictors were creatinine, procalcitonin, white blood cells, lactate dehydrogenase, and lymphocytes. They predicted AKI onset with areas under curves (AUCs) of 0.78, 0.66, and 0.56 at 0, - 1, and - 2 days prior, respectively. When tested on the Tongji Hospital data, the AUCs were 0.80, 0.79, and 0.77, respectively.

Conclusions: Time-locked longitudinal data provide insight into AKI progression. Commonly clinical variables reasonably predict AKI onset a few days prior. This work may lead to earlier recognition of AKI and treatment to improve clinical outcomes.

Keywords: AKI; Chronic kidney disease; Cytokine storm; D-Dimer; Lactate dehydrogenase; Multiorgan failure; Predictive model; SARS-CoV-2.

Fig. 1

Flowchart of patient selection of acute kidney injury (AKI) patients and non-AKI (NAKI) patients of the Stony Brook data. Pts patients, ICU intensive care unit, Cr creatinine, C-AKI community-acquired AKI)

Fig. 2

Histogram of patients developed AKI after hospitalization in days of Stony Brook data

Fig. 3

Time courses of normalized laboratory tests of HAKI and NAKI COVID-19 patients of the Stony Brook data. Normalization was relative to No AKI at t = 0 for individual patient. For HA-AKI patients, t = 0 represents day of AKI onset (Cr first peaked), and for No AKI patients 3 days after hospital admission. Abbreviations: Cr, creatinine. BNP, brain natriuretic peptide. ALT, alanine aminotransferase. AST, aspartate transaminase. PROCAL, procalcitonin. CRP, C-reactive protein. LDH, lactate dehydrogenase. WBC, white blood cell. DBP, diastolic blood pressure. SBP, systolic blood pressure. FERR, ferritin. LYMPH, lymphocyte count. DDIM, d-dimer. HR, heart rate. RR, respiratory rate. SpO2, pulse oxygen saturation. PO2, arterial oxygen pressure. PCO2, arterial carbon dioxide pressure. The * represents a significant difference based on the linear mixed model in mean measures between two groups at each time point. Error bars are SEM

Fig. 4

ROC curves at different days prior to AKI onset for individual and top earliest predictors of AKI of the Stony Brook data

Fig. 5

AUC at different days prior to AKI onset for individual and top earliest predictors of AKI of the Stony Brook data

Fig. 6

Histogram of the treatment initiation prior to AKI onset for A invasive mechanical ventilation, B anticoagulants and C steroids of the Stony Brook data. For example, most of the patients were treated with invasive mechanical ventilation − 1 day prior to AKI onset. For all treatments, treatment initiation day is not significantly associated with mortality (p > 0.05)