The coronavirus disease 2019 (COVID-19) not only had a major impact on patient care and on the mental health of patients and caregivers but also posed specific challenges to medical journals, which faced a substantial number of submissions and publications, literally updating knowledge about this disease in real time.

Early in the pandemic, issues affecting patient care delivery, such as shortages of personal protective equipment (PPE), insufficient testing availability, and lack of effective therapies, uniquely affected patients with kidney diseases. PPE demand was particularly high in hemodialysis units where social distancing was not possible. One study reported case clustering in dialysis units and shifts, underlining the importance of staff and patient screening to limit the spread of the virus. Moreover, fewer infections were recorded when patients used modalities allowing for dialysis at home (home hemodialysis or peritoneal dialysis).1 Inequity was evident internationally, with hoarding of PPE and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests by wealthier countries.2 Proposed early therapies were derived from prior coronavirus outbreaks or on the basis of in vitro data showing improved viral clearance or inhibition of entrance of SARS-CoV-2 into cells. Yet, safety and efficacy among patients with kidney diseases was largely untested.

During the initial phase of the pandemic, mortality among patients on dialysis was particularly high. One study reported that 18 of 59 patients died as a consequence of COVID-19 infection. Among them, however, 11 had an advanced directive against intubation.3 Those dying of COVID-19 were also generally older and were less likely to be active on the deceased donor transplant register.1 Subsequent widespread implementation of testing and screening contributed to reduced mortality rates in these vulnerable populations.

Disruptions in transplant services were also common in the initial stage of the pandemic. According to the United Network for Organ Sharing (UNOS), the number of kidney transplants in the United States decreased in 2020 compared with 2019; in 2020, the number of waitlisted patients also fell by -9.97%. Moreover, fewer patients started KRT. Data from the Centers for Medicare & Medicaid Services indicate a 25% decrease in incident ESKD cases during 2020. This was mainly explained by individuals aged 75 years or older who did not start KRT.4

The introduction of vaccines in December 2020 raised additional challenges. Although few patients with kidney diseases were included in the landmark trials leading to the emergency use authorization of commonly used vaccines, patients with CKD and solid organ transplant recipients were prioritized to receive vaccines in most countries. The Journal contributed significantly to our understanding of vaccine effectiveness, regarding both clinical outcomes and humoral and cellular responses of vaccinated and unvaccinated patient populations. In patients receiving maintenance dialysis, an initial two-dose regimen reduced the risk of infection by 70% and the risk of a severe disease course by almost 85%.5 Early experience in patients undergoing chronic hemodialysis, peritoneal dialysis, or after kidney transplantation revealed vast differences in antibody response. Only a minority of kidney transplant recipients mounted a sufficient humoral response after receiving two doses of an mRNA platform-based vaccine.6 The quality of response of hemodialysis and peritoneal dialysis patients was substantially worse compared with healthy controls, indicating weaker mounted humoral immunity and perhaps more frequent future boosters necessary for this vulnerable population.7 Although a majority of kidney transplant recipients had no or only a weak humoral response, most mounted a cellular response that did not differ from the response of patients on hemodialysis.6 However, uncertainty remains as to whether a cellular response alone is sufficient to prevent severe COVID-19 disease. Adding to the uncertainty about vaccine efficacy, therapies the nephrology community deployed, such as rituximab and mycophenolate mofetil, not only significantly reduced response to vaccines but also increased risk of severe COVID-19 disease.2

Patients with immune-mediated kidney diseases remain an understudied, yet relevant, population. The largest study focusing on COVID-19 outcomes included 125 patients with glomerular diseases.8 Half of them were hospitalized, and patients with a lower eGFR at baseline had a higher likelihood of developing AKI and a lower probability of recovering kidney function after infection. Another major concern in this patient population was whether administration of a potent vaccine that subsequently stimulated the immune system would induce de novo autoimmunity or relapse of an established glomerular disease. A population-level cohort study from British Columbia addressed the latter, including 1105 adult patients with a glomerular disease. A first vaccine dose, generally eliciting a relatively mild humoral response, was not associated with a higher relapse risk while subsequent administrations of COVID-19 vaccines increased the risk of glomerular disease relapse by around two-fold. These results, however, require critical interpretation because only 17% of relapsing patients had altered immunosuppression,9 indicating that most relapses were mild or self-limited.

The rate of AKI as a consequence of COVID-19 was substantial during the first waves of the pandemic. A large observational study from New York City found that 56.9% of 3345 adults with COVID-19 presented with AKI, and the risk was 1.5-fold higher compared with hospitalized patients without COVID-19. The need for KRT in this population was substantial, with a frequency of 4.9% and a 3.1-fold greater risk compared with other hospitalized patients without COVID-19.10 Other studies reported even higher rates of KRT, with frequencies near 9%.11 These findings emphasize the impact of the SARS-CoV-2 variant of the early pandemic and the surge of hospitalized patients on dialysis.

Early reports revealed racial disparities in COVID-19 renal outcomes; AKI was more frequent among non-Hispanic Black patients.10 In a high proportion of Black patients with AKI and de novo nephrotic range proteinuria, kidney biopsies revealed collapsing glomerulopathy, and genotyping identified APOL1 high-risk alleles in many cases.12 Kidney biopsies from patients without signs of concomitant glomerular lesions generally found nonspecific changes, such as acute tubular necrosis and an inflammatory infiltrate comprising lymphocytes and macrophages. SARS-CoV-2 binds the ACE2 protein when entering cells, and ACE2 expression is even higher in the kidneys than in the lungs.13 Several lines of evidence subsequently revealed that SARS-CoV-2 can directly infect the kidney: electron microscopy–imaged virus-like particles, PCR-detected viral RNA, and immunohistochemistry directly detected viral proteins.14 The high burden of AKI might thus be multifactorial, including genetic predisposition to COVID-19–associated glomerular disease, direct infection of kidney tissue, and sepsis, hemodynamic instability, or other factors leading to nonspecific but clinically relevant kidney damage.

As the prognosis of COVID-19 improved because of earlier recognition, therapeutic options, mass vaccination strategies, and reduced virulence when the omicron variant became dominant, postacute sequelae of the viral infection became a focus, and this was termed long COVID. A large database analysis among 1,726,683 US veterans focused on 30-day survivors of COVID-19 and compared these patients with noninfected controls. The study found higher risks of AKI, eGFR decline, ESKD, and major adverse kidney events (the composite of eGFR decline ≥50%, ESKD, or all-cause mortality) among patients surviving a SARS-CoV-2 infection. The subsequent annual eGFR decline of the patients was associated with the severity of infection, with an eGFR reduction of −3.26, −5.20, and −7.69 ml/min per 1.73 m2 per year in those without hospitalization, hospitalized, and those admitted to an intensive care unit, respectively.15

Throughout the pandemic, unique challenges related to disease prevention, acute infection, chronic consequences, and other effects have affected the nephrology community (Figure 1). Additional indirect consequences without a measurable impact on patient outcomes have not been as extensively studied, such as reduced visitor access in hospitals and dialysis units, which was especially relevant in end-of-life care provision. Furthermore, nearly one third of nephrology clinicians reported burnout and mental health distress.7 Many providers have left the nephrology community, and many workplaces could not fill the staff shortage, forcing departments to operate with reduced capacities.

Figure 1:

Challenges to nephrology clinicians and patients during the COVID-19 pandemic. COVID-19, coronavirus disease 2019.

Clinicians have had to remain constantly vigilant for new developments because of the rapid accumulation of new knowledge and frequently changing testing and treatment protocols. Submissions to medical journals increased; published academic papers increased by 7% in 2021. JASN contributed to the dissemination of knowledge relevant to the nephrology community when treating, diagnosing, and following patients with COVID-19; response to vaccines; and whether SARS-CoV-2 directly affects kidney structures. Clinicians depend on trusted sources with high standards for validity to keep abreast of new knowledge, particularly under such extraordinary circumstances. In the past 3 years, JASN has played an important role in disseminating high-quality, important research that advanced scientific understanding of the impact of COVID-19 on patients with kidney disease and on care delivery within the nephrology community.

Disclosures

L.P. Gregg is supported by a Veterans Affairs Clinical Sciences Research and Development Career Development Award (IK2CX002368) and serves as a JASN Editorial Fellow. A. Kronbichler reports consultancy for Catalyst Biosciences, CSL Vifor, Delta4, GSK, Otsuka, and Walden Biosciences; research funding for CSL Vifor and Otsuka; honoraria from CSL Vifor and Otsuka; an advisory or leadership role for the European Renal Association (Immunonephrology Working Group and Electronic Communication Committee); and serves as a JASN Editorial Fellow. J. Bargman reports Consultancy: Davita Healthcare Partners; Glaxo Smith Kline; Bayer,Otsuka; Honoraria: Baxter Healthcare, Davita Healthcare Partners, Glaxo Smith Kline; Advisory or Leadership Role: Editorial Boards: Journal of the American Society of Nephrology, Peritoneal Dialysis International, Clinical Journal of the American Society of Nephrology; and Speakers Bureau: DaVita Healthcare Partners, Baxter Canada, Baxter Global, Glaxo Smith Kline.

Funding

This work was also supported in part by and the Houston VA Health Services Research and Development Center for Innovations grant (CIN13-413).

Acknowledgment

The content of this article reflects the personal experience and views of the authors and should not be considered medical advice or recommendations. The content does not reflect the views or opinions of the American Society of Nephrology (ASN) or JASN. Responsibility for the information and views expressed herein lies entirely with the authors.

Author Contributions

Conceptualization: L. Parker Gregg, Andreas Kronbichler.

Validation: Joanne M. Bargman.

Writing – original draft: L. Parker Gregg, Andreas Kronbichler.

Writing – review & editing: Joanne M. Bargman.

References 1. Corbett RW, Blakey S, Nitsch D, et al. West London Renal and Transplant Centre. Epidemiology of COVID-19 in an urban dialysis center. J Am Soc Nephrol. 2020;31(8):1815–1823. doi:10.1681/ASN.2020040534 2. Geetha D, Kronbichler A, Rutter M, et al. Impact of the COVID-19 pandemic on the kidney community: lessons learned and future directions. Nat Rev Nephrol. 2022;18(11):724–737. doi:10.1038/s41581-022-00618-4 3. Valeri AM, Robbins-Juarez SY, Stevens JS, et al. Presentation and outcomes of patients with ESKD and COVID-19. J Am Soc Nephrol. 2020;31(7):1409–1415. doi:10.1681/ASN.2020040470 4. Wetmore JB, Johansen KL, Liu J, Peng Y, Gilbertson DT, Weinhandl ED. Changes in treatment of patients with incident ESKD during the novel coronavirus disease 2019 pandemic. J Am Soc Nephrol. 2021;32(11):2948–2957. doi:10.1681/ASN.2021040579 5. Oliver MJ, Thomas D, Balamchi S, et al. Vaccine effectiveness against SARS-CoV-2 infection and severe outcomes in the maintenance dialysis population in Ontario, Canada. J Am Soc Nephrol. 2022;33(4):839–849. doi:10.1681/ASN.2021091262 6. Bertrand D, Hamzaoui M, Lemée V, et al. Antibody and T Cell response to SARS-CoV-2 messenger RNA BNT162b2 vaccine in kidney transplant recipients and hemodialysis patients. J Am Soc Nephrol. 2021;32(9):2147–2152. doi:10.1681/ASN.2021040480 7. Danthu C, Hantz S, Dahlem A, et al. Humoral response after SARS-CoV-2 mRNA vaccination in a cohort of hemodialysis patients and kidney transplant recipients. J Am Soc Nephrol. 2021;32(9):2153–2158. doi:10.1681/ASN.2021040490 8. Waldman M, Soler MJ, García-Carro C, et al. COVID-19 in patients with glomerular disease: follow-up results from the IRoc-GN international registry. Kidney360. 2022;3(2):293–306. doi:10.34067/KID.0006612021 9. Canney M, Atiquzzaman M, Cunningham AM, et al. A population-based analysis of the risk of glomerular disease relapse after COVID-19 vaccination. J Am Soc Nephrol. 2022;33(12):2247–2257. doi:10.1681/ASN.2022030258 10. Fisher M, Neugarten J, Bellin E, et al. AKI in hospitalized patients with and without COVID-19: a comparison study. J Am Soc Nephrol. 2020;31(9):2145–2157. doi:10.1681/ASN.2020040509 11. Chan L, Chaudhary K, Saha A, et al. on behalf of the Mount Sinai COVID Informatics Center MSCIC. AKI in hospitalized patients with COVID-19. J Am Soc Nephrol. 2021;32(1):151–160. doi:10.1681/ASN.2020050615 12. Wu H, Larsen CP, Hernandez-Arroyo CF, et al. AKI and collapsing glomerulopathy associated with COVID-19 and APOL1 high-risk genotype. J Am Soc Nephrol. 2020;31(8):1688–1695. doi:10.1681/ASN.2020050558 13. Batlle D, Soler MJ, Sparks MA, et al. COVID-19 and ACE2 in Cardiovascular, Lung, and Kidney Working Group. Acute kidney injury in COVID-19: emerging evidence of a distinct pathophysiology. J Am Soc Nephrol. 2020;31(7):1380–1383. doi:10.1681/ASN.2020040419 14. Khan S, Chen L, Yang CR, Raghuram V, Khundmiri SJ, Knepper MA. Does SARS-CoV-2 infect the kidney? J Am Soc Nephrol. 2020;31(12):2746–2748. doi:10.1681/ASN.2020081229 15. Bowe B, Xie Y, Xu E, Al-Aly Z. Kidney outcomes in long COVID. J Am Soc Nephrol. 2021;32(11):2851–2862. doi:10.1681/ASN.2021060734