Non-Animal Stabilized Hyaluronic Acid/Dextranomer Gel (NASHA/Dx, Deflux) for Endoscopic Treatment of Vesicoureteral Reflux: What Have We Learned Over the Last 20 Years?
August 16, 2021
Non-animal stabilized hyaluronic acid/dextranomer gel (Deflux; NASHA/Dx) was developed as a treatment for vesicoureteral reflux (VUR) in the 1990s. To mark 20 years since the US approval of this agent, we reviewed its properties, best practice for application, and the available clinical safety and efficacy data. Long-term or randomized, controlled studies of treatment with NASHA/Dx have reported VUR resolution rates of 59%−100% with low rates of febrile urinary tract infection post-treatment (4%−25%), indicating long-term protection of the kidneys. An individualized approach VUR management is advocated, and NASHA/Dx is a viable option for many patients requiring intervention.
Long-Term Clinical Outcomes and Parental Satisfaction After Dextranomer/Hyaluronic Acid (Dx/HA) Injection for Primary Vesicoureteral Reflux
Frontiers in Pediatrics,
Endoscopic injection with Dx/HA for primary VUR appears to have good long-term clinical success rates and high parental satisfaction, mirroring our previously reported short-term results. Post-operative ureteral obstruction is rare but may occur years post-operatively, justifying initial sonographic surveillance, and repeat imaging in symptomatic patients.
Intermediate to Long-Term Follow-Up Indicated Low Risk of Recurrence After Double HIT Endoscopic Treatment for Primary Vesicoureteral Reflux
Journal of Pediatric Urology,
The Double HIT technique for injection of Dx/HA, involving relatively high volume injections for the treatment of VUR, leads to a durable clinical and radiographic long-term success rate (93%). Due to this technique, more favorable outcomes were achieved with fewer recurrences than noted in previous studies. In this delayed VCUG protocol, our favorable results question the need for VCUG in the follow-up of asymptomatic patients. However, until our findings can be confirmed it would be prudent for surgeons to know their own longer-term success rates and base radiographic follow-up accordingly.
Non-animal Hyaluronic Acid/Dextranomer Gel (Deflux) Endoscopic Treatment in Grade IV VUR Results After 15-25 years; Durable and Effective
Section of Urology, University Children's Hospital, Uppsala, Sweden,
- Treatment with Deflux was shown to be durable and effective during a follow-up period of 15-25 years
- Three-quarters of patients did not need ureteral reimplantation
- Optimal placement and higher injection volumes were associated with a trend towards improved success.
- There was a low risk of late clinical recurrence (UTI, persistent VUR, or need for open surgery)
- Endoscopic injection of Deflux is a viable option for patients with grade IV VUR, including those with double ureters.
Endoscopic Treatment of Vesicoureteral Reflux
Based on today’s knowledge, endoscopic treatment may be considered as first line therapy for most children with persistent high grade (III-V) reflux. Those with grade II-V with scarred kidneys or ureteral anomalies such as double ureters, are all candidates for early endoscopic treatment as the likelihood for spontaneous resolution is very small in these patients. Open surgery may be reserved for use only in the 5-10% of patients not responding to endoscopic treatment, and in patients with severe ureteral anomalies. With the improvement of the injection techniques described in this chapter, the results of endoscopic treatment can be expected to improve significantly.
Incidence of Urinary Tract Infections in Children After Successful Ureteral Reimplantation Versus Endoscopic Dextranomer/Hyaluronic Acid Implantation
Journal of Urology,
This study suggests that children cured of VUR with Dx/HA implantation fare better postoperatively in terms of the number and severity of UTIs compared to patients cured with open surgery. Therefore, endoscopic injection for VUR may represent a better treatment option when clinical out-come is measured. Despite the limitations of this series, further investigation by way of a prospective study seems warranted.
VUR Related articles
Renal scarring is the most significant predictor of breakthrough febrile urinary tract infection in patients with simplex and duplex primary vesico-ureteral reflux
Journal of Pediatric Urology,
December 11, 2019
Multiple factors have been shown to be significant predictors of radiological VUR resolution, including VUR grade, VUR timing, female gender, anatomical abnormalities, VURx and scarring on DMSA. Univariate analysis of these factors in our prospective study suggests that only scarring on DMSA and VURx are significant predictors of symptomatic non-resolution. On multivariate analysis, scarring on DMSA was the only significant predictive variable. This information will be useful in targeting investigation and treatment in susceptible patients and when counseling families.
Management and Screening of Primary Vesicoureteral Reflux in Children: AUA Guideline
American Urological Association Education and Research 2010,
It is becoming increasingly evident that identification of a child's individual risk factors should be taken into consideration when managing VUR. In recognizing that BBD is a major factor in UTI occurrence, reflux persistence and surgical outcomes, clinical management of BBD is a priority. Similarly, we can be more comfortable with a less intensive intervention in the child with a low risk of renal injury, i.e., those with no prior infections, healthy kidneys, normal voiding and a low-grade of VUR.
Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months
The committee formulated 7 key action statements for the diagnosis and treatment of infants and young children 2 to 24 months of age with UTI and unexplained fever. Strategies for diagnosis and treatment depend on whether the clinician determines that antimicrobial therapy is warranted immediately or can be delayed safely until urine culture and urinalysis results are available.
Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux
New England Journal of Medicine,
Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring.
National Trends in the Management of Primary Vesicoureteral Reflux in Children
Journal of Urology,
The number of voiding cystourethrograms ordered nationally in all children and those with a urinary tract infection decreased sharply with the 2011 AAP urinary tract infection guideline release and did not change thereafter. A steady decline in procedures for primary vesicoureteral reflux occurred after October 2011.
Association of Renal Scarring with Number of Febrile Urinary Tract Infections in Children
Although the proportion of children with UTIs who have febrile recurrences is relatively small, the risk of renal scarring for those who do is substantially higher. This finding suggests that research should focus on the identification of biomarkers that could noninvasively identify children at risk for subsequent febrile infections. More research is also needed to understand the molecular basis of the increased risk of renal scarring in children with recurrent febrile UTIs.
Uropathogen Resistance and Antibiotic Prophylaxis: A Meta-analysis
Continuous antibiotic prophylaxis increases the risk of acquired multidrug resistance among recurrent UTIs. One multidrug-resistant recurrent UTI would develop for every 21 VUR patients treated with prophylaxis. These results have important implications in the selection of empirical treatment of breakthrough UTIs in continuous antibiotic prophylaxis patients and in the risk-benefit assessment of continuous antibiotic prophylaxis as a management option for prevention of recurrent UTIs. Additional study of other commonly used antimicrobial prophylactic agents and further investigation of risk factors related to the development of uropathogen resistance are necessary.
Long-Term Incidence of Urinary Tract Infection After Ureteral Reimplantation for Primary Vesicoureteral Reflux
Journal of Pediatric Urology,
Although some children experience UTI after UR, the incidence of postoperative clinical pyelonephritis is very low, even on very long-term follow-up. Given that most of these patients initially present with pyelonephritis, these findings support the contention that UR is effective in reducing the incidence of pyelonephritis in this population.