According to the present analysis, patients requiring acute hemodialysis during hospitalization due to COVID-19 had an over 90% all-cause mortality over a median 26 days of follow-up. In general, non-CKD patients had fewer comorbidities but more severe presentations. In contrast, patients previously on hemodialysis had the least severe presentation. In a model adjusted for independent predictors of all-cause mortality, CKD patients had an almost 100 percent (95% CI 2-260%) increased, while patients previously on hemodialysis had a 60% lower mortality (95% CI 0.20–0.81) compared to non-CKD patients. After further adjustment for the need for intensive care treatment, the difference in mortality between the non-CKD and the prior hemodialysis groups became non-significant.
A third novel coronavirus leading to coronavirus disease 2019 was first identified in Wuhan, China, in December 2019. Until February 2022, over 386 million people were confirmed to contract COVID-19 worldwide, of whom almost 6 million died . The typical clinical spectrum resulting from infection with the responsible virus, SARS-CoV-2 is broad, ranging from an asymptomatic response or development of a mild upper respiratory tract infection to critical illness .
Kidney involvement in patients with COVID-19 is multifactorial and can range from the presence of proteinuria and hematuria to acute kidney injury (AKI) requiring hemodialysis. According to the current literature, COVID-19 patients with acute kidney injury have an extremely high mortality. Furthermore, it remained an independent predictor of all-cause in-hospital death . Based on the initial Wuhan report, the AKI associated mortality is at least 60%. Similarly high (70%) mortality was reported among chronic hemodialysis patients in the US [13, 14]. We also found that patients requiring acute hemodialysis treatment during a COVID-19 related hospitalization had an extremely high mortality. Our results extend further observations showing a mortality risk over 90% over an extended follow-up.
Among the groups in the present study, we found the highest mortality in CKD patients requiring acute hemodialysis during hospitalization, where almost all patients died. This is a staggering result in light of the fact that patients in the non-CKD group had a more severe presentation with significantly more frequently complaining of dyspnoea at admission and more frequently requiring mechanical ventilation and intensive care.
Mortality in our cohort was associated with the severity of COVID-19 infection, with significantly higher CRP and WBC values among patients who died. Several studies have documented the association between COVID-19 severity and circulating levels of CRP and interleukin-6 . Hypoalbuminemia is common among COVID-19 patients and is closely related with inflammatory markers and clinical outcomes. Overall, there is a strong association of hypoalbuminemia with respiratory impairment, disease severity, and inflammatory state .
Similarly, to our findings, another study found that the development of AKI during hospitalization for COVID-19 was associated with a substantially increased mortality. This risk was further amplified when AKI resulted in dialysis. After adjusting for demographics, comorbid conditions, and illness severity, the risk for death remained higher among those with AKI stages 1–3 (adjusted HR, 3.4 [95% CI, 3.0-3.9]) and AKI stage 3D (adjusted HR, 6.4 [95% CI, 5.5–7.6]) compared with those without AKI . Furthermore, even CKD not requiring renal replacement therapy remained an independent risk factor for in-hospital death [adjusted OR (aOR) 7.35 (95%CI 2.41–22.44)] and poor prognosis [aOR 3.01 (95%CI 1.23–7.33)] . Dialysis treatment (aHR 3.69), post organ transplantation status (aHR 3.53), and CKD itself (aHR 2.52 for patients with eGFR < 30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The relative risk associated with CKD Stages 4 and 5 is higher than that of diabetes (aHR range 1.31–1.95) or chronic heart disease (aHR 1.17) . Nephrologists and intensivists face immense daily challenges while caring for these patients in the inpatient setting and end-stage renal disease patients on chronic dialysis in inpatient and outpatient settings .
In contrast to our findings, a few papers reported of an extremely severe course and prognosis in hemodialysis patients with COVID-19 had. Compared with the expected 1.2% mortality in matched controls on dialysis treatment without COVID-19, COVID-19 patients on hemodialysis had an absolute mortality over 20%, and a relative risk of 21 (95% confidence interval [CI] 18.6–23.9) [20–22]. A large cohort with over 80 thousand participants demonstrated positive associations between social deprivation and the risk of COVID-19, as well as almost all chronic health conditions, including hemodialysis .
Many patients with end-stage renal disease (ESRD) are on peritoneal dialysis (PD). Cohorts from China found that a similar incidence of symptomatic COVID-19 among patients on PD to that of the general population, indicating that the PD population was not at high risk for COVID-19. The multiple and severe comorbidities, but not the infection itself, may contribute to the prolonged hospitalization and increased mortality of patient on PD . The overall mortality (8.5%) of PD patients between 1 January, 2020 and 12 April, 2020 was increased compared to the mortality (5.7%) of the corresponding period of 2019. Two systematic reviews report comparable mortality with PD and extracorporeal dialysis in critically ill patients with AKI . Based on this, acute PD might be a suitable treatment option for COVID-19 related AKI [26, 27].
The surprisingly low mortality of our patients with previous HD treatment and SARS-CoV-2 infection could be partially explained by the fact that an important indication for the hospitalization of patients on chronic HD was the isolation of these patients and to prevent transmission during transport to the dialysis unit. This is supported by the finding that patients in the pHD group had the least severe presentation at admission. Complete isolation of hemodialysis patients with COVID-19 is general clinical practice worldwide .
Although isolation most likely played a vital role in the lower risk of death in patients on chronic hemodialysis, nearly half of these patients still died during the extended follow-up. Mortality reported in other patient groups suggests that in addition to the effect of acute COVID-19 and its immediate complications and severe complications and consequent deaths can be expected months after hospitalization. These factors are likely played a role in the high overall mortality of the non-CKD and CKD non-dialysis patients. Although fewer patients in CKD group not previously on HD required intensive care, in-hospital and overall mortality was highest in this group.
Strengths and limitations
Our study has some strengths that has to be mentioned. As most participants were also included in a prospective data collection, more details were collected with a better precision that one would expect in usual clinical care. Furthermore, the follow-up period did not end with the emission of patients, so mortality follow-up was at least 6 months for each participant (although given the high mortality, the mean and median was much shorter).. To the best of our knowledge, our study has the longest overall follow-up period among HD patients with COVID-19. It should also be noted that we were able to track mortality data of all included participants.
However certain limitations of our study should be acknowledged. First, the number of participants was small leading to limited statistical power. Due to this, we had to limit the number of covariates in the multivariate models and given the wide confidence intervals, the magnitudes of effect sizes cannot be judged well. Our analysis of chronic HD patients is limited by selection bias related to the fact that the indication for hospitalization was not always the severity of disease but the need for isolation. Given the sudden onset of the COVID-19 epidemic and the significant strain on the health care system, we had to exclude a substantial number of potential participants due to missing covariates. Furthermore, as intensive care admission was not decided at the time of admission for all cases, its use in the final model could lead to overadjustment. However, the requirement for intensive care is strongly related to disease severity.