Kidney replacement therapy patients with COVID-19 in the vaccine era: what do we need to know?

Kidney disease is one of the most important factors affecting the prognosis of patients with coronavirus disease 2019 (COVID-19). Patients on kidney replacement therapy (KRT; dialysis and kidney transplant recipients) are vulnerable to severe complications of COVID-19. As the pandemic evolves and preventive strategies, availability of healthcare facilities, treatment approaches and vaccination strategies change, studies are needed on COVID-19 epidemiology and outcomes in KRT patients that contribute to vaccination regimens, treatment protocols and immunosuppressive therapies of KRT patients with COVID-19. In their registry-based study, Quiroga et al. analyzed COVID-19 KRT patients in Spain across six pandemic waves in order to evaluate dynamic treatment approaches and outcomes as well as the efficacy of vaccination.

Long-term cardio-vascular risk assessment in chronic kidney disease and kidney transplanted patients following SARS-COV-2 disease: protocol for multi-center observational match controlled trial.

BACKGROUND: The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced a pandemic since March 2020 by affecting more than 243 million people with more than 5 million deaths globally. SARS-CoV-2 infection is produced by binding to angiotensin-converting enzyme, which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. SARS-CoV-2 and cardiovascular disease (CVD) are interconnected by risk factors association with an increased incidence of the disease and by determining de novo cardiac complications. At the same time, COVID-19 disease can lead to acute kidney injury directly, or due to sepsis, multi-organ failure and shock. Therefore, the pre-existence of both CVD and chronic kidney disease (CKD) is linked with a higher risk of severe disease and worse prognosis. METHODS: The main aim of this study is to assess the CV risk in a CKD (stage 3 to 5), dialysis and kidney transplanted population, following SARS-CoV-2 infection, with focus on the endothelial dysfunction as compared to a control group of matched patients. By using clinical evaluation, flow-mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, lung ultrasound, bioimpedance spectroscopy and a series of novel biomarkers, the investigators will determine the long-term impact of this disease on CV and renal outcomes. DISCUSSION: This study will address the challenges and implications in long-term CV sequeale of COVID-19 and focus on a better understanding of the underlying mechanisms and possible therapeutic options. TRIAL REGISTRATION: Patient enrolment in the trial started in January 2021 and is expected to finish at the end of 2022. The study can be found on ClinicalTrials.gov database with NCT05125913 identifier. Registered on 18 November 2021 - Retrospectively registered.

Acute kidney injury in hospitalized COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) in COVID-19 patients is associated with poor prognosis. However, the incidence, risk factors and potential outcomes of AKI in hospitalized patients are not well studied. MATERIALS AND METHODS:  This is a retrospective cohort study conducted in two major university hospitals. Electronic health records of the patients, 18 years or older, hospitalized between 13 April and 1 June 2020 with confirmed COVID-19 were reviewed. We described the incidence and the risk factors for AKI development in COVID-19 patients. Furthermore, we investigated the effects of AKI on the length of hospital and intensive care unit (ICU) stay, the admission rates to ICU, the percentage of patients with cytokine storm and in-hospital mortality rate. RESULTS: Among 770 hospitalized patients included in this study, 92 (11.9%) patients developed AKI. The length of hospitalized days (16 vs 9.9, p < 0.001) and days spent in the hospital until ICU admission (3.5 vs. 2.5, p = 0.003) were higher in the AKI group compared to patients without AKI. In addition, ICU admission rates were also significantly higher in patients with AKI (63% vs. 20.7%, p < 0.001). The percentage of patients with AKI who developed cytokine storm was significantly higher than patients without AKI (25.9% vs. 14%, p = 0.009). Furthermore, the in-hospital mortality rate was significantly higher in patients with AKI (47.2% vs. 4.7%, p < 0.001). CONCLUSIONS: AKI is common in hospitalized COVID-19 patients. Furthermore, we show that AKI increases the admission rates to ICU and in-hospital mortality. Our findings suggest that AKI should be effectively managed to prevent the adverse outcomes in COVID-19 patients.

Should we continue to use renin-angiotensin-aldosterone system blockers in patients with COVID-19?

Patients with chronic kidney disease, chronic heart failure and hypertension have an increased risk of coronavirus disease 2019 (COVID-19)-related death. Renin-angiotensin-aldosterone system (RAS) blockers are commonly prescribed to decrease morbidity and mortality in these conditions. Following the pre-clinical demonstration of COVID-19 viral entry into cells via angiotensin-converting enzyme-2, the use of RAS blockers was questioned in infected individuals. Theodorakopoulou et al. extensively review the pathophysiology behind that hypothesis and observational or clinical trials on RAS blockers and COVID-19. Despite being a scientific hot spot of an ongoing debate, discontinuation of RAS blockers is not associated with improved clinical outcomes in COVID-19 and may have potential harmful effects, including exacerbation of the underlying disease.

Post-acute COVID-19 syndrome and kidney diseases: what do we know?

COVID-19, a disease caused by a novel coronavirus (SARS-CoV-2), is a major global threat that has turned into a pandemic. Despite the emergence of multiple vaccination alternatives and developing therapeutic options, dramatic short- and long-term clinical outcomes have been recorded with more than 250 million infected people and over 5 million deaths as of November 2021. COVID-19 presents various respiratory, cardiovascular, neuropsychiatric, musculoskeletal and kidney features during the acute phase; nevertheless, renal involvement in the post-infection period has recently been emphasized. The present review aims to evaluate the growing literature on kidney involvement in the SARS-CoV-2 infection along with clinical features reported both in the acute phase of the infection and in the post-acute COVID-19 period by assessing potential pathophysiological frameworks explaining such conditions. Chronic kidney disease and development of acute kidney injury (AKI) in the course of initial hospitalization are associated with high mortality and morbidity rates. Moreover, growing evidence suggests a decline in renal function in the 6-to-12-month follow-up period even in patients without any signs of AKI during the acute phase. Despite such concerns there are no guidelines regulating the follow-up period or therapeutic alternatives for such patient population. In conclusion, the burden of COVID-19 on the kidney is yet to be determined. Future prospective large scale studies are needed with long follow-up periods assessing kidney involvement via multiple parameters such as biopsy studies, urinalysis, measurement of serum creatinine and cystatin C, directly measured glomerular filtration rate, and assessment of tubular function via urinary ß2-microglobulin measurements.

Long-term effect of COVID-19 infection on hemodialysis patients: Should we follow hemodialysis patients more closely?

During the coronavirus disease 2019 (COVID-19) pandemic, hemodialysis patients constitute one of the most vulnerable patient populations as they have more significant comorbidities and need to visit healthcare settings frequently even under pandemic conditions. It was also largely demonstrated that hemodialysis patients have high mortality rates with severe to fatal disease due to COVID-19 during their initial hospitalization. Even though the functional decline and fatigue after severe infections are not a novel entity, some long-term effects of COVID-19 have drawn attention with their prolonged effects even after discharge. A recent prospective, observational study by Carriazo et al. provided the first evidence to compare long-term mortality rates of hemodialysis patients with and without COVID-19. Carriazo et al. stated a hazard ratio of 3.00 for the mortality rates of hemodialysis patients over a 1-year follow-up period after their COVID-19 diagnosis. They emphasized that the high mortality rates of hemodialysis patients with COVID-19 are not limited to the initial hospitalization period but also continue after discharge, especially in the first 3 months. In light of this study, it can be recommended that hemodialysis patients with COVID-19 should be monitored closely and continuously, and hemodialysis patients should be prioritized for vaccination against COVID-19 with close follow-up for their antibody levels.

Long-term effect of COVID-19 infection on hemodialysis patients: Should we follow hemodialysis patients more closely?

During the coronavirus disease 2019 (COVID-19) pandemic, hemodialysis patients constitute one of the most vulnerable patient populations as they have more significant comorbidities and need to visit healthcare settings frequently even under pandemic conditions. It was also largely demonstrated that hemodialysis patients have high mortality rates with severe to fatal disease due to COVID-19 during their initial hospitalization. Even though the functional decline and fatigue after severe infections are not novel entity, some long-term effects of COVID-19 has drawn attention with its prolonged effects even after discharge. A recent prospective, observational study of Carriazo et al provided the first evidence to compare long-term mortality rates of hemodialysis patients with and without COVID-19. Carriazo et al stated a hazard ratio of 3.00 for the mortality rates of hemodialysis patients over a one-year follow-up period after the COVID-19 diagnosis. They emphasized that the high mortality rates of hemodialysis patients with COVID-19 are not limited to the initial hospitalization period but also continue after discharge, especially the first three months. In the light of this study, it can be recommended that hemodialysis patients with COVID-19 should be monitored closely and continuously and hemodialysis patients should be prioritized for a vaccination against COVID-19 with close follow-up for their antibody levels.

Immunogenicity of SARS-CoV-2 mRNA vaccine in dialysis and kidney transplant patients: A systematic review.

Kidney transplant recipients and dialysis patients constitute a risk group for severe COVID-19. They are highly advised to get vaccinated according to the current guidelines. However, data on antibody response, cell responses and protection from events, and factors that might alter this response after a routine full series of vaccination remain incomplete for these populations. The aim of this article was to analyze the antibody responses after a full series of mRNA-based SARS-CoV-2 vaccination in kidney transplantation and dialysis patients and to define the factors that alter seroconversion status in these populations. In this systematic review, 18 studies investigating the antibody response to full vaccination with two doses of COVID-19 mRNA vaccines in hemodialysis, peritoneal dialysis, and kidney transplant patients were included. Kidney transplant and dialysis patients have a lower seroconversion rate after mRNA-based SARS-CoV-2 vaccination than the healthy population: 27.2% for kidney transplantation, 88.5% for dialysis patients while all healthy control in these studies seroconverted. Moreover, anti-S antibody titers were lower in seroconverted kidney transplantation or dialysis patients than in healthy control in all studies that assessed this variable. Older age and dialysis vintage, immunosuppressive or chemotherapy treatment, and lower serum albumin, white blood cell, lymphocyte and hemoglobin counts were associated with lower/no antibody response to vaccination. Dialysis patients and kidney transplant recipients have lower seroconversion rates after a full series of mRNA-based SARS-CoV-2 vaccination than the general population. Several factors are associated with an altered antibody response. A third dose could be considered in this patient group.

COVID-19 and acute kidney injury.

The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) started in December 2019 and has affected millions of lives worldwide, while many aspects of the illness are still unknown. Current data show that many hospitalized COVID-19 patients suffer from kidney damage, in the form of proteinuria, hematuria or acute kidney injury (AKI). AKI is especially prevalent among severe and critically ill COVID-19 patients and is a predictor of mortality. The pathophysiology of AKI in COVID-19 is unclear. Early reports of histopathologic examination from autopsied kidney tissue show SARS-CoV-2 viral particles in renal tubular cells and podocytes, suggesting direct viral infection, as well as findings of acute tubular necrosis, while rhabdomyolysis-associated AKI and glomerulopathies may also occur. As of today, only remdesivir has been authorized to treat COVID-19. Ongoing research investigates potential of anti-viral and anti-inflammatory agents along with safety and efficacy of commonly prescribed drugs such as renin-angiotensin-aldosterone system blockers. This review discusses the prevalence of AKI and its association with outcome, while highlighting possible mechanisms of AKI and suggesting organ protective measures to prevent the development of kidney damage.

A brand-new cardiorenal syndrome in the COVID-19 setting.

Coronaviruses are a major pathogen for adults, causing up to one-third of community-acquired respiratory tract infections in adults during epidemics. Although the pandemic outbreak of coronavirus disease-2019 (COVID-19) targets preferentially patient's lungs, recent data have documented that COVID-19 causes myocarditis, acute myocardial infarction, exacerbation of heart failure and acute kidney injury. Studies show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to its predecessor SARS-CoV, engages angiotensin-converting enzyme 2 (ACE2) as the entry receptor. ACE2 is also expressed in the heart, providing a link between coronaviruses and the cardiovascular system.

Pathological features of COVID-19 infection from biopsy and autopsy series.

Novel coronavirus disease 2019 (COVID-19) which is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) was first identified in December 2019 in Chinese town Wuhan and considered as a pandemic by World Health Organization. The disease has variety of symptoms including fever, shortness of breath, cough, fatigue, loss of smell and taste and diarrhea. While the majority of cases have mild symptoms, some progress to viral pneumonia, multi-organ failure, or cytokine storm and mortality is mostly caused by hypoxemic respiratory failure. Until now, more than 3.5 million people worldwide were infected and more than 240.000 mortality has been occurred. Thus, there is now evidence the disease may affect variety of organs according to accumulating biopsy and autopsy studies. Such pathological studies have potential role on the understanding of clinical outcomes and in the development of novel targeted therapeutic approaches. Given these aforementioned data, in the current manuscript we have summarized the pathological features of COVID-19 derived from biopsy and autopsy series.

Kidney disease and electrolytes in COVID-19: more than meets the eye.

COVID-19 is a global pandemic fuelled in some countries by government actions. The current issue of Clinical Kidney Journal presents 15 articles on COVID-19 and kidney disease from three continents, providing a global perspective of the impact of severe acute respiratory syndrome coronavirus 2 on electrolytes and different kidney compartments (glomeruli, tubules and vascular compartments) and presenting clinically as a syndrome of inappropriate antidiuretic hormone secretion, acute kidney injury, acute kidney disease, collapsing glomerulopathy and thrombotic microangiopathy, among others, in the context of a brand-new cardiorenal syndrome. Kidney injury may need acute dialysis that may overwhelm haemodialysis (HD) and haemofiltration capabilities. In this regard, acute peritoneal dialysis (PD) may be lifesaving. Additionally, pre-existent chronic kidney disease increases the risk of more severe COVID-19 complications. The impact of COVID-19 on PD and HD patients is also discussed, with emphasis on preventive measures. Finally, current therapeutic approaches and potential future therapeutic approaches undergoing clinical trials, such as complement targeting by eculizumab, are also presented.

Exploring Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors for Organ Protection in COVID-19.

Hospital admissions and mortality from the Coronavirus disease 2019 (COVID-19) pandemic are spreading throughout the world, and second and third waves are thought to be likely. Risk factors for severe COVID-19 include diabetes, chronic kidney disease and cardiovascular disease. Currently, there is no vaccine and no approved therapy. Therapeutic approaches are aimed at preventing viral replication and spread, limiting the impact of the inflammatory overdrive (cytokine storm), preventing thromboembolic complications and replacing or supporting organ function. However, despite organ support, mortality is currently 65% for those receiving advanced respiratory support and 78% for those requiring renal replacement therapies. Thus, efforts should be made to provide adjuvant organ protection therapy. This may imply novel therapies in clinical development (e.g., the Fas ligand trap asunercept), but uptake of repurposed drugs already in clinical use may be faster. In this regard, sodium glucose co-transporter-2 (SGLT2) inhibitors were recently shown to protect the heart and kidney both within and outside of a diabetic milieu context. Further, preclinical data support a beneficial effect for the lung. We now discuss the potential benefits and risks of SGLT2 inhibitors in COVID-19 and an ongoing clinical trial testing the impact of dapagliflozin on outcomes in COVID-19 patients with respiratory failure.

Recommendations for the prevention, mitigation and containment of the emerging SARS-CoV-2 (COVID-19) pandemic in haemodialysis centres.

COVID-19, a disease caused by a novel coronavirus, is a major global human threat that has turned into a pandemic. This novel coronavirus has specifically high morbidity in the elderly and in comorbid populations. Uraemic patients on dialysis combine an intrinsic fragility and a very frequent burden of comorbidities with a specific setting in which many patients are repeatedly treated in the same area (haemodialysis centres). Moreover, if infected, the intensity of dialysis requiring specialized resources and staff is further complicated by requirements for isolation, control and prevention, putting healthcare systems under exceptional additional strain. Therefore, all measures to slow if not to eradicate the pandemic and to control unmanageably high incidence rates must be taken very seriously. The aim of the present review of the European Dialysis (EUDIAL) Working Group of ERA-EDTA is to provide recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic. The management of patients on dialysis affected by COVID-19 must be carried out according to strict protocols to minimize the risk for other patients and personnel taking care of these patients. Measures of prevention, protection, screening, isolation and distribution have been shown to be efficient in similar settings. They are essential in the management of the pandemic and should be taken in the early stages of the disease.