The COVID-19 Epidemic: Administration and Outcomes of Hemodialysis and Peritoneal Dialysis Sufferers in Stockholm, Sweden – FullText – Kidney and Blood Strain Analysis 2021, Vol. 46, No. 2

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June 11, 2021 0 Comments

Summary

Background: The COVID-19 outbreak has been related to a excessive morbidity, mortality, and a danger of long-term sequelae, and sufferers with extreme COVID-19 are at elevated danger of acute kidney harm. CKD sufferers are at excessive danger of being uncovered to COVID-19 and endure issues and poor consequence. In Sweden, mitigation methods didn’t embody lockdown. Throughout March–April of 2020, wide-spread an infection occurred in Stockholm. Strategies: Administration and outcomes in forty hemodialysis (HD) sufferers and 4 peritoneal dialysis (PD) sufferers, with symptomatic COVID-19 in higher Stockholm throughout March and April of 2020 are reported. Outcomes: Twenty-four HD sufferers (60%) required medical care and hospitalization, whereas 16 sufferers (40%) have been handled at dwelling. 9 sufferers died (mortality charge of twenty-two.5%), of whom 8 have been males. The median age in non-survivors (78 years) was considerably greater than in survivors (p = 0.003). The median time in dialysis (11.5 years) was additionally considerably longer in non-survivors (p = 0.01). C-reactive protein (CRP) at analysis in 7 of non-survivors (median 213 mg/L, vary 86–329 mg/L) was considerably greater than the CRP in 25 survivors (median 87 mg/L, vary 1–328 mg/L) (p = 0.0003). Most CRP additionally indicated poorer consequence amongst hospitalized sufferers (p = 0.0004). The gender imbalance was hanging with solely males dying aside from 1 aged lady. Solely 4 PD sufferers have been hospitalized with symptomatic COVID-19. One affected person died, 2 have been discharged, and 1 was handled on the intensive care unit and survived. Conclusion: HD sufferers >70 years have been reported with longer dialysis classic, greater CRP, and males have been at an elevated danger of dying from COVID-19, whereas these <70 years appeared to have a milder illness. Mitigation methods to cut back charges of an infection in high-risk populations stay important. Observe-up specializing in long-term prognosis for extrapulmonary manifestations is prone to be essential additionally in dialysis sufferers.

© 2021 The Writer(s) Printed by S. Karger AG, Basel


Introduction

Extreme acute respiratory syndrome-corona virus (SARS-CoV)-2 was first described in China in December 2019, and the COVID-19 outbreak was later declared as a pandemic by the WHO. As of November 26, 2020, near 60 million people have been contaminated and 1.4 million deaths have been reported. Probably the most frequent illness manifestation is fever with viral pneumonia, which in additional extreme circumstances requires hospital care and will result in respiratory failure and wish of mechanical air flow. Hyperinflammation, multiorgan failure, and coagulation dysfunction all contribute to a excessive mortality [1, 2]. Early information from China and Italy indicated that greater age, male intercourse, and comorbidities resembling heart problems, diabetes, and CKD are danger elements for extreme sickness and dying. Nonetheless, the severity of underlying situations might range between people. Therefore, most of those sufferers won’t develop important sickness and require intensive care assets and even hospital care [3, 4]. Weight problems has additionally been highlighted as a danger issue, however in a New York research of over 5,000 COVID-19-infected people, age and underlying CKD have been stronger predictors of extreme illness than weight problems [5]. The most important risk-factor research so far is from the UK which included 17 million digital well being information overlaying 40% of the inhabitants. The information set recognized CKD as a danger issue for mortality in sufferers with COVID-19, specifically in these with a glomerular filtration charge <30 mL/min/1.73 m2 and organ transplantation which each conferred a excessive danger in multivariate analyses. This research additionally highlighted elevated dangers related to deprivation [6].

Though lung involvement is the commonest and most critical illness manifestation, it has been more and more demonstrated that extrapulmonary manifestations are fairly frequent [7]. The kidneys may be affected in a number of methods, and acute kidney harm (AKI) is comparatively frequent in addition to hematuria and proteinuria. From the USA and the UK, AKI figures of 20–46% have been reported, which within the intensive care unit (ICU) setting together with the necessity for kidney substitute remedy (KRT) additionally dramatically will increase the danger of mortality [8, 9].

It’s not but recognized whether or not early indicators of renal harm in COVID-19 will improve the danger of CKD in the long run. Nonetheless, the hanging scientific presentation of hematuria and/or proteinuria in addition to AKI and the destructive influence on consequence provides additional proof to kidneys being an extra goal organ for SARS-CoV-2.

Nephrologists have lengthy been conscious of hyperlinks between viral infections and immune-mediated kidney illness [10]. One well-known instance is hepatitis C, which is related to glomerulonephritis and vasculitis resulting in an elevated danger of CKD [11]. Apparently, reviews of collapsing glomerulopathy in COVID-19-associated AKI have now been revealed, resembling what has beforehand been described in HIV [12]. Final, a really excessive danger of thrombotic issues is especially outstanding in COVID-19, suggesting that the endothelium is also a goal organ [13, 14].

On this article, we describe the COVID-19 epidemic, administration, and outcomes within the dialysis inhabitants of Stockholm, the a part of Sweden with the very best an infection charges in March–April of 2020. We additionally current 2 scientific dialysis affected person case reviews who have been admitted to the ICU.

Materials and Strategies

Symptomatic COVID-19 in Hemodialysis Sufferers and Consequence

The Stockholm area has been the epicenter of the COVID-19 epidemic in Sweden till just lately. The mortality charge within the Stockholm area reached roughly 100 per 100,000 inhabitants by the tip of July 2020 as reported by the Public Well being Company of Sweden [15]. No lockdown was put in place, relatively a collection of suggestions together with social distancing, decreasing the utmost variety of individuals at gatherings, and hand hygiene have been carried out. Working from dwelling was advised if potential and digital classes for college and high-school college students have been began.

At first of March of 2020, there have been 520 hemodialysis (HD) sufferers within the higher Stockholm space. HD sufferers have been examined for SARS-CoV-2 with PCR in the event that they offered with fever, respiratory, or gastrointestinal signs. If confirmed, optimistic sufferers have been to comply with suggestions from the Public Well being Company, and furthermore be remoted throughout their dialysis session. Dialysis classes have been quickly rescheduled to create cohorts the place contaminated sufferers have been dialyzed collectively to guard noninfected sufferers. No obligatory carrying of facemasks was launched. SARS-CoV-2-positive sufferers have been thought of freed from an infection in the event that they have been symptom-free for 72 h and not less than 7 days had handed from first signs. In the course of the interval from March 12 to April 17, 2020, a complete of forty symptomatic sufferers have been examined optimistic for SARS-CoV-2 (see Desk 1). Out of those 40 contaminated sufferers, 24 sufferers had COVID-19 requiring additional medical care. Twenty-two sufferers have been hospitalized, 1 died of cardiac arrest within the emergency room, and one other obtained palliative care at a nursing dwelling. 9 sufferers with extra extreme COVID-19 an infection died (mortality charge of twenty-two.5%), of whom 8 have been males and older than 70 years. The median age within the deceased group (78 years) was considerably greater than those that survived (Pupil´s t-test; p = 0.003), and the median time in dialysis (11.5 years) was considerably longer than that of the survivors (p = 0.01). One of many non-survivors was hospitalized and subsequently handled with mechanical air flow within the ICU (see Case 1). Within the remaining circumstances, a call was made to not admit to the ICU due to the affected person’s needs, age, or comorbidities. The one lady who died was 96 years previous and had undergone dialysis for a complete of 19 years.

Desk 1.

Symptomatic COVID-19 an infection within the Stockholm HD inhabitants, March 12 to April 17, 2020

https://infomed.site/wp-content/uploads/2021/06/The-COVID-19-Epidemic-Management-and-Outcomes-of-Hemodialysis-and-Peritoneal.png

Out of the 15 hospitalized and surviving HD sufferers, 60% have been handled with oxygen, however wanted neither high-flow oxygen remedy nor admission to the ICU. Most sufferers got antibiotics for suspected bacterial superinfections. Apart from the HD affected person admitted to the ICU, none got antimalarial medication or anti-inflammatory remedy. Within the hospitalized survivors, 87% have been males, the median age was decrease (68 years), and the median time in dialysis was considerably shorter (1.5 years) than in non-survivors. Nonetheless, the two ladies on this group had a considerably longer dialysis classic (14 and 19 years, respectively). Among the many 16 sufferers who have been adopted up in an outpatient setting, 63% have been males, with a fair decrease median age (55.5 years), however with a higher age distribution (19–86 years). Median time in dialysis was 3 years. This descriptive information are summarized in Desk 1.

Plasma C-reactive protein (CRP) at analysis was out there in 7 of the non-survivors (median 213 mg/L, vary 86–329 mg/L, reference <3 mg/L) and in 25 of the survivors (median 87 mg/L, vary 1–328 mg/L) and was considerably greater within the non-survivors (p = 0.0003). Most CRP additionally indicated poorer outcomes amongst hospitalized sufferers (p = 0.0004). Lymphocyte rely was out there at analysis in 22 sufferers however didn’t differ considerably between survivors and non-survivors (p = 0.28).

The proportion of sufferers with diabetes didn’t differ between teams (53–56%). Solely 3 of the HD sufferers had a BMI >30 kg/m2, and 5 sufferers have been on immunosuppressive remedy, however none of those elements elevated the danger of extra critical illness on this small group. There have been no variations between the teams concerning hypertension or prior heart problems. Amongst survivors, the proportion of sufferers with ongoing remedy with both an ACE inhibitor or ARB was not considerably completely different from non-survivors (p = 0.08). 13 out of 15 sufferers continued their remedy in the course of the an infection with out growing extra critical illness.

Common masking was launched for all in-center HD sufferers touring from their properties in early April. The dialysis workers have been additionally higher outfitted with private safety gear. From Might via August, solely sporadic circumstances have been recognized.

Peritoneal Dialysis Sufferers with COVID-19 Requiring Hospitalization and Consequence

Sufferers with peritoneal dialysis (PD) handle their dialysis at dwelling and have been solely examined if hospitalized for COVID-19. Within the Stockholm area, there have been 127 PD sufferers at first of the epidemic. Solely 4 of those sufferers have been hospitalized by April 17 as a result of COVID-19. Out of those, a 73-year-old affected person died. One other 54-year-old was admitted to the ICU and survived (see Case 2). The opposite 2 have been 42 and 56 years previous, respectively, wanted oxygen, and have been hospitalized for 8–9 days. The median time in dialysis for these 4 sufferers was 2 years. Two had diabetes and all had ongoing remedy with an ACE inhibitor or ARB.

Case Studies

Case 1: The affected person was a 62-year-old man with end-stage kidney illness (ESKD) as a result of polycystic kidney illness. He beforehand had a kidney transplant however was at present on dwelling HD since 17 years. He offered with GI signs, was hospitalized on March 20, and examined optimistic for SARS-CoV-2. A choice of no admission to the ICU as a result of ESKD with dialysis remedy was made however was retracted after dialogue with the nephrology crew. As a result of worsening pneumonia, the affected person was intubated on March 23. He was nonetheless hemodynamically unstable and more and more troublesome to ventilate. The affected person didn’t reply effectively to proning or excessive doses of vasopressors. The fever was excessive and CRP was 496 mg/L (ref <3 mg/L), which had been rising quickly, regardless of intravenous (IV) cefotaxime. Ferritin was additionally growing to 918 μg/L (ref 30–350 μg/L), in addition to interleukin-6 (IL-6) which was 1,852 ng/L (ref <7 ng/L). Lymphopenia was gentle. The affected person was believed to be affected by hyper-inflammation because of the COVID-19 an infection and was given a single dose of the IL-6 inhibitor RoActemra (tocilizumab) 8 mg/kg on March 25 and in addition obtained a decreased dose of chloroquine phosphate on March 24–28. The next day, the affected person was enhancing concerning air flow, was afebrile, and inflammatory parameters decreased. On March 30, the affected person was extubated and transferred to an intermediate care ward for respiratory oxygen assist. On April 2, he developed an enterococcal sepsis which he succumbed to on April 8.

Case 2: This affected person was a 54-year-old lady with ESKD seemingly as a result of hypertension. She had been on PD for two years ready for a kidney transplant. She offered with 10 days of fever, fatigue, muscle aches, and vomiting. SARS-CoV-2 was optimistic throughout hospitalization, on March 24. An preliminary choice of no admission to the ICU as a result of ESKD with dialysis remedy was made however was modified after dialogue with the nephrology crew. The affected person was subsequently transferred to the ICU and intubated on March 25 as a result of quickly progressive respiratory failure. Plasma ranges of CRP, with a most of 448 mg/L (ref <3 mg/L) had quickly elevated, in addition to these of ferritin, IL-6, and fibrin-D-dimer. Lymphopenia was gentle. IV cefotaxime was initiated. The affected person improved and was extubated after 13 days and was subsequently transferred to an intermediate care ward and ultimately to the nephrology ward with regular oxygen saturation. Sequelae resembling important sickness neuropathy and cognitive signs have been, nonetheless, outstanding. The affected person was despatched to a rehabilitation facility however returned dwelling 2 months after being hospitalized. Apparently, PD remedy was continued all through the hospitalization, additionally within the ICU, utilizing handbook exchanges 4–5 occasions a day.

Dialogue

The COVID-19 pandemic has confirmed to be a brand new problem for nephrology. Now we have right here offered preliminary descriptive information on dialysis sufferers in Stockholm, who have been affected early and severely by the COVID-19 epidemic in Sweden. HD sufferers older than 70 years have been at the next danger of dying from symptomatic COVID-19, whereas these youthful than 70 years appeared to have a milder illness typically. To the very best of our data, we’re the primary to explain that longer dialysis classic and never solely age is related to poor consequence. This seemingly displays the next diploma of frailty, which can be related to an elevated mortality from COVID-19. Apparently, the gender stability was additionally skewed as only a few ladies died in our COVID-19 cohort. Larger and most CRP at admission have been predictive of poor outcomes. Few PD sufferers have been hospitalized with CO­VID-19 an infection. That is seemingly as a result of higher isolation choices having a house dialysis remedy than going to an in-center HD unit a number of occasions per week and thereby risking publicity. Using good hand hygiene in PD may be a bonus.

Early reviews from Italy pointed to KRT sufferers being at excessive danger of an infection and mortality [16]. In April, Spain reported registry information for 868 sufferers in KRT with COVID-19 [17], of which 63% have been in HD, 4% in PD, and 36% had a kidney transplant. A complete of 85% have been hospitalized, of which 8% have been admitted to the ICU. Mortality reached 23% and important danger elements for dying have been age and pneumonia. In Spain, many sufferers obtained hydroxychloroquine as reviews initially had advised that there might be a protecting impact in COVID-19 [18]. Nonetheless, randomized managed trials (RCTs) haven’t proven any scientific profit for hydroxychloroquine neither in hospitalized sufferers nor for early, gentle CO­VID-19 [19]. A research from France reported 38 SARS-CoV-2-infected sufferers out of 200 upkeep HD sufferers, with a mortality of 21%. All contaminated sufferers had lymphopenia and a rise in CRP ranges; nonetheless, any predictive elements concerning consequence weren’t offered [17]. The ERA-EDTA is at present gathering information within the newly established ERA-EDTA COVID-19 Database of Kidney Alternative Remedy sufferers (ERACODA) registry. Preliminary mortality information offered on the absolutely digital ERA-EDTA congress in June 2020 have been 25% in dialysis sufferers and 21% in kidney transplant sufferers, pushed primarily by age and frailty [20]. The primary revealed report from ERA-CODA conveyed that in 3,285 dialysis sufferers, amongst them 125 handled with PD, the 28-day mortality danger was 21.1 occasions greater than the anticipated 1.2% mortality of propensity-score matched historic controls. Our research included far fewer sufferers which is a limitation, however equally to our information, age was a predictive mortality issue and males had decrease survival charges [21]. Knowledge from PD are nonetheless relatively scare however in research from a New York well being system of 11 sufferers on continual PD remedy, 3 sufferers required mechanical air flow, and a pair of died [22]. Apparently, the mortality charge in a research from China was solely 6,5% in an HD cohort [23]. This implies that elements aside from CKD might affect consequence in varied populations.

Though a number of of the dialysis workers and physicians have been contaminated in the course of the top of the epidemic, we didn’t acquire this info. One other downside is that not all dialysis sufferers, regardless of signs, have been examined. It has just lately been proposed {that a} substantial variety of HD sufferers might have asymptomatic COVID-19 an infection. This was studied in London, UK, in 356 grownup sufferers with in-center HD of whom 121 had been symptomatic and screened with a PCR take a look at. A seroprevalence charge of 36% was discovered, and the research additionally confirmed that 40% of sufferers with SARS-CoV-2 antibodies had both asymptomatic an infection or undetected illness by PCR alone [24].

In the course of the early section of the epidemic, there have been discussions, primarily in Stockholm, on who could be prone to profit from intensive care if critically unwell and learn how to greatest decide which sufferers on KRT ought to be admitted. Selections concerning the degree of care are usually made after particular person evaluation, however ought to, at any time when potential, even be mentioned with the affected person’s nephrologist, the affected person, and kin. Nephrologists have experience in assessing purposeful standing, predicting prognosis, and prescribing remedy in sufferers with CKD, dialysis, or a kidney transplant, whereas intensive-care physicians have intensive expertise in remedy and remedy outcomes within the ICU and an outline of present assets. Earlier expertise in sepsis earlier than the COVID-19 pandemic has demonstrated that HD sufferers are vulnerable to greater ICU mortality, however usually have higher consequence than sufferers within the ICU with dialysis-dependent AKI, suggesting that ICU prognosis could also be influenced by elements aside from the underlying renal perform [25]. As COVID-19 is a brand new an infection, it could thus be untimely to determine that dialysis sufferers have a significantly worse prognosis within the ICU setting than different critically unwell affected person teams.

The function of RAAS blockade in COVID-19 has been debated broadly. Current proof means that persevering with RAAS-inhibition remedy just isn’t dangerous [26, 27]. It could, nonetheless, be too early to determine if this class of medication has protecting properties as advised in a retrospective research from the UK and in a report from France [28, 29]. Many of the dialysis sufferers in our cohort didn’t discontinue RAAS blockade.

The Swedish Renal Registry reported in 2019 an annual mortality in dialysis as excessive as 19.2%, in comparison with solely 3% in kidney transplanted sufferers [30]. Nonetheless, dialysis sufferers are a heterogeneous group when it comes to age, comorbidities, time in dialysis, and prognosis. A considerable group is youthful, in any other case wholesome, energetic, and dealing. A sizeable proportion of dialysis sufferers youthful than 70 years and a smaller proportion within the age-group of 70–75 years are on the transplant ready record or have a possible residing donor. They’re often assessed to make sure that they continue to be in a very good situation to endure transplantation, that’s, normal anesthesia, surgical procedure, and issues, and thus have a very good rehabilitation potential and a comparatively long-life expectancy. Different dialysis sufferers can’t be transplanted for varied causes however are nonetheless in good bodily situation and potential candidates for energetic remedy of COVID-19, together with intensive care. Nonetheless, many dialysis sufferers are aged and frail with a number of comorbidities contributing to a excessive mortality, and we usually attempt to doc remedy limitation plans with these sufferers.

Whereas ready for efficient COVID-19 medication, the nephrology crew ought to be consulted when indicators of kidney involvement with hematuria and proteinuria are verified and kidney impairment is growing. The potential function of anti-inflammatory medication within the hyperinflammatory section of COVID-19 is more and more acknowledged, though RCTs have till just lately been missing. In a smaller research from France, the danger to be admitted to the ICU was decreased for sufferers handled with the IL6-inhibitor tocilizumab as in comparison with untreated ones (25 vs. 72%; p = 0.002) [31]. In an American research, a brief course of methylprednisolone in 132 sufferers decreased the composite consequence measure ICU, mechanical air flow, and dying as in contrast with 81 untreated sufferers (34,9% vs. 54,3% p = 0.005) [32]. Not too long ago, the randomized RECOVERY trial demonstrated that dexamethasone decreased mortality in hospitalized sufferers with extreme respiratory issues of COVID-19 [33]. Unpublished information from the RECOVERY trial have additionally discovered a protecting impact for AKI needing KRT (unpublished information, private communication R Haynes). Whether or not these therapies might translate into higher consequence additionally in continual dialysis sufferers will probably be essential to determine.

A current report from Germany confirmed ongoing myocardial irritation and cardiac involvement in a considerable variety of recovering sufferers [34]. It has additionally been reported that roughly 10% of individuals expertise extended sickness after COVID-19 with signs starting from critical sequelae (resembling thromboembolic issues) and people with a nonspecific scientific image, typically dominated by fatigue and breathlessness [35]. It could thus be helpful to evaluate long-term well being and organ perform post-COVID-19 in dialysis sufferers particularly in these ready for kidney transplantation.

CKD sufferers are, nonetheless, typically excluded from RCTs, which has additionally been the case in the course of the present COVID-19 pandemic [36]. One instance is the antiviral drug remdesivir, which is contraindicated with a glomerular filtration charge <30 mL/min, suggesting extra pragmatic remedy methods within the CKD inhabitants [37]. One other characteristic of the present epidemic is the dangers of publicity for in-center HD sufferers suggesting that home-dialysis choices ought to be pursued additional.

AKI in extreme COVID-19 has led to a surge within the want for RRT and elevated mortality. The widespread scientific problem of mobilizing not solely mechanical ventilators but in addition all potential dialysis assets, which can compete with assets for continual dialysis sufferers, has been a formidable enterprise in the course of the first waves of this epidemic [3-6, 16, 17, 20-23]. As new waves of CO­VID-19 emerge, mitigation insurance policies to reduce the danger of exposing high-risk populations to the virus stay essential.

Conclusion

CKD and dialysis sufferers are at excessive danger of CO­VID-19 an infection and poor consequence. Mitigation methods to cut back charges of an infection on this inhabitants stay important. Whether or not COVID-19 will improve the danger of CKD long-term and improve the demand for upkeep dialysis must be noticed and investigated additional. The cumulative reviews of long-standing post-infectious signs and lingering organ harm after COVID-19 counsel that this will probably be essential to observe additionally within the dialysis inhabitants.

Acknowledgement

We thank the Swedish Renal Registry for collaboration.

Assertion of Ethics

The paper is exempt from Moral Committee approval. In accordance with Swedish legislation, affected person information included in High quality Registries can be utilized for analysis. Sufferers are knowledgeable and have a proper to say no to be registered, however no further consent is required for particular initiatives. All sufferers included on this report are registered within the Swedish Renal Registry and thus no additional moral approval is required. Written knowledgeable consent was obtained from the affected person and subsequent of kin for publication of the case reviews.

Battle of Curiosity Assertion

Jessica Smolander declares no battle of curiosity. Annette Bruchfeld reviews grants and private charges from Astra Zeneca, private charges from ChemoCentryx, Merck/MSD, and from Abbvie exterior the submitted work.

Funding Sources

There was no funding for this research.

Writer Contributions

The two authors have contributed equally to this paper.

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Writer Contacts

Annette Bruchfeld, [email protected]


Article / Publication Particulars

First-Web page Preview

Abstract of Brief Report

Obtained: September 17, 2020
Accepted: January 04, 2021
Printed on-line: March 26, 2021
Difficulty launch date: April 2021

Variety of Print Pages: 7
Variety of Figures: 0
Variety of Tables: 1

ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (On-line)

For extra info: https://www.karger.com/KBR


Open Entry License / Drug Dosage / Disclaimer

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