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Knowledge of vesicoureteral reflux obtained by screening voiding cystourethrogram in children with multicystic dysplastic kidney does not change patient management or prevent febrile urinary tract infection
Journal of Pediatric Urology (2019) 15, 267.e1e267.e5
Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA * Corresponding author. 700 Children’s Drive, Columbus, OH 43205, USA. Christopher.brown@nation widechildrens.org (C. Brown) Keywords Multicystic dysplastic kidney; MCDK; Voiding cystourethrogram; VCUG; Febrile urinary tract infection Received 16 November 2018 Accepted 15 March 2019 Available online 22 March 2019
Knowledge of vesicoureteral reflux obtained by screening voiding cystourethrogram in children with multicystic dysplastic kidney does not change patient management or prevent febrile urinary tract infection C. Brown *, D. McLeod, C. Ching Summary
Introduction While children with multicystic dysplastic kidneys (MCDK) are predisposed to contralateral kidney (CK) vesicoureteral reflux (VUR), it is unknown if this results in an increased risk of urinary tract infection (UTI). The authors hypothesized that knowledge of VUR via voiding cystourethrogram (VCUG) would enable altered practices to prevent UTI and thus reduce the number of febrile urinary tract infections (fUTIs).
Methods: The authors performed a retrospective chart review of all patients at their institution of multiple providers caring for patients with a diagnosis of MCDK from 1/1/07 to 7/14/17. Patients were evaluated for age, sex, circumcision status, race, imaging results on renal ultrasound (RUS) and/or VCUG, occurrence of fUTI, and prophylactic antibiotic (ppx) use.
Figure
Results One hundred sixty-five patients were identified; 70% of patients were diagnosed with MCDK on prenatal imaging. Seventy-seven (47%) patients had a screening VCUG after diagnosis of MCDK. Eighteen patients with VCUG had VUR with 13 (17%) having VUR in the CK. Only children undergoing VCUG were placed on ppx with no difference in the use of ppx in patients with and without dilating VUR (45% vs 43%; p Z 0.91). Overall, 11 patients experienced a fUTI. There was no significant difference in fUTI between those children who underwent VCUG compared with those who did not (10% vs 3%; p Z 0.07). Use of ppx and presence of CK renal anomaly on RUS had no impact on incidence of subsequent fUTI. Conclusion Knowledge of VUR based on VCUG results did not reduce the rate of fUTI or predict ppx use in the practice of multiple providers. The authors feel this confirms the low utility of VCUG in the practical management of otherwise healthy children with MCDK.
Use of VCUG and Antibiotic Prophylaxis.
https://doi.org/10.1016/j.jpurol.2019.03.013 1477-5131/ª 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
267.e2
Introduction Children with multicystic dysplastic kidneys (MCDK) have been shown to have high rates of contralateral renal anomalies. These range from ureteropelvic junction obstruction in 3e12% of infants to vesicoureteral reflux (VUR) in 17.3e43% of infants [1e6]. Historically, it was recommended to identify VUR in all children with MCDK to enable appropriate measures such as surgical repair of VUR to prevent sequela of VUR [7,8]. However, there has been a shift recently in the management of VUR (especially low grade), with more patients being managed conservatively and fewer patients receiving surgical correction. The biggest concern of a refluxing kidney is the potential renal scarring that may occur because of pyelonephritic episodes. Prior studies have shown that the majority of VUR in contralateral kidneys of patients with MCDK is low grade and has a high rate of spontaneous resolution [9]. Several authors have questioned the need to obtain a screening voiding cystourethrogram (VCUG) in all patients with MCDK [3,4,10], but none have investigated if the presence of VUR led to an increased incidence of febrile urinary tract infections (fUTIs). The goal of this study was to evaluate incidence of fUTIs in the patient population with MCDK being cared for at the authors institution. The authors hypothesized that knowledge of VUR via VCUG would reduce the number of fUTIs by changing patient management (i.e. initiation of antibiotic prophylaxis or surgical correction to eliminate reflux). The primary outcome was to compare the incidence of fUTI in children undergoing VCUG to those who did not. The secondary outcome was to evaluate if knowledge of VUR resulted in altered patient management such as increased antibiotic prophylactic use that might explain a reduction in fUTIs.
Methods and materials After obtaining approval from the institutional review board, the authors performed a retrospective chart review of the electronic medical records of all patients treated at the authors’ institution with a diagnosis of MCDK between January 1, 2007 and July 10, 2017. This study population consisted of all patients with an inpatient or outpatient diagnosis of MCDK, as identified by International Classification of Diseases, 9th-revision (ICD-9) code 753.19 or ICD10 code Q61.4. The authors excluded from their analysis those patients with significant comorbid congenital conditions, incorrect diagnosis codes, bilateral MCDK, incomplete clinical information within their electronic medical record, patients diagnosed incidentally after 10 years of age, patients without any follow-up, or those patients who died in infancy. The authors determined timing and cause of MCDK diagnosis. The authors evaluated demographic information including age, gender, circumcision status, and race. The authors reviewed imaging results on renal ultrasound (RUS), VCUG (when obtained) and renal scintigraphy (dimercaptosuccinic acid, diethylene triamine penta-acetic acid [DTPA] or mercaptoacetyletriglycine [MAG3]), use of antibiotic prophylaxis
C. Brown et al. (ppx), and all occurrence of fUTI. Febrile urinary tract infection was defined as fever 100.4 F and urine culture with >50,000 colony-forming units per milliliter in appropriately collected specimens in accordance with clinical practice guidelines published by the American Academy of Pediatrics (AAP) [11]. Patients were followed by a nephrologist, a urologist, or a combination of the two. As there was no specific study protocol in place, the decision to prescribe antibiotic prophylaxis or obtain a VCUG was at the discretion of the specific provider managing the patient. The authors sought to determine what impact the knowledge of VUR would have on the rate of fUTI (primary outcome) and the use of antibiotic prophylaxis (secondary outcome). Statistical analysis was performed using chisquare calculations.
Results The authors initial query retrieved 561 patients with a diagnosis of MCDK between January 1, 2007 and July 10, 2017 at a single free-standing pediatric academic center. After excluding those with significant comorbid conditions, incorrect diagnosis codes, bilateral MCDK, incomplete clinical information, patients diagnosed incidentally after 10 years of age, those without follow-up after initial diagnosis, or those patients that died in infancy, this cohort consisted of 165 patients. Patients were managed by pediatric nephrology only in 74 patients (44.8%), by pediatric urology only in 52 patients (31.5%), or a combination of both specialties in 39 patients (23.6%). There were a total of 17 nephrologists, eight pediatric urologists, and four pediatric urology nurse practitioners involved in the care of these patients. Patient demographic information is summarized in Table 1. The majority of patients (115, 70%) were diagnosed prenatally. Postnatal diagnosis was made at a mean age of 24.9 days, most commonly (48, 29%) on a screening RUS for other prenatal anomalies. Diagnosis was made after fUTI, afebrile urinary tract infection (UTI), and episode of abdominal pain in three additional patients. Confirmation of non-functioning MCDK moiety was made by renal scintigraphy in 74 patients (45%): DTPA in one patient and MAG3 in 73 patients. There was an equal distribution between male and female patients; the majority of patients (105, 64%) were Caucasian. Patients had a mean follow-up of 38 months (median 29 months; range 1e158 months). One-third of the patients (55, 33%) were found to have contralateral renal anomalies on their initial RUS. These anomalies included hydronephrosis/pelviectasis, increased echogenicity, duplex configuration, horseshoe kidney, ureterocele, hydroureter, uroepithelial thickening, and/or a pelvic kidney. Hydronephrosis of the contralateral kidney did not predict VUR to that kidney (14% vs 19%, p Z 0.49). Furthermore, the presence of any contralateral renal anomaly did not correlate with any statistically significant increase in the rate of fUTI (13% vs 5%, p Z 0.09). Those with contralateral anomaly on RUS were more likely to undergo screening VCUG than those without a contralateral anomaly (82% vs 31%; p < 0.00001).
Knowledge of vesicoureteral reflux in multicystic dysplastic kidney Table 1
Patient demographics and baseline information.
Total patients, n Gender, n (%) Male Female Circumcision Status, n (%) Circumcised Uncircumcised Unknown Age at diagnosis Prenatal, n Median (postnatal dx) Laterality, n (%) Right Left Follow-up (months) Median (range) Mean (range) Race, n (%) Caucasian African-American Multiracial Hispanic Asian African Unknown
165 82 (50) 83 (50) 67 (82) 4 (5) 11 (13) 115 (70%) 24.9 days 72 (44) 93 (56) 29 (1e158) 38 (1e158) 105 (64) 27 (16) 16 (10) 8 (5) 7 (4) 1 (<1) 1 (<1)
Fig. 1 describes the use of VCUG and antibiotic prophylaxis in these patients. Seventy-seven patients (47%) had a screening VCUG after the diagnosis of MCDK to evaluate for contralateral VUR. VUR was identified in 18 patients, with 13 having reflux to the contralateral kidney. Ten of these patients were observed without use of antibiotic prophylaxis; the remaining eight were placed on antibiotic prophylaxis. Dilating reflux (VUR grades IIIeV) [12] was present in 11 of the 18 patients; however, there was no difference
267.e3
in the use of antibiotic prophylaxis in patients with (45%) or without (43%) dilating reflux (p Z 0.91). No child was placed on prophylactic antibiotics without first undergoing a VCUG. There were four patients without VUR who were placed on ppx (2 due to fUTI; 2 for unknown reasons). It is not clear from the medical record why six of the 11 patients with dilating reflux were not placed on antibiotic prophylaxis. Use of ppx was not associated with circumcision status; only two of the 82 males in the study received ppx, both were circumcised. In total, 67 of the males (82%) were circumcised. One patient developed a breakthrough UTI and underwent ureteral reimplantation. One patient (who did not have VUR) developed a post-VCUG UTI (afebrile). In total, 11 of the 165 patients experienced a fUTI. Specimens were collected in accordance with AAP clinical practice guidelines (catheterized specimens in 10 patients who were not toilet trained at time of fUTI, one via clean catch in toilet trained child) [11]. Three of these children required hospitalization for UTI treatment. Eight had previously undergone a VCUG, with five studies failing to identify reflux, and the other three identifying dilating reflux. Three children had not previously undergone a screening VCUG and still had not undergone VCUG at time of this study. There was no significant difference in fUTI between those children who underwent VCUG and those who did not (10% vs 3%, respectively, p Z 0.07). Of those patients with a fUTI, seven were female, two were circumcised males, and two were uncircumcised males. Incidence of subsequent fUTI was not impacted significantly by use of ppx (25% on ppx vs 10% not on ppx; p Z 0.40) or the presence of CK renal anomaly on RUS (13% with anomaly vs 5% without anomaly; p Z 0.09).
Discussion One hallmark of MCDK is non-function of the affected kidney. These children are left with a functionally solitary contralateral kidney, regardless of if the dysplastic kidney
Fig. 1 Use of VCUG and antibiotic prophylaxis. VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux; CK, contralateral kidney; ppx, prophylactic antibiotic.
267.e4 is removed or not. All efforts should be taken to ensure the functional kidney remains free from injury, infection, scarring, or other insults that could lead to permanent renal damage. In addition to being a solitary functioning kidney, the contralateral kidney is prone to developmental anomalies, most commonly vesicoureteral reflux occurring in 17.3e43% of patients [1e6]. Miller et al. evaluated 75 cases of MCDK, identifying contralateral VUR in 26.4%. Nearly half of the reflux was non-dilating; this group of patients showed a spontaneous resolution rate of 89% [9]. Similarly, in a cohort of 76 patients with MCDK, Ismaili et al. showed 81% of the cases of contralateral VUR to be low grade with a high rate of spontaneous resolution [3]. Twenty-five years ago, it was strongly encouraged that every patient with contralateral VUR be identified [7,8]. However, several authors have recently questioned the need to do so, especially in light of the changing management of VUR in general, and the high rate of spontaneous resolution in those patients with low-grade disease. Calaway et al. reviewed their experience of 133 patients with MCDK to identify how many required surgical intervention [4]. Of the 23 patients found to have VUR, four eventually required ureteral reimplantation. Only six of their patients experienced a fUTI, of whom two had dilating VUR which was subsequently corrected. Because of the low incidence of clinically significant VUR, they advised that routine VCUG in healthy children with MCDK may not be warranted. More recently, Yamamoto et al. evaluated 75 patients with unilateral MCDK and attempted to identify what factors should prompt VCUG in these patients [10]. They concluded that the decision to obtain a VCUG could be made simply by the presence of RUS abnormalities (hydronephrosis,
C. Brown et al. hydroureter, ectopic ureter, renal duplex kidney, ureterocele, contralateral simple renal cyst, dysplastic kidney, cysts in the pelvis, double uterus, and bicornate uterus) and was not required in all patients. Perhaps the more important issue that was not addressed by the previous studies was if the knowledge of VUR in patients with MCDK helped prevent episodes of febrile UTI as the authors are more concerned about the development of scarring due to episodes of pyelonephritis rather than from sterile reflux. Presumably the knowledge of and appropriate management of contralateral VUR would lead to decreased incidence of fUTI in these patients. In the randomized intervention for children with vesicoureteral reflux (RIVUR) trial, use of ppx in children with a history of fUTI and VUR did significantly prevent subsequent fUTIs [13]. In their experience, however, the authors did not find that use of VCUG correlated with a decreased incidence of fUTI. In fact, the percent of children who developed a fUTI was actually higher in those who underwent VCUG compared with those who were not evaluated by VCUG. In addition, the knowledge obtained from the VCUG in this cohort did not prevent the occurrence of fUTI. Of those 11 children that experienced a fUTI, eight either showed no reflux, or VCUG was not performed (Fig. 2). And in the three patients with dilating reflux who developed a fUTI, only one had been on ppx. Indeed, among all of the patients, there was no difference in the use of ppx between those with and without dilating reflux. As VCUG results did not drive the use of ppx in patients with VUR, it did not appear that use of VCUG was used in clinical decision-making and thus was of limited utility in patient management at the authors institution. Some of these findings can be attributed to the
Fig. 2 Occurrences of febrile urinary tract infection. VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux; ppx, prophylactic antibiotic.
Knowledge of vesicoureteral reflux in multicystic dysplastic kidney heterogeneity of providers involved in the care of these patients. This study cohort was under the care of some combination of 17 nephrologists, eight pediatric urologists, and four pediatric urology nurse practitioners. The authors do not have a specific protocol for management of this patient population, and thus, management is left to provider discretion. The authors predict this variability in patient management is actually realistic to practice management throughout the country as there are no specific national guidelines on when to obtain VCUG in the pediatric MCDK population. It would seem that the real utility of obtaining a VCUG in patients with MCDK would be to identify that small percentage of patients with contralateral high-grade reflux potentially warranting medical or surgical intervention. Given the significant morbidity associated with fUTI, and the associated long-term risk of renal damage when this occurs in a solitary kidney, all caregivers of patients with MCDK (and especially those with known reflux) should be educated regarding the signs/symptoms of fUTIs. This will promote timely evaluation and potential mitigation of the harmful effects of a fUTI. This study is not without limitations. It is retrospective in nature, with all patients treated at a single institution. Despite taking place at a single institution, there was high variability in the management of these children (such as inconsistent imaging studies ordered and inconsistent ppx use) because of a lack of a standardized care pathway for patients with MCDK. The authors feel that this is probably reflective of many practices and settings throughout the country as no organized guidelines exist to direct when to obtain VCUG in pediatric MCDK. Less than half of the cohort underwent renal scintigraphy to confirm lack of function of their MCDK moiety. Also, the patient population with fUTI was small which could have prevented detection of significant predictors of developing a fUTI. The study data on fUTI was also limited to encounters at the authors’ institution; it is possible that patients may have presented to another institution or to their primary care physician to receive treatment for a fUTI, and these visits were not captured in this data, and thus, the authors underestimated the occurrence of fUTIs between groups. In addition, less than half of the study patients received a screening VCUG. However, given there was not a significant increase in fUTI among those patients who did not have a VCUG, the recommendation against screening VCUG in this population is further supported when the goal is to prevent fUTIs.
Conclusion Knowledge of VUR based on VCUG results did not seem to alter patient management, reduce the rate of fUTI, or predict antibiotic prophylaxis use based on dilating or nondilating VUR in children with MCDK cared for by the authors’ institution over the 10 years. Thus, VCUG is of low utility at the authors’ academic institution.
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Author statements Ethical approval Approval not required.
Funding No outside funding was used for this study.
Competing interest None of the authors have any conflicts of interest to disclose.
References [1] Pope JC. Renal dysgenesis and cystic disease of the kidney. In: campbell-walsh urology. 11th ed. Philadelphia, PA: Elsevier; 2016. p. 3028e31. [2] Eickmeyer AB, Casanova NF, He C, Smith EA, Wan J, Bloom DA, et al. The natural history of the multicystic dysplastic kidney e is limited follow-up warranted? J Pediatr Urol 2014;10:655e61. [3] Ismaili K, Avni FE, Alexander M, Schulman C, Collier F, Hall M. Routine Voiding Cystourethrogram is of no value in neonates with unilateral multicystic dysplastic kidney. J Peds 2005;146: 759e63. [4] Calaway AC, Whittam B, Szymanski KM, Misseri R, Kaefer M, Rink RC, et al. Multicystic dysplastic kidney: is an initial voiding cystourethrogram necessary? Can J Urol 2014;21:7510e4. [5] Hains DS, Bates CM, Ingraham S, Schwaderer AL. Management and etiology of the unilateral multicystic dysplastic kidney: a review. Pediatr Nephrol 2009;24:233e41. [6] Sarhan OM, Alghanbar M, Alsulaihim A, Alharbi B, Alotay A, Nakshabandi Z. Multicystic dysplastic kidney: impact of imaging modality selection on the initial management and prognosis. J Pediatr Urol 2014;10:645e9. [7] Flack CE, Bellinger MF. The multicystic dysplastic kidney and contralateral vesicoureteral reflux: protection of the solitary kidney. J Urol 1993;150:1873e4. [8] Atiyeh B, Husmann D, Baum M. Contralateral renal abnormalities in multicystic-dysplastic kidney disease. J Pediatr 1992;121:65e7. [9] Miller DC, Rumohr JA, Dunn RL, Bloom DA, Park JM. What is the fate of the refluxing contralateral kidney in children with multicystic dysplastic kidney? J Urol 2004;172:1630e4. [10] Yamamoto K, Kamei K, Sato M, Ogura M, Suzuki M, Hasegawa Y, et al. Necessity of performing voiding cystourethrography for children with unilateral multicystic dysplastic kidney. Pediatr Nephrol 2019;34:295e9. [11] Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 2011;128:595e610. [12] Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Mo ¨bius TE. International system of radiographic grading of vesicoureteric reflux. Pediatr Radiol 1985;15: 105e9. [13] Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 2014;370:2367e76.
Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA * Corresponding author. 700 Children’s Drive, Columbus, OH 43205, USA. Christopher.brown@nation widechildrens.org (C. Brown) Keywords Multicystic dysplastic kidney; MCDK; Voiding cystourethrogram; VCUG; Febrile urinary tract infection Received 16 November 2018 Accepted 15 March 2019 Available online 22 March 2019
Knowledge of vesicoureteral reflux obtained by screening voiding cystourethrogram in children with multicystic dysplastic kidney does not change patient management or prevent febrile urinary tract infection C. Brown *, D. McLeod, C. Ching Summary
Introduction While children with multicystic dysplastic kidneys (MCDK) are predisposed to contralateral kidney (CK) vesicoureteral reflux (VUR), it is unknown if this results in an increased risk of urinary tract infection (UTI). The authors hypothesized that knowledge of VUR via voiding cystourethrogram (VCUG) would enable altered practices to prevent UTI and thus reduce the number of febrile urinary tract infections (fUTIs).
Methods: The authors performed a retrospective chart review of all patients at their institution of multiple providers caring for patients with a diagnosis of MCDK from 1/1/07 to 7/14/17. Patients were evaluated for age, sex, circumcision status, race, imaging results on renal ultrasound (RUS) and/or VCUG, occurrence of fUTI, and prophylactic antibiotic (ppx) use.
Figure
Results One hundred sixty-five patients were identified; 70% of patients were diagnosed with MCDK on prenatal imaging. Seventy-seven (47%) patients had a screening VCUG after diagnosis of MCDK. Eighteen patients with VCUG had VUR with 13 (17%) having VUR in the CK. Only children undergoing VCUG were placed on ppx with no difference in the use of ppx in patients with and without dilating VUR (45% vs 43%; p Z 0.91). Overall, 11 patients experienced a fUTI. There was no significant difference in fUTI between those children who underwent VCUG compared with those who did not (10% vs 3%; p Z 0.07). Use of ppx and presence of CK renal anomaly on RUS had no impact on incidence of subsequent fUTI. Conclusion Knowledge of VUR based on VCUG results did not reduce the rate of fUTI or predict ppx use in the practice of multiple providers. The authors feel this confirms the low utility of VCUG in the practical management of otherwise healthy children with MCDK.
Use of VCUG and Antibiotic Prophylaxis.
https://doi.org/10.1016/j.jpurol.2019.03.013 1477-5131/ª 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
267.e2
Introduction Children with multicystic dysplastic kidneys (MCDK) have been shown to have high rates of contralateral renal anomalies. These range from ureteropelvic junction obstruction in 3e12% of infants to vesicoureteral reflux (VUR) in 17.3e43% of infants [1e6]. Historically, it was recommended to identify VUR in all children with MCDK to enable appropriate measures such as surgical repair of VUR to prevent sequela of VUR [7,8]. However, there has been a shift recently in the management of VUR (especially low grade), with more patients being managed conservatively and fewer patients receiving surgical correction. The biggest concern of a refluxing kidney is the potential renal scarring that may occur because of pyelonephritic episodes. Prior studies have shown that the majority of VUR in contralateral kidneys of patients with MCDK is low grade and has a high rate of spontaneous resolution [9]. Several authors have questioned the need to obtain a screening voiding cystourethrogram (VCUG) in all patients with MCDK [3,4,10], but none have investigated if the presence of VUR led to an increased incidence of febrile urinary tract infections (fUTIs). The goal of this study was to evaluate incidence of fUTIs in the patient population with MCDK being cared for at the authors institution. The authors hypothesized that knowledge of VUR via VCUG would reduce the number of fUTIs by changing patient management (i.e. initiation of antibiotic prophylaxis or surgical correction to eliminate reflux). The primary outcome was to compare the incidence of fUTI in children undergoing VCUG to those who did not. The secondary outcome was to evaluate if knowledge of VUR resulted in altered patient management such as increased antibiotic prophylactic use that might explain a reduction in fUTIs.
Methods and materials After obtaining approval from the institutional review board, the authors performed a retrospective chart review of the electronic medical records of all patients treated at the authors’ institution with a diagnosis of MCDK between January 1, 2007 and July 10, 2017. This study population consisted of all patients with an inpatient or outpatient diagnosis of MCDK, as identified by International Classification of Diseases, 9th-revision (ICD-9) code 753.19 or ICD10 code Q61.4. The authors excluded from their analysis those patients with significant comorbid congenital conditions, incorrect diagnosis codes, bilateral MCDK, incomplete clinical information within their electronic medical record, patients diagnosed incidentally after 10 years of age, patients without any follow-up, or those patients who died in infancy. The authors determined timing and cause of MCDK diagnosis. The authors evaluated demographic information including age, gender, circumcision status, and race. The authors reviewed imaging results on renal ultrasound (RUS), VCUG (when obtained) and renal scintigraphy (dimercaptosuccinic acid, diethylene triamine penta-acetic acid [DTPA] or mercaptoacetyletriglycine [MAG3]), use of antibiotic prophylaxis
C. Brown et al. (ppx), and all occurrence of fUTI. Febrile urinary tract infection was defined as fever 100.4 F and urine culture with >50,000 colony-forming units per milliliter in appropriately collected specimens in accordance with clinical practice guidelines published by the American Academy of Pediatrics (AAP) [11]. Patients were followed by a nephrologist, a urologist, or a combination of the two. As there was no specific study protocol in place, the decision to prescribe antibiotic prophylaxis or obtain a VCUG was at the discretion of the specific provider managing the patient. The authors sought to determine what impact the knowledge of VUR would have on the rate of fUTI (primary outcome) and the use of antibiotic prophylaxis (secondary outcome). Statistical analysis was performed using chisquare calculations.
Results The authors initial query retrieved 561 patients with a diagnosis of MCDK between January 1, 2007 and July 10, 2017 at a single free-standing pediatric academic center. After excluding those with significant comorbid conditions, incorrect diagnosis codes, bilateral MCDK, incomplete clinical information, patients diagnosed incidentally after 10 years of age, those without follow-up after initial diagnosis, or those patients that died in infancy, this cohort consisted of 165 patients. Patients were managed by pediatric nephrology only in 74 patients (44.8%), by pediatric urology only in 52 patients (31.5%), or a combination of both specialties in 39 patients (23.6%). There were a total of 17 nephrologists, eight pediatric urologists, and four pediatric urology nurse practitioners involved in the care of these patients. Patient demographic information is summarized in Table 1. The majority of patients (115, 70%) were diagnosed prenatally. Postnatal diagnosis was made at a mean age of 24.9 days, most commonly (48, 29%) on a screening RUS for other prenatal anomalies. Diagnosis was made after fUTI, afebrile urinary tract infection (UTI), and episode of abdominal pain in three additional patients. Confirmation of non-functioning MCDK moiety was made by renal scintigraphy in 74 patients (45%): DTPA in one patient and MAG3 in 73 patients. There was an equal distribution between male and female patients; the majority of patients (105, 64%) were Caucasian. Patients had a mean follow-up of 38 months (median 29 months; range 1e158 months). One-third of the patients (55, 33%) were found to have contralateral renal anomalies on their initial RUS. These anomalies included hydronephrosis/pelviectasis, increased echogenicity, duplex configuration, horseshoe kidney, ureterocele, hydroureter, uroepithelial thickening, and/or a pelvic kidney. Hydronephrosis of the contralateral kidney did not predict VUR to that kidney (14% vs 19%, p Z 0.49). Furthermore, the presence of any contralateral renal anomaly did not correlate with any statistically significant increase in the rate of fUTI (13% vs 5%, p Z 0.09). Those with contralateral anomaly on RUS were more likely to undergo screening VCUG than those without a contralateral anomaly (82% vs 31%; p < 0.00001).
Knowledge of vesicoureteral reflux in multicystic dysplastic kidney Table 1
Patient demographics and baseline information.
Total patients, n Gender, n (%) Male Female Circumcision Status, n (%) Circumcised Uncircumcised Unknown Age at diagnosis Prenatal, n Median (postnatal dx) Laterality, n (%) Right Left Follow-up (months) Median (range) Mean (range) Race, n (%) Caucasian African-American Multiracial Hispanic Asian African Unknown
165 82 (50) 83 (50) 67 (82) 4 (5) 11 (13) 115 (70%) 24.9 days 72 (44) 93 (56) 29 (1e158) 38 (1e158) 105 (64) 27 (16) 16 (10) 8 (5) 7 (4) 1 (<1) 1 (<1)
Fig. 1 describes the use of VCUG and antibiotic prophylaxis in these patients. Seventy-seven patients (47%) had a screening VCUG after the diagnosis of MCDK to evaluate for contralateral VUR. VUR was identified in 18 patients, with 13 having reflux to the contralateral kidney. Ten of these patients were observed without use of antibiotic prophylaxis; the remaining eight were placed on antibiotic prophylaxis. Dilating reflux (VUR grades IIIeV) [12] was present in 11 of the 18 patients; however, there was no difference
267.e3
in the use of antibiotic prophylaxis in patients with (45%) or without (43%) dilating reflux (p Z 0.91). No child was placed on prophylactic antibiotics without first undergoing a VCUG. There were four patients without VUR who were placed on ppx (2 due to fUTI; 2 for unknown reasons). It is not clear from the medical record why six of the 11 patients with dilating reflux were not placed on antibiotic prophylaxis. Use of ppx was not associated with circumcision status; only two of the 82 males in the study received ppx, both were circumcised. In total, 67 of the males (82%) were circumcised. One patient developed a breakthrough UTI and underwent ureteral reimplantation. One patient (who did not have VUR) developed a post-VCUG UTI (afebrile). In total, 11 of the 165 patients experienced a fUTI. Specimens were collected in accordance with AAP clinical practice guidelines (catheterized specimens in 10 patients who were not toilet trained at time of fUTI, one via clean catch in toilet trained child) [11]. Three of these children required hospitalization for UTI treatment. Eight had previously undergone a VCUG, with five studies failing to identify reflux, and the other three identifying dilating reflux. Three children had not previously undergone a screening VCUG and still had not undergone VCUG at time of this study. There was no significant difference in fUTI between those children who underwent VCUG and those who did not (10% vs 3%, respectively, p Z 0.07). Of those patients with a fUTI, seven were female, two were circumcised males, and two were uncircumcised males. Incidence of subsequent fUTI was not impacted significantly by use of ppx (25% on ppx vs 10% not on ppx; p Z 0.40) or the presence of CK renal anomaly on RUS (13% with anomaly vs 5% without anomaly; p Z 0.09).
Discussion One hallmark of MCDK is non-function of the affected kidney. These children are left with a functionally solitary contralateral kidney, regardless of if the dysplastic kidney
Fig. 1 Use of VCUG and antibiotic prophylaxis. VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux; CK, contralateral kidney; ppx, prophylactic antibiotic.
267.e4 is removed or not. All efforts should be taken to ensure the functional kidney remains free from injury, infection, scarring, or other insults that could lead to permanent renal damage. In addition to being a solitary functioning kidney, the contralateral kidney is prone to developmental anomalies, most commonly vesicoureteral reflux occurring in 17.3e43% of patients [1e6]. Miller et al. evaluated 75 cases of MCDK, identifying contralateral VUR in 26.4%. Nearly half of the reflux was non-dilating; this group of patients showed a spontaneous resolution rate of 89% [9]. Similarly, in a cohort of 76 patients with MCDK, Ismaili et al. showed 81% of the cases of contralateral VUR to be low grade with a high rate of spontaneous resolution [3]. Twenty-five years ago, it was strongly encouraged that every patient with contralateral VUR be identified [7,8]. However, several authors have recently questioned the need to do so, especially in light of the changing management of VUR in general, and the high rate of spontaneous resolution in those patients with low-grade disease. Calaway et al. reviewed their experience of 133 patients with MCDK to identify how many required surgical intervention [4]. Of the 23 patients found to have VUR, four eventually required ureteral reimplantation. Only six of their patients experienced a fUTI, of whom two had dilating VUR which was subsequently corrected. Because of the low incidence of clinically significant VUR, they advised that routine VCUG in healthy children with MCDK may not be warranted. More recently, Yamamoto et al. evaluated 75 patients with unilateral MCDK and attempted to identify what factors should prompt VCUG in these patients [10]. They concluded that the decision to obtain a VCUG could be made simply by the presence of RUS abnormalities (hydronephrosis,
C. Brown et al. hydroureter, ectopic ureter, renal duplex kidney, ureterocele, contralateral simple renal cyst, dysplastic kidney, cysts in the pelvis, double uterus, and bicornate uterus) and was not required in all patients. Perhaps the more important issue that was not addressed by the previous studies was if the knowledge of VUR in patients with MCDK helped prevent episodes of febrile UTI as the authors are more concerned about the development of scarring due to episodes of pyelonephritis rather than from sterile reflux. Presumably the knowledge of and appropriate management of contralateral VUR would lead to decreased incidence of fUTI in these patients. In the randomized intervention for children with vesicoureteral reflux (RIVUR) trial, use of ppx in children with a history of fUTI and VUR did significantly prevent subsequent fUTIs [13]. In their experience, however, the authors did not find that use of VCUG correlated with a decreased incidence of fUTI. In fact, the percent of children who developed a fUTI was actually higher in those who underwent VCUG compared with those who were not evaluated by VCUG. In addition, the knowledge obtained from the VCUG in this cohort did not prevent the occurrence of fUTI. Of those 11 children that experienced a fUTI, eight either showed no reflux, or VCUG was not performed (Fig. 2). And in the three patients with dilating reflux who developed a fUTI, only one had been on ppx. Indeed, among all of the patients, there was no difference in the use of ppx between those with and without dilating reflux. As VCUG results did not drive the use of ppx in patients with VUR, it did not appear that use of VCUG was used in clinical decision-making and thus was of limited utility in patient management at the authors institution. Some of these findings can be attributed to the
Fig. 2 Occurrences of febrile urinary tract infection. VCUG, voiding cystourethrogram; VUR, vesicoureteral reflux; ppx, prophylactic antibiotic.
Knowledge of vesicoureteral reflux in multicystic dysplastic kidney heterogeneity of providers involved in the care of these patients. This study cohort was under the care of some combination of 17 nephrologists, eight pediatric urologists, and four pediatric urology nurse practitioners. The authors do not have a specific protocol for management of this patient population, and thus, management is left to provider discretion. The authors predict this variability in patient management is actually realistic to practice management throughout the country as there are no specific national guidelines on when to obtain VCUG in the pediatric MCDK population. It would seem that the real utility of obtaining a VCUG in patients with MCDK would be to identify that small percentage of patients with contralateral high-grade reflux potentially warranting medical or surgical intervention. Given the significant morbidity associated with fUTI, and the associated long-term risk of renal damage when this occurs in a solitary kidney, all caregivers of patients with MCDK (and especially those with known reflux) should be educated regarding the signs/symptoms of fUTIs. This will promote timely evaluation and potential mitigation of the harmful effects of a fUTI. This study is not without limitations. It is retrospective in nature, with all patients treated at a single institution. Despite taking place at a single institution, there was high variability in the management of these children (such as inconsistent imaging studies ordered and inconsistent ppx use) because of a lack of a standardized care pathway for patients with MCDK. The authors feel that this is probably reflective of many practices and settings throughout the country as no organized guidelines exist to direct when to obtain VCUG in pediatric MCDK. Less than half of the cohort underwent renal scintigraphy to confirm lack of function of their MCDK moiety. Also, the patient population with fUTI was small which could have prevented detection of significant predictors of developing a fUTI. The study data on fUTI was also limited to encounters at the authors’ institution; it is possible that patients may have presented to another institution or to their primary care physician to receive treatment for a fUTI, and these visits were not captured in this data, and thus, the authors underestimated the occurrence of fUTIs between groups. In addition, less than half of the study patients received a screening VCUG. However, given there was not a significant increase in fUTI among those patients who did not have a VCUG, the recommendation against screening VCUG in this population is further supported when the goal is to prevent fUTIs.
Conclusion Knowledge of VUR based on VCUG results did not seem to alter patient management, reduce the rate of fUTI, or predict antibiotic prophylaxis use based on dilating or nondilating VUR in children with MCDK cared for by the authors’ institution over the 10 years. Thus, VCUG is of low utility at the authors’ academic institution.
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Author statements Ethical approval Approval not required.
Funding No outside funding was used for this study.
Competing interest None of the authors have any conflicts of interest to disclose.
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