This new study from Japan investigated possible relationships between tubular injury, COVID-19 severity, and inflammatory markers with development of acute kidney injury.
Urinary levels of liver-type fatty acid binding protein (L-FABP) and α1-microglobulin (uα1MG) were identified as biomarkers to watch for early detection of COVID-19–associated renal injury, according to study findings recently published in Clinical and Experimental Nephrology.
“Studies point to the possibility of direct viral infection to kidney cells via angiotensin-converting enzyme-2,” the authors from Japan’s Juntendo University wrote, “while a previous report found that renal damage in patients with severe acute respiratory syndrome occurred because of hemodynamic changes caused by cytokine storms.”
Their new study investigated possible relationships between tubular injury, COVID-19 severity, and 4 inflammatory markers in urine—N-acetyl-β-d-glucosaminidase (uNAG), β2-microglobulin (uβ2MG), uα1MG, and L-FABP—with development of acute kidney injury (AKI) to describe a potential role played by proinflammatory cytokine-mediated mechanisms among 18 patients with severe (n = 7) or nonsevere (n = 11) cases of COVID-19. The goal was to clarify whether progressive kidney damage resulting from COVID-19 was because of direct viral infection or inflammation mechanisms.
For all of the patients, who were admitted to Juntendo University Hospital in April and May 2020, positivity for SARS-CoV-2 RNA was confirmed with nasopharyngeal swab specimens obtained via reverse transcription-polymerase chain reaction and AKI was defined by 1 of 3 criteria:
None of the patients included in the analysis had a history of chronic kidney disease.
The principal study findings showed the following results:
Patients with severe cases of COVID-19 tended to be older compared with those who had nonsevere cases, at a median (interquartile range) age of 76 (66.5-76.0) vs 56.0 (37.5-65.5) years, respectively. They were also more likely to have comorbid hypertension (43% vs 18%; P = .33), diabetes (57% vs 18%; P = .14), or coronary heart disease (14% vs 9%; P = 1) and elevated median (interquartile range) levels of certain lab findings, namely procalcitonin (0.12 [0.08-0.15] vs 0.03 [0.00-0.04] ng/mL; P = .0019), C-reactive protein (8.40 [8.00-11.88] vs 0.44 [0.19-1.99] mg/L; P = .0012), IL-6 (40.5 [31.1-52.0] vs 5.2 [2.6-12.8] pg/mL; P = .0004), ferritin (976 [932-1310] vs 469 [238-607] mcg/L; P = .0008], and D-dimer (2.70 [2.25-3.95] vs 1.90 [1.40-2.05] mcg/mL; P = .01).
The authors summarize that their findings indicate kidney tubular injury may result from systemic inflammation, itself the result of cytokine storms, and that clinicians may be able to evaluate COVID-19–related kidney injury via levels of the inflammatory markers L-FABP and uβ2MG—but that additional studies are needed to confirm their results.
“Large-scale studies are needed to focus on tubular damage,” they concluded, “and elucidate underlying mechanisms of renal complication in COVID-19 infection.”
Fukao Y, Nagasawa H, Nihei Y, et al. COVID‑19‑induced acute renal tubular injury associated with elevation of serum inflammatory cytokine. Clin Exp Nephrol. Published online July 10, 2021. doi:10.1007/s10157-021-02101-z