Urologic guidelines for the care and management of people with spina bifida

These guidelines were created to assist care providers across disciplines with the basic requirements to maintain normal renal function, establish continence that would be considered socially acceptable, and ultimately allow for transition to self-care. Overarching goals for all guidelines across disciplines was to focus care coordination in a patient- and family-centered fashion and to develop a medical home and neighborhood founded on team-based care.

Institutions create protocols for care based on their philosophy and available resources. Two general philosophies of early urologic management prevail: a proactive approach and a reactive approach. The proactive approach attempts to identify children at risk for upper urinary tract deterioration based on specific hostile parameters. Treatment is initiated before renal compromise occurs. The reactive approach follows a child closely and institutes management at the first sign of any adverse change [7, 9, 12]. Advocates of a proactive approach favor early identification of “at risk” children by assessing bladder function through urodynamic testing and managing hostile bladder parameters. This is undertaken to prevent adverse upper urinary tract changes and preserve normal renal function, thus minimizing possible irreversible upper tract deterioration. It is known that some individuals will be subjected to the consequences of intervention that were unnecessary, exposing them to associated risks, and may needlessly utilize resources. Institutions favoring a reactive approach rely on close evaluation of the upper urinary tract, renal function, and documentation of urinary infections. They feel adverse upper urinary tract changes and renal compromise can be detected early utilizing minimally invasive assessment, renal ultrasonography, and assessing renal function parameters with a serum renal function study. Adverse changes are assumed to be reversed with medical, pharmacologic, and operative management. This approach involves treating children reactively, “as needed,” and allows for a more precise selective management model limiting the stress and potential side effects of invasive procedures, medications, catheterization, and surgery. However, it is not known if all adverse renal changes noted on ultrasonography can be reversed, and if current renal function studies, particularly serum creatinine, truly reflect the renal status in patients with spina bifida. The urologic guidelines merge aspects of both proactive and reactive management.

People with spina bifida are at risk for progressive renal damage secondary to recurrent urinary tract infections and a hostile neurogenic bladder. Bladder hostility may result in upper urinary tract deterioration, hydronephrosis, recurrent pyelonephritis and renal scarring. Some patients may progress to end stage renal disease requiring dialysis or renal transplantation [23, 24]. Infants with spina bifida demonstrate overall normal baseline imaging (including renal US and baseline DMSA) [1]. Hence management of bladder function to prevent adverse upper urinary tract changes to preserve renal function is critical [1, 25].

Establishing guidelines to follow evidence-based management is logical. In 2003, sponsors from the NIH, CDC and SBA convened a conference of 100 authorities across multiple disciplines tasked with creating a research agenda for spina bifida based on what was known and lacking in evidence-based care [26]. Universally, evidence-based management was found to be lacking. Directives in 2003 were provided to help position research that would enhance the level of care based on sound evidence. Those goals had not been achieved through 2015 when work began on these guidelines. Therefore, the guidelines remain by consensus and they are not meant to represent a standard of care.

It is important to understand that these guidelines remain primarily a tool for assessment. Clearly, direction is lacking regarding treatment related to a medical, pharmaceutical, or surgical intervention. Diversity in patient population, regional differences, institutional resources, and local urologic philosophy all play a role in care and prevented the working group from establishing a consensus.

“Clinical questions” were the driving metric used to establish the guidelines. A prevailing question within all age groups was related to urinary tract infections. Our intent was to support a common definition for a urinary tract infection based on symptoms along with objective urinalysis and culture of urine that could be maintained throughout the lifespan. We identified the work of Madden-Fuentes et al. as the most relevant and reflective definition [8]. It is appreciated that intermittent catheterization and other clinical symptoms (abdominal pain, new onset of leakage, etc.) may be additional guiding factors when assessing a positive urine culture. Identifying what truly is a symptomatic urinary tract infection requiring treatment allows for early judicious antibiotic therapy, and hopefully will reduce the cycle of over treating asymptomatic bacteriuria.

The underlying goal of the urologic guidelines is to maintain normal renal function starting from birth. The glaring absence of evidence-based care of newborns, toddlers and young children prompted the CDC to develop a management protocol [27]. Now recognized as UMPIRE (urologic management to preserve initial renal function), the longitudinal protocol was established in 2014 at 9 centers throughout the United States following children from birth through the age of 5 years [25]. This is an iterative quality improvement consensus-based protocol utilizing prospective treatment. Outcomes are routinely assessed based on evidence with adjustments made to optimize care. UMPIRE has primary outcomes focused on urinary tract infection, renal function and bladder characteristics. The role of urodynamic testing is critical to the protocol. The appreciation of nuances related to testing and interpretation has already impacted the standardization of technical aspects of the procedure and objective identification of common urodynamic parameters (i.e., detrusor over activity, detrusor leak point pressure, end fill pressure, detrusor-sphincter-dyssynergy). The CDC has recently extended UMPIRE through 10 years of age. It is envisioned that UMPIRE will provide the lacking evidence to support proactive care.

The foundation of all urologic care is based on maintaining normal renal function, and increased monitoring in people with spina bifida is also one of the guideline goals. We appreciate that a significant deficiency exists within these guidelines regarding the establishment of objective renal function. The Kidney Disease Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the evaluation and management of chronic kidney disease emphasizes the importance of assessing renal function in all patients with chronic kidney disease [28], which is defined as abnormalities of kidney structure or function present for greater than 3 months. Chu et al. suggest that providers are not assessing kidney function in most practices in the spina bifida registry [29].

Currently, there is no consensus on how to best monitor for renal function in children with spina bifida. The UMPIRE study will be assessing serial radiologic imaging studies, urodynamics, renal scarring by DMSA renal scan and various measures of GFR over time [1, 25]. KDIGO guidelines suggest using serum creatinine and a GFR estimating equation (eGFR) for initial assessment, with additional tests such as cystatin C or clearance measurement for confirmatory testing in circumstances when eGFR based on serum creatinine is less accurate. Formulas to calculate eGFR, including Schwartz formula, 2012 CKD-EPI cystatin C formula and CKD-EPI creatinine-cystatin C equation, and alternate cystatin C based GFR equations, are found in the KDIGO guideline paper [28].

In patients with spina bifida, creatinine is a poor marker of eGFR due to low muscle mass, particularly those who are non-ambulatory. This was initially suggested in 1997 by Quan et al., where authors described poor correlation with diethylenetriamine pentaacetate (DTPA) eGFR and the creatinine based Schwartz formula [30]. In addition, creatinine based Schwartz formulas required an accurate height measurement, which can be difficult to obtain in many non-ambulatory patients with spina bifida. Cystatin C, another marker of renal function, is a protein produced at a constant rate by all nucleated cells. It is freely filtered by the glomerulus and not secreted at the renal tubule and is nearly entirely catabolized within the proximal tubule [31, 32]. Several small studies have suggested that cystatin C based eGFR equations may be better in patients with spina bifida. Clearance studies have been considered the gold standard. They require injection of a substance with multiple timed blood draws. Inulin clearance may be the most accurate, but has limited availability [33]. Iohexol, 51-cr-EDTA and 99Tc-DTPA are also options, but require body surface area calculations to give GFR in ml/min/1.73m2 that require accurate weight and height measurements. Lastly, Zappitelli et al. developed a specific spina bifida formula which was studied in a small cohort and also assessed recently in a single center study [29, 31]. Variability in assessment of eGFR in children and adults based on the formula used has been reported [34].

Urinary continence increasingly becomes relevant as children age into adolescence, the teen years, and adult life [35]. It impairs quality of life, ability to function in school and work, and increasingly impacts health quality with aging [36]. For many people with spina bifida, attaining continence requires engagement of the patient and family members. A dedication to self-management skills and careful decision-making with the urologic team regarding the need for and timing of interventions must be established. Nursing support and education for the patient and family before and after continence procedures must be expected. The guidelines recommend that discussions are initiated early in childhood and continue through adult life. It is well documented that continence is not stable throughout the lifespan and declines in adult life in people with spina bifida as well as the general population. Regular discussion with urologic providers related to urinary incontinence episodes, complications associated with leakage, and patient bother is recommended [37, 38]. Data are lacking regarding the optimal definition of continence in patients with spina bifida. However, studies suggest that volume and frequency of leakage events is proportional to quality of life impact [39]. Therefore, patients should be evaluated annually for both frequency and quantity (volume) of leakage events, occurrence of skin breakdown associated with urinary incontinence, and bother associated with urinary incontinence. The goals for continence should be discussed regularly with the urological care team.

The increased lifespan of patients with spina bifida awakened the medical community about the importance and urgent need of transitioning care from the caregiver to young adult, and from the pediatric Urologist to the adult Urologist. Several transition programs have been introduced throughout the nation that focus on educating the young adults about their disease and need for lifelong medical management [40, 41]. Equally important is the involvement of the adult providers in the often-complicated care of these patients as they leave pediatric practices. Transition programs focus on involving the patients and their families in achieving maximal independence and comfort within the adult medical system with the major goal of maintaining compliance with follow up to avert preventable long-term problems.

It has been noted that the primary limitation with these guidelines is the fact they are not directed by evidence-based practice. The small patient population within individual spina bifida centers and the inability to create prospective randomized trials with control groups that withhold care prevents establishment of evidence-based recommendations. Moving forward, multi-institutional assessments and studies (e.g. UMPIRE) will be needed for greater direction in objective care. The CDC’s National Spina Bifida Patient Registry provides a platform to collate patient data in a standardized fashion in hopes of ratifying best practice methodologies [42]. Adding to that, a standardized approach to urologic assessment as these Guidelines provide, should help limit some of the common variables that exist between centers.

5. Conclusion

The urologic guidelines were developed on a platform of clinical questions based on age. The lack of evidence-based studies necessitated our utilization of consensus opinion in order to direct care surrounding our clinical questions. This sheds light on the major gaps in urologic clinical care that need further research. While not the “Standard of Care,” there is justification for utilizing these guidelines as “Best Practice.”