COVID-19 and nephrology

The COVID-19 pandemic was met with large-scale efforts to assess novel and repurposed therapeutic interventions that could reduce patient morbidity and mortality. Here, the authors discuss the different types of therapies available to treat COVID-19, including their relevance to patients with kidney failure and kidney transplant recipients.

In this Review, the authors summarize the challenges associated with the care of patients with kidney disease during the COVID-19 pandemic. They describe the major challenges and missed opportunities, global inequalities in health care, and offer a framework for future pandemic preparedness.

Effective vaccination strategies are crucial to mitigate the high risk of infection-associated morbidity and mortality in patients with kidney failure. Here, the authors examine vaccine-induced immunity in these patients, in particular their responses to COVID-19 vaccination, in the context of the immune impairment induced by kidney dysfunction and the use of immunosuppressive medications.

Patients with kidney disease are at particular risk of the adverse outcomes of COVID-19. Throughout the pandemic, epidemiological studies have been performed to inform clinical care; however, these studies have faced a number of methodological challenges. This Review discusses current understanding of the effects of COVID-19 on patients with kidney disease and some of the major obstacles encountered when conducting epidemiological research in a pandemic setting.

Acute kidney injury (AKI) is a common complication of COVID-19. This Review describes current understanding of the pathophysiology of COVID-19-associated AKI, examining potential mechanisms by which SARS-CoV-2 infection might induce direct and indirect effects on the kidney and non-specific factors, including haemodynamic changes and/or organ crosstalk, that may adversely influence kidney function.

This Review describes our current understanding of the pathogenic mechanisms involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the progression of coronavirus disease 2019 (COVID-19), focusing on the immunological hyper-response and the induction of widespread endothelial damage, complement-associated blood clotting and systemic microangiopathy, as well as the effects of these processes on the kidney. The authors also discuss therapeutic interventions that currently hold most promise.

COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and is an independent risk factor for all-cause in-hospital death in patients with COVID-19. This Consensus Statement from the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI and for areas of future research, with the aim of improving understanding of the underlying processes and outcomes for patients with COVID-19 AKI.

Long COVID, which refers to post-acute and chronic sequelae of SARS-CoV-2 infection, can affect nearly every organ system and all demographic groups. The high and growing toll of long COVID calls for an urgent need to understand how to prevent and treat it. Governments and health systems must address the care needs of people with long COVID.

The COVID-19 pandemic has highlighted the vital role of vaccination in preventing life-threatening diseases and improving global health. Understanding and addressing the concerns of vaccine-hesitant individuals, including those with chronic diseases, is key to increasing vaccine acceptance and uptake.

Although direct kidney infection by SARS-CoV-2 remains controversial, a study based largely on autopsies shows increased tubulointerstitial fibrosis in patients with COVID-19 and suggests direct kidney infection. Moreover, in human kidney organoids, SARS-CoV-2 infection upregulates several pro-fibrotic and pro-inflammatory pathways.

Patients with kidney disease are particularly vulnerable to COVID-19. In 2021, key studies demonstrated the safety of renin–angiotensin blockade in patients with kidney failure and COVID-19, and provided new data on the therapeutic potential of soluble angiotensin-converting enzyme, COVID-19 vaccine responses and the long-term effects of COVID-19 on kidney function.

Vaccines against SARS-CoV-2 are key to ending the COVID-19 pandemic, but their success depends on global availability and acceptance, as well as measures to protect the most vulnerable.

Vaccination against SARS-CoV-2 seems to be safe in patients with immunity-mediated kidney disease, although their immunological responses to vaccination are impaired. Further strategies, including the administration of additional vaccine doses and passive immunization with long-acting monoclonal antibodies, might increase protection in this vulnerable patient group.

Patients receiving dialysis are at high risk of contracting SARS-CoV-2 and developing severe COVID-19. Established SARS-CoV-2 vaccination schemes might lack efficacy in these patients and a personalized approach is therefore necessary. Importantly, given the enhanced infection risks associated with dialysis, current vaccines do not replace non-pharmacological measures to prevent infection.

Kidney transplant recipients receive therapeutic immunosuppression that impairs their immune responses to the COVID-19 mRNA vaccine. For this reason, this vulnerable patient population is insufficiently protected by the standard two-dose COVID-19 vaccination programme and requires a specific follow-up to guide personalization of an intensified vaccination approach.

Kidney involvement is common in patients with acute SARS-CoV-2 infection, and subclinical inflammation and injury may persist for many months, resulting in a progressive decline in kidney function that leads to chronic kidney disease. Continued research is imperative to understand these long-term sequelae and identify interventions to mitigate them.

Interruptions to dialysis services in resource-limited settings, like India, amidst the COVID-19 pandemic has highlighted our ill-preparedness. We need alternative plans to safeguard the provision of this life-sustaining treatment and protect our vulnerable patients.

Patients with kidney diseases should be prioritized for COVID-19 vaccination and the available data suggest that replication-defective viral-vectored vaccines and mRNA vaccines are safe to use. As vaccine responses are likely to be lower in patients with kidney diseases than in the general population, highly potent vaccines should be preferred.

The consequences of the COVID-19 pandemic have been devastating; however, evidence suggests that patients with, or at risk of, kidney disease are disproportionally affected. Patients on dialysis and kidney transplant recipients are at higher risk of adverse outcomes from COVID-19, whereas, conversely, patients with severe COVID-19 are at increased risk of acute kidney injury, with short-term and possibly long-term consequences for nephrological care.

A new study reports the seroprevalence of SARS-CoV-2 antibodies among a cross-section of patients on haemodialysis and uses these data to estimate seroprevalence in the general US population. Although this study demonstrates the potential of monitoring infectious disease prevalence in dialysis populations, the findings should be interpreted with caution.

A new study examined post-mortem kidney tissue from 63 patients with COVID-19. The results suggest that SARS-CoV-2 has kidney tropism, including the ability to replicate in kidney cells, and that kidney transduction by SARS-CoV-2 is associated with shorter survival time and increased incidence of acute kidney injury.

Interest in the use of haemoperfusion for severe COVID-19 has been spurred by anecdotal reports of its efficacy and expert reviews suggesting theoretical benefits. However, on the basis of the limited current evidence, haemoperfusion remains an experimental therapy that should only be applied within the context of well-designed randomized trials.

A new study uses the OpenSAFELY health analytics platform to identify risk factors for COVID-19 mortality. This analysis, which includes data for more than 17 million people in the UK, suggests that patients with chronic kidney disease are at higher risk than those with other known risk factors, including chronic heart and lung disease.

Management of kidney transplant recipients requires a sustainable infrastructure that can provide reliable medical care both before and after transplantation. The COVID-19 pandemic has disrupted transplant referral and listing processes, led to decreases in the numbers of transplant procedures and resulted in changes in practice for pre- and post-transplantation management and follow-up.

The COVID-19 pandemic has placed a tremendous strain on sustaining the clinical research enterprise and will also likely affect key study outcomes; these effects must be considered during data analysis and interpretation. Nevertheless, the responses to the pandemic have also introduced innovations that will advance the conduct of clinical research.

Reports of collapsing glomerulopathy in patients of African ancestry and high-risk APOL1 genotype infected with SARS-CoV-2 have emerged during the COVID-19 pandemic. This new entity, which we term COVID-19-associated nephropathy (COVAN), may particularly impact individuals in some regions of the world. Awareness of this potentially ominous complication of COVID-19 must be raised.

Brazil has been severely affected by the novel coronavirus. At a time when the country needs to concentrate on controlling and fighting the virus, President Bolsonaro has minimized the importance of the pandemic and focused on political battles.

Health-care workers involved in the response to the COVID-19 pandemic are often required to work in highly challenging conditions and may therefore be at increased risk of experiencing mental health problems. This Comment sets out a practical approach to protecting the mental health of health-care workers based on contemporary evidence.

The coronavirus disease 2019 (COVID-19) pandemic poses important challenges to the care of patients with immune-mediated kidney diseases and to kidney transplant recipients. Here, we discuss the management of immunosuppression for these patients during the pandemic and suggest potential approaches that could be considered in the absence of validated strategies.

The prevalence of direct kidney involvement in novel coronavirus disease (COVID-19) is low, but such involvement is a marker of multiple organ dysfunction and severe disease. Here, we explore potential pathways of kidney damage and discuss the rationale for extracorporeal support with various blood purification strategies in patients who are critically ill with COVID-19.

Patients on haemodialysis or peritoneal dialysis are likely to be at increased risk of novel coronavirus disease (COVID-19). Preventive strategies must be implemented to minimize the risk of disease transmission in dialysis facilities, including education of staff and patients, screening for COVID-19 and separation of infected or symptomatic and non-infected patients.

The current COVID-19 pandemic is associated with unprecedented morbidity and mortality. Early reports suggested an association between disease severity and hypertension but did not account for sources of confounding. However, the responsible virus — SARS-CoV-2 — gains entry to host cells via angiotensin-converting enzyme 2 (ACE2), highlighting the need to understand the relationship between the virus and the renin–angiotensin system (RAS) and how this might be affected by RAS inhibitors.

eHealth is gaining momentum in nephrology, although evidence for its efficacy remains unclear and challenges to its widespread adoption persist. Successful integration of eHealth into kidney care will require patient engagement to develop effective interventions and issues such as data validity, regulation, oversight and adequate infrastructure to be addressed.