Spina bifida (SB) is a congenital birth defect that causes a wide spectrum of neurourological complications related to a neuropathic bladder. Since the bladder is inherently connected to the kidneys, individuals with SB experience a lifelong risk of developing kidney dysfunction. As improved care has extended life expectancy and kidney dysfunction increases with age, it is not surprising that admissions for chronic renal insufficiency in SB patients is increasing. ¹ Management of individuals with SB therefore prioritizes protecting kidney health. This prioritization is reflected in myriad international, national and societal guidelines and serves as the basis for the Centers for Disease Control and Prevention (CDC)-sponsored Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida (UMPIRE) study. ² However, recent research demonstrates that monitoring kidney function in individuals with SB is a greater challenge than in other urological patients, for reasons we will highlight here.

First, determining kidney function in children often relies on common equations to calculate an estimated glomerular filtration rate (eGFR). Unlike adults, where a creatinine value alone often suffices as a surrogate for kidney function, creatinine values in children change inherently during growth. Hence, eGFR equations were created to “normalize” kidney function, adjusting laboratory values, such as creatinine, to growth parameters, such as height. Unfortunately, the large cohorts in which these eGFR equations were developed usually excluded children with SB. Given the discrepancy in height and muscle mass in children with SB compared to children without SB, there has been increasing evidence showing that commonly used eGFR equations give highly variable results. ³ Specifically, creatinine based eGFR equations generally give higher eGFR values (ie better estimates of kidney function) than cystatin C based eGFR equations. Additionally, over time, creatinine based eGFR equations give increasing values for eGFR with age, although it is extremely unlikely that kidney function improves with time. Cystatin C based eGFR equations meanwhile report declining eGFR values as children age, which seems more realistic. These results question the reliability and accuracy of current eGFR equations in children with SB.

A second challenge reflects artefactual changes in eGFR through application of adult vs pediatric eGFR equations. In populations excluding individuals with SB, eGFR equations were developed separately for children and adults, often using a cutoff age of 18 years to determine which set of equations to apply to calculate eGFR. However, in a single institutional study of patients 18 to 28 years old with SB, when corresponding adult eGFR equations were applied using the same creatinine or cystatin C values as a pediatric eGFR equation, there was an artefactual increase in eGFR by 20% to 25%. ⁴ In other words, application of an adult eGFR equation automatically “improves” the eGFR, even if cystatin C is used. This artifact may downstage the severity of kidney function, which further complicates the recognized difficulties of successfully transitioning an individual with SB from pediatric to adult medical care.

A third challenge is that studies of practice patterns suggest that adherence to routine kidney function surveillance is suboptimal. Despite the limitations of creatinine, as aforementioned, there is still value inherent in the data, eg an abnormally low creatinine based eGFR is likely to reflect true kidney dysfunction. Additionally, several SB guidelines include a role in checking serum creatinine. However, within a large cohort of 5,445 patients with SB who participate in the CDC-sponsored National Spina Bifida Patient Registry (NSBPR) at clinics committed to SB research and care, wide variability was found across clinics in terms of their adherence to kidney function surveillance, which was defined as at least 1 renal ultrasound and at least 1 serum creatinine within a 2-year window. ⁵ The average adherence to this combined surveillance definition was only 62%, ranging from 6% to 100% across 23 clinics participating in NSBPR. Notably, more clinics checked routine ultrasound (93%) than routine serum creatinine (69%) to assess kidney health.

However, this practice pattern segues to a fourth challenge to monitoring kidney function in individuals with SB, which is that ultrasound based hydronephrosis is a poor screening test for low eGFR. In a single center retrospective series of 247 patients with SB, using cystatin C eGFR as the gold standard, hydronephrosis as determined by ultrasound had 23% to 48% sensitivity in children for eGFR <90 ml/min/1.73 m ². ⁶ High grade hydronephrosis was even worse, with 4% to 15% sensitivity. Results were unchanged after excluding patients with small kidneys or scarring. In other words, many children with SB can have low eGFR and kidney dysfunction without hydronephrosis. Coupled with the prior results showing a bias toward surveillance ultrasounds rather than creatinine testing, many patients with SB may not be having their kidney function monitored accurately with current, commonly used tools.

It is important to put these challenges in monitoring kidney function into the global context of the overall care of children with SB. The lifelong health risks of this population are not limited to kidney health, but also apply to other key issues including bladder and bowel continence, skin care, prevention of obesity and obesity-related health problems, loss of mobility and neuropsychosocial concerns. In this context, several opportunities arise for additional kidney health-related research. For example we do not know how individuals with SB perceive kidney health relative to their other health risks, nor how these perceptions change during their lifetime. Patient reported outcomes followed longitudinally may shed light on this knowledge gap. Additionally, as shown in the prior work within NSBPR, dissemination and implementation of clinical guidelines remain suboptimal. Efforts are needed to enhance uptake of ideally evidence-based protocols, or consensus protocols if high quality definitive evidence is unavailable. Better laboratory or imaging based methods or tools must be developed to accurately and reliably assess kidney health in the SB population. Hopefully, within multi-institutional infrastructures such as those offered by the UMPIRE and NSBPR studies, these and other important research and clinical questions can be adequately answered.