Comparing the role of renal ultrasound vs MAG3 renal scans for evaluation of neurogenic bladder after spinal cord injury

Abstract

Objective

Compare ability of renal ultrasound and Tc-99m mercaptoacetyltriglycine (MAG3) renal scan to identify upper urinary tract stasis.

Design

Retrospective chart review.

Setting

Outpatient Neuro-urology clinic serving a large SCI population.

Participants

One hundred and sixty-five individuals with spinal cord injury, presenting for annual evaluation.

Interventions

Renal ultrasound, MAG3 renal scan.

Outcome Measures

Radiologic evidence of upper urinary tract stasis as reviewed by independent radiologist. For renal ultrasounds, this included: mild hydronephrosis, dilation of collecting systems, pelviectasis, or caliectasis. For MAG3 renal scans, this included evidence of slow drainage of radioisotope, dilation of collecting systems, or reverse peristalsis.

Results

Forty-five individuals with spinal cord injury demonstrated upper tract stasis, with 12 identified by renal ultrasound and 43 identified by MAG3 renal scan. There was a strong relative correlation between test results (Yule’s Q = 0.90), though MAG3 renal scan identified a significantly higher rate of upper tract stasis within the same patients (P < 0.0001). The odds ratio of improved identification using MAG3 renal scan was 16.5 (95% CI 3.96–68.76).

Conclusions

While renal ultrasound is more effective at evaluating renal anatomy, MAG3 renal scan identifies significantly more upper urinary tract stasis than renal ultrasound and should be considered for SCI individuals with risk factors of upper tract injury.

Introduction

Following spinal cord injury (SCI), neurogenic bladder is nearly ubiquitous.^1–3 Currently, a major focus of bladder management following SCI is the prevention of urinary tract infections since they are the most common secondary complication and frequently cause hospitalization. However, while less prominent, renal failure was previously the most common cause of death after SCI.⁴ Fortunately, renal failure following SCI is now very uncommon. This is due largely to an understanding of upper tract drainage, the use of anticholinergic medications, identification of risk factors of upper and lower tract damage with urodynamics and, importantly, careful monitoring of the upper tracts.

Chronic elevated bladder pressures are the primary reason for upper tract renal deterioration. This high-pressure environment within the bladder is commonly due to detrusor overactivity combined with functional outlet obstruction (through increased bladder neck tone or detrusor sphincter dyssynergia). These high pressures in the bladder cause compression of the intramural ureters that travel between the bladder submucosa and the detrusor muscle before opening into the bladder. Compression of the ureters, in turn, restricts drainage from the kidneys into the bladder, causing urinary stasis.⁵ If left unchecked, this stasis can cause direct renal damage, first in the renal tubules and then later in the glomeruli.⁶ This eventually leads to hydronephrosis, irreversible scarring of the renal parenchyma, progressive renal functional deterioration, and renal failure. This process can be accelerated in those with a congenital posterior ureteral orifice, in which there is no anatomic mechanism to prevent vesicoureteral reflux.⁷ Moreover, stasis of the upper tracts can also cause significant secondary complications such as pyelonephritis and renal calculi. As such, it is imperative to detect upper tract stasis as early as possible.

Currently, the two most widely used imaging modalities to assess the upper urinary tracts are renal ultrasound and Tc-99m mercaptoacetyltriglycine (MAG3) renal scans, with the former being much more commonly used in today’s practice environment.⁸ Past studies have demonstrated that renal ultrasound has improved sensitivity (96%) at identifying hydronephrosis over MAG3 renal scans, with 90% specificity.⁹ This direct imaging also provides a higher resolution of the underlying anatomy that can be compromised with prolonged increased bladder pressures.¹⁰ However, there is uncertainty regarding whether waiting for anatomic dilation to be visualized is the best strategy in terms of reducing the risk of complications in patients with high intravesicular pressures.

MAG3 is a radioisotope that is eliminated largely by tubular secretion, and as such, allows a direct measure of each kidney’s renal plasma filtration. As this identifies early decreased functional excretion,¹¹ MAG3 renal scans may detect renal complications before they become advanced and present with anatomic changes visible on ultrasound.⁶ This early identification of decreased renal functional secretion, in turn, may allow earlier detection of renal compromise in individuals with SCI and prompt, timely intervention.^12,13 MAG3 renal scans have 83% sensitivity and 92% specificity at broadly detecting upper urinary tract complications, though there have been limited head-to-head studies between this and renal ultrasound.¹⁴ With renal ultrasound currently being most commonly utilized for screening, we looked to evaluate the utility of MAG3 renal scan at screening for upper tract stasis as part of the annual urologic evaluation for individuals with SCI.

Methods

This retrospective chart review of patients with SCI included consecutive individuals with neurogenic bladder who were being seen for annual urologic evaluation at our single-site academic medical center in the Northeastern United States from 1997 to 1999. This date range was selected as a unique time period when the standard of care included both MAG3 renal scans and renal ultrasound, performed together as part of a single evaluation. All ages and sexes, individuals with both upper and lower motor neuron bladders, and individuals using any methods of urinary drainage were included. At the time of the retrospective review, all individuals with SCI had a MAG3 renal scan without diuretic, renal ultrasound and cystogram as part of their annual evaluation. Since vesicoureteral reflux has the potential to appear as upper tract stasis and not give the true picture of urine transport from the kidneys, individuals were excluded if they demonstrated ureteral reflux or had a history of urinary diversion procedures with ureteral reimplantation.

For the purpose of identifying radiologic evidence of upper urinary tract stasis, stasis on renal ultrasound was defined as the presence of any of the following: mild hydronephrosis, dilation of collecting systems, pelviectasis, or caliectasis. For MAG3 renal scans, radiologic evidence of slow drainage of radioisotope, dilation of collecting systems, or reverse peristalsis were all used as markers of upper tract stasis. All images were read by a radiologist who was not a formal part of this study and reviewed by the senior author.

Statistics

Descriptive statistics were utilized for the characterization of stasis during both renal ultrasound and MAG3 renal scans. To compare the utility of each diagnostic test at identifying evidence of upper tract stasis, McNemar’s test was computed. A 2 × 2 contingency table was assembled with dichotomous endpoints of either stasis or no stasis for each diagnostic test and marginal homogeneity was analyzed (Table 1). Briefly, McNemar’s test uses exact binomial probability to identify the marginal frequency of +/− to −/+ results, allowing comparisons between tests under the null hypothesis that these marginal frequencies should be statistically equivalent if the tests are interchangeable. While the reliability of McNemar’s test can decrease when the summation of such discordant cells is less than 25, our sum (35) surpasses this threshold and thus demonstrates appropriate accuracy. Yule’s Q statistic, a special case of Goodman Kruskal’s gamma coefficient, was also calculated to assess the correlation between renal ultrasound and MAG3 renal scans for historical purposes. Statistical significance was set at a P value of <0.05 and all statistical calculations were performed in R Studio (version 1.1.463). To estimate effect size, odds ratios with 95% confidence intervals were calculated.

Table 1.

2 × 2 contingency table reporting radiologic evidence of stasis on renal ultrasound and MAG3 renal scan.

		MAG3 Renal Scan
		Stasis (+)	Normal (−)
Renal Ultrasound	Stasis (+)	10	2
	Normal (−)	33	120

Results

On review, 165 individuals with SCI (328 renal units) met our inclusion criteria. Of those, 120 (239 renal units) demonstrated no stasis for both renal ultrasound and MAG3 renal scan. Forty-five individuals (89 renal units) demonstrated radiologic evidence of upper urinary tract stasis on renal ultrasound, MAG3 renal scan, or both (Table 1). Of note, two individuals had congenital solitary kidneys.

Anatomic abnormalities were noted in 10 patients on renal ultrasound (2 with renal scaring, 3 with renal cysts, 4 with renal stones, and 1 with a renal stone and a cyst). Anatomic abnormalities noted on MAG3 renal scans included renal cysts in the same 3 individuals identified by renal ultrasound. No further anatomic abnormalities were noted on MAG3 renal scans.

Upper tract stasis was observed in 45 different individuals (Figure 1). Renal ultrasound demonstrated dilation of the collecting system in 12 individuals with SCI. MAG3 renal demonstrated dilation of the collecting system in 11 individuals, slow drainage of the collecting system in 27 individuals, and reverse peristalsis of the ureters in 5 individuals.

Figure 1.

Venn diagram demonstrating incidence of upper tract stasis identification (n = 45) with both renal ultrasound and MAG3 renal scan. Notably, MAG3 renal scan identified 33 individuals (73%) with upper tract stasis that would have been missed by renal ultrasound alone.

Using McNemar’s test of the marginal probabilities, MAG3 renal scan was able to predict upper tract stasis at a significantly higher rate than renal ultrasound within the same patients with SCI (P < 0.0001). The odds ratio of this improved identification was 16.5 (95% CI, 3.959–68.763). Yule’s Q statistic was 0.900, demonstrating a strong relative correlation between the results of renal ultrasound and MAG3 renal scans-powered largely by the agreement of both diagnostic tests being negative.

Discussion

In this study of 165 individuals with SCI, MAG3 renal scan demonstrated significantly higher rates of identifying upper urinary tract stasis. While renal ultrasound was able to identify additional anatomic abnormalities such as renal scarring and stones, radiologic evidence of stasis by dilation of the collecting system was seen with both diagnostic tests (albeit at higher rates with renal ultrasound, consistent with previous literature^9,15). However, MAG3 renal scans identified an additional 33 individuals with upper tract stasis that was not detected on renal ultrasound, demonstrating the dynamic ability of MAG3 renal scans to evaluate flow through the renal tubules.⁶ Stasis was not seen on renal ultrasound in these individuals, and this likely represents early physiologic changes in the upper urinary tracts prior to later anatomic manifestations such as hydronephrosis or deterioration in renal function.

The results of our study appear to counter the limited previous literature looking at renal ultrasound versus MAG3 renal scans following SCI. Gousse et al.¹⁶ performed a very similar retrospective study of 162 patients with SCI having both renal ultrasounds and MAG3 renal scans. Notably this study included a broader range of anatomic abnormalities seen on renal ultrasound in their calculations, as opposed to just signs of upper tract stasis. They computed a Yule’s Q statistic of 0.924 (demonstrating a strong correlation between results of the diagnostic tests) and rationalized that one test (renal ultrasound) could be substituted for the other (MAG3 renal scans). Similarly, our data also generates a high Yule’s Q statistic (0.900, demonstrating that the results of the two diagnostics are similar). However, Yule’s Q statistic, or Goodman Kruskal’s gamma coefficient from which it is derived, is powered in each of these studies primarily by the large number of both diagnostic tests being normal. Since identification of abnormal upper tract findings is the goal, this statistical test decreases in utility. Further, Yule’s Q statistic is typically calculated for nominal data not ordinal data as is the case here. For ordinal data, McNemar’s test is preferential. In fact, calculating McNemar’s test on Gousse et al.’s available data demonstrates that the diagnostic tests in their dataset are significantly different, with MAG3 renal scans again outperforming renal ultrasound (P = 0.004, OR 2.21, 95% CI 1.285–3.800). Even with their wider definition of renal dysfunction seen on renal ultrasound, this study adds to the evidence that MAG3 renal scan has superior efficacy at detecting early upper tract stasis when compared to renal ultrasounds.

Given the significantly increased precision of identifying early pathophysiologic changes to the upper urinary tracts, the use of MAG3 renal scans should be strongly considered, particularly in those with urodynamic risk factors for upper tract damage. There is a strong consensus that elevated voiding pressures on urodynamics place the upper tracts at risk for damage. There is less consensus on what the exact pressure or duration of pressure in the bladder will affect the upper tracts. In myelodysplastic children, abdominal leak point pressures greater than 40 cm H₂0 were considered a risk factor.¹⁷ In those with SCI, detrimental voiding pressures have varied definitions, from 70 cm H₂0 to 109 cm H₂0 to 115 cm H₂0.^18–20 Similarly, the definition of reduced compliance varies with the generally accepted normal values are less than 12.5–15.0 mL/cm H2O in the absence of a detrusor contraction. Moreover, the actual duration of a bladder contraction has been found to be a risk factor for upper tract damage.²¹ Since urodynamics will identify potential risk factors but not exact values that need to be treated, renal scans can serve as an important adjunct both to identify and guide treatment for those who are potentially at high risk for upper tract stasis. Early identification of these issues not only avoids late diagnosis, where renal physiologic deterioration has already occurred, but allows for potential interventions to prevent these consequences and reverse early physiologic changes.^2,13,22 Use of renal ultrasound continues to be clinically indicated as a more precise tool for identifying anatomic and structural abnormalities.

Existing guidelines by experts in the field^15,23,24 commonly recommend renal ultrasound and serum creatinine as key components of upper urinary tract monitoring. Of note, serum creatinine may be significantly depressed after SCI due to decreased muscle mass. To this end, even creatinine levels within typical normal limits may indicate impaired renal function after SCI. These guidelines recommend the use of MAG3 renal scans, if these tests are abnormal. MAG3 renal scans contribute negligible ionizing radiation and have proven safe following SCI.⁶ Further, given their ability to identify renal stasis before anatomic manifestations, they allow a window of time to reverse these renal changes before the anatomy is altered and long-term complications occur. In light of these findings, we suggest that MAG3 renal scans be considered strongly by SCI clinicians for patients at high risk for upper tract stasis.

Limitations

Being a retrospective study, this represents a single time point, and as such, we did not assess if these 33 individuals who demonstrated renal stasis on MAG3 renal scan went on to later develop anatomic changes visible on renal ultrasound. Subsequently, these patients were treated with the goal of preventing the development of such long-term anatomic changes, negating chronologic analysis. Further, individuals were selected for this retrospective study if they had both renal ultrasound and MAG3 renal scan performed. While some individuals had only one of the two sans completed, there is no reason to believe this would alter the observed imaging discrepancy within our study population. Finally, demographics, race/ethnicity, and comorbidities were not recorded within this dataset, limiting potential subanalyses to identify if the incongruency between MAG3 renal scans and renal ultrasound results were concentrated within a certain group. However, given that these individuals were consecutive, typical patients with SCI presenting to an outpatient Urology practice for routine annual evaluation, we feel the results remain highly generalizable.

Conclusions

This study shows that MAG3 renal scan identifies significantly more upper urinary tract stasis than renal ultrasound, but renal ultrasound was superior to MAG 3 renal scans at identifying anatomical changes. Thus, when deciding on what test to use to evaluate the upper tracts, MAG3 renal scans should be considered as an adjunct to renal ultrasound in those identified with urodynamics to have high-risk factors for upper tract damage.

Disclaimer statements

Contributors None.

Funding This research was unfunded. Dr Solinsky’s time was supported by an NIH career development award, K23HD102663.

Conflicts of interest Authors have no conflict of interests to declare.