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==Collateral circulation==
==Patients on Hemodialysis before the pandemic==
===Overview===
===Overview===
Collateral circulation is a network of blood vessels that provide a bypass or alternate conduit of blood flow in tissue. These specialized blood vessels are naturally present in tissue and undergo adaptive growth and development in response to ischemia. The main function of collateral vessels is to provide an alternate pathway for nutrient and oxygen supply in the case of stenosis or obstruction of the main artery.
The Covid-19 infection has high mortality among dialysis patients as compared to normal individuals. One of the factors for increased mortality for dialysis patients as compared to the general population due to COVID-19 infection is the increased age of the patients. Adequate measures should be taken to prevent the spread of COVID 19 infection in dialysis patients.
===Classification===
Rentrop devised a grading system to assess the filling of collateral arteries. <ref name="pmid3156171">{{cite journal| author=Rentrop KP, Cohen M, Blanke H, Phillips RA| title=Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. | journal=J Am Coll Cardiol | year= 1985 | volume= 5 | issue= 3 | pages= 587-92 | pmid=3156171 | doi=10.1016/s0735-1097(85)80380-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3156171  }} </ref>
*Grade 0: no visible filling of any collateral channels
*Grade I: collateral filling of branches of the vessel to be dilated without any dye reaching the epicardial segment of that vessel
*Grade 2: partial collateral filling of the epicardial segment of the vessel being dilated
*Grade 3: complete collateral filling of the vessel being dilated.
Collateral circulation can be classified on the basis of size. <ref name="pmid12665484">{{cite journal| author=Werner GS, Ferrari M, Heinke S, Kuethe F, Surber R, Richartz BM | display-authors=etal| title=Angiographic assessment of collateral connections in comparison with invasively determined collateral function in chronic coronary occlusions. | journal=Circulation | year= 2003 | volume= 107 | issue= 15 | pages= 1972-7 | pmid=12665484 | doi=10.1161/01.CIR.0000061953.72662.3A | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12665484  }} </ref>
*CC0: no continuous connection between donor and recipient artery.
*CC1: continuous, threadlike connection. The diameters of collaterals are ≤0.3 mm.
*CC2: continuous, small side branch-like size throughout its course. The estimated diameter of CC2 ≥0.4 mm.
===Pathophysiology===
===Pathophysiology===
There are four stages in the development of mature collateral blood vessels from collateral microvasculature.  
Patients on hemodialysis have a mild clinical course of COVID 19 infection. It could be due to multiple reasons.
*Phase 1 lasts for approximately two days following stenosis or obstruction of the main artery by an embolus. The stenosis of the main artery results in diversion and increase blood flow through small collateral blood vessels. This increases the circumferential diameter of small collateral vessels and augments sheer stress on its walls. The increased stress on the vessel wall causes activation of the Nf-kb gene. <ref name="pmid23091063">{{cite journal| author=Tirziu D, Jaba IM, Yu P, Larrivée B, Coon BG, Cristofaro B | display-authors=etal| title=Endothelial nuclear factor-κB-dependent regulation of arteriogenesis and branching. | journal=Circulation | year= 2012 | volume= 126 | issue= 22 | pages= 2589-600 | pmid=23091063 | doi=10.1161/CIRCULATIONAHA.112.119321 | pmc=3514045 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23091063 }} </ref> There is an increased expression of adhesion molecules on endothelial cells which attracts monocytes at the site of the blocked blood vessels. The monocytes from the bone marrow start accumulating at the extracellular site of collateral vessel formation. The main distinguishing features of this phase is an increase in the permeability of the blood vessel and the transformation of smooth muscle and endothelial cells in the proliferative phase.  
*Patients with chronic kidney disease or end-stage renal disease have low immunity. The low immunity results in low-intensity cytokine storm in response to viral antigens. The patients on maintenance hemodialysis rarely present with a full-blown clinical picture of pneumonia.<ref name="pmid32434211">{{cite journal| author=Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z | display-authors=etal| title=Viral and host factors related to the clinical outcome of COVID-19. | journal=Nature | year= 2020 | volume= | issue= | pages= | pmid=32434211 | doi=10.1038/s41586-020-2355-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32434211 }} </ref>
*In the second phase, there is an infiltration of monocytes followed by the release of various cytokines including matrix metallopeptidases, tumor necrosis factor-alpha, platelet-derived growth factors, and vascular endothelial growth factors. There is controlled digestion of extracellular matrix and internal elastic lamina. The cytokines also promote increased proliferation of vascular smooth muscles and endothelial cells.
Hypercoagulation plays an important role in aggravating the disease. Hypercoagulation initiates the coagulation cascade resulting in disseminated intravascular coagulation (DIC). DIC results in organ dysfunction and high mortality in COVID 19 infection. Anticoagulants administered during hemodialysis inhibit coagulation cascade preventing hypercoagulation and DIC.<ref name="pmid32073213">{{cite journal| author=Tang N, Li D, Wang X, Sun Z| title=Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. | journal=J Thromb Haemost | year= 2020 | volume= 18 | issue= 4 | pages= 844-847 | pmid=32073213 | doi=10.1111/jth.14768 | pmc=7166509 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32073213 }} </ref>
*In phase three, there is a maturation of smooth muscle cells in uniform circular layer with increase synthesis of elastin and collagen and formation of the cell to cell contacts. This results in the formation of a large-caliber blood vessel.
In a study done at a hemodialysis center at Renmin Hospital in Wuhan, 37 out of a total of 230 patients were infected with covid 19 infections in one month. Four members of the health care staff were also infected. The peripheral blood examination of the covid 19 infected hemodialysis patients had reduced levels of killer T cells, helper T cells, Natural killer cells, and lower level of inflammatory cytokines as compared to non-dialysis infected patients.<ref name="pmid02.24.20027201">{{cite journal| author=Bose KS, Sarma RH| title=Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution. | journal=Biochem Biophys Res Commun | year= 1975 | volume= 66 | issue= 4 | pages= 1173-9 | pmid=02.24.20027201 | doi=10.1016/0006-291x(75)90482-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2 }} </ref>
*In phase four, there is dissolution and reduction of small collateral vessels in which there is less blood flow. The collateral vessels which have more flow of blood enlarges and forms mature blood vessels while smaller collateral vessels regress due to decreased flow of blood. <ref name="pmid10782885">{{cite journal| author=Scholz D, Ito W, Fleming I, Deindl E, Sauer A, Wiesnet M | display-authors=etal| title=Ultrastructure and molecular histology of rabbit hind-limb collateral artery growth (arteriogenesis). | journal=Virchows Arch | year= 2000 | volume= 436 | issue= 3 | pages= 257-70 | pmid=10782885 | doi=10.1007/s004280050039 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10782885 }} </ref>
===Epidemiology and Demographics===
 
*Patients on maintenance hemodialysis and end-stage kidney disease have low immunity and multiple co-morbidities. They are at an increased risk of contracting the covid-19 infection. A case series of 5,700 patients with covid-19 infection was done in 12 hospitals under the Northwell Health system in New York. It showed a prevalence of 5% chronic kidney disease and 3.5% end-stage renal disease in hospitalized covid-19 patients.<ref name="pmid32320003">{{cite journal| author=Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW | display-authors=etal| title=Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. | journal=JAMA | year= 2020 | volume= | issue= | pages= | pmid=32320003 | doi=10.1001/jama.2020.6775 | pmc=7177629 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32320003 }} </ref>
===Blood flow in Collaterals===
* A research study done in Japan showed a higher mortality 16.2% (16/99) in dialysis patients as compared to the general population 5.3% (874/16,532). The average age of patients on dialysis was 70 to 90 years while of the general population was 20 to 60 years.<ref name="pmid32506762">{{cite journal| author=Kikuchi K, Nangaku M, Ryuzaki M, Yamakawa T, Hanafusa N, Sakai K | display-authors=etal| title=COVID-19 in dialysis patients in Japan: Current status and guidance on preventive measures. | journal=Ther Apher Dial | year= 2020 | volume= | issue= | pages= | pmid=32506762 | doi=10.1111/1744-9987.13531 | pmc=7301044 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32506762 }} </ref>
Collateral blood vessels are communicating vessels that bridge two main arteries. There is bidirectional blood flow in it with the minimal flow in the midpoint of the vessel. This results in low resistance blood flow with reduced incidence for thrombosis. <ref name="pmid25012127">{{cite journal| author=Faber JE, Chilian WM, Deindl E, van Royen N, Simons M| title=A brief etymology of the collateral circulation. | journal=Arterioscler Thromb Vasc Biol | year= 2014 | volume= 34 | issue= 9 | pages= 1854-9 | pmid=25012127 | doi=10.1161/ATVBAHA.114.303929 | pmc=4140974 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25012127 }} </ref>
*A study was done in 208 acute care hospitals in the UK. The total patients studied were 20,133. It showed chronic kidney disease was one of the most common co-morbidity in hospitalized covid-19 patients present in 16% of patients.<ref name="pmid32444460">{{cite journal| author=Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L | display-authors=etal| title=Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. | journal=BMJ | year= 2020 | volume= 369 | issue= | pages= m1985 | pmid=32444460 | doi=10.1136/bmj.m1985 | pmc=7243036 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32444460  }} </ref>
===Benefits of Collateral Circulation===
*Clinical research was done by Alberici et al. at four outpatient dialysis facilities in Italy showed high overall mortality of 29% in dialysis patients.<ref name="pmid32437768">{{cite journal| author=Alberici F, Delbarba E, Manenti C, Econimo L, Valerio F, Pola A | display-authors=etal| title=A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection. | journal=Kidney Int | year= 2020 | volume= 98 | issue= 1 | pages= 20-26 | pmid=32437768 | doi=10.1016/j.kint.2020.04.030 | pmc=7206428 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32437768 }} </ref>
Circle of Willis is a primary collateral vessel in the brain. Anterior and posterior communicating artery serves as a connection between the internal carotid and posterior cerebral artery. It provides blood flow if there is obstruction at any site at the circle of Willis. Collateral circulation is a protective adaptive response to restore blood flow in the hypoxic region due to stenosed blood vessels. A slowly developing plaque gives sufficient time for the development and maturation of collateral blood vessels. A study showed an increase in angiographic collaterals from 66% to 75% three to six hours after the onset of symptoms. There was also a reduced incidence of cardiogenic shock in patients with collateral vessels which further proved the protective role of collateral circulation. <ref name="pmid12001540">{{cite journal| author=Waldecker B, Waas W, Haberbosch W, Voss R, Wiecha J, Tillmanns H| title=[Prevalence and significance of coronary collateral circulation in patients with acute myocardial infarct]. | journal=Z Kardiol | year= 2002 | volume= 91 | issue= 3 | pages= 243-8 | pmid=12001540 | doi=10.1007/s003920200018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12001540 }} </ref>
==References==
===Drawbacks of Collateral Circulation===
====Coronary steal syndrome====
In situations of increased blood flow to heart i.e. administration of vasodilators like nitrates or exercise, the resistance to blood flow to collaterals is less compared to the obstructed artery. This results in enhanced blood flow through collateral vessels and further compromises blood flow through the stenosed artery. The supply of oxygen and nutrients to the hypoxic area of the heart is worsened exacerbating angina clinical symptoms. <ref name="pmid9416891">{{cite journal| author=Seiler C, Fleisch M, Meier B| title=Direct intracoronary evidence of collateral steal in humans. | journal=Circulation | year= 1997 | volume= 96 | issue= 12 | pages= 4261-7 | pmid=9416891 | doi=10.1161/01.cir.96.12.4261 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9416891 }} </ref>
====Re-stenosis of the main artery====
In a percutaneous intervention at the site of a coronary stent, there is a competition of anterograde blood flow through the main coronary artery and retrograde flow via a stenosed artery. This results in resistance to blood flow, with a slow velocity of blood flow. It causes a cascade of reactions including platelet aggregation, endothelial proliferation, and thrombus formation which results in restenosis of the vessel. <ref name="pmidhttps://doi.org/10.1186/1741-7015-10-62">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=https://doi.org/10.1186/1741-7015-10-62 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10 }} </ref>
===References===
{{Reflist}}
{{Reflist}}

Revision as of 13:02, 25 June 2020

Associate Editor(s)-in-Chief: Mydah Sajid, MD[1]

Patients on Hemodialysis before the pandemic

Overview

The Covid-19 infection has high mortality among dialysis patients as compared to normal individuals. One of the factors for increased mortality for dialysis patients as compared to the general population due to COVID-19 infection is the increased age of the patients. Adequate measures should be taken to prevent the spread of COVID 19 infection in dialysis patients.

Pathophysiology

Patients on hemodialysis have a mild clinical course of COVID 19 infection. It could be due to multiple reasons.

  • Patients with chronic kidney disease or end-stage renal disease have low immunity. The low immunity results in low-intensity cytokine storm in response to viral antigens. The patients on maintenance hemodialysis rarely present with a full-blown clinical picture of pneumonia.[1]

Hypercoagulation plays an important role in aggravating the disease. Hypercoagulation initiates the coagulation cascade resulting in disseminated intravascular coagulation (DIC). DIC results in organ dysfunction and high mortality in COVID 19 infection. Anticoagulants administered during hemodialysis inhibit coagulation cascade preventing hypercoagulation and DIC.[2] In a study done at a hemodialysis center at Renmin Hospital in Wuhan, 37 out of a total of 230 patients were infected with covid 19 infections in one month. Four members of the health care staff were also infected. The peripheral blood examination of the covid 19 infected hemodialysis patients had reduced levels of killer T cells, helper T cells, Natural killer cells, and lower level of inflammatory cytokines as compared to non-dialysis infected patients.[3]

Epidemiology and Demographics

  • Patients on maintenance hemodialysis and end-stage kidney disease have low immunity and multiple co-morbidities. They are at an increased risk of contracting the covid-19 infection. A case series of 5,700 patients with covid-19 infection was done in 12 hospitals under the Northwell Health system in New York. It showed a prevalence of 5% chronic kidney disease and 3.5% end-stage renal disease in hospitalized covid-19 patients.[4]
  • A research study done in Japan showed a higher mortality 16.2% (16/99) in dialysis patients as compared to the general population 5.3% (874/16,532). The average age of patients on dialysis was 70 to 90 years while of the general population was 20 to 60 years.[5]
  • A study was done in 208 acute care hospitals in the UK. The total patients studied were 20,133. It showed chronic kidney disease was one of the most common co-morbidity in hospitalized covid-19 patients present in 16% of patients.[6]
  • Clinical research was done by Alberici et al. at four outpatient dialysis facilities in Italy showed high overall mortality of 29% in dialysis patients.[7]

References

  1. ↑ Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z; et al. (2020). "Viral and host factors related to the clinical outcome of COVID-19". Nature. doi:10.1038/s41586-020-2355-0. PMID 32434211 Check |pmid= value (help).
  2. ↑ Tang N, Li D, Wang X, Sun Z (2020). "Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia". J Thromb Haemost. 18 (4): 844–847. doi:10.1111/jth.14768. PMC 7166509 Check |pmc= value (help). PMID 32073213 Check |pmid= value (help).
  3. ↑ Bose KS, Sarma RH (1975). "Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution". Biochem Biophys Res Commun. 66 (4): 1173–9. doi:10.1016/0006-291x(75)90482-9. PMID 02.24.20027201 Check |pmid= value (help).
  4. ↑ 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).
  5. ↑ Kikuchi K, Nangaku M, Ryuzaki M, Yamakawa T, Hanafusa N, Sakai K; et al. (2020). "COVID-19 in dialysis patients in Japan: Current status and guidance on preventive measures". Ther Apher Dial. doi:10.1111/1744-9987.13531. PMC 7301044 Check |pmc= value (help). PMID 32506762 Check |pmid= value (help).
  6. ↑ Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L; et al. (2020). "Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study". BMJ. 369: m1985. doi:10.1136/bmj.m1985. PMC 7243036 Check |pmc= value (help). PMID 32444460 Check |pmid= value (help).
  7. ↑ Alberici F, Delbarba E, Manenti C, Econimo L, Valerio F, Pola A; et al. (2020). "A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection". Kidney Int. 98 (1): 20–26. doi:10.1016/j.kint.2020.04.030. PMC 7206428 Check |pmc= value (help). PMID 32437768 Check |pmid= value (help).
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