+
MODEL
Journal of Pediatric Urology (2015) xx, 1.e1e1.e4
The “flowerpot” sign: Inference of poor renal function in high grade vesicoureteral reflux by calyceal orientation Children’s National Medical Center, The George Washington University School of Medicine, 111 Michigan Ave NW, Washington, D.C. 20010, USA Correspondence to: A.D. Martin, Louisiana State University Health Sciences Center, Children’s Hospital New Orleans, 200 Henry Clay Ave, New Orleans, LA 70118, USA, Tel.: þ1 5048969233; fax: þ1 5048969861 [email protected] (A.D. Martin) [email protected] (K. Gupta) [email protected] (K.A. Swords) [email protected] (A.B. Belman) [email protected] (M. Majd) [email protected] (H.G. Rushton) [email protected] (H.G. Pohl) Keywords Vesicoureteral reflux; Nephropathy; Voiding cystourethrogram; Pediatrics
Abbreviations DRFdifferential renal function; VURvesicoureteral reflux; UTIurinary tract infection; VCUGvoiding cystourethrogram Received 5 February 2014 Accepted 27 July 2014 Available online xxx
Aaron D. Martin, Kavita Gupta, Kelly A. Swords, A. Barry Belman, Massoud Majd, H. Gil Rushton, Hans G. Pohl Summary
Introduction/objective Modern radiographic advances have allowed for detailed and accurate imaging of not only urologic anatomy but also urologic function. The art of observational inference of subtle anatomic features and function from a static radiograph is being traded for new, more precise, and more expensive modalities. While the superiority of these methods cannot be denied, the total information provided in simpler tests should not be ignored. The relationship between high grade vesicoureteral reflux with the dilated calyces arranged cephalad to a dilated funnel-shaped renal pelvis on VCUG and reduced differential renal function has not been previously described, but has been anecdotally designated a “flowerpot” sign by our clinicians. We hypothesize that the appearance of a “flowerpot” kidney as described herein is an indicator of poor renal function in the setting of high grade VUR.
Study design IRB approval was obtained and 315 patients were identified from system-wide VCUG reports from 2004e2012 with diagnosed “high grade” or “severe” vesicoureteral reflux. Inclusion into the study required grade IV or V VUR on initial VCUG and an initial radionuclide study for determination of differential function. Patients with a solitary kidney, posterior urethral valve, multicystic dysplastic kidney, renal ectopia, or duplex collecting systems were excluded. Grade of reflux, angle of the inferior-superior calyceal axis relative to the lumbar spine, and differential uptake were recorded along with presence of the new “flowerpot” sign. Variables were analyzed using the ManneWhitney U test to determine statistical significance.
Results Fifty seven patients met inclusion criteria with 11 being designated as “flowerpot” kidneys. These “flowerpot” kidneys could be objectively differentiated from other kidneys with grade IV and/or grade V VUR both by inferioresuperior calyceal axis (median angle, 52 [37e66] vs. 13 [2e37], respectively p < 0.001) and by differential renal uptake (median, 23% [5e49] vs. 45% [15e81], respectively p < 0.001). Likewise, there was no difference between either calyceal axis (median angle, 13 [3e20] vs. 13 [2e37]) or differential function (median, 48% [24e81] vs. 40% [15e66], p Z 0.129) when comparing kidneys with grade IV and grade V VUR, respectively, that did not demonstrate the “flowerpot” sign. Discussion/conclusion Grading of VUR is used to provide a common language for scientific discussion and determine prognosis for children with similar attributes. The dysmorphic calyceal system in the “flowerpot” kidneys supports the theory of abnormal renal blastema induction associated with abnormal differentiation of the ureteral bud. Even in the absence of urinary tract infections and/or pyelonephritis, renal abnormalities and decreased differential function can be observed on renal scintigraphy. This study also confirms the male predominance and functional similarities between grade 4 and 5 refluxing renal units. Recognizing this is a limited observational study based on imaging alone, the “flowerpot” sign is an indicator of the most severe form of grade 5 VUR but is only one factor in predicting long term overall renal prognosis. However, 14% (8/57) of our cohort had a relative uptake of less than 20% with 5 of these exhibiting the “flowerpot” sign. The “flowerpot” sign on VCUG can be used as indirect evidence of poor differential renal function and, therefore, useful in guiding parental expectations prior to formal functional imaging.
http://dx.doi.org/10.1016/j.jpurol.2014.07.014 1477-5131/ª 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Martin AD, et al., The “flowerpot” sign: Inference of poor renal function in high grade vesicoureteral reflux by calyceal orientation, Journal of Pediatric Urology (2015), http://dx.doi.org/10.1016/j.jpurol.2014.07.014
+
MODEL
1.e2
A.D. Martin et al.
Ureteral polyps on retrograde pyelogram.
Introduction Modern radiographic advances have allowed for detailed and accurate imaging of not only urologic anatomy but also urologic function. The art of observational inference of subtle anatomic features and function from a static radiograph is being traded for new, more precise, and more expensive modalities. While the superiority of these methods cannot be denied, the total information provided in simpler tests should not be ignored. A voiding cystourethrogram (VCUG) is the gold standard in diagnosing and grading vesicoureteral reflux (VUR). While it is not a functional study, it is a robust anatomic study for the astute observer with the ability to provide information regarding not only the bladder, ureters, and urethra but also the axial skeleton, bowel, liver, diaphragm, and more. The inference of function from anatomic shape of various urologic organs is widely assumed clinically, but rarely validated. We hypothesized that the appearance of a “flowerpot kidney” as described herein is an indicator of poor renal function in the setting of high-grade VUR. This information can be used to prepare patients’ expectations of quantitative functional studies and help facilitate discussions of further treatment decisions.
patients were further screened by a pediatric urologist viewing the films to determine eligibility based on presence of grade IV or V VUR on initial VCUG and an initial radionuclide study (DMSA or MAG-3) for determination of differential renal function (DRF). Patients were excluded for any of the following anatomic abnormalities: solitary kidney, posterior urethral valve, multicystic dysplastic kidney, renal ectopia, or duplex collecting system. Patients who satisfied all the study criteria were then categorized based on grade of VUR, angle of the inferioresuperior calyceal axis relative to the lumbar spine (Fig. 2), DRF, and presence of the “flowerpot” sign. Although flowerpot kidneys would typically be considered grade V VUR, we included grade IV VUR in our analysis to not only eliminate potential biased mischaracterization of grade V VUR but also determine if axis changes could be seen with increasing grade alone. Statistical comparison of renal units with and without this radiologic finding was performed using the ManneWhitney U test in GraphPad Prism version 5.0 for Windows (San Diego, CA, USA).
Methods The initial description and categorization of this distinct radiologic entity was made by two senior faculty at our institution, who related the image likeness to a “flowerpot” (Fig. 1). During maximal reflux, the calices of these kidneys appear to be located largely cephalad to the renal pelvis as opposed to lateral in the normal configuration (Fig. 2). To explore the scientific validity of this anecdotal observation, IRB approval was obtained to screen VCUGs from our institution from 2004 to 2012. This was accomplished using the Montage radiology search engine (Montage Healthcare Solutions, Philadelphia, PA, USA) to obtain all VCUG reports containing the words “high grade, severe, grade IV, and/or grade V” in the radiology report text. These initial 315
Figure 1
Overlays demonstrating the likeness to a flowerpot.
Please cite this article in press as: Martin AD, et al., The “flowerpot” sign: Inference of poor renal function in high grade vesicoureteral reflux by calyceal orientation, Journal of Pediatric Urology (2015), http://dx.doi.org/10.1016/j.jpurol.2014.07.014
+
MODEL
The “flowerpot” sign
1.e3
Figure 2 Migration of calyceal axis superiorly and renal pelvis inferiorly with increased filling producing the flowerpot configuration. The blue line represents the spine axis and the red-dotted line represents the calyceal axis for a normal right grade V VUR and a left grade V VUR with the flowerpot sign. VUR Z vesicoureteral reflux. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Results Of the 315 patients identified through the initial radiologic records search, 57 patients met all inclusion/exclusion
criteria. Eleven of these renal units were designated as “flowerpot” kidneys. Interestingly, all of the “flowerpot” kidneys were male patients. “Flowerpot” renal units had statistically significant lower DRF (p 0.001) than those without the sign. Median DRF of “flowerpot” renal units was 23% (range 5e49%). Grade IV VUR units, grade V VUR units, and combined grade IV or V VUR units demonstrated median DRF of 48% (range 24e81%), 40% (range 15e66%), and 45% (range 15e81%), respectively (Fig. 3a). The median renal calycealespine angle was found to be significantly greater in the “flowerpot” kidney than kidneys with grade IV VUR, grade V VUR, and grade IV or V VUR combined (52 [range 37e66] vs. 13 [range 3e20], 13 [range 2e37], 13 [range 2e37], respectively; p < 0.001) (Fig. 3b). This confirmed the visual cues used to identify these kidneys informally.
Discussion
Figure 3 Scatter plots of (a) relative uptake and (b) renalespine angle by group. Bars represent median value. Dots represent individual values. FP Z flowerpot sign; Roman numerals Z grade of VUR. VUR Z vesicoureteral reflux.
Grading of VUR is used to provide a common language for scientific discussion and determine prognosis for children with similar attributes. The current International Scale is a five-point scale based on level of retrograde contrast, shape and fullness of the collecting system, and tortuosity of the ureter [1]. Grade IV or V reflux is fortunately rare representing only 12% of VUR [2]. Evidence supports that children with early reflux related renal abnormalities may be at risk for future renal deterioration [3]. Many of these kidneys have congenital renal function abnormalities as demonstrated by studies performed in infants with high grade VUR detected during the evaluation of prenatally detected hydronephrosis prior to any episodes of urinary tract infection (UTI). Pathologic examination of poorly functioning kidneys with primary VUR reveals areas of segmental dysplasia adjacent to normal renal parenchyma [4]. Theories of VUR-associated renal functional abnormalities include congenital developmental abnormalities, including both dysplasia and hypoplasia, associated with an abnormal or ectopic ureteral bud [3,5]. The dysmorphic calyceal system in the “flowerpot” kidneys supports the theory of abnormal renal blastema induction associated with abnormal differentiation of the ureteral bud. Renal abnormalities are also known to be more common in
Please cite this article in press as: Martin AD, et al., The “flowerpot” sign: Inference of poor renal function in high grade vesicoureteral reflux by calyceal orientation, Journal of Pediatric Urology (2015), http://dx.doi.org/10.1016/j.jpurol.2014.07.014
+
MODEL
1.e4 patients with early reflux at low bladder volumes and pressures and in males [6e8]. Even in the absence of urinary tract infections and/or pyelonephritis, renal abnormalities and decreased differential function can be observed on renal scintigraphy. Nguyen et al. [9] found decreased differential function (defined as uptake
MODEL
Journal of Pediatric Urology (2015) xx, 1.e1e1.e4
The “flowerpot” sign: Inference of poor renal function in high grade vesicoureteral reflux by calyceal orientation Children’s National Medical Center, The George Washington University School of Medicine, 111 Michigan Ave NW, Washington, D.C. 20010, USA Correspondence to: A.D. Martin, Louisiana State University Health Sciences Center, Children’s Hospital New Orleans, 200 Henry Clay Ave, New Orleans, LA 70118, USA, Tel.: þ1 5048969233; fax: þ1 5048969861 [email protected] (A.D. Martin) [email protected] (K. Gupta) [email protected] (K.A. Swords) [email protected] (A.B. Belman) [email protected] (M. Majd) [email protected] (H.G. Rushton) [email protected] (H.G. Pohl) Keywords Vesicoureteral reflux; Nephropathy; Voiding cystourethrogram; Pediatrics
Abbreviations DRFdifferential renal function; VURvesicoureteral reflux; UTIurinary tract infection; VCUGvoiding cystourethrogram Received 5 February 2014 Accepted 27 July 2014 Available online xxx
Aaron D. Martin, Kavita Gupta, Kelly A. Swords, A. Barry Belman, Massoud Majd, H. Gil Rushton, Hans G. Pohl Summary
Introduction/objective Modern radiographic advances have allowed for detailed and accurate imaging of not only urologic anatomy but also urologic function. The art of observational inference of subtle anatomic features and function from a static radiograph is being traded for new, more precise, and more expensive modalities. While the superiority of these methods cannot be denied, the total information provided in simpler tests should not be ignored. The relationship between high grade vesicoureteral reflux with the dilated calyces arranged cephalad to a dilated funnel-shaped renal pelvis on VCUG and reduced differential renal function has not been previously described, but has been anecdotally designated a “flowerpot” sign by our clinicians. We hypothesize that the appearance of a “flowerpot” kidney as described herein is an indicator of poor renal function in the setting of high grade VUR.
Study design IRB approval was obtained and 315 patients were identified from system-wide VCUG reports from 2004e2012 with diagnosed “high grade” or “severe” vesicoureteral reflux. Inclusion into the study required grade IV or V VUR on initial VCUG and an initial radionuclide study for determination of differential function. Patients with a solitary kidney, posterior urethral valve, multicystic dysplastic kidney, renal ectopia, or duplex collecting systems were excluded. Grade of reflux, angle of the inferior-superior calyceal axis relative to the lumbar spine, and differential uptake were recorded along with presence of the new “flowerpot” sign. Variables were analyzed using the ManneWhitney U test to determine statistical significance.
Results Fifty seven patients met inclusion criteria with 11 being designated as “flowerpot” kidneys. These “flowerpot” kidneys could be objectively differentiated from other kidneys with grade IV and/or grade V VUR both by inferioresuperior calyceal axis (median angle, 52 [37e66] vs. 13 [2e37], respectively p < 0.001) and by differential renal uptake (median, 23% [5e49] vs. 45% [15e81], respectively p < 0.001). Likewise, there was no difference between either calyceal axis (median angle, 13 [3e20] vs. 13 [2e37]) or differential function (median, 48% [24e81] vs. 40% [15e66], p Z 0.129) when comparing kidneys with grade IV and grade V VUR, respectively, that did not demonstrate the “flowerpot” sign. Discussion/conclusion Grading of VUR is used to provide a common language for scientific discussion and determine prognosis for children with similar attributes. The dysmorphic calyceal system in the “flowerpot” kidneys supports the theory of abnormal renal blastema induction associated with abnormal differentiation of the ureteral bud. Even in the absence of urinary tract infections and/or pyelonephritis, renal abnormalities and decreased differential function can be observed on renal scintigraphy. This study also confirms the male predominance and functional similarities between grade 4 and 5 refluxing renal units. Recognizing this is a limited observational study based on imaging alone, the “flowerpot” sign is an indicator of the most severe form of grade 5 VUR but is only one factor in predicting long term overall renal prognosis. However, 14% (8/57) of our cohort had a relative uptake of less than 20% with 5 of these exhibiting the “flowerpot” sign. The “flowerpot” sign on VCUG can be used as indirect evidence of poor differential renal function and, therefore, useful in guiding parental expectations prior to formal functional imaging.
http://dx.doi.org/10.1016/j.jpurol.2014.07.014 1477-5131/ª 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Martin AD, et al., The “flowerpot” sign: Inference of poor renal function in high grade vesicoureteral reflux by calyceal orientation, Journal of Pediatric Urology (2015), http://dx.doi.org/10.1016/j.jpurol.2014.07.014
+
MODEL
1.e2
A.D. Martin et al.
Ureteral polyps on retrograde pyelogram.
Introduction Modern radiographic advances have allowed for detailed and accurate imaging of not only urologic anatomy but also urologic function. The art of observational inference of subtle anatomic features and function from a static radiograph is being traded for new, more precise, and more expensive modalities. While the superiority of these methods cannot be denied, the total information provided in simpler tests should not be ignored. A voiding cystourethrogram (VCUG) is the gold standard in diagnosing and grading vesicoureteral reflux (VUR). While it is not a functional study, it is a robust anatomic study for the astute observer with the ability to provide information regarding not only the bladder, ureters, and urethra but also the axial skeleton, bowel, liver, diaphragm, and more. The inference of function from anatomic shape of various urologic organs is widely assumed clinically, but rarely validated. We hypothesized that the appearance of a “flowerpot kidney” as described herein is an indicator of poor renal function in the setting of high-grade VUR. This information can be used to prepare patients’ expectations of quantitative functional studies and help facilitate discussions of further treatment decisions.
patients were further screened by a pediatric urologist viewing the films to determine eligibility based on presence of grade IV or V VUR on initial VCUG and an initial radionuclide study (DMSA or MAG-3) for determination of differential renal function (DRF). Patients were excluded for any of the following anatomic abnormalities: solitary kidney, posterior urethral valve, multicystic dysplastic kidney, renal ectopia, or duplex collecting system. Patients who satisfied all the study criteria were then categorized based on grade of VUR, angle of the inferioresuperior calyceal axis relative to the lumbar spine (Fig. 2), DRF, and presence of the “flowerpot” sign. Although flowerpot kidneys would typically be considered grade V VUR, we included grade IV VUR in our analysis to not only eliminate potential biased mischaracterization of grade V VUR but also determine if axis changes could be seen with increasing grade alone. Statistical comparison of renal units with and without this radiologic finding was performed using the ManneWhitney U test in GraphPad Prism version 5.0 for Windows (San Diego, CA, USA).
Methods The initial description and categorization of this distinct radiologic entity was made by two senior faculty at our institution, who related the image likeness to a “flowerpot” (Fig. 1). During maximal reflux, the calices of these kidneys appear to be located largely cephalad to the renal pelvis as opposed to lateral in the normal configuration (Fig. 2). To explore the scientific validity of this anecdotal observation, IRB approval was obtained to screen VCUGs from our institution from 2004 to 2012. This was accomplished using the Montage radiology search engine (Montage Healthcare Solutions, Philadelphia, PA, USA) to obtain all VCUG reports containing the words “high grade, severe, grade IV, and/or grade V” in the radiology report text. These initial 315
Figure 1
Overlays demonstrating the likeness to a flowerpot.
Please cite this article in press as: Martin AD, et al., The “flowerpot” sign: Inference of poor renal function in high grade vesicoureteral reflux by calyceal orientation, Journal of Pediatric Urology (2015), http://dx.doi.org/10.1016/j.jpurol.2014.07.014
+
MODEL
The “flowerpot” sign
1.e3
Figure 2 Migration of calyceal axis superiorly and renal pelvis inferiorly with increased filling producing the flowerpot configuration. The blue line represents the spine axis and the red-dotted line represents the calyceal axis for a normal right grade V VUR and a left grade V VUR with the flowerpot sign. VUR Z vesicoureteral reflux. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Results Of the 315 patients identified through the initial radiologic records search, 57 patients met all inclusion/exclusion
criteria. Eleven of these renal units were designated as “flowerpot” kidneys. Interestingly, all of the “flowerpot” kidneys were male patients. “Flowerpot” renal units had statistically significant lower DRF (p 0.001) than those without the sign. Median DRF of “flowerpot” renal units was 23% (range 5e49%). Grade IV VUR units, grade V VUR units, and combined grade IV or V VUR units demonstrated median DRF of 48% (range 24e81%), 40% (range 15e66%), and 45% (range 15e81%), respectively (Fig. 3a). The median renal calycealespine angle was found to be significantly greater in the “flowerpot” kidney than kidneys with grade IV VUR, grade V VUR, and grade IV or V VUR combined (52 [range 37e66] vs. 13 [range 3e20], 13 [range 2e37], 13 [range 2e37], respectively; p < 0.001) (Fig. 3b). This confirmed the visual cues used to identify these kidneys informally.
Discussion
Figure 3 Scatter plots of (a) relative uptake and (b) renalespine angle by group. Bars represent median value. Dots represent individual values. FP Z flowerpot sign; Roman numerals Z grade of VUR. VUR Z vesicoureteral reflux.
Grading of VUR is used to provide a common language for scientific discussion and determine prognosis for children with similar attributes. The current International Scale is a five-point scale based on level of retrograde contrast, shape and fullness of the collecting system, and tortuosity of the ureter [1]. Grade IV or V reflux is fortunately rare representing only 12% of VUR [2]. Evidence supports that children with early reflux related renal abnormalities may be at risk for future renal deterioration [3]. Many of these kidneys have congenital renal function abnormalities as demonstrated by studies performed in infants with high grade VUR detected during the evaluation of prenatally detected hydronephrosis prior to any episodes of urinary tract infection (UTI). Pathologic examination of poorly functioning kidneys with primary VUR reveals areas of segmental dysplasia adjacent to normal renal parenchyma [4]. Theories of VUR-associated renal functional abnormalities include congenital developmental abnormalities, including both dysplasia and hypoplasia, associated with an abnormal or ectopic ureteral bud [3,5]. The dysmorphic calyceal system in the “flowerpot” kidneys supports the theory of abnormal renal blastema induction associated with abnormal differentiation of the ureteral bud. Renal abnormalities are also known to be more common in
Please cite this article in press as: Martin AD, et al., The “flowerpot” sign: Inference of poor renal function in high grade vesicoureteral reflux by calyceal orientation, Journal of Pediatric Urology (2015), http://dx.doi.org/10.1016/j.jpurol.2014.07.014
+
MODEL
1.e4 patients with early reflux at low bladder volumes and pressures and in males [6e8]. Even in the absence of urinary tract infections and/or pyelonephritis, renal abnormalities and decreased differential function can be observed on renal scintigraphy. Nguyen et al. [9] found decreased differential function (defined as uptake
