| Abstract|| |
Vesicoureteral reflux (VUR) is a common congenital renal tract anomaly in children. Reports from Sudan are scanty. We report the characteristics, presentation and outcome of primary VUR in a tertiary care hospital. The records of 30 patients (16 males; 53%) followed-up between January 2004 and December 2010 were reviewed. The mean age at the time of diagnosis was 4 ± 3.9 years and 47% were <2 years of age. Renal ultrasound scan (USS) failed to predict VUR in 17% of the patients. On voiding cysturethrogram (VCUG), VUR was bilateral in 57% and severe grade in 64%. Grades were not significantly associated with age, gender or site of VUR. Initial dimercaptosuccinic acid radionuclide scan showed renal damage in 61.5% of the patients. Renal damage was significantly associated with female gender and severe VUR, but not with age of onset or history of urinary tract infection (UTI). Thirteen patients (43.3%) presented with acute UTI, eight (26.6%) with non-specific urinary tract symptoms and nine (30%) with persistently elevated serum creatinine. Urine cultures were positive in 73% of patients, and E. coli was the most common pathogen. Renal impairment at presentation was significantly associated with bilateral severe VUR and history of UTI but not age or gender. After a mean follow-up period of 1.78 years (6 months to 5 years), 70% of patients remained with normal renal function and 30% progressed to chronic kidney disease; two of them died. In conclusion, our data is different from many studies. Features of primary VUR in Sudanese children are late age of onset, equal gender affection and predominance of severe grade. Presentation is associated with a high rate of UTI, renal damage and advanced renal impairment. Measures to improve early detection and treatment of VUR may reduce the risk of kidney damage.
|How to cite this article:|
Ali ETM, Alfaki EM, Abdelraheem MB. Primary vesicoureteral reflux in Sudanese children. Saudi J Kidney Dis Transpl 2014;25:900-5
| Introduction|| |
Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder into the upper urinary tract. Primary reflux is caused by congenital abnormality of vesicoureteral junction. It is the most common congenital urological anomaly in children, found in about 1% of newborns and as high as 30-45% of young children presenting with urinary tract infection (UTI). ,, Girls are more likely to have reflux than boys,  but in patients with prenatally detected hydronephrosis males were predominantly affected.  Young infants and children <2 years of age were more likely to have VUR than older children.  VUR predisposes patients to acute UTI, which may lead to renal scarring. Extensive scarring may lead to further renal damage with subsequent hypertension, impaired renal function, proteinuria and, sometimes, end-stage renal failure (ESRF). ,, However, progression to ESRF in patients with reflux has been increasingly debated. Most children with VUR present with hydroneph-rosis, often prenatally detected or with clinical UTI. Occasionally, they can present with advanced reflux nephropathy (RN) manifesting as heart failure from untreated hypertension or with uremic symptoms. 
| Patients and Methods|| |
We reviewed the records of all children with a diagnosis of primary VUR presenting to the Paediatric Nephrology Unit at the Soba University Hospital from January 2004 to December 2010. The diagnosis of VUR was based upon the demonstration of reflux of urine from the bladder into the upper urinary tract by contrast voiding cystourethrogram (VCUG). The grades of VUR were defined according to the International Reflux Study Group (IRSG) classification system.  The severity of VUR is classified as mild (grade I- II), moderate (III) and severe grade (IV-V).  UTI diagnosis was based on positive urine culture with colony count of more than 100,000 colony forming units/mL of a single pathogen. Glomerular filtration rate (GFR) was estimated by the Schwartz formula and chronic kidney disease stages were defined according to the National Kidney Disease Outcome Quality Initiative guidelines. , Chronic kidney disease was defined as GFR <60 mL/min/1.73 m  for ≥3 months with or without kidney da-mage.  Blood pressure values and definitions were based on the Fourth Task Force Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Ado-lescence.  Data collected from patients records were age, gender, clinical features, laboratory investigations (urine cultures, serum creatinine and hemoglobin), imaging [ultrasound scan (USS), VCUG and dimercapto-succinic acid radionuclide (DMSA) scan] and outcome measures (recovery, chronic kidney disease or death).
| Statistical Analysis|| |
Data entry and analysis were performed using SPSS (Statistical Package for Social Sciences) version 18 was used to calculate the means and frequencies and to run the tests of significance (chi-squire tests). P-value <0.005 was considered as significant.
| Results|| |
There were 30 children (16 male, 53.3%) with primary VUR enrolled in the study. The male to female ratio was 1.1:1, and the mean age at the time of presentation was 4 ± 3.9 years (range 4 months to 13 years). The mean age at diagnosis was younger in boys than girls (3.4 versus 4.5 years), but this was statistically insignificant, P = 0.472). Fourteen patients (47%) were below two years of age of whom nine (30%) were below one year. There was no significant gender difference between the different age groups (P = 0.68). USS showed renal tract abnormality in one or both kidneys in 25 patients (87%), i.e. USS failed to predict VUR in 17% [Table 1]. VCUG studies showed that VUR was bilateral in 17/30 patients (56.6%), giving a total of 47 refluxing ureters. Thirty of 47 (64%) refluxing ureters were severe grade (grades IV-V), four (8%) were moderate grade (grade III) and 13 (28%) were mild grade (grades I-II) [Table 2]. The association of VUR grades were not statistically significant for age (P = 0.062), gender (P = 0.078) or site (P = 0.093). A DMSA scan was performed at the time of initial diagnosis in 13 patients (43.3%). It showed evidence of renal damage in eight of 13 patients (61.5%). Renal damage was significantly more common in females than in males (6:1, P = 0.005) and in those with severe than mild to moderate grade (7:1 versus 6:12, P = 0.0135). However, it was not significantly associated with age of onset (2.3 years versus 1.8 years, P = 0.725) or history of UTI (54% versus 46%, P = 0.416).
Patterns and frequency of presentations in patients with VUR are shown in [Table 3]. Thirteen patients (43.3%) presented with acute UTI, eight (26.7%) with non-specific urinary tract symptoms (bed wetting, frequency and flank pains) and nine (30%) with elevated serum creatinine. In 27 of 30 patients (90%), there was a history of recurrent UTI. Fever was reported in ten of 13 patients presenting with acute UTI. All the nine patients with high serum creatinine at presentation also had UTI. Significant growth in urine cultures was detected in 22 of 30 (73%) patients, and E. coli was the most common pathogen, accounting for 59% of the cultures. Other organisms were Klebsiella species in 27.5%, Pseudomonous auriginosa in 9% and Staphylococcus aureus in 4.5% of patients. Patients presenting with high serum creatinine had a mean serum crea-tinine of 3.7 mg/dL ± 2.18 (range 0.9-6.9) and a mean GFR of 18.1 ± 1.19 mL/min/1.73 m  (range 6.1-41). Severe anemia (Hb of 6.4 g/dL ± 3.4 SD) was diagnosed in all of the nine patients, failure to thrive in eight and hypertension in seven of them. Renal impairment at presentation was significantly associated with presence of bilateral VUR (P = 0.001), severe grade VUR (P = 0.003) and history of UTI (P = 0.034), but not with age or gender (P = 0.133 and P = 0.858, respectively). Characteristics of patients with normal renal function and those with impaired function at presentation are shown in [Table 4].
|Table 4: Characteristics of VUR patients with normal versus impaired renal function at presentation.|
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Surgical treatment was offered to eight out of 30 patients (26.7%) of whom VUR was bilateral in five and unilateral in three (13 refluxing ureters). In nine of 13, reflux were of severe grade (IV-V). The remaining patients were either medically treated or conservatively managed, depending on the state of their renal function. After a mean follow-up period of 1.78 ± 1.53 years (6 months to 5 years), 21 patients (70%) remained with normal renal function and nine (30%) progressed to chronic kidney disease (three with chronic kidney disease III-IV and six with ESRF). Two of six ESRF patients died. Ureteric reimplantation was successful in preserving normal renal function in six of eight surgically treated patients.
| Discussion|| |
Primary VUR is detected in more than one third of young children presenting with UTI ,, and is more common in younger children, especially in infancy. ,, Our finding is consistent with these studies as 47% of our patients were below two years of age.
In prenatally detected VUR, males were predominantly affected.  Conversely, in VUR detected by the investigation of UTI, girls were more likely to be affected. ,, However, other studies have shown a male predominance. , Some other studies from a similar population of children have reported different sex ratios. , In our series, both sexes were approximately equally affected. Therefore, this gender variation could be related to the methods of detection of VUR rather than genetic predisposition. All our patients were detected during UTI investigation.
In this study, VUR was demonstrated bilaterally in 56% of patients, which is consistent with other studies, also in Nepal (60%) and Brazil (54%). , Many studies have shown a high incidence of lower-grade VUR, ,,, whereas other data have shown variable incidences of VUR grades. , Our finding sharply contrasts with these studies as 64% of patients in this series had severe grade VUR. Many of our VUR patients were detected late with advanced renal impairment and are therefore likely to have severe rather than low-grade VUR.
Although USS is used in the evaluation of patients with UTI, many cases of VUR can be missed if USS is used alone for VUR screening. ,, In our study, USS failed to predict VUR in 17% of patients as compared with other studies from KSA and Nepal (25% and 45.8%, respectively). , This difference could also be related to the high incidence of severe grade VUR in our series. Severe grade VUR is commonly predicted by USS than mild grade.
VUR tends to be associated with renal damage at diagnosis in about 30-60% of cases in some studies. ,,, In this series, the DMSA scan detected renal damage in 61% of patients at initial diagnosis. Males, especially with pre-natally detected VUR, , and those with severe grade VUR had a higher risk of developing renal damage. , In our study, renal damage was significantly more common in females and in those with severe grade VUR (P = 0.02 and 0.013, respectively). This finding is expected as no patient in our series was detected pre-natally. We could not find a significant association between the incidence of renal damage and age of onset as in other studies. ,,
Many children with VUR present either with hydronephrosis, often prenatally detected, or with clinical UTI, which often presents with non-specific signs and symptoms. They can also present with manifestations of advanced RN or may be asymptomatic.  Most of our patients presented with evidence of UTI, with E. coli being the most common pathogen, which is consistent with the reports from other studies. ,, Thirty percent of our patients presented with advanced RN associated with severe anemia, failure to thrive and hypertension. This finding contrasts sharply with other studies showing either no or a lower incidence of advanced RN at diagnosis. ,, However, one study from India has demonstrated advanced RN in more than 75% of their young adults with VUR.  In our series, advanced RN was significantly associated with bilateral severe grade VUR and UTI but not with age or gender. Bilateral severe grade VUR in the presence of recurrent UTI is likely to lead to RN if remained undetected.
Follow-up VCUG was not performed for most of our patients, as many parents did not agree for a repeat procedure. The follow-up period was relatively short. However, surgery was successful in preserving normal renal function in six of eight patients having bilateral severe grade VUR. Despite prophylaxis and surgery, about 30% of our patients progressed to chronic kidney disease, mostly ESRF. It is likely that such high incidence of CKD is due to failure of early detection of VUR in the presence of recurrent UTI.
Our study was not without limitations. This study was a retrospective study in which some data may not be accurately collected. The relatively small number of patients in a hospital-based study may not precisely reflect the whole spectrum of VUR features. However, the study provides information about this important health problem.
In conclusion, our data are different from that in western and some developing countries having better facilities. Characteristics of primary VUR in Sudanese children were late age of onset, equal gender affection and predominance of severe grades. Presentation is associated with a high incidence of UTI, renal damage and advanced renal impairment. Despite surgery, about one-third of patients remained with chronic kidney disease or died. Efforts directed toward improving early detection and treatment of this disorder may reduce the risk of renal damage. Training of doctors on UTI management guidelines and introduction of protocols for prenatal detection of VUR may help in the early detection and management of such patients.
| Acknowledgments|| |
This work is a part of a Thesis submitted for partial fulfillment of Clinical MD in Pediatrics, University of Khartoum, 2010. The authors thank all the staff in the Medical Records Departments in the Soba University Hospital for helping with data collection. Their thanks are extended to the Health Statistic Department, University of Khartoum, for help with data analysis.
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El-Tigani M. A. Ali
Department of Pediatrics and Child Health, Soba University Hospital, Faculty of Medicine, University of Khartoum, Khartoum
[Table 1], [Table 2], [Table 3], [Table 4]