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

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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.
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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

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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 : September | Volume : 16 | Issue : 9 | Page : SC04 - SC06 Full Version

Urine Spot Protein Creatinine Ratio as a Predictor of Disease Severity and Adverse Outcome in Children with Dengue: A Cross-sectional Study


Published: September 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/56751.16882
Edinta Joseph, Senthilmurugan Sivaraman, Kamalanathan Padmanabhan, Selvakumar Shanmugam, Lakshmi Velmurugan

1. Resident, Department of Paediatrics, Institute of Child Health, Chennai, Tamil Nadu, India. 2. Assistant Professor, Department of Paediatrics, Institute of Child Health, Chennai, Tamil Nadu, India. 3. Assistant Professor, Department of Paediatrics, Institute of Child Health, Chennai, Tamil Nadu, India. 4. Assistant Professor, Department of Paediatrics, Institute of Child Health, Chennai, Tamil Nadu, India. 5. Professor, Department of Paediatrics, Institute of Child Health, Chennai, Tamil Nadu, India.

Correspondence Address :
Dr. Selvakumar Shanmugam,
15/8 MIG Senganthal Flats, Ayapakkam, Chennai-77, Tamil Nadu, India.
E-mail: drlionselva@gmail.com

Abstract

Introduction: Dengue is a viral infection with different presentations, hence predicting the disease severity at admission is essential to triage patients needing meticulous monitoring. In severe dengue there is increase of urinary protein clearance due to the increase in systemic vascular permeability. Simple urine protein excretion screening test could guide the triage and monitor the patients with suspected dengue infection.

Aim: To evaluate the urine spot Protein Creatinine Ratio (PCR) as a tool in predicting the disease severity and adverse outcome in children with dengue.

Materials and Methods: The present cross-sectional study was conducted in Institute of Child Health, Egmore, Tamil Nadu, India, from October 2021 to December 2021. All children aged 1 month to 12 years presenting with symptoms of fever, thrombocytopenia (less than 1, 50, 000 /μL) with or without dengue non structural protein component (NS1)/ Immunoglobulin M Enzyme Linked Immunosorbent Assay (ELISA) positivity were recruited for the study. Study parameters included were demographic factors, severity of dengue classification based on National Vector Borne Disease Control Programme (NVBDCP) guidelines, urine spot PCR. The UPCR (urine protein creatinine ratio) was compared between dengue and non dengue cases and within the different categories of dengue cases. Chi-square was used for comparing proportions.

Results: Among 150 children enrolled in present study, 134 (89.3%) were dengue positive, 16 (10.7%) were non dengue. Most predominant age group involved was 6-9 years followed by 3 to 6 years. Among 134 children with dengue, 98 (73.1%) had high UPCR and among 16 non dengue children, 2 (12.5%) had high UPCR which was statistically significant (p<0.0001). Mean spot UPCR was 0.32±0.12 in mild dengue, 0.77±0.40 in moderate dengue and 1.68±1.67 in severe dengue which was statistically significant (p<0.0001). Children with severe dengue had higher PCR values in comparison to mild and moderate dengue.

Conclusion: There was a statistically significant association of urine spot PCR with severity of dengue and this simple test can be used for triaging and monitoring children with suspected dengue.

Keywords

Fever, Thrombocytopenia, Urine protein clearance, Viral infection

Dengue is an arboviral infection affecting especially humans and represents a major global public health issue. Its incidence is increasing steadily and, in many places, like in developing countries it has become an endemic problem (1). Dengue mainly affects the paediatric age group and is associated with considerable morbidity and mortality (2). Mortality in dengue is due to abnormal capillary permeability, abnormalities of haemostasis and in severe cases dengue shock syndrome. The annual incidence rate of dengue is 49.5 per 1000 child years among children with fever >3 days (3). The risk factors for development of severe disease are poorly characterised and consequently uncomplicated cases are frequently hospitalised for observation during the critical phase for capillary leakage syndrome, thereby making the situation cumbersome to both patients and treating physician. Therefore, improvements in early diagnosis and risk prediction for severe disease are urgently needed. This would enable appropriate and early intervention. Ideally, the test should be cheap, fast, easy to perform, highly sensitive and specific (2).

The presence of microalbuminuria has been postulated as potential risk predictor for severe dengue (4),(5), but there is little information on the magnitude, timing of onset, or evolution of urinary protein excretion during infection. Also 24-hour urinary albumin measurements are time consuming to perform. Both measurement of spot urine protein estimation as well as urine protein to creatinine ratio is a less cumbersome and are more practical method. Measurement of spot urine protein to creatinine ratio is much easier approach and hence acceptable method (6).

The spot PCR is obtained by the ratio between urine protein excretion (measured by 24-hour protein excretion or spot urine sample) and creatinine excretion, expressed as mg/mmol or mg/mmol. Spot PCR represents a practical alternative to the 24-hour urine collection because it is easier to obtain and is not influenced by variations in water intake or diuresis (6). While it has been studied in adult dengue cases (1), its usefulness as a predictor tool has not been well tested in paediatric population. Hence, present study emphasise at simple laboratory investigation of UPCR as a predictor of disease severity of dengue infection in children who are very crucial for monitoring and management of children at risk especially during dengue epidemics. Hence this study was planned to evaluate the UPCR as a tool in predicting the disease severity and adverse outcome in children with dengue.

Material and Methods

The present cross-sectional study was conducted in a tertiary hospital, Institute of Child Health, Egmore, Madras Medical College, Tamil Nadu, India, from October 2021 to December 2021. Study was proceeded after obtaining consent from Institutional Ethics Committee (IEC) (No17112021) and written informed consent from parents.

Inclusion criteria: All children aged between 1 month to 12 years, presenting with symptoms of fever, thrombocytopenia (<1,50,000/μL) with or without dengue NS1/IgM positivity were recruited for the study.

Exclusion criteria: Children who developed fever >48 hour after admission or following surgery were excluded from the study.

Initially 134 children turned to be dengue positive based on dengue NS1 /IgM ELISA positivity and 16 were dengue negative. Positivity or negativity was based only on dengue NS1/IgM reports.

Sample size: A total of 150 neonates, who presented in the department with fever within the study period from October 2021 to December 2021 were enrolled in the study by purposive sampling.

Study parameters included in the study were demographic factors including age and sex, laboratory parameters such as urine protein and creatinine were evaluated. Urine spot protein was detected and quantified by pyrogallol red method. Creatinine by modified Jaffe’s method. Urine spot protein creatinine ratio is calculated by dividing the level of protein (mg/dL) in a spot urine by the creatinine level (mg/dL) (7).

UPCR was done after admission. In children with age <2 years, UPCR value of <0.5 and in subjects with age ?2 years a value <0.2 is considered as normal) (8). Small amount of protein in the urine is considered acceptable, proteinuria is defined as protein excretion greater than 100 mg/m2 per day or more than 0.2 mg protein/mg creatinine (also known as a urine protein/creatinine ratio ([U p/c] >0.2) on a single spot urine collection; in neonates and infants, higher amount of protein excretion, up to 300 mg/m2 is permissible (9). Urine creatinine (24-hour urine collection) values can range from 500 to 2000 mg/day (4,420 to 17,680 mmol/day) (10),(11). The UPCR was compared between dengue and non dengue cases based on dengue NS1/IgM positivity. After dengue NS1/IgM positivity further UPCR was assessed in mild, moderate and severe categories of dengue cases. Severity of dengue classification was based on NVBDCP guidelines (12) and World Health Organisation (WHO) 1997 classification scheme, which comprises three categories–Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS)– based on clinical signs was used to classify the degree of severity of the disease (13).

Statistical Analysis

Analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 20.0 (SPSS Inc,Chicago, IL). Descriptive data were presented as mean±SD or percentages. Chi-square was used for comparing proportions. The p-value of <0.05 was considered statistically significant.

Results

Among 150 children admitted with fever and thrombocytopenia 134 (89.3%) were dengue serology positive, 16 (10.7%) were cases of fever with thrombocytopenia who were dengue negative. Maximum patients 52 (38.8%) in dengue positive group were aged between 6-9 years followed by the 47 (35.1%) children in age group 3-6 years and 21 (15.7%) in age group 1-3 years. In dengue negative group maximum children 6 (37.5%) aged between 6-9 years followed by 5 (31.2%) in 3-6 years. In dengue positive group there were 73 (54.5%) males and 61 (45.5%) females while in dengue negative group 11 (68.7%) were male and 5 (31.3%) were female (Table/Fig 1).

Among 134 children with dengue, 98 (73.1%) had high urine PCR and among the 16 non dengue children, 2 (12.5%) had high UPCR which was statistically significant (p<0.0001) (Table/Fig 2).

Among 134 dengue children, 93 children with mild dengue had mean spot PCR 0.32± 0.12, 33 children with moderate dengue had mean spot PCR 0.77±0.40, 8 children with severe dengue had mean urine spot PCR 1.68±1.67 which showed a statistical significance of (p-value=0.0017) (Table/Fig 3).

16 cases were in age group <2 years and 118 cases in ?2 years and urine spot PCR was high in age group ?2 years with 93 (78.8%) and thus children ?2 years were more likely to have high UPCR (Table/Fig 4).

Out of the 134 dengue positive children male: female ratio was 1.2:1. Among 73 male, 50(42.4%) children and among 61 female, 43(36.4%) children had high urine PCR. There was no statistical association between gender and UPCR (Table/Fig 5). Out of 134 dengue children studied only one child died.

Discussion

Dengue fever is now a widely distributed viral illness causing varied range of presentation and carries its own mortality rate. Mortality in dengue is due to abnormal capillary permeability, abnormalities of haemostasis and in severe cases, dengue shock syndrome. In the paediatric age group with severe dengue, outcome depends on the high suspicion level and scrutiny in monitoring the children for complications. This study was undertaken to study the significance of UPCR as an early predictor of severity of illness in children with dengue fever. This study revealed a statistically significant increased incidence of proteinuria among children with dengue in comparison to children with non dengue thrombocytopenia. These findings were similar to the observation of Graham RR et al., (14). The study revealed that among the children with dengue positivity, the degree of proteinuria was high in severe dengue children than when compared with mild and moderate dengue cases which was statistically significant (p<0.001) which concludes that there exists a positive association between the degree of proteinuria and the disease severity. Similar findings were consistent with study done by Vasanwalla FF et al., patients with DHF had significantly higher median peak proteinuria levels (0.56 versus 0.08 g/day; p<0.001) compared to dengue fever (15).

The study revealed a high UPCR value in children more than 2 years when compared with infants which was statistically significant (p<0.0001) which reveals that children >2 years may manifest severe dengue illness whereas in study done by Datla P et al., age did not show any association with UPCR values (1). The comparison of degree of proteinuria among male and female gender did not show any statistical significance which concludes that severity of dengue doesn’t have a gender predisposition according to the study which was coincident with the study done by Datla P et al., (1). Higher incidence in males was noted in the study done by Wali JP et al., (16)

Since out of 134 dengue children studied only one child died, the association of degree of proteinuria with adverse outcome like mortality cannot be commented on unlike study done by Datla P et al., where the association of raised UPCR with mortality showed a positive correlation and was statistically significant (1). This study establishes a simple laboratory investigation of urine spot PCR as a predictor of disease severity of dengue infection in children which is very crucial for monitoring and management of children at risk especially during dengue epidemics.

Limitation(s)

The limitation of present study was that it did not take into account the day of illness when the proteinuria was assessed and also the day of peak proteinuria in dengue illness. Since out of 134 dengue children studied only one child died, the association of degree of urine spot PCR with adverse outcome like mortality cannot be commented.

Conclusion

Given the increase in occurrence of dengue fever in children and its associated complications, the need for early predictors of disease severity is important for easy and apt monitoring of children at risk. Urine spot protein creatinine ratio assessment is easy to perform and inexpensive test. There was a statistically significant association of urine spot PCR with severity of dengue and this simple test can be used for triaging and monitoring children with suspected dengue. This study found higher urine spot protein creatinine ratio to be a non invasive marker in predicting the severity of dengue in children with dengue fever. Urine spot protein creatinine ratio in children with dengue fever can be used as a screening test in predicting the severity of disease at admission.

References

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Datla P, Raju U, Reddy P, Srikrishna S, Deshmukh T. Study establishing correlation of proteinuria and urine protein/creatinine ratio with disease severity in paediatric dengue fever. Int J Med Paedia Oncol. 2017:3(1):24-28.
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Dengue: Guidelines for diagnosis, treatment, prevention and control. World Health Organization. Special Programme for Research and Training in Tropical Diseases, World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. New ed. Geneva: TDR: World Health Organization; 2009. Accessed date: September 17, 2021.
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Chen Y, Maguire T, Hileman RE, Fromm JR, Esko JD, Linhardt RJ, et al. Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat Med. 1997;3(8):866-71. [crossref] [PubMed]
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Lumpaopong A, Kaewplang P, Watanaveeradej V, Thirakhupt P, Chamnanvanakij S, Srisuwan K. Electrolyte disturbances and abnormal urine analysis in children with dengue infection. Southeast Asian J Trop Med Public Health. 2010,41:7276.
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Bakker AJ. Detection of microalbuminuria. Receiver operating characteristic curve analysis favours albumin-to creatinine ratio over albumin concentration. Diabetes Care. 1999;22:307-13. [crossref] [PubMed]
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Kaminska J. Dymicka-Piekarska I, Tomaszewska J, Matowicka-Karna J, Koper-Lenkiewicz OM Diagnostic utility of protein to creatinine ratio (P/C ratio) in spot urine sample with in routine clinical practice. Crit Rev Clin Lab Sci. 2020;57(5):345-64. [crossref] [PubMed]
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Woroniecki R. Proteinuria: Signs and symptoms in paediatrics. American Academy of Paediatrics. 2015;709-17. [crossref]
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Viteri B, Reid-Adam JH. Hematuria and proteinuria in children. Pediatr Rev. 2018;39(12):573-87. [crossref] [PubMed]
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DOI and Others

DOI: 10.7860/JCDR/2022/56751.16882

Date of Submission: Mar 30, 2022
Date of Peer Review: May 19, 2022
Date of Acceptance: Jul 25, 2022
Date of Publishing: Sep 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: Apr 06, 2022
• Manual Googling: Jul 23, 2022
• iThenticate Software: Aug 31, 2022 (25%)

ETYMOLOGY: Author Origin

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