| Abstract|| |
Proteinuria is one of the common manifestations of kidney disease that has a serious impact on the progressive deterioration of kidney function. In developed countries, school screening for asymptomatic proteinuria is routinely performed, especially in adolescent students, to detect early stage of chronic kidney disease. This study aimed to find out the prevalence of asymptomatic persistent proteinuria in adolescent students. This was a multi-assessment study. Screening for proteinuria was conducted on five junior high schools across Jakarta, Indonesia, in April-June 2015. Healthy students aged 12–14 years whose parents provided informed consent were selected randomly. Urine collections were performed thrice. We used dipstick tests and protein-to-creatinine ratio to measure protein in the urine. From 536 students, 485 were eligible and recruited for this study. They were more female and well-nourished students. Hypertension constituted 12.9% of students. Proteinuria accounted for 7.42%. Transient, orthostatic, and persistent proteinuria were found in 5.77%, 1.03%, and 0.62% of students, respectively. The prevalence of asymptomatic persistent proteinuria among adolescent students in Jakarta is higher than that in other populations in Asia. Consequently, a routine screening to detect proteinuria should be considered in Indonesia to detect chronic kidney disease in children.
|How to cite this article:|
Trihono PP, Wulandari N, Supriyatno B. Asymptomatic proteinuria in Indonesian adolescent students. Saudi J Kidney Dis Transpl 2019;30:694-700
|How to cite this URL:|
Trihono PP, Wulandari N, Supriyatno B. Asymptomatic proteinuria in Indonesian adolescent students. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Jul 23];30:694-700. Available from: http://www.sjkdt.org/text.asp?2019/30/3/694/261347
| Introduction|| |
Globally, the prevalence of proteinuria was 5%–15%.,,,,,, Children with persistent protei-nuria have higher mortality risk from kidney failure. A mass-screening urinalysis becomes a useful tool to identify asymptomatic progressive kidney condition in children. Japan, Korea, and Taiwan have implemented a mass-screening program to detect proteinuria for school-aged children and the rate of progressive kidney diseases decreased in these countries.
Indonesia has not yet implemented this screening pathway in children. The data regarding the prevalence of proteinuria in Indonesian adolescents are still limited. This study aimed to find out the prevalence of persistent protei-nuria in asymptomatic adolescent students.
| Subjects and Methods|| |
We used cluster random sampling method to obtain representative samples of Jakarta’s population. We selected five junior high schools (junior high school of 216, 74, 115, 111, and 140) from different municipalities (Central, East, South, West, and North) in Jakarta. Healthy students aged 12–14 years whose parents provided informed consent were selected randomly.
We excluded students with known kidney disease; those having symptoms of kidney diseases such as dysuria, edema, and oliguria; females who were going through their messes at the time of recruitment, and those on medications such as acetazolamide, cephalosporin, bicarbonate, and Vitamin C 24 h before urine collection. In addition, students whose urine dipstick revealed either urinary pH <5 or >7.5, urinary specific gravity <1.010 or >1.030, and positive leukocyte esterase or nitrite were excluded from the study.
The data regarding the proportion of adolescents with asymptomatic proteinuria are not available. Therefore, we estimated that the minimum population prevalence was 50%, and the minimum sample size should be 385, with the allowable error being controlled within a range of 0.5%. Considering a 10% dropout rate, the final sample size required was 428.
The Research Ethics committee of the Faculty of Medicine of Universitas Indonesia approved this multi-assessment study. On enrollment, students were asked to have their questionnaire fulfilled by parents/guardian and examined for signs or symptoms related to kidney disorders, age, weight, height, nutritional status, and blood pressure after informed consent was given. The questionnaire included the family history of kidney diseases, consumption of specific medication, signs or symptoms related to kidney disorders, and birth weight.
Weight was recorded using spring scale with 0.5 kg accuracy. Height was recorded with an accuracy of 0.1 cm using the Seca stadiometer. Nutritional status was based on clinical examination and anthropometry plotted on NCHS/ CDC 2000 curve and then classified into: (1) obese: weight/height >120% and body mass index (BMI) according to age and gender above percentile 95; (2) overweight: weight/ height 110%–120% and BMI according to age and gender between percentile 85-95; (3) normal: weight/height 90%–110%, (4) underweight: weight/height 70%–90%; and (5) severely underweight: weight/height <70%. Blood pressure was measured on the upper right arm using a digital sphygmomanometer with 10 cm-width cuff. Blood pressure was recorded as the average of three measurements with 5 min interval. Hypertension was calculated according to the Fourth Report on The Diagnostic: Evaluation and Treatment of High Blood Pressure in Children and Adolescents 2004.
Urine screening was performed thrice. Students were asked to collect the midstream urine ( first 1–2 mL of urine was discarded) with a minimum volume of 20 mL in the urine sample pot. The first urine screening was a spot urine test at school. We used a dipstick test to measure proteinuria. The reagent pads on the dipstick were immersed completely in the urine for 30 s and the results were interpreted. The intensity of color changed from yellow to blue and it is correlated with the amount of protein in the urine: trace ± = 10 mg/dL; +1 = 30 mg/dL; +2 = 100 mg/dL; +3 = 300 mg/dL; and +4 = 1,000 mg/dL. If no protein was detected with this test, the strip remained yellow. The result of at least +1 was considered positive.
Students with positive result proceeded to second and third screening in the following 23 weeks. On the second screening, students brought the urine sample pot to their home. They were instructed to void just before sleeping and remain supine throughout the night. A first-morning void was obtained (with minimum mobility). Then, the urine specimen was carried to school within 2-h after collection; otherwise, the specimen was stored in a 4°C container to preserve quality. 5 mL urine was separated and tested using dipstick; if dipstick showed a positive result, the remaining urine was stored in 4°C and transported to Prodia Lab for urinary protein/creatinine ratio (Upr/Cr) measurement. The cutoff for high Upc/Cr was 0.2 mg/mg. The third urine specimen was obtained during break time on the same day and measured with a dipstick. We classified the results into transient (only the first specimen was positive), orthostatic (the first and the third specimen were positive), and persistent (all specimens were positive) proteinuria.
| Statistical Analysis|| |
The study results were managed electronically using IBM SPSS Statistics for Windows, Version 22.0. (IBM Corp., Armonk, NY, USA).
| Results|| |
A total of 536 students were screened and 51 of them were excluded because the urine dipstick revealed that urinary pH was <5 or >7.5; specific gravity was <1.010 or >1.030; or positive leukocyte esterase or nitrite.
The female-to-male ratio was 1.15:1. The majority of students were well nourished. The median for body weight, body height, and BMI were 48 kg (range, 27–98 kg), 156 cm (range, 133–182 cm), and 19.71 kg/m2 (range, kg/m2), respectively. The median of birth weight was 3200 g (range, 1250–5100 g), and 31 students did not report because the parents cannot recall. Fifty-six (11.5%) students had Stage I hypertension and seven (1.4%) had Stage II hypertension. The median systolic blood pressure was 110 mm Hg (range, 72180 mm Hg), and the mean diastolic blood pressure was 71.11 mm Hg (SD, 9.537 mm Hg). Thirty (6.2%) students had a family history of kidney disease [Table 1].
Prevalence of proteinuria
In the first urine screening, 36 (7.42%) students showed positive results. In the subsequent tests, sevens students remained positive and three of them had Upr/Cr >0.2 mg/mg. Three students with Upr/Cr >0.2 mg/mg remained positive in the third dipstick test.
The prevalence of asymptomatic proteinuria in initial screening was 7.42% (n = 36). The prevalence of transient, orthostatic, and persistent proteinuria was 5.77% (n = 28), 1.03% (n = 5), and 0.62% (n =3), respectively [Figure 1].
[Table 2] shows the students’ characteristics with persistent proteinuria. Two girls and one boy had persistent proteinuria. The degree of proteinuria varied among students. One student had hematuria and Stage I hypertension in all three tests. Another student was underweight. Two out of three students refused to have a further examination at Dr. Cipto Mangunkusumo Hospital. A student referred to the hospital to do repeated urinalysis, and it showed a normal result.
| Discussion|| |
This study is the first study investigating asymptomatic proteinuria among adolescent students in Jakarta. The urine screening was performed thrice to obtain clinically significant proteinuria. According to the initial screening, the prevalence of asymptomatic proteinuria was 7.4% in students aged 12–14 years. The prevalence of transient, orthostatic, and persistent proteinuria among adolescent students was 5.77%, 1.44%, and 0.62%, respectively. This finding was similar with other studies, particularly in Asian countries, with positive protein in single urine test found in up to 10%, and decreased to 0.01% in repeated urinalysis tests.,,,
In a study in Japan, the prevalence of persistent proteinuria was 0.37% among children aged 12–14 years. Studies in Korea and Taiwan found the prevalence of persistent proteinuria to be 21.7% (aged 6–18 years) and 4.9% (aged 6–15 years). In Nepal, a study reported the prevalence of 0.31% in 5–15-year old students. A study in Egypt found that 0.5% of students aged 6–13 years had persistent proteinuria. In Malaysia, a similar study found that 0.12% of children aged 7–12 years had persistent proteinuria. The prevalence of persistent proteinuria was higher in Korean and Taiwanese students because the studies only involved students diagnosed with kidney disease., These discrepancies might be due to the difference of ethnic background and etiology in each population.
The prevalence of orthostatic proteinuria in our study was lower than the previous study (1.03% vs. 2%–5%). This result could be due to the fact that our study only involved teenagers aged 12–14 years.
In our study, two out of three students with persistent proteinuria were female, which was similar to the previous study. However, a study by Lin et al reported that asymptomatic proteinuria was more prevalent in boys. This might be due to different proportions of gender involved in the study.
The prevalence of asymptomatic persistent proteinuria among adolescents was lower compared to our previous study on elementary school students (1.1%). A study from Japan showed the opposite result with a higher prevalence in adolescents. It is because our previous study only included children aged 7–14 years.
One of three students with asymptomatic persistent proteinuria in our study had Stage I hypertension. A study by Parakh et al reported that among clinical parameters they investigated (body weight, body height, upper arm circumference, and blood pressure), only diastolic blood pressure was found to be abnormal in the patients with urine disorder. Hypertension might be a cause or a consequence of kidney disease. In Singapore, Yap et al used multivariate analysis to identify the predictors for proteinuria in school-aged children, and they found that underweight, hypertension, and lack of exercise were significant risks for persistent proteinuria.
We found that one student with persistent proteinuria and Stage I hypertension had hematuria in all urine tests. A study by Parakh et al reported that the prevalence of protei-nuria with hematuria was 0.09%, which was slightly lower than isolated proteinuria (0.22%) and isolated hematuria (0.40%). Few studies demonstrated that the proteinuria and hematuria and the degree of asymptomatic hematuria in children correlated with the severity of glomerulus morphology changes.,
In this study, we found 56 (11.5%) children suffering from Stage I hypertension and seven (1.4%) suffering from Grade II hypertension. The family history of hypertension and overweight/obesity was identified as significant risk factor. This study did not investigate the family history of hypertension, but the prevalence of overweight and obesity was higher with 19.8% and 11.1%, respectively.
We found that two students with Stage I hypertension had transient proteinuria, and none of the students with Stage II hypertension had proteinuria. In a cohort study, severe proteinuria was one of the risk factors of an increased systolic and diastolic blood pres-sure. Conversely, systemic hypertension causes proteinuria by increasing glomerular capillary blood pressure and subsequent damage to the glomerular permeable membrane.
The most common etiology in persistent proteinuria varied in different populations. Parakh et al found that 50% of patients with persistent proteinuria had glomerulonephritis. Murakami et al and Bakr et al reported that the incidence of glomerulonephritis was 76.6% and 66.6%, respectively. Four cases had clinical manifestation of lupus nephritis and one case had acute poststreptococcal glomerulo-nephritis. Lin et al reported that the most frequent cause of persistent proteinuria was lupus nephritis (31.6%). Park et al found IgA nephropathy as the most prevalent cause. A study by Cho et al reported that the most common etiology was mesangioproliferative glomerulonephritis (21.9%) and then followed by IgA nephropathy (11.3%).
Two of three students with persistent protei-nuria refused to do further examinations at Dr. Cipto Mangunkusumo Hospital, Jakarta. One student showed a normal result in repeated urinalysis.
Routine mass screening has been proven to provide benefits in many Asian countries.,,, However, North American and European countries were no longer conducting this screening due to cost-effectiveness. Sekhar et al found that this screening was ineffective and they supported the recommendation of the American Academy of Pediatrics for not conducting this screening in school children. According to a systematic review, primary glomerulonephritis in Asian children was higher than the Caucasian race, with 6.2–15.6/100,000 per year (Asian), 9.2/100,000 per year (Arab), and 2.0/100,000 per year (Caucasian). We could not perform statistical tests to analyze the association between asymptomatic persistent proteinuria in Indonesian adolescents and nutritional status, hypertension, birth weight, gender, and genetic factor because of the small sample size.
The prevalence of asymptomatic persistent proteinuria in our study was 0.62%. This equates to around 70,000 adolescents will have asymptomatic persistent proteinuria across the country who are at risk of developing progressive kidney disease.
| Conclusion|| |
The prevalence of asymptomatic persistent proteinuria among adolescents in Jakarta was higher than that in other populations in Asia. Consequently, routine screening for proteinuria should be considered to detect the chronic kidney disease at an early stage.
Conflict of interest: None declared.
| References|| |
Hogg RJ, Portman RJ, Milliner D, Lemley KV, Eddy A, Ingelfinger J. Evaluation and management of proteinuria and nephrotic syndrome in children: Recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics 2000;105:1242-9.
Murakami M, Yamamoto H, Ueda Y, Murakami K, Yamauchi K. Urinary screening of elementary and junior high-school children over a 13-year period in Tokyo. Pediatr Nephrol 1991;5:50-3.
Murakami M, Hayakawa M, Yanagihara T, Hukunaga Y. Proteinuria screening for children. Kidney Int Suppl 2005;94:S23-7.
Ramirez SP, Hsu SI, McClellan W. Low body weight is a risk factor for proteinuria in multiracial Southeast Asian pediatric population. Am J Kidney Dis 2001;38:1045-54.
Parakh P, Bhatta NK, Mishra OP, et al.
Urinary screening for detection of renal abnormalities in asymptomatic school children. Nephrourol Mon 2012;4:551-5.
El-Shafie AM, El-Nemr FM, Bahbah MH, Shokry M, Attia A. The role of urine screening (in school children of Menoufiya Governorate) in early detection of renal disorders. J Am Sci 2014;10:143-50.
Trihono PP, Timan IS, Bektiwibowo S, Aulia D, Edwar L. Screening urinalysis for protei-nuria in school children. Paediatr Indones 1999;41:231-3.
Byoung SC. Screening urinalysis for protei-nuria in school children. In: Man CC, Hui KY, editors. Practical Paediatric Nephrology: An Update of Current Practices. Hong Kong: Medcom Limited; 2005. p. 96-102.
Zhai YH, Xu H, Zhu GH, et al.
Efficacy of urine screening at school: Experience in Shanghai, China. Pediatr Nephrol 2007;22: 2073-9.
Falkner B, Daniels SR, Flynn JT, Gidding S, Green LA, Ingelfinger JR. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555-76.
Halim H. Proteinuria. In: Noer MS, Soemyarso NA, Subandiyah K, Prasetyo RV, Alatas H, Tambunan T, editors. Kompendium Nefrologi Anak. Jakarta: Badan Penerbit Ikatan Dokter Anak Indonesia; 2011. p. 27-31.
Vehaskari VM, Rapola J. Isolated proteinuria: Analysis of a school-age population. J Pediatr 1982;101:661-8.
Cho BS, Kim SD, Choi YM, Kang HH. School urinalysis screening in Korea: Prevalence of chronic renal disease. Pediatr Nephrol 2001; 16:1126-8.
Yap HK, Quek CM, Shen Q, Joshi V, Chia KS. Role of urinary screening programmes in children in the prevention of chronic kidney disease. Ann Acad Med Singapore 2005;34:3-7.
Lin CY, Sheng CC, Lin CC, Chen CH, Chou P. Mass urinary screening and follow-up for school children in Taiwan province. Acta Paediatr Taiwan 2001;42:134-40.
Lin CY, Hsieh CC, Chen WP, Yang LY, Wang HH. The underlying diseases and follow-up in Taiwanese children screened by urinalysis. Pediatr Nephrol 2001;16:232-7.
Zainal D, Baba A, Mustaffa BE. Screening proteinuria and hematuria in Malaysian children. Southeast Asian J Trop Med Public Health 1995;26:785-8.
Sebestyen JF, Alon US. The teenager with asymptomatic proteinuria: Think orthostatic first. Clin Pediatr (Phila) 2011;50:179-82.
Park YH, Choi JY, Chung HS, et al.
Hematuria and proteinuria in a mass school urine screening test. Pediatr Nephrol 2005;20:1126-30.
Lin CY, Sheng CC, Chen CH, Lin CC, Chou P. The prevalence of heavy proteinuria and progression risk factors in children undergoing urinary screening. Pediatr Nephrol 2000;14: 953-9.
Yamagata K, Iseki K, Nitta K, et al.
Chronic kidney disease perspectives in Japan and the importance of urinalysis screening. Clin Exp Nephrol 2008;12:1-8.
Vehaskari VM, Rapola J, Koskimies O, Savilahti E, Vilska J, Hallman N. Microscopic hematuria in school children: Epidemiology and clinicopathologic evaluation. J Pediatr 1979;95:676-84.
Cho BS, Kim SD. School urinalysis screening in Korea. Nephrology (Carlton) 2007;12 Suppl 3:S3-7.
Flynn JT, Mitsnefes M, Pierce C, et al.
Blood pressure in children with chronic kidney disease: A report from the chronic kidney disease in children study. Hypertension 2008; 52:631-7.
Metcalfe W. How does early chronic kidney disease progress? A background paper prepared for the UK consensus conference on early chronic kidney disease. Nephrol Dial Transplant 2007;22 Suppl 9:ix26-30.
Bakr A, Sarhan A, Hammad A, et al.
Asymptomatic urinary abnormalities among primary school children in Egypt. World J Pediatr 2007;3:214-7.
Sekhar DL, Wang L, Hollenbeak CS, Widome MD, Paul IM. A cost-effectiveness analysis of screening urine dipsticks in well-child care. Pediatrics 2010;125:660-3.
McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: A systematic review of the literature. Nephrol Dial Transplant 2011 ;26: 414-30.
Indonesia Basic Health Research 2013. National Institute of Health Research and Development, Ministry of Health (Indonesia). http://www.litbang.depkes.go.id
. [Last accessed on 2015 Aug 06].
Partini Pudjiastuti Trihono
Department of Child Health, Faculty of Medicine, Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta
[Table 1], [Table 2]