Clinical Profile and Outcome of Haemodialysis in Patients With COVID-19 – A Single Centre Experience

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 disease is the third coronavirus to have emerged in the last 20 years. The COVID-19 infection causes more severe illness in patients with comorbid diseases, especially in patients with diabetes, hypertension and kidney failure. Methods This is a retrospective study using electronic records and laboratory data of adult patients hospitalised at All India Institute of Medical Sciences (AIIMS), Patna between May 1st, 2020 and March 31st, 2021, who were diagnosed with COVID-19 and needed haemodialysis. The demographic characteristics, co-morbidities, symptoms, clinical course, laboratory parameters, and treatments were recorded. The aim of this study is to evaluate the clinical profile and outcome of patients on hemodialysis with COVID-19 infection. Results The study included 261 COVID-19 patients who needed haemodialysis. The most common symptoms on admission were fever (72.8%), cough (64.3%) and dyspnoea (46.6%). The mean age was 58.4 +/-15 years. A total of 195 patients (74.7%) were male. The most common co-morbid condition was hypertension (85.1%) followed by diabetes (71.9%). A total of 118 (45.2) patients had acute on chronic kidney disease (CKD), 40 (15.3) were on maintenance haemodialysis (MHD) and 103 (39.5) were having acute kidney injury (AKI). Eight patients were renal transplant recipients. At presentation, 183 (70.1%) patients were having mild to moderately severe infection and 78 (29.9%) patients were having severe disease. A total of 213 patients required ICU admissions, 186 (75.3%) of whom required invasive ventilation. Overall mortality was 66% (172/261) and the rest were discharged. Conclusion The study suggests that COVID-19 disease has a significantly more severe course and poorer outcome in patients requiring haemodialysis.


Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 disease, was first described in humans in December 2019 in Wuhan, China [1] and is the third coronavirus to have emerged in the last 20 years. Previous outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and the Middle East respiratory syndrome coronavirus in 2012 have been toppled in case incidence by COVID-19 [2] and was declared a pandemic by the World Health Organization. Worldwide 176,945,596 cases have been reported with 3,836,828 deaths till June 18, 2021 [3]. In India, this infection has also caused a significant impact on public health with 2,98,22,411 cases reported till June 18, 2021 with 3,85,164 deaths. The rising cases and its impact on public health forced the Indian government to impose a nationwide lockdown and this impacted the care of patients with kidney disease especially those on maintenance haemodialysis (MHD) [4][5][6]. The potential impact of SARS-CoV-2 on the kidneys is still undetermined, but emerging evidence indicates that kidney complications are frequent, and COVID-19 disease may have unique features in individuals on chronic dialysis and kidney transplant recipients [4][5][6][7].
Our centre was declared a dedicated COVID hospital by the state government. Initially, we were the only dedicated dialysis centre for COVID-19 patients in our state.

Materials And Methods
This is a hospital record-based retrospective observational analytical study conducted at All India Institute of Medical Sciences (AIIMS), Patna focusing on the clinical characteristics and outcome of confirmed cases of COVID-19 who were admitted from May 1st, 2020 to March 31st, 2021 and underwent haemodialysis. The aim of this study is to evaluate the clinical profile and outcome of patients on hemodialysis with COVID-19 infection. This study was approved by the ethics committee of AIIMS Patna (AIIMS/Pat/IRC/2020/672).
Data regarding 261 patients were collected and analysed. A confirmed case with COVID-19 was defined as a positive result to high-throughput sequencing or real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay for nasal and pharyngeal swab specimen. The subjects were followed from admission to death or discharge. Demographic details, medical history, clinical features and laboratory parameters including the inflammatory markers were noted. History elicited regarding smoking habits and co-morbidities like diabetes mellitus (DM), hypertension (HTN), chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) were also noted. Renal condition was summarized in three categories: acute kidney injury (AKI), acute on chronic kidney disease and end-stage renal disease (ESRD) on MHD. Other clinical details comprised of history of renal transplant and number of sessions of haemodialysis done during the treatment, oxygen saturation and respiratory rate at the time of admission.
The degree of severity of COVID-19 was defined as mild, moderate and severe according to "National Clinical Management Protocol COVID-19". AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) guideline as having one of the following: an increase in serum creatinine (Cr) by ≥0.3 mg/dL within 48 h, or an increase in Cr to >1.5 times baseline within the previous seven days, or urine volume <0.5 mL/kg/h for >6 h [8].

Results
The baseline characteristics of the patients are shown in Table 1  Conventional haemodialysis was done in hemodynamically stable patients and sustained low-efficiency dialysis (SLED) in those who were hemodynamically unstable. A total of 143 patients received SLED, 24 at presentation and 119 during the course of treatment while others were managed with conventional haemodialysis. The facility of continuous renal replacement therapy (CRRT) was not available at our centre.
Vascular access was arterio-venous fistula (AVF) in 39 patients and right tunnelled dialysis catheter in one of the patients on MHD. While in patients with acute on CKD and AKI haemodialysis was done through a temporary dialysis catheter.
Indications of dialysis in patients with acute on CKD and AKI were refractory hyperkalaemia, refractory metabolic acidosis, fluid overload and worsening azotemia.
In this study, we did not report any clotting of the dialysis circuit. The baseline laboratory parameters taken at the time of admission of patients are shown in Table 2.    However, no association was noted for procalcitonin and creatinine. Although, median values for both the parameters were significantly higher among the non-survivors. On applying multiple logistic regression, invasive ventilation, deranged total leucocyte count (TLC) and hypalbuminaemia were identified as independent predictors of mortality among COVID patients undergoing haemolysis at the institute. The regression model explained 60.4% variability in patient mortality. Furthermore, the area under receiver operating characteristic (ROC) curve plotted for the regression model was found to be 0.942 which indicates acceptable discrimination for the model (Figure 1).

Discussion
Our hospital is a tertiary care centre in the state of Bihar in India and it was declared a dedicated hospital for patients with COVID-19 infection. For the initial few months, we were the only government facility providing dialysis services to these patients in our state.
Patients on MHD were the most disadvantageous cohort, as accesses to health care facility were limited especially during the lockdown period [5]. There have been few reports providing the outcome of MHD patients but none so far looked into the outcome of all patients including MHD, AKI and acute on CKD who underwent haemodialysis [9][10][11][12][13][14][15][16][17][18].
The hospitalised patients who require haemodialysis need additional manpower and logistics which puts more burden on the already overstretched health care facilities, especially in a developing country like ours. Increased requirement of haemodialysis in critically ill COVID-19 patients leads to a shortage of dialysis machines and other accessories [19].
Patients with kidney diseases had more severe COVID-19 infection with higher mortality as compared to non-CKD patients [21][22][23][24][25][26]. In this study, 118 patients had AKI with underlying CKD, out of which 88 (74.6%) patients died. Among survivors also, 33 remained dialysis-dependant at the time of discharge. The incidence of AKI was higher in patients with established CKD [25].
In this study, 103 patients had AKI who underwent haemodialysis, out of which 77 (74.7%) patients died.
Most of these patients required ICU care and invasive ventilation. Silver et al. in their systematic review and meta-analysis reported a pooled prevalence of AKI as 28% in non-ICU setting and 46% in ICU setting in patients with COVID-19 infection. The pooled prevalence of renal replacement therapy (RRT) was 9% in non-ICU setting and 19% in ICU setting [25].
Mortality in AKI ranged from 1% to 61% in various studies and depends on the study population and mortality amongst those requiring RRT ranged from 45% to 80% [25,26]. Xu et al. reported a 60-day mortality of around 90% in AKI requiring RRT in critically ill patients [26]. Among survivors in AKI cohort, nine were dialysis-dependant at discharge in this study.
No clotting of the dialysis circuit was reported in this study with routine anticoagulation with unfractionated heparin. While other studies report a high incidence of clotting mainly during CRRT [27]. The pathogenesis of high thrombosis in COVID-19 infection is incompletely understood but endothelial inflammation, hyper viscosity and pulmonary hypoxemia leading to vasoconstriction may contribute [28].
A significantly higher proportion of patients who died were suffering from AKI (44.8%) as compared with those who survived (i.e., 29.2%) [<0.001]. On applying multiple logistic regression need for invasive ventilation, raised TLC and hypalbuminaemia were identified as independent predictors of mortality.
Age more than 45 years, the mean saturation of oxygen at presentation, higher respiratory rate at presentation and the requirement for invasive ventilation were found to be significantly associated with mortality. Also, the majority of patients who died had raised leucocyte count (76.7%), lymphopenia (97.1%), hypoalbuminemia (95.4%), raised LDH (93.6%), raised CRP (98.8%), D-dimer (98.3%), serum ferritin (92.4%) and interleukin 6 level (95.4%). While raised leucocyte count, lymphopenia, hypoalbuminemia, raised serum ferritin and raised IL-6 were found to be significantly associated with mortality of patients. In the study by Wu et al., older age, higher Sequential Organ Failure Assessment (SOFA) score and D-Dimer greater than 1 µg/mL on admission were associated with mortality [29].
Shang et al. in their study reported certain laboratory parameters including CRP, neutrophil count, LDH, white blood cell count, albumin, and procalcitonin predictive of the prognosis of MHD patients with COVID-19 with CRP being the strongest single predictive indicator [30].

Limitation
The main limitation of this study is its design; being a single-center retrospective study. Final outcome of patients who were discharged is not available. The outcome of this cohort was not compared with patients without renal dysfunction or with patients not requiring dialysis. We need a larger multicentric study looking at the outcomes of haemodialysis patients so that it can guide the policy makers for better health care delivery in patients with kidney disease especially in a resource-limited setting.

Conclusions
Our study suggests that COVID-19 patients who needed hemodialysis had more severe course and had the worst outcome. Patients with AKI had higher mortality as they had more severe disease and required ICU care. Need for invasive ventilation, raised TLC and hypalbuminaemia were independent predictors of mortality. Age, mean oxygen saturation at presentation and raised inflammatory markers were significantly associated with mortality. All efforts should be made to search for preventable causes of AKI. Clinicians should be aware of the potential risk factors of poor outcomes in hemodialysis patients.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. The Institutional Ethics Committee, All India Institute of Medical Sciences, Patna issued approval (AIIMS/Pat/IRC/2020/672). This study was approved by the institutional ethics board of AIIMS Patna vide letter number (AIIMS/Pat/IRC/2020/672) and written informed consent was waived. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.
Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.