Kidney involvement in COVID-19

1
KIDNEY INVOLVEMENT IN COVID-19 PATIENTS
Jafar Alsaid, M.B. CHB. MD. FASN. FACP
Nephrology and Internal Medicine Consultant

Jafar Alsaid,M.B.ChB. MD. FASN. FAC
2

Jafar Alsaid,M.B.ChB. MD. FASN. FACP 12 Hemodialysis session. 20/11/2020 3

GLOBAL COVID-19 EPIDEMIOLOGY

ORGAN INVOLVEMENT IN COVID-19
• Lungs.
• Heart.
• Kidney.
• Liver.
• GI.
• Blood & Immun.
• Nervous system.
Jafar Alsaid,M.B.ChB. MD. FASN. FACP 12 Hemodialysis session. 20/11/2020
7
M. Dong et al. ACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19 Biomedicine &
Pharmacotherapy 131 (2020) 110678

PRESENTATION SCHEME
• Introduction.
• Epidemiology.
• Kidney involvement.
• AKI.
• Management.
• Conclusion
8

JOHN’S HOPKINS CORONA RESOURCE CENTER
HTTPS://CORONAVIRUS.JHU.EDU/MAP.HTML
10

GLOBAL COVID-19 DAILY CASES
11
John’s Hopkins Corona Resource Center. https://coronavirus.jhu.edu/map.html

NUMBERS OF CONFIRMED COVID CASES PER COUNTRY
12
0
10000000
20000000
30000000
40000000
50000000
60000000
Global USA India Brazil KSA UAE Bahrain Kuwait Oman
55943189
11695711
8912907
5911758
353918 152809 85008 137885 120718

Percentage of cases and mortality rates
7.10%
3.50%
0.60%
2.70%
1%
1.50%
4.90%
3.20%
2.30%
2.40%
2.10%
1.40%
1.10%
1.60%
0.35% 0.39%
0.61%
1.10%
0.00%
1.00%
2.00%
3.00%
4.00%
5.00%
6.00%
7.00%
8.00%
Global USA India Brazil KSA UAE Bahrain Kuwait Oman
Cases Mortality

VIRAL ENTRY TO THE KIDNEY
14

J. Alsaid. 38th HTN and CV highlight session 22nd Aug. 2020. 15
https://www.nejm.org/doi/pdf/10.1056/NEJMsr2005760?articleTools=true

J. Alsaid. 38th HTN and CV highlight session 22nd Aug. 2020.
16
D’Ardes D., Boccatonda A., et al. COVID-19 and RAS: Unravelling an Unclear Relationship. Int. J. Mol. Sci. 2020, 21, 3003;
doi:10.3390/ijms21083003
RAAS CASCADE AND TARGET OUTCOME

ACE2 & TMPRSS2
DISTRIBUTION
17

ACE2 RECEPTORS IN THE KIDNEY
18

COVID-19 entrance site in the kidney and
the specific receptors and
Yongqian Cheng1 & Wenling Wang1 & Liang Wu1 & Guangyan Cai, SARS-CoV-2-Related Kidney Injury: Current Concern and Challenges.
Accepted: 17 September 2020 # The Author(s) 2020. SN Comprehensive Clinical Medicine https://doi.org/10.1007/s42399-020-00529-0
•Inflammation.
•Complement.
•Coagulopathy.
•Endothelial damage.
•Collapsing
Glomerulopathy
19

ENTRY OF SARS- COVID
INTO THE CELLS
• ACE2.
• TMPRESS2
Found in Epith, Endoth,
Messangial & Podocyt.
20

KIDNEY INVOLVEMENT WITH COVID-19
• Acute Kidney Injury.
• CKD patient infection with COVID.
• Effect on Hemodialysis and Peritoneal dialysis patients.
• COVID-19 in Transplant patients.
21

AKI IN COVID-19 PATIENTS
22

ACUTE KIDNEY INJURY
3-9% of early report from China.
Naicker S, Yang C-W, Hwang S-J, Liu B-C, Chen J-H, Jha V. The Novel Coronavirus 2019 epidemic and kidneys. Kidney Int . 2020;97(5):824–828. doi: 10.1016/j.kint.2020.03.001 .
Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet
Respir Med . 2020;8(5):475–481. doi: 10. 1016/S2213-260 0(20)30 079-5 .
19% - > 50% of ICU patients.
Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ILL Patients with COVID-19 in Washington State. JAMA . 2020;323(16):1612. doi: 10.1001/jama.2020.4326 .
Yang, X. et al. Clinical course and outcomes of critically ill patients with SARS- CoV-2 pneumonia in Wuhan, China: a single- centered, retrospective, observational study. Lancet. Respir.
Med. 8, 475–481 (2020).
28- 43% of Hospitalized patients.
Hirsch JS, Ng JH, Ross DW, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int . 2020 Published online MayS0085253820305329. doi: 10.1016/j.kint.2020.05.006 .
61-79% of severely ill patients.
Chan L, Chaudhary K, Saha A, et al. Acute kidney injury in hospitalized patients with COVID-19. Nephrology . 2020. doi: 10.1101/2020.05.04.20090944 .
Mortality among AKI COVID-19 is between 35%-90%.
Cheng, Y. et al. Kidney disease is associated with inhospital death of patients with COVID-19. Kidney Int. 97, 829–838, (2020).
23

INCIDENCE OF AKI
REPORTED IN
DIFFERENT STUDIES.
Cheng Y, Luo R, Wang K et al (2020) Kidney disease is
associated with in-hospital death of patients with COVID-
19. Kidney Int 97:829–838. https
://doi.org/10.1016/j.kint.2020.03.005.
Arentz M, Yim E, Klaff L et al (2020) Characteristics and
outcomes of 21 critically ill patients with COVID-19 in
Washington State. JAMA 323:1612–1614. https
://doi.org/10.1001/ jama.2020.4326
Hirsch JS, Ng JH, Ross DW et al (2020) Acute kidney injury
in patients hospitalized with COVID-19. Kidney Int. https
://doi. org/10.1016/j.kint.2020.05.006
Mohamed MM, Lukitsch I, Torres-Ortiz AE et al (2020)
Acute kidney injury associated with coronavirus disease
2019 in urban New Orleans. Kidney.
https://doi.org/10.34067 /KID.00026 52020
Pei G, Zhang Z, Peng J et al (2020) Renal involvement and
early prognosis in patients with COVID-19 pneumonia. J
Am Soc Nephrol. https ://doi.org/10.1681/ASN.20200
30276Jafar Alsaid,M.B.ChB. MD. FASN. FACP 12 Hemodialysis session. 20/11/2020 24

PRECIPITATING FACTORS FOR AKI:
• CKD.
• Age.
• Male.
• Black
• DM.
• HTN.
• Heart Failure.
• Obesity.
• COPD.
Sargiacomo, C., Sotgia, F. & Lisanti, M. P. COVID-19 and chronological aging: senolytics and other anti-aging drugs for the treatment
or prevention of corona virus infection? Aging 12, 6511–6517. (2020).
Chen, N. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.
Lancet 395, 507–513, (2020).
Arentz, M. et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA 323, 1612–1614 (2020).
USA
CHINA
EUROPE
AKI prevalence
25

COVID 19 AND AKI IN 5 LARGE REPORTED SAMPLES
Please cite this article as: D. Patel, T. Truong and N. Shah et al., COVID-19 Extrapulmonary illness - The Impact of COVID-19 on Nephrology care, Disease-a-Month,
https://doi.org/10.1016/j.disamonth.2020.101057

RATES OF AKI
AND RRT IN
PATIENTS
HOSPITALIZED
WITH COVID-19
Nadim, Mitra et. al. COVID-19- associated
acute kidney injury: consensus report of the
25th. Acute Disease Quality Initiative (ADQI)
Workgroup. Nature Reviews | Nephrology.
https://doi.org/10.1038/s41581-020-00356-5
27

RENAL REPLACEMENT THERAPY REQUIREMENT IN COVID-19
• 15-20% of patient with COVID AKI.
• 34-73% of ICU admission.
Chan L, Chaudhary K, Saha A, et al. Acute kidney injury in hospitalized patients with COVID-19. Nephrology . 2020. doi:
10.1101/2020.05.04.20090944 .
28

POTENTIAL RISK
FACTORS FOR AKI IN
COVID-19 PATIENTS
https://doi.org/10.1038/s41581-020-00356-5
29
Patient
Management
Viral disease

MORTALITY AMONG
AKI WITH SARS,
MARS AND COVID
AKI
mortality
Overall
mortality
SARS 86.6% 36%
MERS 68.5% 59%
COVID 78% 32%
Chen et al. Mortality rate of acute kidney
injury in SARS, MERS, and COVID-19
infection: a systematic review and meta-
analysis Critical Care. (2020) 24:439

RENAL PATHOLOGY

PATHOLOGICAL FINDING
Pathological lesion Collapsing Glomerulopathy.
Larsen CP, Bourne TD, Wilson JD, Saqqa O, Sharshir MA. Collapsing glomerulopathy in a patient with
COVID-19. Kidney Int Rep . 2020;5(6):935–939. doi: 10.1016/j.ekir.2020.04.002 .
Mainly in African American with APOL1 genotype.
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(6) ASN.2020050558. doi:
10.1681/ASN.2020050558 .
32

POSTMORTEM & KIDNEY BIOPSY STUDIES
• Viral particles in the Podocytes and Tubular cells by EM.
Su, H. et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney
Int. 98, 219–227 (2020).
• Collapsing glomerulopathy. Among African American with APOL1 allele gene.
Peleg, Y. et al. Acute kidney injury due to collapsing glomerulopathy following COVID-19 infection. Kidney
Int. Rep. 5, 940–945 (2020).
• Acute tubular injury. Negative for vital particles.
Rossi, G. M. et al. Kidney biopsy findings in a critically ill COVID-19 patient with dialysis- dependent acute
kidney injury: a case against “SARS- CoV-2 nephropathy”. Kidney Int. Rep. 5, 1100–1105 (2020).
33

CLINICAL MANIFESTATION
34

CLINICAL RENAL INVOLVEMENT
• Proteinuria 63%.
The Team of Zhong Nanshan Responded that the Isolation of SARS-CoV-2 from Urine Remind Us to Pay More Attention to the
Cleaning of Individuals and Families. Guangzhou Daily. Published February 22, 2020.
• Proteinuria and Hematuria. 44%.
• Hematuria. 26.6%.
• Elevated Creatinine. 19%.
• Elevated Urea. 27%
Li, Z., Wu, M., Guo, J. et al. Caution on Kidney Dysfunctions of 2019-nCoV Patients. medRxiv 2020.02.08.20021212.
• Hyperkalemia and Acidosis 23%.
Chen, Tao et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 368,
m1295 (2020).
36

CAUSES OF AKI IN COVID:
• Hemodynamic.
• ATN.
• Toxic Acute Interstitial Nephritis.
• Rhabdomyolysis.
• Azotemia.
Mohamed MM, Lukitsch I, Torres-Ortiz AE, et al. Acute kidney injury associated with coronavirus disease 2019 in Urban New Orleans.
Kidney360 . 2020 Published online May 13,. doi: 10.34067/KID.0 0 0265202010.34067/KID.
• Clinical picture is variable associated with Proteinuria and Hematuria. Granular and Waxy casts.
Hernandez-Arroyo C.F., Varghese V., Mohamed M.M.B., Velez J.C.Q. Urinary sediment microscopy in acute
kidney injury associated with COVID-19. Kidney360 . Published online June 2, 2020:10.34067/KID.0 0 03352020.
doi:10.34067/KID.0 0 03352020
37

MECHANISM OF RENAL INJURY IN COVID-19
P. Meena et al. / Current Medicine Research and Practice 10 (2020) 165e168.
Farouk, Samira S. COVID-19 and the kidney: what we think we know so far and what we don’t Journal of Nephrology. https://doi.org/10.1007/s40620-020-00789-y
Direct Viral injury
Glomerular Fibrin Thrombi
Collapsing FSGSPigmented tubular casts
Hemodynamic
Thrombotic Microangiopathy
KIDNEY INJURYNephrotoxicity Secondary infections
Sepsis
38

MECHANISM OF RENAL INJURY

Positive ventilation pressure, PEEP.
MECHANISM OF RENAL INJURY IN COVID-19
Sympathetic
stimulation
RAAS
stimulation
Venous
congestion
Decreased
GFR
Increased Intrathoracic Pressure
Koyner, J. L. & Murray, P. T. Mechanical ventilation and lung- kidney interactions. Clin. J. Am. Soc. Nephrol. 3, 562–570 (2008).
Dudoignon, E. et al. Activation of the renin- angiotensinaldosterone system is associated with acute kidney injury in COVID-19. Anaesth. Crit. Care Pain Med. 39,
453–455 (2020).

ORGAN CROSS TALK
DAMP: Damage Associated Molecular Patterns
Cytokines
Vasoactive
substances
Chemokines
Joannidis, M. et al. Lung- kidney interactions in critically ill patients: consensus report of the acute disease quality initiative (ADQI) 21 workgroup. Intensive Care
Med. 46, 654–672 (2020).
Armutcu, F. Organ crosstalk: the potent roles of inflammation and fibrotic changes in the course of organ interactions. Inflamm. Res. 68, 825–839 (2019).
41

KDIGO
AKIN classification of AKI.
http://www.nephjc.com/news/2015/2/17/kdigo-aki-staging
42
AKI staging

COMORBIDITIES AMONG COVID-19 PATIENTS
Cheng1, Yongqian. SARS-CoV-2-Related Kidney Injury: Current Concern and ChallengesSN Comprehensive Clinical Medicine.
https://doi.org/10.1007/s42399-020-00529-0

COMORBIDITIES AMONG COVID PATIENTS
1.3
16.9
8.2
3.7
1.9 1.8 1.5
0
2
4
6
8
10
12
14
16
18
CKD HTN DM CVD Stroke HBV COPD
Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM, et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: a
nationwide analysis.
Eur Respir J. 2020;55(5):2000547. https://doi.org/10.1183/13993003.00547-2020

INCIDENCE OF COVID IN HEMODIALYSIS POPULATION
D. Patel, T. Truong and N. Shah et al., COVID-19 Extrapulmonary illness - The Impact of COVID-19 on Nephrology care, Disease-a-
Month, https://doi.org/10.1016/j.disamonth.2020.10105
45

MANAGEMENT OF RENAL INVOLVEMENT
46

MANAGEMENT
Kidney function
Hemodynamics
Fluids
Blood Pressure
Glucose
Anticoagulation
Statins
Antiviral
Steroids
Nephrotoxic
Contrast
Serine inh.TMPSS2 inh ACE2 inh
RAAS inh.
https://doi.org/10.1038/s41581-020-00356-5
Nutrition
Renal
replacement
47

POSSIBLE TREATMENT
MODALITIES FOR
COVID-19 RELATED
KIDNEY INJURY

TREATMENT
TRIALS
Claudia Benedetti 1, Meryl
Waldman2, Gianluigi Zaza3,
Leonardo V. Riella4 and
Paolo Cravedi 1*COVID-19
and the Kidneys: An Update’
REVIEW published: 21 July
2020 doi:
10.3389/fmed.2020.00423

COVID POTENTIAL TREATMENT AND DRUG INTERACTIONS
D. Patel, T. Truong and N. Shah et al., COVID-19 Extrapulmonary illness - The Impact of COVID-19 on Nephrology care, Disease-a-
Month, https://doi.org/10.1016/j.disamonth.2020.101057

THERAPEUTIC OPTIONS
• Ramdesivir: Adenosine analog. Broad spectrum antiviral.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged
novel coronavirus (2019-nCoV) in vitro. Cell Res. (2020) 30:269–71. doi: 10.1038/s41422-020-0282-0.
• Covalescent Plasma: Induce passive immunity.
Shen C,Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically Ill patients with COVID-19 with convalescent
plasma. JAMA. (2020) 323:1582–9. doi: 10.1001/jama.2020.4783.
• Steroids: Dexaméthasone.
Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med. (2006) 3:e343. doi:
10.1371/journal.pmed.0030343
• JAK-STAT. Inh. Bacitinib, Fedatinib & Ruxolitinib.
Cantini F, Niccoli L, Matarrese D, Nicastri E, Stobbione P, Goletti D. Baricitinib therapy in COVID-19: a pilot study on
safety and clinical impact. J Infect. (2020). doi: 10.1016/j.jinf.202 0.04.017. [Epub ahead of print].
51

• IV Immunoglobuline.
Xie Y, Cao S, Dong H, Li Q, Chen E, Zhang W, et al. Effect of regular intravenous immunoglobulin therapy on prognosis of
severe pneumonia in patients with COVID-19. J Infect. (2020). doi: 10.1016/j.jinf.2020.03.044.
• Stem Cell Therapy.
Uccelli A, de Rosbo NK. The immunomodulatory function of mesenchymal stem cells: mode of action and pathways:
mesenchymal stem cells and immunity: an update. Ann N Y Acad Sci. (2015) 1351:114–26. doi: 10.1111/nyas.12815
• IL6 inhibitors: Tocilizumab.
Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The novel coronavirus 2019 epidemic and kidneys. Kidney Int. (2020)
97:824– 8. doi: 10.1016/j.kint.2020.03.001
• Ulinastatin: Serin protein inh. With Anti-inflammatory action.
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J Infect. (2020) 80:607– 13. doi:
10.1016/j.jinf.2020.03.037.
• Anakinra: IL1 Antagonist.
Ma Y, Diao B, Lv X, Zhu J, Liang W, Liu L, et al. COVID-19 in hemodialysis (HD) patients: report from one HD center in Wuhan, China. medRxiv. (2020).
doi: 10.1101/2020.02.24.20027201. [Epub ahead of print].
52
THERAPEUTIC OPTIONS

PREVENTION
53

CONCLUSION
1. The kidney is one of the organs that is affected with COVID-19 virus.
2. Monitoring of the renal function is required among the patients.
3. AKI is the most common type of injury .
4. The cause of the insult is usually Multifactorial.
5. Kidney involvement is one of parameters of the severity.
6. These cases have high mortality.
7. Multiple agent are being under investigation.
54

Kidney involvement in COVID-19

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