Vesicoureteral Reflux Detected with 99mTc-DTPA Renal Scintigraphy during Evaluation of Renal Function

BACKGROUND: Radionuclide techniques, as direct radionuclide cystography and 99mTc-DMSA scintigraphy, have been used in evaluation of vesicoureteral reflux (VUR) and reflux nephropathy (RN) in children. Dynamic 99mTc-DTPA scintigraphy is reserved for evaluation of differential renal function and obstruction in children, where hydronephrosis is detected by ultrasonography (US) pre- or postnatally. CASE REPORT: Six year old boy was prenatally diagnosed with bilateral hydronephrosis. Postnatal, severe bilateral VUR was detected by voiding urethrocytography. US and 99mTc-DTPA scintigraphy performed in the first month of life showed small left kidney that participated with 2% in the global renal function. Bilateral cutaneous ureterostomy has been performed in order to obtain good renal drainage and promote optimal renal growth. Twelve months later, classic antireflux procedure was done. Control 99mTc-DTPA scintigraphy, 5 ys after antireflux surgery, revealed persisting radioactivity during the diuretic phase, in the left kidney that indicated antireflux procedure failure with VUR reappearance. CONCLUSION: 99mTc-DTPA scintigraphy is the first method of choice for long-term monitoring of individual kidney function in children with VUR and other congenital urinary tract anomalies. Additionally, it can be used as indirect radionuclide cystography when rising of radioactivity in the kidney region, during the diuretic phase can indicate presence of VUR.


Introduction
Vesicoureteral reflux (VUR) is a congenital defect of the urinary tract leading to retrograde urine flowfrom the bladder towards the kidney. It occurs in 1% of the general population and is one of the main risk factors in children for renal scar development after infection of the urinary tract [1].
Several studies stress the importance of diagnosing VUR as a risk factor for repeated urinary tract infections (UTIs), which if left untreated, can lead to serious kidney damage in the future. Especially severe VUR (grades 4 and 5) has been associated with renal damage and represents an important cause of chronic renal failure in children [2]. Radionuclide techniques, as direct radionuclide cystography and cortical scintigraphy with 99m Tc-dimercaptosuccinic acid ( 99m Tc-DMSA), have been used in evaluation of VUR and reflux nephropathy in children. The dynamic renal scintigraphy with 99m Tc-diethylene triamine pentaacetic acid ( 99m Tc-DTPA) provides important functional information of kidney function in children with VUR.
We aimed to report vesicoureteral reflux detected with 99m Tc-DTPA renal scintigraphy during evaluation of renal function in a boy who was prenatally diagnosed with bilateral hydronephrosis. http://www.mjms.mk/ http://www.id-press.eu/mjms/

Case Report
We present a case of VUR detection during evaluation of renal function by dynamic scintigraphy with 99m Tc-DTPA.
A 6-year old boy was prenatally diagnosed with bilateral hydronephrosis. Postnatal imaging by voiding urethrocystography revealed severe bilateral VUR (grade IV/V on left and grade III/V on the right side). Renal ultrasonography showed bilateral hydronephrosis and reduction of the renal parenchyma of the left kidney. The renal function was evaluated by dynamic scintigraphy (year 2005). After i.v bolus injection of 99m Tc-DTPA, 120 short time frames (4 s in vascular phase and 10 s in dynamic phase) within 20 minutes were taken, matrix size 64 x 64, using one headed SOPHA gamma camera. It has been shown that left kidney participated in the global renal function with only 2% (Fig. 1). Surgical treatment was implemented, initially bilateral cutaneous ureterostomy have been created in order to obtain good renal drainage and promote optimal renal growth. Classic antireflux procedure (Leadbetter-Politano ureterocystoneostomy) was performed after 12 months. During the following five years, the child has been regularly checked in outpatient pediatric Nephrology Clinic. Renal functional studies, as degradation products and clearance of endogenous creatinine, were in normal range, as well as proteinuria. The child had neither urinary infection, nor hypertension.
The follow up 99m Tc-DMSA scintigraphy (year 2008), showed improvement of the findings at the side of the right kidney, without any change in the left renal function (Fig. 3). Three years after (year 2011), control renal diuretic scintigraphy with 99m Tc-DTPA was performed. Diuretic (furosemid) was given 15 minutes after the start of the dynamic renal scintigraphy. This scan data showed almost identical findings concerning the renal function in comparison with initial scan. However, during the diuretic phase an increase in the radioactivity in the region of the left kidney was noticed. This finding suggested failure of the antireflux procedure on the left side, with reappearance of VUR (Fig. 4).

Discussion
Neonatal hydronephrosis (identified if pelvic diameter is > 4mm on antenatal ultrasound) is a common abnormality that can be diagnosed ante-or postnatal, with incidence of 2-9 per 1000 infants [3]. Involving of ultrasonography as a routine test during pregnancy, allows detection of eventually intrauterine anomalies especially if they are performed during 18-20 week of gestation [4].
Among the urinary tract anomalies, hydronephrosis is the most common one. The appearance of intrauterine hydronephrosis was first described by Garett et al., in 1975 [5]. The causative factors of antenatal hydronephrosis (AH) can be categorized into those leading to obstruction (ureteropelvic junction obstruction -UPJO), those leading to reflux (vesicoureteral reflux -VUR) and a group of non-obstructing and non-refluxing "idiopathic" hydronephrosis [6]. VUR as a common cause of AH occurs in 10-15% of them [7].
Primary VUR is associated with congenital defect in the valve mechanism that prevents urine to flow backward from the bladder into the ureters. The valve does not close properly resulting in an ureterovesical junction anomaly. It is diagnosed in the early child age, as a consequence of often repeated UTIs resistant to conservative treatment. Secondary VUR, where valve mechanism is intact, is due to urinary tract malfunction, often caused by infection or increased vesicular pressures associated with obstruction. This conditions result in elevation of the bladder pressure, which distorts the ureterovesical junction [8].
In 1981, international grading system consisting of five grades was established.
The most important consequence of VUR is reflux nephropathy and renal scarring which occurs in 25% of children and younger adults with chronic renal failure. In the study of Ajdinovic et al., children with UTI and VUR (53%) had significantly higher percent of abnormal DMSA findings, than children with UTI without VUR (15%) [9].
VUR is relatively common disorder in childhood which is associated with recurrent urinary tract infection, hydronephrosis, hypertension, renal dysplasia and parenchyma damage, failure to thrive and end-stage renal disease.
Dilating reflux (grades III-V) has been shown to be significantly associated with reflux nephropathy. Prognosis is worst when RN is bilateral. Unilateral RN is compensated for the hypertrophy of the contralateral normal kidney [10].
Farhat reported 48% of neonates with AH had high grade of VUR (IV-V), while Ismail showed 36% of 43 infants with primary VUR had high grade VUR [11,12].
Direct radionuclide cystography with 99m Tclabeled agent (sulfur colloid, DTPA, or pertechnetate) is a well-accepted alternative to fluoroscopic VCUG. It is an investigation for initial diagnosis, follow-up examination of children with VUR or for postoperative evaluation after ureteral reimplantation. This technique requires bladder catheterization and it cannot delineate anatomy of bladder and urethra. The advantages of this method include continuous monitoring and imaging, high sensitivity, and a decreased radiation dose for a voiding imaging study [13].
In the study of Thakral et al., DRCG was found to be a sensitive technique for the detection of VUR. There was a direct relationship between the grade of reflux and renal scarring.The study also reveals that there is a cause-and-effect relationship between UTI and renal scarring that is made worse by VUR [14].  [16].
In our case during control dynamic renal scintigraphy with 99m Tc-DTPA, as a standard procedure of evaluation of the renal function in child with surgically treated VUR and reflux nephropathy, progressive accumulation of radioactivity was noted on the late scan images, in the region of the left nonfunctional kidney. This finding suggested presence of VUR and has been confirmed by subsequent conventional voiding uretrocystography. Consequently, 99m Tc-DTPA dynamic renal scyntigaphy in our case served as an indirect radionuclide cystography, giving additional information and helping clinicians to optimize further clinical workout.
In conclusion, early undiagnosed VUR could be a reason for developing urinary tract infection, which can lead to serious renal damage as increasing risk of pyelonephritis and progressive renal failure. The gold standard method for diagnosing VUR is voiding cystourethrography (VCUG), but it is invasive, exposes the patient to radiation and increases the risk of reinfection. 99m Tc-DMSA is a sensitive and specific method for detecting renal scars in children with persistent UTI, as a consequence of VUR. 99m Tc-DTPA scintigraphy is the first method of choice for long-term monitoring of individual kidney function and structure in children with VUR and other congenital urinary tract anomalies. Additionally, it can be used as indirect radionuclide cystography, as an important independent predictor of early failure to resolve VUR.