Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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On Aug 2018




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Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
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Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : November | Volume : 16 | Issue : 11 | Page : OC07 - OC10 Full Version

Effect of ACEi and ARBs vs Non ACEi/ARBs in Hypertension with Respect to Renal Outcomes in COVID-19 Infection: A Retrospective Cohort Study


Published: November 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/59592.17015
S Ravitej, HA Krishnamurthy

1. Senior Resident, Department of General Medicine, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India. 2. Associate Professor, Department of General Medicine, Mysore Medical College and Research Institute, Mysuru, Karnataka, India.

Correspondence Address :
Dr. HA Krishnamurthy,
EWS 44, 1 Stage, 2 Cross, Kuvempu Nagara, Mysuru-570023, Karnataka, India.
E-mail: kmha79@gmail.com

Abstract

Introduction: The Acute Kidney Injury (AKI) is one of the most common complications following Coronavirus Disease-2019 (COVID-19) infection. The presence of high density of Angiotensin Converting Enzyme 2 (ACE2) receptors in type 2 alveolar epithelial cells, vascular endothelium and proximal convoluted tubules explains the involvement of systemic organs in COVID-19 infection. Systemic hypertension is one of the most common co-morbidities associated with COVID-19 infection with high mortality, especially in patients of severe disease with AKI. The antihypertensives, which work by Renin Angiotensin Aldosterone System (RAAS) inhibition like ACE inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs) can upregulate the enzyme ACE2, so, the incidence and risk of AKI in hypertensive patients, who have COVID-19 infection is common.

Aim: To determine the risk of developing AKI and mortality in hypertensive patients, with COVID-19 infection, on ACEi or ARBs as compared to non ACEi and non ARBs.

Materials and Methods: This was a retrospective cohort study conducted on 116 admitted hypertensive patients, who were positive for COVID-19 infection from the month of April 2021 to September 2021. The study patients were divided into two groups- group A and group B. The group A was on ACEi or ARBs and group B was on non ACEi/ARBs. The patients baseline history, clinical examination and the blood investigations like Renal Function Test (RFT), Liver Function Test (LFT), Echocardiography (ECG), Chest X-ray, 2 Dimensional-ECHO (2D-ECHO), Arterial Blood Gases (ABG) were done for all the patients. The normal Blood Pressure (BP) was less than 140/90 mmHg. The normal creatinine was 0.6 to 1.5 mg/dL and normal urea was 19 to 45 mg/dL. The RFT was repeated on every day of hospital stay duration. The patients were followed-up for one month from day of starting the study. The parameters were recorded, assessed on day 7th and day 30th, of the study. All parameters were compared between the final outcome of the patients by 30th day of study and the class of antihypertensives used to control hypertension. The Pearson’s Chi-square test, Fisher’s-Exact and one-way Analysis of Variance (ANOVA) were used for testing the significance of relationship and outcome between group A and group B study patients.

Results: The mean duration of hypertension in both the groups was 7.6 years. In group A 53 (45.7%) were on ACEi and ARBs, in group B, 63 (54.3%) were on non ACEi/ARBs. In the group A, the serum creatinine of more than >1.5 mg/dL at 7th day of study was found in 28 (52.8%) patients and on 30th day, it was found in 8 (15.09%) patients (p-value=0.065). Again in the group A, blood urea of more than 45 mg/dL on 7th day of study was found in 30 (56.6%) patients and on 30th day it was found in 9 (16.98%) patients (p-value=0.064). In group B, the serum creatinine >1.5 mg/dL on day 7th of study was found in 36 (57.14%) patients and on day 30th, it was in 24 (38.09%) patients (p-value=0.061). Again in group B, the blood urea of >45 mg/dL on day 7th was found in 35 (55.55%) patients and on day 30th it was found in 16 (25.39%) patients (p-value=0.074). Of the patients on group A (ACEi and ARBs) 28 (52.83%) were on supplemental oxygen, 12 (22.6%) were on Non Invasive Ventilation (NIV), one was intubated and 12 (22.6%) did not require oxygen (p-value=0.727). Of the patients on group B (non ACEi/ARBs) 33 (52.4%) were on supplemental oxygen, 12 (19.04%) were on NIV, 5 (7.93%) were intubated and 13 (20.63%) did not require oxygen. In the patients of group A, 35 (66.03%) were recovered and 18 (33.96%) died, in the group B 40 (63.49%) cases were recovered, while 23 (36.50%) died (p-value=0.781).

Conclusion: There was no significant and demonstrable association between specific groups of antihypertensives with renal outcomes and mortality in hypertensive patients with COVID-19 infection. By above observations, the present study concluded that, there is no specific role of ACE2 receptors in renal outcome and mortality in hypertension with COVID-19 infection.

Keywords

Acute kidney injury, Angiotensin receptor blockers, Renin angiotensin aldosterone system inhibitors, Systemic hypertension

The AKI is one of the most common complications following COVID-19 infection. The extent of AKI can range from the presence of proteinuria, haematuria and can go to the level of requiring renal replacement therapy. The COVID-19-associated AKI (COVID-19 AKI) is having high mortality and acts as an independent risk factor for all-cause in-hospital mortality in patients with COVID-19 infection (1). Systemic hypertension is one of the most common co-morbidities associated with COVID-19 infection with high mortality, especially in patients with severe disease with AKI. The presence of high density of ACE2 receptors expression in type 2 alveolar epithelial cells, vascular endothelium and proximal convoluted tubules explains, the involvement of systemic organs in COVID-19 infection. The hypertension is a major risk factor for renal and cardiovascular diseases (2). The antihypertensives used in the age group of less than 55 years are mainly ACEi and ARBs inview of high sympathetic activity and hyper-reninaemia with hypertension. But in the age group of more than 55 years, the main antihypertensives used are hypertension. But in Blockers (CCBs) and Thiazide diuretics (3),(4). The antihypertensives which work by RAAS inhibition like ACE inhibitors and ARBs can upregulate the enzyme ACE2, so the incidence and risk of facilitating COVID-19 infection with systemic organ injury and AKI in hypertensive patients is very common (5). So, the present study was done to determine the risk of developing AKI and mortality in hypertensive patients with COVID-19 infection on ACEi or ARBs, as compared to non ACEi and ARBs.

Material and Methods

This was a retrospective cohort study conducted on 116 COVID-19 infected hypertensive patients admitted at Krishna Rajendra Hospital, Mysuru, Karnataka, India from April 2021 to September 2021.The Institutional Ethical Clearance (IEC) for the study was taken from Ethical committee, Mysore Medical College and Research Institute, Mysuru, Karnataka, India [ECREG:ECR/134/Inst/KA/2013/RR-19].

Inclusion criteria:

• Age more than 18 years.
• Hypertensive patients, who were tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by Polymerase Chain Reaction (PCR) technique.

Exclusion criteria:

• Known case of Chronic Kidney Disease (CKD).
• Derangement in kidney function at the time of admission.
• Those on nephrotoxic drugs.
• Type 2 diabetes mellitrus
• Connective tissue diseases.
• Autoimmune diseases.
• Patients on corticosteroids.
• Any other chronic drugs intake in any form.

Study Procedure

Blood pressure of more than 140/90 mmHg is considered as systemic hypertension (3),(4). The serum creatinine of 0.4 to 1.5 mg/dL and urea of 19 to 45 mg/dL was taken as the normal levels in the current study. The serum creatinine of above 1.5 mg/dL and the blood urea of above 45 mg/dL was considered to be having AKI (2),(6). The patients were divided into two groups. The group A was on ACEi or ARBs, the group B wason non ACEi/ARBs. The patients’ history were recorded, clinical examination and the investigations, such as complete blood count, Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), RFT, LFT, ECG, Chest X-ray, 2D-ECHO and ABG were done. The RFT was repeated on every day of the hospital stay. The patients were followed-up for one month from the day of starting the study. The parameters were recorded and assessed on day 7th and day 30th of the study. All the parameters were compared between the final outcome of the patient by 30th day of the study and the class of antihypertensives used to control hypertension. The patients’ data was collected after obtaining the informed consent. The study proforma was used to collect the data of cases, such as age, gender, hypertension duration, antihypertensive medication details, co-morbidities, mode of oxygen/pressure support delivery, duration of ward/ICU stay, renal outcome and mortality.

Statistical Analysis

The data was analysed by using Statistical Package for the Social Sciences (SPSS) software version 22.0. The Pearson’s Chi-square test, Fisher’s-Exact and ANOVA was used for testing the significance of relationship between group A (ACE inhibitors and ARBs) with the group B (non ACEi/non ARBs) drugs of systemic hypertension subjects with COVID-19 infection.

The association between variables was done by using the Chi-square test. The unpaired t-test and Pearson’s correlation formula was used for the assessment of qualitative and quantitative variables. The ANOVA test was used for testing the significance between the both groups. A p-value of <0.05 was considered statistically significant.

Results

Total 53 (45.7%) patients were on group A (ACEi and ARBs) drugs and 63 (54.3%) on group B (non ACEi /ARBs) drugs. The mean duration of hypertension in group A was 7.1 years, and in group B, was 6.8 years. The antihypertensive drugs used in the group A patients were Enalapril in 14 (26.41%), Ramipril in 16 (30.18%), Telmisartan in 20 (37.73%) and Olmesartan in 3 (5.6%) patients. The group B patients were on Amlodipine in 36 (57.14%), Amlodipine and Hydrochlorothiazide in 21 (33.3%) and Prozosin in 6 (9.5%) patients (Table/Fig 1).

In both the groups, day 7th blood urea and serum creatinine were elevated as compared to the day 30th values (not significant) (Table/Fig 2).

The association between the groups of drugs used to manage hypertension with the respiratory outcome was similar (p-value=0.727) (Table/Fig 3). The recovery and death pattern was similar in both the groups (Table/Fig 4).

Discussion

The present study was done to look for the outcome with RAAS (ACEi and ARBs) inhibitors in COVID-19 infection with hypertension. In the present study, there was no significant difference in renal outcome and mortality between the drugs used to treat hypertension in COVID-19.The mechanisms postulated for the pathogenesis of AKI in COVID-19 are the direct injury to endothelium by viral tropism, induction of coagulopathy and complement activation. The indirect injury to kidney occurs through organ crosstalk, dehydration, and exposure to nephrotoxins (7),(8),(9).

The mean age of the study population was 60 years in group A and 61.5 years in group B patients, with a male preponderance of 55.2%.which was in comparison with the study by Lanzani C et al., where the average age was 67 years with 75% of male preponderance. This reflects the higher prevalence of hypertension in the elderly age group and also the higher risk of hospitalisation if they contract COVID-19 infection (10). In the present study, the renal parameters, such as serum creatinine and blood urea were significantly elevated in both the groups in the first week of the infection. This was similar to the study by Angel-Korman A et al., (11). AKI was common among those with COVID-19 infection and on antihypersive treatment with ACEi and ARBs. AKI was due to the elevation of ACE2 receptor with their effect on vascular endothelium (7). The study by Khruleva Y et al., also reported that, the AKI was common in this group of patients (12).

In the present study, by the end of 30th day, the renal parameters started to come down as compared to the first week, inspite of continuing ACEi and ARBs for hypertension. This shows that the renal failure in COVID-19 infection is not completely associated with ACE2 receptors hyperfunctioning (7).

The ACE2 receptors level is higher in patients with cardiac dysfunction, hypertension, and renal abnormality on ACEi and ARBs therapy (13),(14),(15). In the present study, the mean duration of hospital stay in both the groups was 18 days, which was similar to the study by Lanzani C et al., who reported an average hospital stay of 10 days (10). This indicates that the COVID-19 virus infected patients would have significant systemic organs dysfunction, so such patients needs prolonged hospital admission (14),(16). In the present study, the respiratory outcomes were similar to the study by Peng M et al., where the same drugs (ACEi and ARBs or non ACEi/ARBs) were used to treat hypertension with COVID-19 infection. This shows that, there wouldn’t be any association between drugs used to treat hypertension and respiratory outcomes in COVID-19 infection (17). In the present study, the number of deaths happened between both groups were same and it was not skewed towards any specific antihypertensives group. This was in comparison with the study by An J et al., who also reported no significant correlation between the mortality and any class of drugs, used to treat hypertension in COVID-19 infection (18). The RAAS inhibitors and all other class of antihypertensives, used to treat hypertension in COVID-19 infection for short duration, alone were not associated with poor renal outcomes (19),(20),(21). The ACE2 receptors alone cannot be linked with any significant systemic organ dysfunction in COVID-19 infection (22),(23),(24).

Limitation(s)

This sample size was limited. The follow-up period was limited to one month.

Conclusion

The use of any class of antihypertensive drugs (ACEi and ARBs or non ACEi/ARBs) in hypertensive patients with COVID-19 infection alone, cannot be associated with adverse renal outcomes and mortality. From the above observations, the present study suggests that, there is no specific role of ACE2 enzyme level with the renal outcomes and mortality in COVID-19 infection.

References

1.
Nadim MK, Forni LG, Mehta RL, Connor MJ, Liu KD, Ostermann M, et al. COVID-19-associated acute kidney injury: Consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup. Nat Rev Physiol. 2020;16(12):747-64. [crossref] [PubMed]
2.
Zaim S, Chong JH, Sankaranarayanan V, Harky A. COVID-19 and multiorgan response. Current Problems Cardiology. 2020;45(8):100618. [crossref] [PubMed]
3.
Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JF, et al. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): Summary. BMJ. 2004;328(7440):634-40. [crossref] [PubMed]
4.
NICE Guideline (NG136): Hypertension in Adults: Diagnosis and Management. British and Irish Hypertension Society. Published March 2022.
5.
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DOI and Others

DOI: 10.7860/JCDR/2022/59592.17015

Date of Submission: Aug 09, 2022
Date of Peer Review: Aug 20, 2022
Date of Acceptance: Sep 19, 2022
Date of Publishing: Nov 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Aug 10, 2022
• Manual Googling: Sep 16, 2022
• iThenticate Software: Sep 17, 2022 (6%)

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