Clinicopathological Features and Outcomes of Acute Kidney Injury in Critically Ill COVID-19 with Prolonged Disease Course: A Retrospective Cohort

Abstract

Background: The incidence, severity, and outcomes of AKI in COVID-19 varied in different reports. In patients critically ill with COVID-19, the clinicopathologic characteristics of AKI have not been described in detail.

Methods: This is a retrospective cohort study of 81 patients critically ill with COVID-19 in an intensive care unit. The incidence, etiologies, and outcomes of AKI were analyzed. Pathologic studies were performed in kidney tissues from ten deceased patients with AKI.

Results: A total of 41 (50.6%) patients experienced AKI in this study. The median time from illness to AKI was 21.0 (IQR, 9.5-26.0) days. The proportion of Kidney Disease Improving Global Outcomes (KDIGO) stage 1, stage 2, and stage 3 AKI were 26.8%, 31.7%, and 41.5%, respectively. The leading causes of AKI included septic shock (25 of 41, 61.0%), volume insufficiency (eight of 41, 19.5%), and adverse drug effects (five of 41, 12.2%). The risk factors for AKI included age (per 10 years) (HR, 1.83; 95% CI, 1.24 to 2.69; P=0.002) and serum IL-6 level (HR, 1.83; 95% CI, 1.23 to 2.73; P=0.003). KDIGO stage 3 AKI predicted death. Other potential risk factors for death included male sex, elevated D-dimer, serum IL-6 level, and higher Sequential Organ Failure Assessment score. The predominant pathologic finding was acute tubular injury. Nucleic acid tests and immunohistochemistry failed to detect the virus in kidney tissues.

Conclusions: AKI was a common and multifactorial complication in patients critically ill with COVID-19 at the late stage of the disease course. The predominant pathologic finding was acute tubular injury. Older age and higher serum IL-6 level were risk factors of AKI, and KDIGO stage 3 AKI independently predicted death.

Keywords: COVID-19; acute renal failure; critically ill; kidney disease; renal pathology.

Graphical abstract

Figure 1.

The patients with AKI who had a shorter disease course before death showed faster decline of renal function. Cubic polynomial regression of (A) sCr and (B) eGFR of patients with AKI who died within 21 days (n=11), between 21 and 35 days (n=17), after 35 days (n=6), and those who survived (n=7).

Figure 2.

The compositions of AKI stages and etiologies during the disease course. (A) The proportion of KDIGO stage 1, stage 2, and stage 3 AKI were 26.8%, 31.7%, and 41.5%, respectively. Most stage 3 AKI occurred in the first 4 weeks. KDIGO stage 1: increase in sCr to 1.5–1.9 times baseline within 7 days or ≥0.3 mg/dl (≥26.5 μmol/L) increase within 48 hours, or urine output <0.5 ml/kg per hour for 6–12 hours. KDIGO stage 2: increase in sCr to 2.0–2.9 times baseline within 7 days, or urine output <0.5 ml/kg per hour for ≥12 hours. KDIGO stage 3: increase in sCr to three or more times baseline, or increase in sCr to ≥4.0 mg/dl (≥353.6 μmol/L) within 7 days, or initiation of RRT, or anuria for ≥12 hours. (B) Various AKI etiologies were identified: 61.0% (25/41) of the AKIs were considered to be related to septic shock; eight patients (19.5%) had histories of poor intake or volume loss before AKI; 12.2% (5/41) of AKIs occurred after administration of antiviral drugs or antibiotics, and no other triggers were identified. In general, AKI caused by septic shock and adverse drug effects occurred throughout the whole disease course, whereas volume insufficiency usually occurred in the early phase of the disease.

Figure 3.

Pathologic findings in kidney tissues from patients critically ill with COVID-19 and AKI. (A) Diffuse tubular injury and cytoplasmic vacuolization in tubular epithelial cells (black arrow). (B) Crystallizations in casts and proximal tubular cells in a patient (black arrows). (C) Localized inflammatory cell infiltration was present in the interstitial area (black arrow). (D) Venous thrombosis in a patient with positive anti-phospholipid antibodies. (E–G) Scattered distribution of CD3-, CD20-, and CD8-positive lymphocytes in the interstitial area (black arrows). (H) Scattered distribution of CD68-positive macrophages in the interstitial area (black arrows). HE, hematoxylin and eosin.

Figure 4.

Pathologic findings in kidney tissues from patients critically ill with COVID-19 and AKI (continued). (A) Glomerulus with nonremarkable changes. (B) Glomerulus with swollen endothelial cells (white arrow), wrinkling of the glomerular basement membrane with double contours (black arrows), which was consistent with chronic glomerular ischemia. (C) Arteriolar hyalinosis (black arrow). (D) Intimal hyperplasia in interlobular artery. (E) CD4-positive cells around a glomerulus. (F) CD3 was occasionally positive within the glomerulus (black arrows). HE, hematoxylin and eosin; PAS, Periodic acid–Schiff.

Figure 5.

Immunochemistry staining of ACE2 and SARS-CoV-2. (A) ACE2 was strongly expressed in both parietal epithelial cells of glomeruli and tubular epithelial cells (brown area). (B) ACE expression in paracarcinoma normal kidney tissue from a patient with clear cell renal carcinoma. (C) IHC failed to detect SARS-CoV-2 in kidney tissues of patients with COVID-19. (D) Positive SARS-CoV-2 detection in both alveolar pneumocytes and macrophages in lung tissues (black arrows) of a patient with AKI (patient 5 in Table 6).

Figure 6.

EM findings in patients with AKI. (A) EM studies showed small particles (black arrows) in the cytoplasm in renal proximal tubular epithelium. The diameter of these particles varied from about 60 to 100 nm. (B) Particles in vesicles (black arrows) in proximal tubular epithelium. (C) Wrinkling of the glomerular basement membrane (black arrow), subendothelial space expansion, and varying degrees of foot process effacement were present occasionally. (D) Remnants of mitochondrial cristae at the periphery (black arrows) were observed in proximal tubular epithelial cells.