Introduction

The coronavirus disease 2019 (COVID-19) pandemic has impacted the kidney community on multiple levels. Acute kidney injury (AKI) is a common consequence of hospitalization with COVID-19 and portends high mortality1. Moreover, the rate of severe COVID-19 have been high in patients with chronic kidney disease (CKD), including dialysis patients and kidney transplant recipients1,2,3. Throughout the pandemic, a number of dilemmas have occurred, contributing to poor outcomes in patients with kidney disease. These include decisions surrounding the delivery of safe clinical care, triaging provision of kidney replacement therapy (KRT), the safety of donors and recipients for kidney transplantation, managing COVID-19 in patients with kidney disease, modulating immunosuppression in immune-mediated kidney disease and transplant recipients, and the best ways to protect patients and health care providers. Despite being at a high risk, however, patients with kidney disease were excluded from therapeutic clinical trials of COVID-19, largely because of a higher risk of mortality and concerns that CKD may alter the safety profile of drugs. As such, the lack of pre-specified subgroup analyses resulted in the application of novel therapies to this population with low evidence. Additional challenges in patient care faced by nephrologists have included nursing shortages and supply chain issues. Moreover, the pandemic has raised ethically challenging questions about the allocation of scant health care resources. Finally, there has been a significant impact on trainee education and on the emotional well-being of the nephrology workforce and patients4,5.

In this review, we discuss the challenges encountered in the care of patients across the spectrum of kidney disease during the COVID-19 pandemic. Strategies that were adopted to address these challenges, innovations in patient care delivery and advocacy efforts are described. We further discuss the global inequities in the provision of health care and highlight how the pandemic may exacerbate pre-existing disparities in kidney disease. Although some lessons learned by the kidney community during the pandemic have been heartening and stimulated innovation, others have had profoundly devastating effects. These experiences by the kidney community shape preparedness efforts for future pandemics. From the lessons learned thus far, we provide a framework for the management of patients with kidney disease for future pandemics.

Challenges and opportunities of COVID-19

AKI incidence throughout the pandemic

AKI is common in patients diagnosed with COVID-19 (ref.1). The mechanism of COVID-19 infection-induced AKI is multifactorial, involving both direct invasion of the virus and indirect mechanisms through acute tubular necrosis, dysregulation of the immune system, hypercoagulopathy and collapsing glomerulopathy6. In the early stages of the pandemic, the reported incidence of AKI ranged from 0.5 to 42%1,7,8, with a large percentage of patients requiring dialysis. Investigating how this incidence rate changed over time, one study found that in critically ill patients with COVID-19, although the incidence of AKI was 29.3%, the rates of AKI and KRT declined throughout the pandemic8. This reduced rate of AKI was likely attributable to multiple factors, including improved recognition and management, vaccine rollout and transmission of less virulent strains9. However, in low- and lower-middle-income countries, challenges were present in the management of COVID-19-associated AKI10. In a study of over 1,000 patients with COVID-19 in two teaching hospitals in South Africa, AKI occurred at a rate of 33.9%, with approximately a quarter of patients with AKI requiring ICU management and 8.6% receiving KRT11.

APOL1 and risk of COVID-19-related AKI

In April 2020, several case reports described collapsing glomerulopathy in patients with COVID-19. A subsequent study confirmed this finding, reporting that, out of 240 native kidney biopsies in patients with COVID-19, 62 (26%) had evidence of collapsing glomerulopathy12. Interestingly, a case series of six patients with collapsing glomerulopathy found that all six had variants in the APOL1 gene13. APOL1 genotyping studies have subsequently demonstrated that patients with high-risk APOL1 alleles had significantly higher odds of AKI and death than low-risk patients with 0 or 1 risk variants14. Furthermore, in African Americans who tested positive for COVID-19, APOL1 high-risk alleles were associated with greater odds of AKI and higher rates of persistent AKI and requirement for dialysis14.

Possible reasons for the higher risk of adverse kidney outcomes in individuals carrying APOL1 high-risk alleles include a heightened inflammatory response to COVID-19, leading to inflammatory kidney injury. Thus, the incidence and severity of AKI are likely increased in the presence of APOL1 variants, with an increased requirement for chronic dialysis.

COVID-19 and long-term kidney issues

Hospitalized patients with COVID-19 have a higher incidence of AKI overall, and an increased risk of higher stages of AKI when compared with patients with influenza15. The risk of developing CKD is high in patients with COVID-19, as demonstrated by an observational study from the UK showing that 16% of AKI survivors had progressed to CKD at 90 days16. Similarly, approximately 20% of critically ill patients with COVID-19 and AKI requiring KRT had no recovery at 3 months after discharge in a multicentre study from the USA17. A veterans administration study on long COVID reported a higher risk of CKD with COVID-19 (refs.18,19). Similarly, in a Chinese cohort study, a third of COVID-19-infected patients had reduced kidney function 6 months post-hospitalization18. Interestingly, patients developing AKI during their COVID-19 disease course had no increased risk of CKD at 12 months follow-up compared with non-COVID-19 AKI cases20, indicating that kidney disease progression is similar in patients with or without COVID-19. Further studies are needed to evaluate risk factors for progression to CKD following COVID-19-associated AKI.

Chronic kidney disease

The incidence of COVID-19 in patients with CKD is difficult to establish owing to under-reporting, under-diagnosis of CKD, and variations in access to SARS-CoV-2 testing. A large, nationally representative cohort from the UK demonstrated a CKD incidence and prevalence ranging from 0.5% to 37% and reported that CKD is associated with a high co-morbidity burden and high 1-year mortality21. CKD, including end-stage kidney disease (ESKD), is associated with an increased risk of COVID-19 and subsequent adverse outcomes including hospitalization, respiratory failure and mortality2,22,23,24, with risk proportional to kidney dysfunction22,24. There have been care delivery repercussions, including the postponement of kidney biopsies25, delays in arteriovenous fistula surgery and salvage, and disruption in the initiation of KRT26. There was a notable decline in incident ESKD in the USA early in the pandemic, because of both increased mortality in patients with advanced CKD and compromised access preparation for KRT27. Large-scale lockdowns resulted in interruption of routine health care, including access to dialysis, leading to preventable deaths, especially in those parts of the world where access to dialysis was already compromised, while highlighting the advantages of telemedicine in patients with CKD28,29,30.

There is a lack of guidelines related to the management of COVID-19 in patients with CKD. Dexamethasone was associated with both a reduced requirement for KRT and lower mortality in all patients with severe COVID-19, although fewer than 10% of patients in this trial had an estimated glomerular filtration rate of <30 ml/min/1.73 m2 (ref.31). Remdesivir, a direct-acting antiviral, remains off label in patients with an estimated glomerular filtration rate <30 ml/min/1.73 m2 (ref.32). Several monoclonal antibody therapies have been afforded emergency use authorization but their net benefit in patients with CKD remains untested. Tocilizumab, a recombinant anti-IL-6 receptor antibody was granted emergency use authorization in patients with moderate-to-severe COVID-19 (ref.33), and case reports demonstrate successful deployment in patients with ESKD. Unfortunately, phase III trials evaluating the benefits of vaccination against COVID-19 have placed little focus on specific subgroups such as patients with CKD34. Nonetheless, patients with CKD mounted a seroconversion rate that was comparable with the general population (Supplemental Table 1) and were prioritized for vaccination. It is noteworthy, however, that patients who did not receive a third dose of the vaccine had a significant decline in antibody titre after 3 to 6 months35.

Immune-mediated kidney disease

Managing patients with immune-mediated glomerular disease has presented unique challenges. At the start of the pandemic, the primary concerns for patients receiving immunosuppression included the assessment of the risk and severity of COVID-19, ways to mitigate infection risk, methods of clinical and laboratory surveillance, strategies to treat active disease and evaluation of the need for continued immunosuppressive therapy. After the vaccine rollout, questions were posed regarding the immunogenicity and safety of the vaccine in this patient subgroup, measurement of vaccine efficacy and need for modification of immunosuppressive therapy to improve vaccine response.

Although immunosuppressive therapy increases the risk of COVID-19 infection, there is currently no evidence to support deviation in the standard of care treatment of active kidney disease36. COVID-19 in patients with immune-mediated kidney disease conferred an increased risk of AKI and death37. Additionally, case reports of de novo immune-mediated kidney disease, including collapsing focal and segmental glomerulosclerosis, vasculitis and IgA nephropathy, have been described with COVID-19 infection. Among the immunosuppressive medications commonly used in this cohort, rituximab and prednisone dose ≥10 mg were associated with increased severity of COVID-19 (ref.38); information on other therapies such as cyclophosphamide has remained scarce.

Although patients with immune-mediated kidney disease were prioritized for vaccines, understanding of the safety and immunogenicity of vaccines in this cohort was based only on observational studies. Studies in patients with rheumatic diseases on immunosuppressive therapy have consistently shown impaired humoral response with largely preserved cellular response following vaccination (Supplemental Table 1). Additionally, these studies have shown that prednisone (dose ≥10 mg), mycophenolate mofetil and rituximab were associated with impaired humoral response and that the response in rituximab-treated patients was improved when B cells were reconstituted or when time elapsed since the last rituximab administration was longer39. Temporary cessation of mycophenolate mofetil augmented humoral response following vaccination in patients with rheumatic disease40. In non-responders, administration of a booster vaccine dose was shown to increase the response rate. De novo or relapsing autoimmunity triggered by COVID-19 vaccines remains a concern, with isolated reports of de novo and relapsing minimal change disease, membranous nephropathy, IgA nephropathy and ANCA vasculitis having been described41. However, large cohorts with increased inflammatory disease incidences have not been described following COVID-19 vaccination.

In the absence of guidelines, caring during a pandemic requires personalizing immunosuppressive therapy to balance the risk of infection and disease control, and recognizing that treatment of active disease cannot be delayed. An important lesson learned is that the early establishment of global collaborative registries is critical to assessing the severity and risk factors of infection and guiding modulation of immunosuppressive therapy in this population.

Patients on chronic dialysis

Early data from Wuhan foreshadowed the major challenges that other regions would have to tackle in caring for patients on dialysis during the COVID-19 pandemic. Patients on dialysis were amongst those at highest risk of death, not just because of the propensity for serious illness but also because of missed treatments. These data generated a mandate for dialysis facilities to intensify infection prevention protocols to reassure patients and staff, to ultimately prevent missed sessions and loss of workforce. There was a strong recommendation for transition to home modalities42.

However, without additional resources to match the new guidance, there was a constant shortage of personal protective equipment (PPE)43 and SARS-CoV-2 tests. Data from universal screening of a single dialysis unit in the UK showed that patients experienced a spike in infection following a spike in infection of health care workers, implying potential transmission from health care worker to patient44. Nonetheless, widespread in-facility transmission was not reported. Lack of transportation, staff shortages and possibly personal fear or symptoms may have contributed to missed treatments in up to half of the surveyed facilities in Africa, Latin America, Middle East, South East Asia and South Asia43. Mortality among infected and hospitalized patients receiving dialysis exceeded 50% in most regions of the world45. The pivot to home modalities was not feasible in many environments that were already strained. Thus, despite early and sensible guidance on infection prevention and management — a majority of which still holds relevance in face of the changing nature of the pandemic — there was a stark loss of life among patients receiving dialysis46. With improvement in testing capacity and identification of patients with no or minimal symptoms, there has been improvement in crude mortality rates between the first and second wave of COVID-19 (ref.47).

The success of vaccines has been accompanied by challenges. Among countries that procured vaccine supply in late 2020 or early 2021, only European countries prioritized vaccination for patients receiving dialysis. In the USA, there was no specific prioritization until March 2021, at which point policy makers acknowledged that patients receiving dialysis were disproportionately from underserved populations and at a high risk of complications from COVID-19 illness. This led to a federal effort to offer vaccination in dialysis clinics, which improved vaccine access, especially for Hispanic and Black patients48. Despite this effort, however, some patients on dialysis expressed vaccine hesitancy, albeit to a lower extent than in the general population. Capitalizing on central record keeping, the US Centers for Disease Control and Prevention has created a real-time dashboard tracking vaccination in dialysis facilities, which indicates that more than 75% of patients on dialysis have had at least two doses of COVID-19 vaccine.

Several lines of evidence suggest that the immunogenicity of vaccination is lower among patients on dialysis than in the general population (Supplemental Table 1). Although the majority of patients ‘seroconverted’ post-vaccination, the strength of the early antibody response to vaccination was suboptimal. Furthermore, 20% lost a detectable antibody response within 6 months. Consistent with data from hepatitis B vaccination, low circulating antibody titres were associated with a 10-fold higher risk of infection among patients who had completed the initial vaccination series45. Data from a large not-for-profit dialysis centre indicated efficacy against hospitalization or death of 81%, only slightly lower than contemporaneous data for the general population, noting vaccine effectiveness of around 86–87%49. Vaccine immunogenicity by vaccine type has been studied closely, and concerns have been raised regarding the lack of immunogenicity of Ad26.COV2.S, although clinical effectiveness of this vaccine may be similar to the mRNA platform vaccines50. Furthermore, there was no difference in vaccine response by vaccine type among home dialysis versus in-centre patients51.

Boosters (third doses for persons with mRNA platform vaccines) have seen a lower uptake among patients on dialysis in the USA, with roughly 50% of patients reporting an additional dose to date. Again, there was a heterogenous policy implementation, with countries in Europe implementing earlier offers of third doses among patients on dialysis. Data from France and the USA on immunogenicity are encouraging, with strong responses reported even among older patient groups.

In this landscape, given the uncertainty around persistent immunogenicity to COVID-19 vaccines and substantial risk of ‘breakthrough’ infection — a majority of which will have some clinical consequences for patients receiving dialysis, and at the very least a need for isolation during in-centre dialysis — it will be critical to continue to develop future protocols for prevention, detection and early treatment of COVID-19.

Lessons for policymakers

Policymakers have important lessons to learn from the COVID-19 pandemic that are specific to the dialysis population28. Below, we outline key lessons learned from the USA.

First, policymakers should strongly consider extending waivers to exempt providers from pre-existing value-based purchasing programmes, including the Quality Incentive Program52 and the End-stage Renal Disease Treatment Choices model53. These programs have laudable goals but might pose a distraction for dialysis facilities that need to remain nimble during a public health emergency. To its credit, the Centers for Medicare and Medicaid Services rapidly implemented waivers early in the pandemic, allowing facilities to focus on the emergency54.

Second, the risk that in-centre dialysis poses for patients, particularly with airborne diseases, must be addressed. Early in the pandemic, providers rightly recognized that facilities could quickly become hubs for widespread infection55. One welcome addition was the broad expansion of telehealth benefits56. However, the beginning of the COVID-19 pandemic was also fraught because of strapped supply chains that exacerbated the already limited supply of PPE. The American Society of Nephrology (ASN), the European Renal Association and the International Society of Nephrology issued calls for governments around the world to prioritize PPE for dialysis personnel and increasing access to lifesaving dialysis. To prepare for the next pandemic, not only should policymakers stockpile more emergency medical equipment but they should also place a strong emphasis on distributing these supplies to providers of populations with complex medical issues, including dialysis facilities. A major concern is ongoing shortages in dialysis supplies, including dialysate.

Third, we must customize policies to address the specific needs of the dialysis population. For instance, per Centers for Medicare and Medicaid Services guidance, many hospitals deferred “non-essential” surgical procedures. However, these deferrals may have inadvertently harmed incident ESKD patients who needed dialysis access procedures27.

New therapeutics that can treat COVID-19 have shown incredible promise in reducing hospitalizations and mortality57,58. Dialysis facilities are unique in the health care industry because patients must return to the facility regularly. In the future, dialysis facilities should be considered a major site for the distribution of new therapeutics and vaccines.

Kidney transplant recipients

The pandemic has created significant challenges for kidney transplantation. Transplant candidates and recipients, especially in the early post-transplant period, experienced significant excess mortality related to COVID-19, with a disproportionate impact on racial minorities and socio-economically disadvantaged individuals59,60. Both the innate and adaptive immune systems seemed profoundly altered in transplant patients, with significantly lower levels of anti-spike antibodies up to 2 months following the onset of COVID-19 symptoms compared with patients on dialysis61. As such, prime concerns have been centred around continuing kidney transplant surgeries while minimizing the risk of infection and management of post-transplant immunosuppression.

Globally, living and deceased donor transplantation has been adversely impacted to various extents and at different periods of time. This is due, in large part, to efforts to conserve resources during a COVID-19 surge and concern for the risk of newly immunocompromised individuals given their increased risk and poor outcomes, particularly during periods of high community transmission3. The mortality rate was 20–30% in kidney transplant recipients during the first wave of the pandemic, with a reduction in mortality during the second wave47. Although there was a 16% global decrease in transplant activity, most notably during the first 3 months of the pandemic, there were substantial differences in transplant activity between countries62. Although living donation came to a nearly complete stop early on during the pandemic, it has resumed since then, but does not appear to have reached pre-pandemic levels63. Notably, previously decreased donor transplantation rates have continued to increase in the US allocation system, despite a dramatic increase in organ discards, reflecting increased selectivity of organs and patients64. There are notable differences in mortality rates of waitlisted individuals compared with transplant recipients, with the USA reporting higher mortality in waitlisted individuals, and Europe and the UK reporting higher mortality in transplant recipients. The decision to continue transplants during a pandemic needs to be individualized for each country and should take into consideration the mortality risk of waitlisted individuals as well as transplant recipients and infection risk in the immediate post-transplant period. In addition, the pandemic has also impacted transplant activity owing to concerns regarding donor-derived viral transmission. A systematic review of 69 transplants from 57 donors infected with SARS-CoV-2 demonstrated than non-lung transplantation was safe, with a low risk of transmission65.

Efforts to lower the risk of transmission along with overwhelmed health care systems created significant challenges in the care of patients. Health care systems pivoted quickly towards telehealth strategies and there was increased interest in the use of non-invasive biomarkers when kidney biopsies became a challenge66,67,68. Although the value of monitoring strategies for allograft health remains uncertain, there does not appear to have been a dramatic uptick in acute rejection episodes69.

The mainstay of treatment for COVID-19 in transplant recipients included reduction or cessation of antimetabolite therapy for 2 weeks or longer, in addition to standard adjuvant therapies used in the general population70. Although this approach also contributed to early concerns about adverse allograft consequences, recent data suggest that brief cessation of therapy was not associated with the development of donor-specific antibodies71. Additional concerns in the SARS-CoV-2-infected recipient include the abrupt increase in tacrolimus levels that has been observed at the time of presentation72. Immunosuppressed individuals also appear to have a prolonged high viral burden with persistent positive PCR results, which may have implications for when to allow patients with previous COVID-19 infection back in to the transplant clinic setting.

Although immunosuppressed patients and those with kidney disease were excluded from the initial vaccine trials, significant real-world experience has been gained in these groups. Studies of immunogenicity after vaccination revealed poor humoral responses to two doses of both mRNA and viral vector vaccines73,74. Older age, impaired allograft function, and use of triple maintenance immunosuppression, belatacept, steroids and anti-metabolites were associated with poor humoral response. Additionally, breakthrough infections were frequently observed in kidney transplant recipients, even before the omicron surge. An enhanced humoral response was observed after a third and fourth vaccine dose, use of heterologous vaccination and modulation of immunosuppression75,76,77.

Kids, kidneys and COVID-19

Outcomes in children

Children and adolescents are a vulnerable group and are subject to special considerations in health care, research and public policy. Although the clinical impact of COVID-19 on paediatric patients has been less profound than in adults so far, successive waves of the pandemic have led to more children being directly impacted. At the start of the pandemic in the USA, there was an initial decrease in deceased and living donor kidney transplantation; however, rates of transplantation had returned to pre-pandemic levels by May 2020 (ref.78). Unlike in adults, children taking immunosuppression for kidney disease or kidney transplant and children on dialysis have not had worse outcomes from COVID-19 infection than the general paediatric population79,80,81,82. When sick enough to be admitted, however, 12–23% of hospitalized children with COVID-19 developed AKI83,84,85 and AKI is more common in patients with the multisystem inflammatory syndrome in children83. Consistent with other studies of AKI in children, AKI was associated with increased levels of care, length of hospital stay and worse outcomes83,85,86,87.

Gaps in science and child health policy

Compared with adults, many gaps in science remain for the paediatric population. Long-term COVID-19 outcomes are an important area of future study, and emphasis should be placed on developing safe and effective strategies to incorporate children into such studies. Research studying long COVID is lacking in children, despite evidence that it is at least as common for children as for adults88. Furthermore, although vaccination rates are much lower for children than for adults, we need to learn more about vaccination patterns and perceptions among children with kidney disease and their caregivers89. It will take years to understand the impact of educational disruptions that affected children with CKD, who already have lower cognition than the general population90. Moreover, paediatric research addressing the impact of pandemic disruptions on access to transplants, the early detection of kidney disease and the impact on family dynamics could aid in the development of more equitable and durable paediatric care delivery models and public policy. Table 1 outlines the challenges and missed opportunities faced by the kidney community in managing patients during the pandemic.

Table 1 Challenges in managing patients with kidney disease during the COVID-19 pandemic
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Psychosocial aspects of COVID-19

The COVID-19 pandemic has necessitated a change in almost every aspect of kidney care. Health care resources shifted to prevent, detect and manage waves of COVID-19, leading to dramatic alterations in routine kidney care in many countries. This section highlights some of the changes instituted, and their impact on patients, caregivers and health care providers.

As the potential severity of COVID-19 disease became clear, international efforts were made to identify people at risk. Many nations endorsed targeted public health measures to minimize both mortality and economic impact91,92. For example, in the UK, a targeted national policy of ‘shielding’ was implemented. Those considered most at-risk from COVID-19 were centrally identified using electronic records, and government letters were issued advising individuals to socially isolate themselves, restricting contact even within their household group, with the help of financial and logistical support. Many people with advanced kidney disease, kidney transplantation, and/or those requiring immunosuppressive treatment, were advised to shield93,94. Although these measures were broadly supported, the personal impact varied, with some feeling protected while others felt fearful and isolated94. In countries without such protective policies, public health messaging likely encouraged similar exposure-avoidant behaviours, particularly in at-risk groups95,96,97.

Additional strategies to minimize infection were implemented internationally, including reduced visitor access in hospitals98,99 and dialysis units100. End-of-life care provision was dramatically altered because of the restrictions, with limitations of social contact and rituals before and after death101. Even with technological innovations to provide human connection, the impact of reduced physical contact between patients, caregivers and clinicians was significant. Some patients experienced loneliness and depressive symptoms, and caregivers described heightened anxiety and an increased desire for information from health care professionals102. Many patient and provider groups described ethical compromise and psychological distress, as they felt unable to provide or receive care at pre-pandemic levels103,104. Furthermore, patient and provider groups have described adversity, fear, abandonment, hope and resilience105,106,107,108. A multinational mixed methods study of 251 kidney health care providers found that nearly one-third of respondents were at a high risk of burnout and mental health distress during the pandemic, with feelings of emotional exhaustion, depersonalization and a reduced sense of personal accomplishment109.

Moral distress in health care during the COVID-19 pandemic has been extensively described and may explain some of the negative psychological consequences described above104. Moral distress can occur when an individual perceives that they are unable to act according to their ethical values owing to external barriers110. If individuals perceive that their ethical duties are compromised in settings of severe resource constraints — where institutional, health policy or financial barriers limit access to optimal treatments that are clinically indicated — moral distress can occur111,112. Notably, it occurs in both patients and caregivers and has been described in relation to the intentional separation between loved ones during end-of-life care and hospital visitation restrictions103,108. The consequences of moral distress include experiences of anger, guilt, depersonalization and, for health care professionals, a desire to leave the workforce entirely113. If persistent, moral distress can result in moral injury, resulting in long-term social and psychological trauma114,115.

Children and young adults with kidney disease face unique and pervasive mental and behavioural health challenges, with higher rates of depression, anxiety and neurocognitive disorders than their peers90. One survey reported that children felt that they were missing out on work-related and educational opportunities, missing family and friends, and compared with their peers, they lived with more COVID-related restrictions90. Health-related quality of life and physical activity decreased significantly for both children and adolescents during the pandemic owing to school closures, social distancing and home confinement116. Although these strategies were employed to reduce virus transmission, their prolonged use requires assessment to mitigate the adverse psychological effects, especially in populations at a high risk of COVID-19. Furthermore, parents and caregivers of children with kidney disease experience significant psychosocial stressors that leave many families dysfunctional and disempowered. During the pandemic, this often-unseen care burden has been experienced disproportionately by families struggling with adverse social determinants of health and health disparities. Caregivers of children with kidney disease reported feelings of stress, anxiety, depression and insomnia during the pandemic, mirroring findings in parents of children with other chronic conditions117,118. Children with medical complexities have lost access to therapies, educational services and peer interactions, all while parents and caregivers have taken on additional responsibilities to navigate changes in employment and keeping their families healthy119.

A global health perspective

With its rapid spread across the globe, the COVID-19 pandemic revealed that most health systems were unprepared for, or at least underestimated, the challenge it would pose. Initially, the lack of readiness, combined with an almost lack of belief that such a pandemic could occur in the current day and age, resulted in acute shortages of many items needed for an effective response. A pertinent example is the scarcity of PPE early on in the pandemic, which sometimes resulted in hoarding by countries and by individuals. This “catastrophic breakdown in global cooperation”120 highlighted the need to develop global strategies to improve equity and access equipment, treatment and vaccines to treat COVID-19 (refs.120,121). Unfortunately, a lack of equity and empathy persists, with booster doses of vaccines being administered to most adults and children in some countries before adults at risk of poor outcomes even receive their first vaccine in others122. Hoarding, pricing, protection of intellectual property and dissemination of misinformation regarding vaccines have exacerbated inequities and contributed to deaths123. These persistent and pervasive inequities, which impact how individuals and nations have been (un)able to tackle the challenges posed by the pandemic have coined the term “political determinants of health”124.

Political and social determinants of health exist within as well as between countries, and the same populations who have experienced centuries of structural violence (such as African Americans and Indigenous populations) are those at the highest risk of serious illness from COVID-19 and most at risk of poor outcomes125,126,127,128,129,130,131. People living with chronic diseases, and especially kidney disease, are at the highest risk132. These facts have finally raised global awareness that we cannot continue to overlook non-communicable diseases, including when looking beyond the pandemic133,134. As the demand for hospital beds and health care services outstripped availability at various stages, triage guidance had to be urgently drawn up to allocate scarce intensive care unit beds, raising debates around which criteria would be morally acceptable135,136. Rationing of health care services became a reality, faced by many for whom the concept had been merely theoretical before then137,138,139,140.

The nephrology community was rapidly drawn into the eye of the storm. The capacity to provide dialysis became strained in some settings, leading to complex triage algorithms and in some cases deaths, even in high-income countries (HICs) because of a lack of access to dialysis140,141. People living with kidney disease are an at-risk population, tending to have lower socio-economic status, belong to minority populations and live with multiple co-morbidities142.

The pandemic has had a significant global impact on health care delivery in general, with consequences being particularly evident in low- and lower-middle-income countries (LLMICs)43. Notably, there were gross inequities in the provision of dialysis services143. Many guidelines were developed and disseminated for the management of patients with kidney disease, including those on dialysis, but most of these guidelines could not be adhered to because of the lack of resources in most LLMICs144. Surveys conducted by the International Society of Nephrology in partnership with the Dialysis Outcomes and Practice Patterns group were aimed at understanding how clinical practice was being impacted by the pandemic, and if and how people living with kidney disease were being prioritized across the globe43,145. Challenges affecting both staff and patients were common in LLMICs. The patient level impact reported by survey respondents included challenges in access to diagnostic testing, interruptions in haemodialysis delivery, restricted access to intensive care, mechanical ventilation and in-hospital haemodialysis, affecting patients in LLMICs more frequently than those in upper-middle-income countries and HICs. Staff in dialysis units in LLMICs had less access to COVID-19 testing, PPE (Fig. 1) and training in infection control, and suffered a greater psychological impact43.

Fig. 1: Shortage of personal protective equipment across countries by income status.
figure 1

Data on country income derived from World Bank data. The graphs show the results of a global online survey of haemodialysis units, which was aimed at determining patterns and access to resources associated with haemodialysis care during the COVID-19 pandemic. As shown, LICs had the greatest shortage of personal protective equipment (PPE) at the peak of the pandemic (a) and the greatest use of PPE beyond manufacturer’s shelf life (b), the latter representing a need to continue using out-of-date PPE owing to a shortage of supply. HIC, high-income countries; LIC, low-income countries; LMIC, lower-middle-income countries; UMIC, upper-middle-income countries.

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At the time of the survey, conducted during the first year of the pandemic, diagnostic tests for SARS-CoV-2 were unavailable or of limited availability, with longer turnaround times for test results in the majority of LLMICs43. Patients in LICs frequently had to pay out-of-pocket for diagnostic (PCR) testing. Owing to multiple factors including lockdowns, curfews and delays awaiting COVID-19 test results, patients in LLMICs missed dialysis with a greater frequency than pre-pandemic and these delays cost lives145.

A subsequent survey focused on access to vaccination for people living with advanced kidney disease. At least one COVID-19 vaccine was available in 97% of respondent countries. Over 90% of the respondent countries reported prioritization of health care workers within the first two phases of vaccine rollout, whereas patients living with stage 4/5 CKD, dialysis, or kidney transplants were prioritized within the first two phases in 51%, 71% and 62% of countries respectively. Overall, at least 50% of patients receiving in-centre haemodialysis, peritoneal dialysis or living with a kidney transplant were reported to have completed vaccination in around half of respondent countries, with the lowest rates reported in Africa and the highest rates in Western Europe. Vaccine hesitancy, vaccine shortages and difficulties in mass distribution of vaccines were common and reported more frequently in LLMICs than in HICs. Although the vaccination rate in the dialysis population may appear relatively high in lower income settings, indicating that the vulnerability of this group has been acknowledged globally, the global disparities echo the call by the World Health Organization for more equitable access to vaccines, having set a global target of 40% of the population of every country to have completed vaccination by the end of 2021 and 70% by mid-2022. Two major global efforts, COVAX and ACT-Accelerator, where richer countries should contribute to supplying and distributing vaccines to poorer countries, have been launched to facilitate global vaccination120,121,146. These schemes, however, have not yet translated into action in terms of global solidarity, although equity gaps may be beginning to narrow147,148.

Children are an inherently vulnerable population that modern society has a duty to protect. However, the unique social status of children places them at an equally unique risk of health inequities. Current research and pharmaceutical development processes are designed to protect children by studying drugs and diseases in adults first; however, the lack of interventions and immunizations that are available in a timely manner for children, including those with underlying chronic disease during the pandemic, has raised concern for age-based health inequity that should be re-evaluated. Protection of children is paramount; however, equipoise with timely availability of emerging therapies and robust safety information are critical to this endeavour for the ethical management of COVID-19 vaccines. At a national level, the prevalence of childhood poverty, specifically its relationship to health and its disproportionality across sociodemographic groups most at risk during the pandemic, highlights another important paediatric kidney health risk119. Evidence of social deprivation along racial, ethnic and class divisions has been shown to have adverse consequences in both children and adults with kidney disease, but the specific effect of the pandemic on this population is yet to be studied149,150.

The almost miraculous rapidity with which the scientific community tackled the COVID-19 pandemic has been a simultaneous triumph and a failure. The rapid development of tests, vaccines and therapeutics has been life-saving for many, but has left many behind. The early, robust efforts to identify and publish potential management strategies led to great advances in clinical understanding and rapid knowledge sharing but also led to dissemination of pseudoscience and misinformation. This has severely impacted trust in health systems globally and has led to loss of life. The COVID-19 pandemic has revealed how necessary solidarity is at all levels, beginning with global governance and trickling down to the individual in the dialysis chair in a remote dialysis unit123,151,152 (Fig. 2). This requires attention being paid to justice and ethics at all levels. Global collaboration and cooperation are needed between countries, institutions, industry and academia. Collaborative focus on “building back better” is required such that health systems and societies emerge from the pandemic stronger, more resilient and fairer.

Fig. 2: Factors contributing to COVID-19-related health inequities.
figure 2

A number of factors have resulted in COVID-19 health inequities, ranging from those that affect individuals (such as age and co-morbidities) to factors at the global level.

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Trainee education

The surge of patients with COVID-19 also impacted nephrology training. Nephrology trainees have been at the front-line of care for COVID-19 patients, including in the intensive care units, dedicated COVID-19 wards and the new era of telemedicine. Although this comes with the possibility of reinvigorating interest in nephrology, it also comes with the threats of increased workload, stress and burnout for our trainees.

Activities our nephrology trainees have typically relied on for education and career advancement have undergone significant adjustments in this era. Major conferences such as the ASN Kidney Week and the European Renal Association meetings were held virtually with fewer opportunities for networking. Local conferences at one’s own institution were also shifted overnight to virtual formats, limiting in-person interaction with faculty, and requiring additional effort to stay engaged.

In the USA, adult and paediatric fellows and recent graduates of nephrology training were surveyed by the ASN Workforce and Training Committee in August–September 2020 using our Annual Fellows’ Survey instrument153. The impact of COVID-19 on fellows’ training experiences and wellbeing was measured, yielding 425 respondents (42% response rate). The majority of current fellows (84%) felt that their education was maintained during the pandemic. Fellows needed to adapt to this new landscape in real time, with up to 91% reporting adoption of telemedicine and 76% remote conferences. Although their education was maintained overall, 42% of fellows reported a negative impact of the pandemic on their overall quality of life, 33% reported a poorer work–life balance, and 15% scored as experiencing high distress measured using the Resident Well-Being Index. Similar findings were seen for trainees in the UK154, France and Belgium155.

The pandemic has offered opportunities to better understand, develop and train future nephrologists. Training programmes, such as those in Canada156, have seized this opportunity to develop personalized learning plans for postgraduate nephrology trainees. It remains to be seen whether resilience of nephrology fellows will be maintained through this pandemic, and what impact the pandemic will have on board certification, job prospects and recruitment of the next generation of nephrologists.

A patient’s voice on the pandemic

Telehealth offered a safe way to continue medical care and conferred multiple advantages, but limitations exist and must be acknowledged and addressed. A scoping review identified technical difficulties, digital illiteracy, lack of physical examination, privacy and confidentiality and loss of interpersonal interaction as the main barriers to telehealth157.

COVID-19 patient communication impacted the entire spectrum of patients with kidney disease throughout the pandemic. Since the beginning of the pandemic, COVID-19 communication with kidney disease patient communities has remained unclear. From a patient perspective, the most impactful communications centred around the use of personal protective measures, risk and consequences of AKI, vaccine efficacy and updates and guidance on the use of COVID-19 therapeutics. In the absence of direction, navigation was dependent upon the initiative of the individual patient. Town halls were conducted by the American Society of Transplantation and webinars were facilitated by the ASN, but these were accessed only by patients who were part of professional patient advocacy groups.

Patient organizations such as the American Association of Kidney Patients, National Kidney Foundation and Kidney Care UK have attempted to address the gap in COVID-19 information. Although their efforts have been successful, they have reached only a small percentage of the CKD and ESKD patients. A process is needed in which all patients hear directly from their care team about the current guidance, and what actions they can take to avoid COVID-19 infection.

Future guidance and conclusions

The COVID-19 pandemic has highlighted the challenges posed by surges in hospital occupancy, and has forced the digital transformation of many health care systems, underscored the need for authoritative and consistent communication from local, state and federal governments, and has identified striking global inequities in the care of patients with kidney disease. Additionally, the pandemic has highlighted the importance of proactively addressing psychosocial and ethical issues to ensure patient, caregiver and clinician wellbeing. The strategies to address the challenges faced by the kidney community during a pandemic are shown in Fig. 3. It is clear that these strategies will differ between low-, lower-middle-, upper-middle- and high-income countries, with a requirement for global collaboration and cooperation at all levels to ensure equity in health care delivery for patients with kidney disease.

Fig. 3: Strategies to address challenges during a pandemic.
figure 3

PD, peritoneal dialysis; PIRRT, prolonged intermittent renal replacement therapy; PPE, personal protective equipment.

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In summary, the COVID-19 pandemic has been one of the worst infectious disease crises in over a century and, given the increase in emerging diseases, pandemic threats may become a new normal. Our experience within the nephrology community has been extremely challenging. Hospitalization surges during the pandemic exposed fundamental weaknesses in all health care systems. Although this led to innovations in health care delivery and policy change, there remains an urgent need to invest in resilient health care systems and develop transparent and fair triage guidelines for scarce resources. The breakdown of global cooperation further exacerbated existing health care inequities. The pandemic illustrated that building public trust in scientific recommendations is critical to avoiding social and political divisions over following risk mitigation strategies. Moral distress has increased and must be recognized and addressed. One in 10 people is living with kidney disease. There is a need to include patients with kidney disease in clinical trials, especially during pandemics, to accelerate access to potential therapeutics, and to invest in the establishment of global collaborative disease registries to study risk factors and outcomes. Finally, we must be prepared to run a faster regulatory process during future public health emergencies. Strategic deregulation would accelerate the development and distribution of new therapeutics.