In this study, the clinical data of 140 children with grade I–V VUR receiving CAP at the Department of Nephrology, Children’s Hospital of Xiamen were analyzed. Children were grouped based on the presence or absence of NRS while receiving CAP. Children with renal function impairment on a DMSA scan after the initial diagnosis of UTI and who had BT-UTI while receiving CAP were more prone to NRS.
In this study, the time between index UTI and first DMSA was 1(0.6) months. Loukogeorgakis et al.12 performed a retrospective analysis on 61 VUR children found that renal scarring is the most significant risk factor for breakthrough UTI in primary VUR patients and could be used to determine those at risk of symptomatic VUR persistence. Harper et al. also found that abnormal post-UTI DMSA scan is associated with a higher risk of recurrence of UTI at 24 months13. So a DMSA scan for VUR children after the first urinary tract infection is necessary.
In this study, children with VUR receiving regular CAP and specialist follow-up still had renal scarring. 140 children underwent a follow-up DMSA scan, and 73 children had NRS, including 41 males and 32 females, an incidence of 52.14%. Even when active clinical intervention is given to children with VUR, 30–50% of children still experience renal scarring, which is consistent with the findings14,15. In some recent randomized studies, the number of cases reported with renal scarring in children with VUR correlated with patient sex. Studies with more males reported significantly more cases of renal scarring, which is more likely to be congenital than acquired RN16,17. For girls, the risk of BT-UTI remains higher overall and the new scars were acquired and found to be related to severe inflammatory processes, while in boys the renal damage was often congenital18.
Univariate and multivariate analyses showed that in VUR children received CAP, the recurrence of BT-UTI was independent risk factor for NRS. Sevgi et al.19 performed a retrospective analysis on 90 VUR children receiving CAP and found that BT-UTI was a risk factor for renal scarring. Previous studies have suggested that renal parenchymal infection is a prerequisite for renal scarring20,21. This study showed that the rate of renal scarring in children with BT-UTI was 1.995 times that in children without BT-UTI recurrence, indicating that renal parenchymal infection is an important condition for renal scarring. But Morello et al.22 performed a investigator-initiated, randomized, open-label trial analysis on 292 grade IV or V VUR children receiving CAP and found that the number of new lesions was independent of the occurrence of UTIs during the trial period. They also founded that new defects were identified in 27 of 144 participants (18.8%) who had no UTI and in 11 of 57 (19%) who had at least one UTI (rate ratio, 0.97; 95% CI 0.52 to 1.83)22. Some studies have suggested that VUR children older than 2 years at the initial diagnosis of UTI have a greater likelihood of renal scarring, which may be related to the lack of timely treatment due to their late diagnosis of UTI23,24. In the RIVUR study, children with a second UTI had significantly more renal scars when compared with those with a single UTI16. A post hoc analysis of the RIVUR and CUTIE (Careful Urinary Tract Infection Evaluation) studies revealed that the odds of renal scarring after a second febrile UTI were 11.8 times higher and after 3 or more febrile UTIs were 13.7 times greater than after a single febrile infection25.
Previous studies have found that in children with VUR who use CAP intervention, high-level VUR, especially IV-V grade VUR, is an independent risk factor for NRS26. Mattoo et al.5 found in a prospective randomized controlled clinical study (RIVUR) that children with IV-V grade VUR were more likely to develop BT-UTI and renal scars, 24.2 and 1.88 times higher than those with I–III grade VUR, respectively. Sitarah Mathias et al.27 also found that patients with high-grade VUR patients were more likely than those with low-grade VUR patients to have renal scarring (75% vs. 49%, p < 0.01), low eGFR (23% vs. 13%, p Z 0.04) and significant hypertension (26% vs. 13%, p Z 0.02). In our study, neither the univariate nor multivariate analysis found a correlation between VUR grade and NRS. This result may be related to the high proportion of high-grade VUR children included in this cohort (84.28% of III–V grade VUR children and 42.14% of IV-V grade VUR children).
This study has some limitations. First, the study was a single-center, small cohort study. Second, although the children were regularly followed up in our hospital, there was no quantitative standard for CAP compliance. In addition, there were some data defects during data acquisition, such as the lack of etiology during the initial diagnosis of UTI. These factors may have led to biased results. Multicenter, prospective clinical studies are needed to confirm the reliability of our results.