VUR is a condition in which urine flows back from the bladder to the ureter or pelvis. VUR can be classified as primary or secondary according to its etiology. The enrolled cases in this study were all primary VUR cases, mainly caused by abnormal development of the vesicoureteral flap, which is closely related to genes.15 VCUG is the “gold standard” technique for detecting VUR. It provides high-resolution anatomical images of the renal parenchyma, calyx, pelvis, and bladder. The ureters and urethra can be partially visualized. VUR was divided into 1–5 grades according to the degree of urine reflux. Higher VUR grades had a greater probability of renal dysplasia or scarring formation and a greater chance of urinary tract infection.2 Recurrent urinary tract infections can easily cause renal scarring, proteinuria, hypertension, and other symptoms of reflux nephropathy. Severe reflux, bilateral reflux with renal scarring, hypertension, proteinuria, and decreased GFR are risk factors for the progression to CKD or ESRD.13 The early assessment of renal function in children with VUR is conducive to early intervention and improved prognosis.
This study included 104 children with unilateral VUR, and the mean age at diagnosis was not significantly different from that of the control group. The diameter of the reflux kidney was smaller than that of the control group, indicating that kidney development in the reflux kidney was significantly affected. The renal ERPF value in the reflux kidney was significantly lower than that in the contralateral unaffected and ipsilateral kidneys in the control group. Split renal function in reflux kidneys was significantly impaired. Nevertheless, the total ERPF value in unilateral VUR was not significantly different from that in the control group, suggesting that the contralateral kidney in unilateral VUR had a certain compensatory function. The split renal ERPF value of the bilateral reflux kidneys was lower than that of the same side in the control group, and the total ERPF value of the bilateral VUR was significantly lower than that of the control group. Patients with bilateral VUR have obvious renal impairment, which should be strengthened during long-term follow-up monitoring.
99mTc-DMSA is the gold standard for diagnosing renal scarring. It is commonly used to measure split-renal function. Split renal function is considered to range from 45–55% of the total uptake in healthy kidneys.16 It may be difficult to accurately evaluate lesions in bilateral VUR because the relative uptake remains stable. 99mTc-EC dynamic renal scintigraphy is beneficial for evaluating transplant kidney function.8 Following intravenous administration of 99mTc-EC, some (17%) of it is filtered in the glomeruli, while a major portion (50%) is secreted in the proximal part of the tubules by organic anion transporters.16 ERPF correlates with eGFR.17 99mTc-EC was used to evaluate split renal function in hydronephrosis or UTI.18 The unilateral renal ERPF value of bilateral VUR was lower than that of the same side in the control group, and the total ERPF value of bilateral VUR was significantly lower than that of the control group.
The predictive factors for deterioration were recurrent febrile urinary tract infections, bilateral abnormalities, and reduced total glomerular filtration rate. Deteriorated renal status was more common in cases diagnosed prenatally than in those detected after urinary tract infection.19,20 In this study, the predictive factors for renal function deterioration were analyzed. Renal scarring (P = 0.003), VUR grade (P = 0.008), transverse diameter (P = 0.002), and renal pelvic separation were significantly correlated with renal function damage. Severe VUR was associated with impaired renal function.13 Renal parenchymal defects were observed in 87% of children at baseline, with a strong correlation with renal function, which is in accordance with several previous reports on congenital renal dysplasia.4,6,7 VUR is often associated with recurrent urinary tract infections, which can lead to scarring and impaired kidney function. The average reflux was above grade 3, indicating moderate and severe reflux. Moderate and severe reflux are often accompanied by renal pelvis and ureteral dilation. Therefore, the degree of renal pelvic separation and ureteral dilation on the reflux side were higher than those in the control group.
The study screened 348 VUR kidneys at a tertiary center, and the outcomes were objectively measured by professional physicians. Nevertheless, owing to the retrospective design of the study, we cannot make a causal conclusion. Additionally, selection bias for a single-center study with measurement bias might not be excluded. It is possible that residual confounders, such as socioeconomic factors, which might introduce study bias. Due to the short term follow up and single-center study design, the generalization of our conclusions might be limited. Our findings warrant further study with the need for a well-designed, large-scale, long term follow up, prospective study.
We analyzed the effect on renal function in primary vesicoureteral reflux children in this retrospective study. Split renal function in the reflux kidney was impaired. The total ERPF in the bilateral VUR group was lower than that in the unilateral VUR group. Renal function deterioration was correlated with renal scarring, a VUR grade, a transverse diameter, and renal pelvis separation. Bilateral VUR with high VUR grade, more renal scarring and hydronephrosis requires attention to strengthen follow-up.