In this multi-hospital observational study, we found that renal function was closely related to the prognosis of hospitalized COVID-19 patients. More than 25% of the patients had impaired renal function, with an eGFR lower than 90 mL/min/1.73 m2. Patients with abnormal eGFR (< 90 mL/min/1.73 m2) are more susceptible to severe COVID-19 infection. Although patients with impaired renal function received more intensive oxygen therapy, continuous blood purification, and glucocorticoid treatment, their prognosis was unsatisfactory, with a higher incidence of the composite endpoint (ICU admission, IMV, or death) and complications (AKI, respiratory failure, ARDS, acute cardiac injury, coagulation disorders, sepsis, shock, anemia, hypoproteinemia, electrolyte disturbances, and acidosis). Multivariate regression analysis showed that both eGFR < 60 mL/min/1.73 m2 on admission and AKI occurrence during hospitalization were independent risk factors for poor in-hospital prognosis.
As the best overall index of kidney function, eGFR is the only criterion for staging CKD and determining long-term renal outcomes12. A study of a multicenter registry found that 30% of COVID-19 patients had kidney dysfunction upon admission (eGFR < 60 mL/min/1.73 m2), which was associated with higher in-hospital mortality13. Our study showed that the incidence of complications, the composite endpoint (15.4% vs. 19.6% vs. 54.5%, P = 0.000), and mortality (2.4% vs. 7.4% vs. 27.7%, P = 0.000) increased gradually with decreasing eGFR. The risk of reaching the composite endpoint among patients in the middle and lowest eGFR tertiles was 2.1 and 5.6 times, respectively, of the risk among those in the highest tertile (P = 0.000). This suggests that patients with renal function impairment (eGFR < 90 mL/min/1.73 m2) on admission had significantly worse in-hospital outcomes, although the significance was lost in the middle tertile group (eGFR: 60–89 mL/min/1.73 m2) after adjustments for baseline and follow-up clinical data using the Cox regression model. Our results indicated that patients with an eGFR of 60–89 mL/min/1.73 m2 had already escalated risks of poor prognosis, emphasizing the need for early and continuous monitoring of renal function.
The prevalence of CKD in China is 10.8% 14. However, in our study, only 2.6% of patients with COVID-19 had a history of CKD. We also found that 19.1% and 30.5% patients had proteinuria and hematuria, respectively. Thus, CKD may be underestimated in these patients on admission. Fever is the most common clinical symptom in COVID-19 patients, with a high incidence of 87.9–94%15,16. An interesting finding in our study was that patients with kidney injury, especially those with GFR < 60 mL/min/1.73 m2, were less likely to develop fever, with an incidence of less than 50%. Despite a low incidence of clinical symptoms, patients with eGFR < 90 mL/min/1.73 m2 had a higher incidence of complications, the composite endpoint, and mortality. This may be due to low immunity (reduced lymphocyte count)17,18 coagulation disorders (decreased platelet count, prolonged prothrombin time, and increased d-dimer)19,20, poor nutrition (anemia and hypoproteinemia), and persistent inflammatory states (high procalcitonin, interleukin-6, and C-reactive protein)21 in patients with impaired renal function (eGFR < 90 mL/min/1.73 m2). Therefore, these patients should receive immunotherapy, nutrition support, and anti-inflammatory and anticoagulant therapy. Some novel treatments have good therapeutic effects in COVID-19, such as tocilizumab21, umbilical cord mesenchymal stem cells11, and convalescent plasma22. However, we could not evaluate the effects of these treatments in patients with different renal function due to the small number of cases.
Acute kidney injury (AKI), as a common complication of COVID-19, is usually related to disease mortality23. A postmortem patient series found significant acute tubular injury in all patients who had died of COVID-1924. The mechanisms of kidney injury in SARS-CoV-2 infection include direct viral injury via the angiotensin-converting enzyme 2 receptor, which is highly expressed in the kidneys25, an imbalanced renin-angiotensin-aldosterone system26,27 and release of proinflammatory cytokines elicited by the viral infection and microvascular thrombosis28. We found that patients with eGFR < 60 mL/min/1.73 m2 were more likely to develop AKI during hospitalization, with an incidence of 17%. Furthermore, 10% of patients with eGFR < 60 mL/min/1.73 m2 received CRRT. A study in New York has reported a high incidence of AKI (37–46%) among COVID-19 patients23 and 19% of patients with AKI required dialysis, and half of them died in the hospital. We found that AKI was an independent risk factor in patients with COVID-19 after adjustments. Therefore, regular monitoring of renal function and timely diagnosis of AKI are conducive to the treatment of COVID-19 patients.
Our study has some limitations. First, the incidence of CKD and AKI may be underestimated in some patients due to the lack of baseline medical records, late admission, and lack of renal function examination after admission. Second, a small proportion of patients were still in the hospital, and their outcomes were unknown at the time of the data cutoff, which might lead to the underestimation of the endpoint events. Third, due to different diagnostic paradigms in different hospitals, not all laboratory tests were performed in all patients, which led to some missing data. Last but not the least, there was no direct evidence of renal damage caused by the virus in the urine or kidney tissue.
In conclusion, impaired renal function on admission and the occurrence of AKI during hospitalization are independent predictors of poor prognosis among hospitalized COVID-19 patients. Therefore, early and continuous monitoring of renal function and early diagnosis of AKI are necessary interventions to predict and prevent the progression of COVID-19.