Therapeutic Efficacy of Vitamin A in the Treatment of Idiopathic Microscopic Hematuria in Children

AUTHORS

Parsa Yousefichaijan 1 , Masoud Rezagholizamenjany ORCID 2 , * , Fatemeh Dorreh 3 , Hassan Taherahmadi 3 , Mohamad Rafiei 4 , Saeide Abbasi 2 , Ali Arjmand 3 , Zahra Mousavi 2

1 Amir Kabir Hospital, Department of Pediatric Nephrology, Arak University of Medical Sciences, Arak, Iran

2 School of Medicine, Arak University of Medical Sciences, Arak, Iran

3 Department of Pediatric, Arak University of Medical Sciences, Arak, Iran

4 Department of Biostatistics, Arak University of Medical sciences, Arak, Iran

How to Cite: Yousefichaijan P, Rezagholizamenjany M, Dorreh F , Taherahmadi H , Rafiei M , et al. Therapeutic Efficacy of Vitamin A in the Treatment of Idiopathic Microscopic Hematuria in Children, Nephro-Urol Mon. Online ahead of Print ; 13(1):e111783. doi: 10.5812/numonthly.111783.

ARTICLE INFORMATION

Nephro-Urology Monthly: 13 (1); e111783
Published Online: February 16, 2021
Article Type: Research Article
Received: December 1, 2020
Accepted: January 15, 2021
Crossmark
Crossmark
CHECKING
READ FULL TEXT

Abstract

Background: Hematuria is a symptom with a prevalence of 0.5% to 2% in those aged 5 - 12 years. Different factors can influence the severity of hematuria, including vitamin A (as a micronutrient).

Objectives: The current study aimed to evaluate the therapeutic effect of vitamin A on hematuria in children.

Methods: In this clinical trial study, 156 children aged 5 - 12 years with Idiopathic Microscopic Hematuria are studied. Participants were divided into two groups of treatment and control (each with 76 subjects). Those in the treatment group received vitamin A as a pearl of 25000 in 14 days, in addition to the routine treatment. The control group only received routine handling. The basic information of patients were recorded using an author-develop form by the supervisor and intern. Urine samples were collected on 14, 28, and 42 days. Data were analyzed using SPSS. Statistical significance was considered when P-value < 0.05.

Results: There was no significant difference between the two groups concerning gender (P = 0.202), age (P = 0.330), father's education (P = 0.152), mother's education (P = 0.392), father's occupation (P = 0.125), mother's occupation (P = 0.265), and numbers of children in the family (P = 0.209) variables. Hematuria status on days 14 (P = 0.014), 28 (P = 0.001), and 42 after treatment (P = 0.001) was statistically more positive in the vitamin A group, compared to the placebo group. Hence, there was a significant difference between the two groups.

Conclusions: Vitamin A can improve idiopathic microscopic hematuria. Hence, vitamin can be used as an alternative treatment to treat idiopathic hematuria in children.

1. Background

Hematuria is the presence of 5 or more red blood cells (RBCs) per high-power field in 3 of 3 consecutive centrifuged specimens that obtained at least 1 week apart. School-age children account for 3 - 4% of all microscopic hematuria detected in a single urine sample, which falls to 1% or less for two or more positive samples (1-3). This condition may be gross or microscopic, microscopic hematuria is classified into asymptomatic and symptomatic, which can be with or without proteinuria. Asymptomatic isolated microscopic hematuria is the most common presentation of microscopic hematuria. In the present study, we evaluated microscopic idiopathic (4, 5).

Hematuria management contains focusing on weight gain to increase retroperitoneal fat, which in turn leads to decompression of the left renal vein due to a change in the position of the left kidney. However, other methods and drugs may improve this condition (6, 7). From these drugs, we evaluate probably effect of vitamin A in children. Vitamin A is an important micronutrient factor that can influence different systems of the body. In addition, vitamin A, as an unsaturated nutritional organic compound, influences the growth, development, maintenance of the immune system and is an important hormone-like growth factor for epithelial and other cells. Globally, it is estimated that vitamin A deficiency (VAD) affects approximately one-third of children under the age of five (8, 9).

2. Objectives

Health care providers are faced with the challenge of better managing and treating hematuria in children as well as preventing its complications. In addition, vitamin A, as a micronutrient factor, can effectively control hematuria. Therefore, the current study aimed to investigate the effects of vitamin A in controlling hematuria as an alternative therapeutic compound.

3. Methods

3.1. Study Setting

This study was conducted in Amir-Kabir hospital in Arak city.

3.2. Study Population

In this clinical trial study, 156 children aged 5 - 12 years with Idiopathic Microscopic Hematuria are studied. Participants were divided into two groups of treatment and control (each with 76 subjects). The objectives of the study were explained to the parents. For children in the experiment group, parents were explained about the safety of the intervention. After obtaining informed written consent from eligible participants, patients were randomly allocated to two groups of treatment and control, each with 76 subjects. Those in the treatment group received vitamin A as a pearl of 25000 in 14 days, in addition to the routine treatment. The control group only received routine handling without knowledge of vitamin A recipients. Inclusion criteria were being aged 5 to 12 years and definitive diagnosis of microscopic idiopathic hematuria with no reason for hematuria. The exclusion criteria included suffering from renal anomalies, receiving other drugs, identified etiology of hematuria, and unwillingness to participate or continuing the study.

3.3. Ethical Considerations

With performed necessary proceedings, including monitoring and follow-up of continuing hematuria, for all children with microscopic idiopathic hematuria, only we started vitamin A as an alternative therapeutic option in the interventional group. As the recommended vitamin A used in the present study causes no side effects, the current study contains no ethical issue. However, the present study is confirmed by the Ethics Committee of the Arak University of Medical Sciences (code: 93-165-29) and is registered at Iran clinical trial center (code: IRCT 2014091013366N3). Besides, the authors did their best to observe all ethical issues, including plagiarism, data fabrication, and double publication.

3.4. Measurement

The profile of each patient was individually recorded using author-developed forms. Call number of project managers was accessible for patients, in order to remove and prevention of any ambiguity in the study process. After coding all forms, information collected by the supervisor and intern, patients were divided into two groups of treatment and control. Then, urine samples were collected on 14, 28, and 42 days after treatment.

3.5. Statistical Analysis

Data were analyzed by X2 test for qualitative variables and t-test for quantitative variables using SPSS. Statistical significance was considered when P-value < 0.05.

4. Results

The mean age of participants was 7.41 ± 2.16 (control group: 7.52 ± 2.42; treatment group: 7.31 ± 1.90). There was no significant difference between the two groups concerning the age of participants (P = 0.202). Also, 48% of participants were male, and 52% were female. In both groups, the number of males was equal to females (P = 0.330). In addition, other demographic information including father's education (P = 0.152), mother's education (P = 0.392), father's occupation (P = 0.125), mother's occupation (P = 0.265), and numbers of children in the family (P = 0.209) were equal in both groups (Table 1). Hematuria status of children was observed before and after vitamin A consumption. Fourteen days after treatment, hematuria was positive in 90.8% (n = 69) of the treatment group and 100% (n = 76) of the control group (P = 0.014). Also, 28 days after treatment, hematuria was positive in 59.2% of subjects in the treatment group and 94.7% of subjects in the control group (P = 0.001). Forty-two days after treatment, hematuria was positive 40.8% and 75% of subjects in treatment and control groups (Table 2), respectively. Hence, there was a significant difference between the two groups (P = 0.001).

Table 1. Demographic and Epidemiologic Information of Children in Treatment and Control Groups
VariablesGroupsTotalP Value
TreatmentControl
Age0.202
Mean7.317.527.41
SD1.902.422.16
Gender 0.330
Male33(43.4)40(52.6)73(48)
Female 43(56.6)36(47.4)79(52)
Fathers’ education0.152
Diploma and lower45(59.2)37(48.7)82(54.0)
Associate degree2(2.6)6(7.9)8(5.2)
Bachelor20(26.3)28(36.8)48(31.6)
Master degree and higher9(11.9)5(6.6)14(9.2)
Mothers’ education0.392
Diploma and lower42(55.3)41(53.9)83
Associate degree2(2.6)2(2.6)4
Bachelor24(31.6)18(23.7)42
Master degree and higher8(10.5)15(19.8)23
Fathers’ occupation0.125
Employee24(31.6)36(47.4)60
Employer1(1.3)2(2.6)3
Self-employer45(59.2)36(47.4)81
Medical doctor or engineer6(7.9)2(2.6)8
Mothers’ occupation0.265
Employee31(40.8)31(40.8)62
Housewife44(57.9)39(51.3)83
Employer1(1.3)6(7.9)7
Number of children in family0.209
031(40.8)34(44.7)65
132(42.1)20(26.3)52
210(13.2)17(22.4)27
33(3.9)4(5.3)7
4 and higher0(0)1(1.3)1
Table 2. Hematuria Status of Children after Treatment with Vitamin A in Three Periods
Periods of Treatment with Vitamin A
14 Days After Treatment28 Days After Treatment42 Days After Treatment
TreatmentControlTreatmentControlTreatmentControl
Hematuria
Positive69 (90.8)76 (100)45 (59.2)72 (94.7)31 (40.8)57 (75)
Negative7 (9.2)0 (0)31 (40.8)4 (5.3)45 (59.2)19 (25)
P value0.0140.0010.001

5. Discussion

Hematuria is a urological disorder that depends on the nutritional status. Vitamin A is an important micronutrient that can improve several health conditions. In the present study, we evaluated hematuria status in two groups of children, with and without vitamin A consumption, to assess the therapeutic effects of vitamin A on hematuria. Few studies have investigated the effect of vitamin A hematuria. Hence, in the following, the most related studies are discussed. Yesilkaya et al., investigated 88 patients who were treated for 6 months and monitored them monthly by complete urinalysis, found no significant difference between the two groups. However, in the present study, hematuria was lower in the treatment group compared to the control group (10). Solak et al. present a case report study, on the correlation between the level of serum uric acid and vitamin A consumption. They concluded that vitamin A could increase the level of serum uric acid (11). Bass et al. observed clinical manifestations of VAD in infants. They discussed two cases and found severe anemia, hydrocephalus, hematuria, and xerophthalmia as complications of VAD (12).

Ming Yang et al. evaluated the therapeutic effects of vitamin A in measles and found no significant decline in mortality in both groups (13). Richard et al., in a study about the effects of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus-infected children, evaluated the efficacy of vitamin A supplementation. They found that vitamin A supplementation was associated with a decreased mortality rate in HIV-infected children (14). Victor et al. considered VAD as an effective factor in children's survival. A study by Sarah et al. (15) on 141 severely anemic children, which used vitamin A (100000 or 200000 IU depending on the age) as the intervention found that vitamin A could significantly decrease erythropoietin concentration and inflammation. In addition, they found that vitamin A could mobilize iron from stores and stimulated the production of new erythrocytes (16). Seal et al., in a study, evaluated VAD in the long term and concluded that poor nutrition and public health programs contribute to vitamin deficiency (17). The current study has limitations, including parental noncompliance, that after explaining to them about the importance of this issue, they were convinced. However, because of few clinical studies about the therapeutic effect of vitamin A in hematuria and unclear mechanism, further studies are needed to provide valid evidence. In addition, the authors recommend further studies with a larger sample size and higher doses of vitamin A and in longer durations on hematuria.

5.1. Conclusions

This study demonstrated that vitamin A could reduce the hematuria status of children. So it can be used for treating children with idiopathic microscopic hematuria.

Acknowledgements

Footnotes

References

  • 1.

    Mladenov BS, Mariyanovski V, Hadzhiyska V. Macroscopic hematuria in patients on anticoagulation therapy. Cent European J Urol. 2015;68(3):330-3. doi: 10.5173/ceju.2015.658. [PubMed: 26568876]. [PubMed Central: PMC4643714].

  • 2.

    Elias K, Svatek RS, Gupta S, Ho R, Lotan Y. High-risk patients with hematuria are not evaluated according to guideline recommendations. Cancer. 2010;116(12):2954-9. doi: 10.1002/cncr.25048. [PubMed: 20564400]. [PubMed Central: PMC2940122].

  • 3.

    Rezagholi-Zamnjany M, Yousefichaijan P. An overview on peritoneal dialysis. Annals of Research in Dialysis. 2016;1.

  • 4.

    Deltas C, Pierides A, Voskarides K. The role of molecular genetics in diagnosing familial hematuria(s). Pediatr Nephrol. 2012;27(8):1221-31. doi: 10.1007/s00467-011-1935-5. [PubMed: 21688191]. [PubMed Central: PMC3382641].

  • 5.

    Yousefichaijan P, Rezagholizamenjany M, Rafiei F, Taherahmadi H, Rafiei M. The relationship between blood biomarkers level and the prognosis of nephrotic syndrome in the children. Int. J. Pediatr. 2016;4(9):3489-97.

  • 6.

    Margulis V, Sagalowsky AI. Assessment of hematuria. Med Clin North Am. 2011;95(1):153-9. doi: 10.1016/j.mcna.2010.08.028. [PubMed: 21095418].

  • 7.

    Yousefichaijan P, Rezagholizamenjany M, Dorreh F, Rafiei M, Taherahmadi H, Niyakan Z, et al. Comparison of development indicators, according to ages and stages questionnaires in children with pollakiuria compared to healthy children. Nephro-Urology Monthly. 2017;9(4). doi: 10.5812/numonthly.45898.

  • 8.

    Tanumihardjo SA. Vitamin A: biomarkers of nutrition for development. Am J Clin Nutr. 2011;94(2):658S-65S. doi: 10.3945/ajcn.110.005777. [PubMed: 21715511]. [PubMed Central: PMC3142734].

  • 9.

    Grune T, Lietz G, Palou A, Ross AC, Stahl W, Tang G, et al. Beta-carotene is an important vitamin A source for humans. J Nutr. 2010;140(12):2268S-85S. doi: 10.3945/jn.109.119024. [PubMed: 20980645]. [PubMed Central: PMC3139236].

  • 10.

    Yesilkaya B, Alli N, Artuz RF, Ulu E, Kartal D, Cinar SL. The frequency of hematuria in acne vulgaris patients during isotretinoin treatment. Cutan Ocul Toxicol. 2017;36(1):74-6. doi: 10.3109/15569527.2016.1155595. [PubMed: 26938860].

  • 11.

    Solak B, Erdem T, Solak Y. Isotretinoin use for acne vulgaris is associated with increased serum uric acid levels. J Dermatolog Treat. 2017;28(1):82-5. doi: 10.1080/09546634.2016.1178374. [PubMed: 27151312].

  • 12.

    Bass MH, Caplan J. Vitamin A deficiency in infancy. Int. J. Pediatr. 1955;47(6):690-5. doi: 10.1016/s0022-3476(55)80097-2.

  • 13.

    Yang HM, Mao M, Wan C. Vitamin A for treating measles in children. Cochrane Database Syst. Rev. 2005;(4).

  • 14.

    Semba RD, Ndugwa C, Perry RT, Clark TD, Jackson JB, Melikian G, et al. Effect of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus-infected children in Uganda: A controlled clinical trial. Nutrition. 2005;21(1):25-31. doi: 10.1016/j.nut.2004.10.004. [PubMed: 15661475].

  • 15.

    Aguayo VM, Baker SK. Vitamin A deficiency and child survival in sub-Saharan Africa: a reappraisal of challenges and opportunities. Food Nutr Bull. 2005;26(4):348-55. doi: 10.1177/156482650502600404. [PubMed: 16465981].

  • 16.

    Cusick SE, Tielsch JM, Ramsan M, Jape JK, Sazawal S, Black RE, et al. Short-term effects of vitamin A and antimalarial treatment on erythropoiesis in severely anemic Zanzibari preschool children. Am J Clin Nutr. 2005;82(2):406-12. doi: 10.1093/ajcn.82.2.406. [PubMed: 16087986].

  • 17.

    Seal AJ, Creeke PI, Mirghani Z, Abdalla F, McBurney RP, Pratt LS, et al. Iron and vitamin A deficiency in long-term African refugees. J Nutr. 2005;135(4):808-13. doi: 10.1093/jn/135.4.808. [PubMed: 15795439].

  • Copyright © 2021, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
    COMMENTS

    LEAVE A COMMENT HERE: