Correlation Between Asymptomatic Persistent Microscopic Hematuria and Reflux Nephropathy

authors:

avatar Yasaman Mirmoeini 1 , avatar Parsa Yousefichaijan ORCID 2 , avatar Manijeh Kahbazi 2 , avatar Pezhman Parsa 1 , avatar Ali Khosrobeigi 1 , *

Students Research Committee, Arak University of Medical Sciences, Arak, Iran
Clinical Research Development Center, Amirkabir Hospital, Arak University of Medical Sciences, Arak, Iran

how to cite: Mirmoeini Y, Yousefichaijan P, Kahbazi M, Parsa P, Khosrobeigi A. Correlation Between Asymptomatic Persistent Microscopic Hematuria and Reflux Nephropathy. Nephro-Urol Mon. 2019;11(1):e86920. https://doi.org/10.5812/numonthly.86920.

Abstract

Background:

Asymptomatic persistent microscopic hematuria is one of the common symptoms in children with kidney disorders and may be one of the most important signs of glomerular damage. Vesicoureteral reflux (VUR) also is one of the common disorders in children that causes scarring, secondary lesions, and subsequent problems, including hypertension, chronic renal failure, and end-stage renal disease (ESRD).

Methods:

This is a case-control study that was conducted on 100 children with VUR (50 children with reflux nephropathy as the case group and 50 children without reflux nephropathy as the control group) at Amirkabir Hospital, Arak, Iran. The frequency of asymptomatic persistent microscopic hematuria was evaluated in both groups of children.

Results:

The mean age of the children in the case group was 2.93 ± 2.30 and in the control group was 3.46 ± 2.68 years old (P = 0.268). Thirty-four percent of the case group and 14% of the control group were males (P = 0.019). In addition, 22% of children in the case group and only 8% of children in the control group showed asymptomatic persistent microscopic hematuria (P = 0.049).

Conclusions:

According to the results of this study, it seems that the asymptomatic persistent microscopic hematuria is more in children with reflux nephropathy.

1. Background

Asymptomatic persistent microscopic hematuria is one of the common symptoms in children with kidney disorders. Its prevalence is 1 to 2 percent (1, 2). There is a long list of the causes related to this condition most of which are benign conditions (3, 4). However, hematuria may be one of the most important signs of glomerular damage, especially if hematuria is persistent. The American Academy of Pediatrics recommends screening for urine analysis at the age of entrance to the school and during adolescence (5). Despite the high prevalence of this disorder, the exact nature of this condition is not precisely defined (6, 7).

The incidence of vesicoureteral reflux (VUR) is 1% in asymptomatic children and 25% to 40% in symptomatic children and shows itself with urinary tract infection (8, 9). Urinary tract infections are one of the most important factors associated with vesicoureteral reflux that causing scarring, secondary lesions, and subsequent problems, including hypertension, chronic renal failure, and end-stage renal disease (ESRD) (10, 11). It has been observed that 30% - 49% of the patients have parenchymal scars at the time of diagnosis (12, 13).

2. Objectives

In the current study, we have investigated the association between asymptomatic persistent microscopic hematuria and reflux nephropathy.

3. Methods

This is a case-control study that was conducted on 100 children with VUR at Amirkabir Hospital, Arak, Iran. Fifty children with reflux nephropathy as the case group and 50 children without reflux nephropathy as the control group enrolled in this study. The patients were enrolled in the study based on inclusion and exclusion criteria.

Diagnosis of reflux was done based on VCUG and diagnosis of nephropathy was done based on DMSA criteria. The grading of the reflux was done according to the VCUG and by the pediatric nephrologist (14-16).

For all children in the study, urine analysis was performed in 3 consecutive times and cases with asymptomatic persistent microscopic hematuria were recorded.

Asymptomatic persistent microscopic hematuria was defined as repeated microscopic hematuria without any symptoms in 3 consecutive urine analysis (17). Finally, the data were collected through a checklist and the results of diagnostic tests were analyzed by SPSS software version 23.

Inclusion criteria consisted of children without any age limitation. In addition, both genders and any grade of VUR entered the study.

Exclusion criteria were comprised of children who had nephropathy due to congenital kidney disease. The children who had gross hematuria and asymptomatic hematuria were excluded from the study.

This study was approved by the Ethics Committee of Arak University of Medical Sciences with ethics code IR.ARAKMU.REC.1395.296. Written informed consent was obtained from all children’s parents.

Eventually, collected data was statistically analyzed via the SPSS-23 software, using independent sample t test, and chi-square tests.

4. Results

The mean age of the total children was 3.20 ± 2.50 and 24% of them were boys and 76% of them were girls. More detailed information on their age and gender are summarized in Table 1. Also, the Gestational factors of the children are summarized in Table 2.

Table 1.

General Characteristics of the Studied Childrena

ParameterGroupP Value
CaseControl
Age, y (mean ± SD)2.93 ± 2.303.46 ± 2.680.268
Gender, No. (%)0.019*
Male17 (34)7 (14)
Female33 (66)43 (86)
Table 2.

Gestational Factors of the Studied Childrena

ParameterGroupP Value
CaseControl
Birth weight, g0.009*
< 10003 (6)0 (0)
1000 - 15003 (6)1 (2)
1500 - 250026 (52)15 (30)
2500 - 400017 (34)34 (68)
> 40001 (2)0 (0)
Gestational age0.001*
Pre-term31 (62)14 (28)
Term19 (38)33 (66)
Post-term0 (0)3 (6)
Feeding0.420
Breast-feeding39 (78)34 (68)
Milk powder10 (20)13 (26)
Both1 (2)3 (6)
Parity0.139
First33 (66)24 (48)
Second9 (18)17 (34)
3rd and more8 (16)9 (18)
Mother’s age at pregnancy, (mean ± SD)25.68 ± 4.6527.56 ± 4.780.049*

In the results of this study, it was observed that among children with reflux nephropathy, 22% of children had asymptomatic persistent microscopic hematuria while among children without reflux nephropathy, 8% of them had asymptomatic persistent microscopic hematuria (P = 0.049). Imaging and laboratory factors of children are summarized in Table 3.

Table 3.

Imaging and Laboratory Factor of Childrena

ParameterGroupP Value
CaseControl
Age at diagnose time, y (mean ± SD)1.27 ± 1.921.44 ± 1.840.687
Positive family history of VUR1 (2)2 (4)0.513
VUR grading0.001
I1 (2)12 (24)
II11 (22)19 (38)
III19 (38)18 (36)
IV12 (24)0 (0)
V7 (14)1 (2)
VUR side0.819
Right15 (30)14 (28)
Left12 (24)10 (20)
Both side23 (46)26 (52)
Asymptomatic persistent microscopic hematuria11 (22)4 (8)0.049

5. Discussion

The recent study aimed to investigate the association between asymptomatic persistent microscopic hematuria and reflux nephropathy among children with VUR.

The results of this study showed that boys were significantly more likely to have reflux nephropathy than girls (reflux nephropathy were seen in 70.83% of the boys and 43.42% of the girls). Wennerstrom et al. reported that renal scar was seen in 86% of the males and 30% of the females (18). It is observed that the results of their study are similar to our study. This confirms the role of the gender in the development of reflux nephropathy.

The results of this study showed that low birth weight and pre-term labor (less than 37 weeks) had a significant effect on the incidence of reflux nephropathy in children with VUR. In another study that was done by Yousefichaijan et al. it was reported that pre-term labor had a relationship with reflux nephropathy in the children (19).

It was also observed in this study that high-grade VUR had a relationship with the incidence of reflux nephropathy. Shaikh et al. also reported that the higher grades of VUR are related to the incidence of reflux nephropathy (20).

In this study, we observed that asymptomatic persistent microscopic hematuria is more in children with reflux nephropathy. To the best of our knowledge, this is the first study that has studied the asymptomatic persistent microscopic hematuria in children with reflux nephropathy.

In this study, we encountered some limitations. First, the population of the experimental and control group was small. Second, some of the parents did not cooperate in the study. Third, Lack of prior research studies on the topic, thus it is recommended that future studies should be done with fewer restricting factors in this area.

5.1. Conclusions

Regarding the higher prevalence of reflux nephropathy in boys and pre-term infants, the attention should be paid to pre-term infants and boys with VUR and their follow-up with higher precision to prevent the development of nephropathy-related reflux. Also, regarding the higher frequency of asymptomatic persistent microscopic hematuria in children with reflux nephropathy, it is possible to improve the prognosis of the patients with VUR by taking this hematuria more seriously in patients with VUR and detecting and treating them at the right time.

However, this study requires more investigations. Similar studies with a higher proportion of samples at different centers are recommended in order to help these patients.

Acknowledgements

References

  • 1.

    Güven S, Gökçe İ, Denİz NÇ, Altuntaş Ü, Yildiz N, Alpay H. Clinical and histopathological features of asymptomatic persistent microscopic hematuria in children. Turk J Med Sci. 2016;46(6):1707-11. [PubMed ID: 28081313]. https://doi.org/10.3906/sag-1511-10.

  • 2.

    Feld LG, Waz WR, Perez LM, Joseph DB. Hematuria. An integrated medical and surgical approach. Pediatr Clin North Am. 1997;44(5):1191-210. [PubMed ID: 9326958]. https://doi.org/10.1016/S0031-3955(05)70553-8.

  • 3.

    Feng CY, Xia YH, Wang WJ, Xia J, Fu HD, Wang X, et al. Persistent asymptomatic isolated hematuria in children: Clinical and histopathological features and prognosis. World J Pediatr. 2013;9(2):163-8. [PubMed ID: 23677832]. https://doi.org/10.1007/s12519-013-0415-3.

  • 4.

    Feld LG, Meyers KE, Kaplan BS, Stapleton FB. Limited evaluation of microscopic hematuria in pediatrics. Pediatrics. 1998;102(4). E42. [PubMed ID: 9755279].

  • 5.

    Meyers KE. Evaluation of hematuria in children. Urol Clin North Am. 2004;31(3):559-73. x. [PubMed ID: 15313065]. https://doi.org/10.1016/j.ucl.2004.04.015.

  • 6.

    Bergstein JM. Hematuria, proteinuria, and urinary tract infections. Pediatr Clin North Am. 1982;29(1):55-66. [PubMed ID: 7058075]. https://doi.org/10.1016/S0031-3955(16)34107-4.

  • 7.

    Lee JH, Choi HW, Lee YJ, Park YS. Causes and outcomes of asymptomatic gross haematuria in children. Nephrology (Carlton). 2014;19(2):101-6. [PubMed ID: 24237720]. https://doi.org/10.1111/nep.12181.

  • 8.

    Merguerian PA, Jamal MA, Agarwal SK, McLorie GA, Bagli DJ, Shuckett B, et al. Utility of SPECT DMSA renal scanning in the evaluation of children with primary vesicoureteral reflux. Urology. 1999;53(5):1024-8. [PubMed ID: 10223500]. https://doi.org/10.1016/S0090-4295(99)00049-7.

  • 9.

    Mir S, Ertan P, Ozkayin N. Risk factors for renal scarring in children with primary vesicoureteral reflux disease. Saudi J Kidney Dis Transpl. 2013;24(1):54-9. [PubMed ID: 23354192]. https://doi.org/10.4103/1319-2442.106241.

  • 10.

    Shiraishi K, Yoshino K, Watanabe M, Matsuyama H, Tanikaze S. Risk factors for breakthrough infection in children with primary vesicoureteral reflux. J Urol. 2010;183(4):1527-31. [PubMed ID: 20172558]. https://doi.org/10.1016/j.juro.2009.12.039.

  • 11.

    Yousefichaijan P, Ghandi Y, Alavi M, Rafiei M, Khosrobeigi A, Arjmand A, et al. Evaluation of blood pressure in children with hydronephrosis in comparison with healthy children. Nephro-Urol Mon. 2018;10(4). https://doi.org/10.5812/numonthly.68998.

  • 12.

    Duzova A, Ozen S. Vesicoureteral reflux in childhood. Saudi J Kidney Dis Transpl. 2003;14(3):290-5. [PubMed ID: 17657100].

  • 13.

    Yousefichaijan P, Dorreh F, Rafiei M, Nouri Kopaei S, Naziri M. [Effective Factors in Growth and development in children and infants with Vesicoureteral reflux (VUR)]. Pract Clin Psychol. 2014;54(5):690-696. Persian. https://doi.org/10.22038/MJMS.2014.3408.

  • 14.

    Tekgul S, Riedmiller H, Hoebeke P, Kocvara R, Nijman RJ, Radmayr C, et al. EAU guidelines on vesicoureteral reflux in children. Eur Urol. 2012;62(3):534-42. [PubMed ID: 22698573]. https://doi.org/10.1016/j.eururo.2012.05.059.

  • 15.

    Skoog SJ, Peters CA, Arant BS Jr, Copp HL, Elder JS, Hudson RG, et al. Pediatric vesicoureteral reflux guidelines panel summary report: Clinical practice guidelines for screening siblings of children with vesicoureteral reflux and neonates/infants with prenatal hydronephrosis. J Urol. 2010;184(3):1145-51. [PubMed ID: 20650494]. https://doi.org/10.1016/j.juro.2010.05.066.

  • 16.

    Bocquet N, Sergent Alaoui A, Jais JP, Gajdos V, Guigonis V, Lacour B, et al. Randomized trial of oral versus sequential IV/oral antibiotic for acute pyelonephritis in children. Pediatrics. 2012;129(2):e269-75. [PubMed ID: 22291112]. https://doi.org/10.1542/peds.2011-0814.

  • 17.

    Chandar J, Gomez-Marin O, del Pozo R, Sanders L, Montane B, Abitbol C, et al. Role of routine urinalysis in asymptomatic pediatric patients. Clin Pediatr (Phila). 2005;44(1):43-8. [PubMed ID: 15678230]. https://doi.org/10.1177/000992280504400105.

  • 18.

    Wennerstrom M, Hansson S, Jodal U, Stokland E. Primary and acquired renal scarring in boys and girls with urinary tract infection. J Pediatr. 2000;136(1):30-4. [PubMed ID: 10636970]. https://doi.org/10.1016/S0022-3476(00)90045-3.

  • 19.

    Yousefichaijan P, Safi F, Rafiei M, Taherahmadi H, Fatahibayat GA, Naziri M. Prenatal risk factors for infantile reflux nephropathy. J Pediatri Nephrol. 2015;3(4):135-8. https://doi.org/10.22037/j%20ped%20nephrology.v3i4.8302.

  • 20.

    Shaikh N, Ewing AL, Bhatnagar S, Hoberman A. Risk of renal scarring in children with a first urinary tract infection: A systematic review. Pediatrics. 2010;126(6):1084-91. [PubMed ID: 21059720]. https://doi.org/10.1542/peds.2010-0685.