ABSTRACT

Aim:

In 2016, the Centers for Disease Control and Prevention published a management algorithm for Spina Bifida (SB) cases from birth and started collecting data prospectively. They designated risk factors from urodynamic studies as end filling pressure or detrusor leak point pressure (DLPP) ≥40 cmH₂O or neurogenic detrusor overactivity (NDO) with detrusor sphincter dyssynergia (DSD), and categorized this type of bladder dysfunction as “hostile bladder” (HB). They recommended the immediate start of clean intermittent catheterization and anticholinergics in these patients. Having similar concerns regarding this patient population, we designed a retrospective study to identify and reveal the long-term outcomes of SB patients with HB.

Materials and Methods:

All urodynamic studies and hospital records of SB patients admitted and followed between 1994-2014 were reviewed retrospectively. The demographic data, the presence of DLPP, DSD and NDO in the first urodynamic examination, bladder compliance, first and last radiologic and scintigraphic imagings, and surgical interventions were evaluated. Upper tract damage was defined as new scars in dimercaptosuccinic acid scans.

Results:

A total of 58 patients were included in this study. The mean follow-up was 12.17±5.17 years. The presence of a scar in the first scintigraphy (p=0.01) and the presence of hydronephrosis in the first and last ultrasonography (p=0.03) were found to be independent risk factors for new scar development. When DLPP values were evaluated with receiver operating characteristic curve analysis, 50 cmH₂O was observed as a significant threshold value with 73% sensitivity and 60% specificity.

Conclusion:

Our study confirmed the detrimental effects of high pressure and detrusor-sphincter dyssynergia; however, HB parameters were not sufficient to distinguish high-risk group patients. The presence of scars in the first scintigraphic evaluation, DLPP above 50 cmH₂O, and the presence of hydronephrosis in the first ultrasound were found to be risk factors for renal deterioration. More frequent monitoring and detailed evaluation may be necessary for patients with these risk factors.

Introduction

Spina Bifida (SB) is a condition that may result in chronic kidney disease secondary to bladder dysfunction. Despite a worldwide varying incidence, 1-6 cases are seen in every 1,000 live births (1). Several studies reported better results with pro-active management strategies (2,3). Different urodynamic parameters or scoring systems were suggested to detect patients who are at risk of upper urinary tract damage (4-6). In 2016, the Centers for Disease Control and Prevention (CDC) published a management algorithm for SB cases from birth and started collecting data prospectively (7). They designated risk factors from urodynamic studies as end filling pressure or detrusor leak point pressure (DLPP) 40 cmH₂O or greater, or neurogenic detrusor overactivity (NDO) with detrusor sphincter dyssynergia (DSD), and categorized this type of bladder dysfunction as “hostile bladder”. They recommended the immediate start of clean intermittent catheterization and anticholinergics in these patients. Having similar concerns regarding this patient population in our region, we designed a retrospective study with an aim to identify and reveal the long-term outcomes of SB patients with “hostile bladders”.

Materials and Methods

All urodynamic studies and hospital records of SB patients admitted and followed between 1994 and 2014 were reviewed retrospectively to identify patients with “hostile” bladders according to the above-mentioned criteria. Patients with the first admission after infancy, those who did not comply with the SB follow-up protocol of our department, and those patients followed for less than five years were excluded from this study.Urodynamic tests (pressure-flow study) were performed according to our protocols in all cases using a double-lumen 6 Fr urodynamic catheter by Dyno (AYMED Istanbul, Turkey). Pelvic floor activity was evaluated with a total of 3 electromyography electrodes, 2 of them placed on the perianal skin (right and left of the anus), and one for reference on the thigh. Intraabdominal pressure was measured using an 8 Fr rectal balloon catheter. At least two fillings were done for each case. The lowest leakage pressure was described as DLPP. DSD was defined as involuntary pelvic floor activation during voiding. The involuntary phasic or terminal detrusor contractions during filling were described as NDO. The demographic data of the cases, the presence of DLPP, DSD and NDO in the first urodynamic examination, bladder compliance, first and last dimercaptosuccinic acid (DMSA) scans, first and last voiding cystourethrograms, surgical interventions, first and last kidney ultrasound, and the medications they received were evaluated. All patients were followed according to the standardized program of our department (Table I). Urodynamic and clinical data, along with the above-defined hostile bladder parameters, were evaluated for predicting upper tract damage. Upper tract damage was defined as new scars in DMSA scans.

Statistical Analysis

Statistical analysis was done with the IBM SPSS 21 program. Kolmogorov-Smirnov test was used to evaluate the distribution, Pearson chi-square, Mann-Whitney U, Kruskal-Wallis, regression analysis, and receiver operator characteristics curve (ROC) tests were used for analysis where appropriate. Institutional Ethical approval was obtained for the retrospective patient chart review (20-8T/26).

Results

The flow-chart describes patient selection for the study (Figure 1). A total of 58 patients (33 boys and 25 girls) with “hostile” bladder were included in this study. The mean follow-up was 12.17±5.17 years. Hydronephrosis was present in the first ultrasonography (US) in eight cases. It resolved in five cases and was present in a total of 5 cases with two being new-onset cases. Renal scars were observed initially in the first DMSA scans of 10 cases. Nine patients had developed new scars at the last DMSA, making a total of 19 cases with renal parenchymal scars. The mean DLPP value at the first urodynamic study was 54.88±30.43 cmH₂O. Of the 58 patients, DSD was present in 48 (82.7%) in the first and 49 (84.5%) in the last urodynamic study. NDO was present in 38 cases (65.5%) in the first and last urodynamics (with nine of these being new-onset cases in the last and nine others having resolved after the first).

The presence of a scar in the first scintigraphy (p=0.01) and the presence of hydronephrosis in the first and last US (p=0.03) were found to be independent risk factors for new scar development (Table II). When 40 cmH₂O was accepted as the threshold value, no significant relation was found between DLPP and new scar development (p=0.05). When DLPP values were evaluated with ROC analysis for new scar development, 50 cmH₂O was observed as a significant threshold value with 73% sensitivity and 60% specificity. A significant correlation was found between this threshold of DLPP and the development of a new scar (p=0.03).Kidney failure was observed in only one case. Bladder augmentation was performed in 7 (12.1%) of the cases. All patients who underwent augmentation cystoplasty had NDO (p=0.041). There was no relation to other variables, such as the presence of vesicoureteral reflux or DSD. The mean DLPP values (63.86±24.98 cmH₂O) in the first urodynamic studies of the patients who required bladder augmentation were higher than in other cases (53.65±31.12 cmH₂O), but it was not significant (p=0.41).

Discussion

The necessity of urological follow-up is not questioned for patients with SB, but the frequency and design of follow-up are not well-defined or standardized. Close monitoring and pro-active patient management are shown to reduce upper urinary tract damage and bladder surgery (2,3). The follow-up protocol of our department involves outpatient visits every 6 months until the age of 2, followed by annual visits even in uneventful cases. Long-term follow-up of all cases is recommended due to the risk of tethered cord and its urological consequences (8). However, our study revealed that only a small number of patients were compliant with this protocol, and only a small group of the patients we followed could be included in the study (flow-chart/Figure 1). Many factors, such as mobility restrictions of the patients, or socio-economic problems, may hinder attending the outpatient visits regularly. Identifying patients at risk and arranging follow-up intervals according to these risk factors may lead to better adherence of the families to the protocols and decrease the burden on those centers caring for these patients.

International Children’s Continence Society classifies detrusor anomalies in the voiding phase as overactive and underactive (8). In the voiding phase, the inability of the urethral sphincter to relax due to neuropathic reasons has been defined as DSD. By the addition of cases with no sphincter activity, basically, four types of neuropathic bladder-sphincter disorders are revealed (9,10). Various studies were conducted showing the possible negative effects of high detrusor pressure on kidney function. Steinhardt et al. (11) showed that in patients with SB, the glomerular filtration rate decreased when the bladder filling pressure was 35-40 cmH₂O (11). Austin et al. (12) highlighted that DLPP over 40 cmH₂O is a high value that can cause upper urinary system damage. The cases with overactive bladder and DSD would be the most vulnerable patients who have higher bladder pressure (13). For these reasons, DLPP over 40 cmH₂O, DSD, and high-pressure overactivity are defined as urodynamic “hostile bladder” parameters by the CDC (7).

There have been different studies to determine the threshold DLPP value that causes urinary tract damage. The threshold value that generally indicates the hostility of the bladder has been determined to be 40-50 cmH₂O (11,12). Intravesical pressure reaching high values during the filling phase will likely affect the upper urinary tract. Determining this threshold may help to guide treatment. Although this threshold value appeared to be 50 cmH₂O in our study, it might be safer to accept a lower threshold value as different results were found in different studies, and some of these were as low as 20 cmH₂O (14). Prospective large series are needed in order to find the answer to this question.

Tanaka et al. (4) found the renal scar rate in the first scintigraphic examination of children with SB to be 7.5%. This rate seems to be lower than in our study. This may be due to unintentional sampling bias in our study as patients with more problems tend to comply better with longer follow-up periods.

Vesicoureteral reflux studies revealed existing renal scars to be a risk factor for developing new scars (15,16). Our study showed similar results with having a scar in the first scan being an independent risk factor for new scar development.Hydronephrosis was observed in 8 (13.7%) of our cases; six of these were high grade. Tanaka et al. (4) detected hydronephrosis in 44.1% of cases with SB, and 3.7% had high-grade hydronephrosis in the initial US examinations. This rate is quite high compared to the rate in our study. In our series, 6 of 8 cases with hydronephrosis in the first US developed new scars (p<0.05). A high degree of HN was present in 5 of these six cases. High-grade HN was found to be a significant risk factor in terms of new scar development. Due to the sequelae dilatations observed in some patients, hydronephrosis in SB patients can sometimes be considered insignificant. Our study emphasizes the importance of high-grade hydronephrosis as a warning sign for further evaluation to prevent kidney damage.

Bladder augmentation is performed in cases with high bladder pressure, low capacity, incontinence, and upper tract damage despite appropriate management (17). The rate of patients undergoing bladder augmentation in pre-treated patients varies between 5-17%, while in untreated cases, this rate can rise to 41% (3,17-19). In our study, the bladder augmentation rate was 12.1%, similar to these, and similar to that of American SB Centers (12.7%) (19). In a study by Corona et al. (20), VUR and a DLPP of 40 cmH₂O or above at the end of the filling phase were defined as the factors that increase the need for bladder augmentation. In studies conducted by different researchers, VUR incidence in patients with SB was between 27-34% (6,21). The VUR incidence in our study was similar to other studies at 24.1%. The mean first DLPP of patients who underwent augmentation cystoplasty was higher than those patients who did not require this procedure; however, the difference was not significant. The presence of NDO in the first urodynamic examination emerged as an independent risk factor for the need for augmentation.

Study Limitations

The most important limitation of our study is its retrospective nature. Also, the lack of compliance with protocols caused many patients to be excluded from this study. This is mostly secondary to being a tertiary center with patients referred from other provinces and centers, to re-evaluate their management.

Conclusion

Loss of low-pressure reservoir function of the bladder in cases with SB can cause upper urinary tract damage. Therefore, "hostile bladder" was defined by CDC to predict patients at risk of kidney damage. Our study confirmed the detrimental effects of high pressure and detrusor-sphincter dyssynergia; however, the hostile bladder parameters were not sufficient to distinguish high-risk group patients. The presence of scars in the first scintigraphic evaluation, DLPP above 50 cmH₂O, and the presence of hydronephrosis in the first ultrasound were found to be risk factors for renal deterioration. More frequent monitoring and detailed evaluation may be necessary for those patients with these risk factors. Prospective studies are required to design better management strategies individualized for each patient.