COVID-19-associated acute kidney injury
COVID-19 Microchapters |
Diagnosis |
---|
Treatment |
Case Studies |
COVID-19-associated acute kidney injury On the Web |
American Roentgen Ray Society Images of COVID-19-associated acute kidney injury |
Risk calculators and risk factors for COVID-19-associated acute kidney injury |
For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nasrin Nikravangolsefid, MD-MPH [2],Sogand Goudarzi, MD [3]
Synonyms and keywords: COVID-19-associated AKI
Overview
COVID-19 can involve many organs leading to organ failure, one of which is kidneys that manifest with mild proteinuria to advanced acute kidney injury (AKI).
Historical Perspective
- Early reports from China revealed that COVID-19 rarely involves the kidneys, as acute renal failure was not seen among COVID-19 hospitalized patients and mild BUN or creatinine rise [10.8%] and mild proteinuria [7.2%] occurred. [1]
- However, recent study found 75.4% of hospitalized patients with COVID-19 pneumonia developed hematuria, proteinuria, and AKI. But, these findings are not significantly different from other critical diseases.[2]
Classification
Pathophysiology
- Angiotensin-converting enzyme 2 (ACE2), which is a primary receptor for SARS-CoV-2 entry into cells, mostly presents in renal tubular epithelial cells as well as lungs and heart.[4]
- Despite kidney injury following COVID-19 infection is less frequent than severe lung injury, ACE2: ACE ratio is higher in the kidneys compared to the respiratory system. (1:1 in the kidneys VS 1:20 in the respiratory system)[4]
- After SARS-CoV-2 enters through the nasal cavity, it may travel to the kidneys and enters the bloodstream leading to severe inflammatory response activation and cytokine storm.
- Cytokine induced AKI may occur due to intrarenal inflammation, hyperpermeability of vessels, hypovolemia and cardiomyopathy, leading to cardiorenal syndrome type 1 that is characterized by third space volume overload such as pleural effusion, edema and intravascular volume loss (hypovolemia) and hypotension.[5]
- cardiomyopathy and COVID-19-associated myocarditis can lead to hypotension and reduction in renal perfusion.
- The major cytokine is IL-6, which induces inflammation and lung endothelial cell injury, leading to ARDS and hypoxia that subsequently cause renal tubular cell injury and AKI. [6][5]
- Cytokine induced AKI may occur due to intrarenal inflammation, hyperpermeability of vessels, hypovolemia and cardiomyopathy, leading to cardiorenal syndrome type 1 that is characterized by third space volume overload such as pleural effusion, edema and intravascular volume loss (hypovolemia) and hypotension.[5]
- To conclude, COVID-19-associated AKI can occur as a result of[4]:
- Sepsis and cytokine storm
- Hypovolemia and Hypotension
- Hypoxemia
- Blood clots formation due to hypercoagulable state, leading to impaired blood flow in the renal arterioles.
Causes
- SARS-CoV-2 may have a Kidney tropism. As a recent study found SARS-CoV-2 antigens in renal tubules which suggests the direct damage of SARS-CoV-2 on the kidneys. https://www.medrxiv.org/content/10.1101/2020.03.04.20031120v4. Missing or empty
|title=
(help)
Epidemiology and Demographics
- AKI is frequently seen among patients with COVID-19 hospitalized in ICU, with prevalence of 0.6-29% in China "Acute Kidney Injury in COVID-19 Patients | COVID-19". and 22.2% in the USA.[9]
- Approximately 43% of critically ill patients with COVID-19 developed AKI during the admission period. [3]
- In a cohort study on 99 patients with severe COVID-19, AKI was reported in 42 patients (42.9%) and among them 32 (74.4%) patients had severe AKI (stage III based on KDIGO definition). [10]
- The actual incidence of AKI in critcally ill patients with COVID-19 is uncertain but estimated between 27-85%. "Acute Kidney Injury in COVID-19 Patients | COVID-19".
- Differences of AKI prevalence among studies could be related to several factors, including[10]:
- Patient characteristics
- Comorbidities
- smoking history
- Medications history
- Race
- Severity of COVID-19
- Differences of COVID-19 Management among countries
- Patient characteristics
Age
Gender
- Men are more likely to be affected and have higher risk of COVID-19 complications. [11]
- 57.1% of AKI cases following COVID-19 were male.[3]
Race
Risk Factors
- The most potent risk factors in the development of COVID-19 associated AKI include[12] [13]:
- Elderly
- Age>60 years
- Comorbidities
- Elderly
Natural History, Complications, and Prognosis
Natural History
- AKI is more likely to develop in the late stages of COVID-19 in critically ill patients.[14]
- Severe COVID-19 pneumonia and severe acute respiratory distress syndrome are associated with developing AKI.[2]
Diagnosis
Symptoms
- COVID-19-associated AKI commonly occurs between 5 to 9 days after hospitalization. [10]
- Patients in the early stages of kidney failure may be asymptomatic.
- If left untreated, patients may progress to develop Azotemia and Uremia, which occur due to the buildup of waste materials in the blood.
- Symptoms of kidney injury include [15]:
Physical Examination
- Physical examination of patients with AKI is usually remarkable for:
- Signs of dehydration, such as tachycardia, tachypnea, hypotension, and dry mucosa
- Fluid retention, leading to edema and swelling of periorbital and extremities
- Confusion due to severe dehydration and electrolyte imbalances
- Decrease in urine output:Oliguria or Anuria
- cardiac arrhythmia due to electrolyte imbalances such as high level of Potassium
Laboratory Findings
- Laboratory findings of COVID-19-associated AKI include:
- Elevated BUN level
- Plasma BUN-creatinine ratio> 20 in prerenal AKI
- Plasma BUN-creatinine ratio< 15 in intrinsic AKI or acute tubular necrosis
- Based on KDIGO definition for the diagnosis of AKI[16]:
- Elevated serum Creatinine by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours; or
- Elevated serum Creatinine to ≥1.5 times baseline within the previous 7 days; or
- Urine volume < 0.5 ml/kg/h for >6 hours
- Fractional excretion of sodium (FENa)
- Urinary sediment
- Hyaline casts in prerenal AKI
- Granular or Muddy brown casts in intrinsic AKI or acute tubular necrosis
- Several biomarkers have been found to diagnose and predict AKI that include[17] [18] [19]:
- Elevated BUN level
Electrocardiogram
- There are no specific ECG findings associated with AKI. However, electrolyte disturbances such as hyperkalemia might lead to various ECG abnormalities.
Approach to Patients with Elevated Biomarkers
Treatment
Medical Therapy
- Management of AKI following COVID-19 includes antiviral therapies, identifying electrolyte disorders, and intravenous fluid resuscitation.
- Treatment of AKI following COVID-19 includes:[14] [13]
- Correction of hypovolemia and hypotension by the administration of adequate intravenous fluid
- Isotonic crystalloid is recommended among all patients who develop AKI. [16]
- Correction of electrolyte disorders
- antiviral therapy:
- Recently, Remdesivir has been found effective against COVID-19. [20]
- Anticoagulants in hypercoagulable conditions
- Loop diuretics
- In volume overload conditions
- Diuretics should not be used regularly as they predispose patients to volume depletion.
- Correction of hypovolemia and hypotension by the administration of adequate intravenous fluid
Interventions
- renal replacement therapy
- If AKI is unresponsive to conservative therapy
- In volume overload conditions
- Modality of choice in unstable hemodynamic status and ESRD, severe metabolic acidosis, severe hyperkalemia
- renal replacement therapy is associated with hypercoagulation.[13]
- Sequential extracorporeal therapy
- It removes cytokines, which reduces systemic inflammation and subsequent organ failure.
Prevention
- Patients with COVID-19 should be evaluated for intravascular volume status based on physical examination and fluid balance.[13]
- Serial monitoring of BUN, serum creatinine, and electrolytes such as sodium, potassium and bicarbonate should be considered frequently every 48 hours or more in high risk patients.[13]
- Isotonic saline is recommended as a prevention strategy for patients who are at increased risk for AKI by expanding intravascular volume. [16]
References
- ↑ Wang, Luwen; Li, Xun; Chen, Hui; Yan, Shaonan; Li, Dong; Li, Yan; Gong, Zuojiong (2020). "Coronavirus Disease 19 Infection Does Not Result in Acute Kidney Injury: An Analysis of 116 Hospitalized Patients from Wuhan, China". American Journal of Nephrology. 51 (5): 343–348. doi:10.1159/000507471. ISSN 0250-8095.
- ↑ 2.0 2.1 2.2 Pei, Guangchang; Zhang, Zhiguo; Peng, Jing; Liu, Liu; Zhang, Chunxiu; Yu, Chong; Ma, Zufu; Huang, Yi; Liu, Wei; Yao, Ying; Zeng, Rui; Xu, Gang (2020). "Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia". Journal of the American Society of Nephrology. 31 (6): 1157–1165. doi:10.1681/ASN.2020030276. ISSN 1046-6673.
- ↑ 3.0 3.1 3.2 3.3 Pei G, Zhang Z, Peng J, Liu L, Zhang C, Yu C; et al. (2020). "Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia". J Am Soc Nephrol. 31 (6): 1157–1165. doi:10.1681/ASN.2020030276. PMC 7269350 Check
|pmc=
value (help). PMID 32345702 Check|pmid=
value (help). - ↑ 4.0 4.1 4.2 4.3 Malha, Line; Mueller, Franco B.; Pecker, Mark S.; Mann, Samuel J.; August, Phyllis; Feig, Peter U. (2020). "COVID-19 and the Renin-Angiotensin System". Kidney International Reports. 5 (5): 563–565. doi:10.1016/j.ekir.2020.03.024. ISSN 2468-0249.
- ↑ 5.0 5.1 5.2 Ronco C, Reis T (2020). "Kidney involvement in COVID-19 and rationale for extracorporeal therapies". Nat Rev Nephrol. 16 (6): 308–310. doi:10.1038/s41581-020-0284-7. PMC 7144544 Check
|pmc=
value (help). PMID 32273593 Check|pmid=
value (help). - ↑ Husain-Syed F, Slutsky AS, Ronco C (2016). "Lung-Kidney Cross-Talk in the Critically Ill Patient". Am J Respir Crit Care Med. 194 (4): 402–14. doi:10.1164/rccm.201602-0420CP. PMID 27337068.
- ↑ Ye M, Wysocki J, William J, Soler MJ, Cokic I, Batlle D (2006). "Glomerular localization and expression of Angiotensin-converting enzyme 2 and Angiotensin-converting enzyme: implications for albuminuria in diabetes". J Am Soc Nephrol. 17 (11): 3067–75. doi:10.1681/ASN.2006050423. PMID 17021266.
- ↑ Perico L, Benigni A, Remuzzi G (2020). "Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade". Nephron. 144 (5): 213–221. doi:10.1159/000507305. PMC 7179544 Check
|pmc=
value (help). PMID 32203970 Check|pmid=
value (help). - ↑ Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; et al. (2020). "Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area". JAMA. doi:10.1001/jama.2020.6775. PMC 7177629 Check
|pmc=
value (help). PMID 32320003 Check|pmid=
value (help). - ↑ 10.0 10.1 10.2 Gabarre P, Dumas G, Dupont T, Darmon M, Azoulay E, Zafrani L (2020). "Acute kidney injury in critically ill patients with COVID-19". Intensive Care Med. 46 (7): 1339–1348. doi:10.1007/s00134-020-06153-9. PMC 7290076 Check
|pmc=
value (help). PMID 32533197 Check|pmid=
value (help). - ↑ Sharma G, Volgman AS, Michos ED (2020). "Sex Differences in Mortality from COVID-19 Pandemic: Are Men Vulnerable and Women Protected?". JACC Case Rep. doi:10.1016/j.jaccas.2020.04.027. PMC 7198137 Check
|pmc=
value (help). PMID 32373791 Check|pmid=
value (help). - ↑ Rabb H (2020). "Kidney diseases in the time of COVID-19: major challenges to patient care". J Clin Invest. 130 (6): 2749–2751. doi:10.1172/JCI138871. PMC 7259985 Check
|pmc=
value (help). PMID 32250968 Check|pmid=
value (help). - ↑ 13.0 13.1 13.2 13.3 13.4 Selby NM, Forni LG, Laing CM, Horne KL, Evans RD, Lucas BJ; et al. (2020). "Covid-19 and acute kidney injury in hospital: summary of NICE guidelines". BMJ. 369: m1963. doi:10.1136/bmj.m1963. PMID 32457068 Check
|pmid=
value (help). - ↑ 14.0 14.1 14.2 Ronco C, Reis T, Husain-Syed F (2020). "Management of acute kidney injury in patients with COVID-19". Lancet Respir Med. doi:10.1016/S2213-2600(20)30229-0. PMC 7255232 Check
|pmc=
value (help). PMID 32416769 Check|pmid=
value (help). - ↑ Skorecki K, Green J, Brenner BM (2005). "Chronic renal failure". In Kasper DL, Braunwald E, Fauci AS, et al. Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp. 1653–63. ISBN 978-0-07-139140-5.
- ↑ 16.0 16.1 16.2 Khwaja A (2012). "KDIGO clinical practice guidelines for acute kidney injury". Nephron Clin Pract. 120 (4): c179–84. doi:10.1159/000339789. PMID 22890468.
- ↑ Kashani K, Cheungpasitporn W, Ronco C (2017). "Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption". Clin Chem Lab Med. 55 (8): 1074–1089. doi:10.1515/cclm-2016-0973. PMID 28076311.
- ↑ Schrezenmeier EV, Barasch J, Budde K, Westhoff T, Schmidt-Ott KM (2017). "Biomarkers in acute kidney injury - pathophysiological basis and clinical performance". Acta Physiol (Oxf). 219 (3): 554–572. doi:10.1111/apha.12764. PMC 5575831. PMID 27474473.
- ↑ Oh DJ (2020). "A long journey for acute kidney injury biomarkers". Ren Fail. 42 (1): 154–165. doi:10.1080/0886022X.2020.1721300. PMC 7034110 Check
|pmc=
value (help). PMID 32050834 Check|pmid=
value (help). - ↑ Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A; et al. (2020). "Compassionate Use of Remdesivir for Patients with Severe Covid-19". N Engl J Med. 382 (24): 2327–2336. doi:10.1056/NEJMoa2007016. PMC 7169476 Check
|pmc=
value (help). PMID 32275812 Check|pmid=
value (help).