OBJECTIVES To assess the prevalence of pelvic ectopic kidneys (PEK) and compare renal parameters of the PEK to the orthotopic kidney following pubic bone approximation. METHODS In four Omphalocele-Exstrophy-Imperforate Anus-Spinal Defects Syndrome (OEIS) patients undergoing second-stage repair with known pelvic and orthotopic kidneys, changes in the renal pelvis pressure (RPP), peak systolic velocity (PSV), and resistive index (RI) were measured in the pelvic and orthotopic kidneys following pubic bone approximation. A paired t-test was performed for analysis. Prevalence was tabulated using a multi-institutional retrospective review. RESULTS Mean rise in RPP was + 26.0 mmHg in the PEK and + 10.3 mmHg in the orthotopic kidney (P = .55). One patient had immediate increase in RPP of 66 mmHg in the PEK (7 mmHg in the orthotopic kidney) which decreased to + 17 mmHg in the PEK upon release of the pubic approximation stitch. Mean change in PSV was + 67.7 cm/s in the PEK compared to - 25.7 cm/s in the orthotopic kidney (P = .09). Mean change in renal RI was + 0.06 in PEK compared to - 0.01 in the orthotopic kidney (P = .29). Among 80 OEIS patients, 24 (30%) had a PEK. 3 (4%) had a solitary PEK. CONCLUSION During second-stage OEIS closure, we witnessed patterns of higher change in RPP, PSV, and RI of the PEK compared to the orthotopic kidney. Furthermore, PEKs were found in nearly a third of our OEIS patients. Real-time RPP monitoring, especially those with solitary PEK, may aid in the management of OEIS patients during the perioperative period.

You have accessJournal of UrologyCME1 May 2022V08-05 THE ANATOMIC BLADDER NECK TAILORING IN CPRE: THE PATH TO NORMAL ANATOMY Dana Weiss, Elizabeth Roth, Travis Groth, John Kryger, Richard Lee, Aseem Shukla, Joseph G., Michael Mitchell, and Douglas Canning Dana WeissDana Weiss More articles by this author , Elizabeth RothElizabeth Roth More articles by this author , Travis GrothTravis Groth More articles by this author , John KrygerJohn Kryger More articles by this author , Richard LeeRichard Lee More articles by this author , Aseem ShuklaAseem Shukla More articles by this author , Joseph G.Joseph G. More articles by this author , Michael MitchellMichael Mitchell More articles by this author , and Douglas CanningDouglas Canning More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002606.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The goals of the complete primary repair of bladder exstrophy include the anatomic closure of the bladder, bladder neck and urethra. During this reconstruction, the bladder, bladder neck and urethral complex are placed into the deep pelvis to allow for optimal function and successful closure. METHODS: Over time, the bladder neck reconstruction has evolved with the identification of the continence zone – the area between the verumontanum and the midpoint of the bladder neck in males, and between the anterior edge of the vaginal orifice and the midpoint of the bladder neck in females. The bladder neck reconstruction involves careful measurements and then tailoring of the proximal urethra, which allows for gentle outlet resistance without outlet obstruction. RESULTS: Among all bladder phenotypes, the anatomy of the bladder neck area is consistent. The length of the verumontanum to the bladder neck is equivalent to the length from the vaginal orifice to the bladder neck. The distance of this continence zone has been consistently between 1-1.5cm in both males and females. Starting a gradual taper from the verumontanum to the bladder neck allows for a natural, funneled shape once healed. CONCLUSIONS: Through attention to detail and constant re-evaluation of game film, we have identified a consistent section of the proximal urethra and bladder neck that we believe is the continence zone. This section is readily identifiable based on fixed landmarks in the urethra, at the verumontanum or anterior vaginal opening, and the midpoint of bladder neck striations. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e715 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dana Weiss More articles by this author Elizabeth Roth More articles by this author Travis Groth More articles by this author John Kryger More articles by this author Richard Lee More articles by this author Aseem Shukla More articles by this author Joseph G. More articles by this author Michael Mitchell More articles by this author Douglas Canning More articles by this author Expand All Advertisement PDF DownloadLoading ...

You have accessJournal of UrologyCME1 May 2022MP11-12 PRENATAL DIAGNOSIS OF BLADDER AND CLOACAL EXSTROPHY OVER 20 YEARS Ted Lee, Dana Weiss, Elizabeth Roth, Sahar Eftekharzadeh, Saafia Masoom, Susan Jarosz, John Kryger, Aseem Shukla, Travis Groth, Michael Mitchell, Richard Lee, Douglas Canning, and Joseph Borer Ted LeeTed Lee More articles by this author , Dana WeissDana Weiss More articles by this author , Elizabeth RothElizabeth Roth More articles by this author , Sahar EftekharzadehSahar Eftekharzadeh More articles by this author , Saafia MasoomSaafia Masoom More articles by this author , Susan JaroszSusan Jarosz More articles by this author , John KrygerJohn Kryger More articles by this author , Aseem ShuklaAseem Shukla More articles by this author , Travis GrothTravis Groth More articles by this author , Michael MitchellMichael Mitchell More articles by this author , Richard LeeRichard Lee More articles by this author , Douglas CanningDouglas Canning More articles by this author , and Joseph BorerJoseph Borer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002533.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder exstrophy (BE) and cloacal exstrophy (CE) presents significant challenges during the newborn period. In contrast to the unexpected diagnosis in the newborn, prenatal diagnosis of BE and CE affords valuable opportunities for education and preparation for caregivers and healthcare providers. Based on small sample populations, previously reported prenatal diagnosis rates of BE and CE were 13-25% and 17%, respectively. In this study, we aimed to examine the prenatal diagnosis rates of BE and CE in a large cohort of patients over a 20-year period. We hypothesized that prenatal diagnosis rates improved over time in both BE and CE due to evolving techniques and technologies in prenatal ultrasonography. METHODS: We queried a multi-institutional exstrophy-epispadias complex database of three centers to identify patients with BE or CE who underwent primary closure between 2000 and 2020. Retrospective review was performed to assess whether BE or CE diagnosis was made prenatally versus postnatally. Those with unknown prenatal history were excluded from analysis. Univariate analysis of categorical data was performed using Pearson’s Chi-square test. Multivariable logistic regression was used to investigate temporal pattern in the rate of prenatal diagnosis while adjusting for sex and institution. RESULTS: Among 197 BE and 52 CE patients that were identified, 155 BE and 45 CE patients had known prenatal history. The overall prenatal diagnosis rates of BE and CE were 47.1% (73/155) and 82.2% (37/45), respectively. Prenatal diagnosis rate was significantly lower in BE compared to CE (p<0.0001) across the 20-year period. The prenatal diagnosis rate for BE significantly increased over time (OR 1.10; [95% CI: 1.03, 1.17]; p = 0.003). Between 2000 and 2005, the prenatal diagnosis rate of BE was 30.3% (10/33). Between 2015 and 2020, the prenatal diagnosis rate of BE was 61.1% (33/54). The prenatal diagnosis rate for CE did not change over time. Rates of prenatal diagnosis did not differ by sex or institution in both BE and CE. CONCLUSIONS: The rates of prenatal diagnosis of BE and CE are higher than previously reported. Prenatal diagnosis rate of BE doubled in the last 5 years compared to the first 5 years of the study period. Nonetheless, a significant proportion of both BE and CE patients remain undiagnosed prior to delivery. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e161 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ted Lee More articles by this author Dana Weiss More articles by this author Elizabeth Roth More articles by this author Sahar Eftekharzadeh More articles by this author Saafia Masoom More articles by this author Susan Jarosz More articles by this author John Kryger More articles by this author Aseem Shukla More articles by this author Travis Groth More articles by this author Michael Mitchell More articles by this author Richard Lee More articles by this author Douglas Canning More articles by this author Joseph Borer More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyPediatric Urology II (MP44)1 Sep 2021MP44-03 COMPARISON OF AESTHETIC PREFERENCES FOLLOWING 3 NEOUMBILICOPLASTY TECHNIQUES Susan Jarosz, Ted Lee, Jen Frazier, Aseem Shukla, Dana Weiss, Travis Groth, Joseph Borer, Douglas Canning, John Kryger, Michael Mitchell, and Elizabeth Roth Susan JaroszSusan Jarosz More articles by this author , Ted LeeTed Lee More articles by this author , Jen FrazierJen Frazier More articles by this author , Aseem ShuklaAseem Shukla More articles by this author , Dana WeissDana Weiss More articles by this author , Travis GrothTravis Groth More articles by this author , Joseph BorerJoseph Borer More articles by this author , Douglas CanningDouglas Canning More articles by this author , John KrygerJohn Kryger More articles by this author , Michael MitchellMichael Mitchell More articles by this author , and Elizabeth RothElizabeth Roth More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002065.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neoumbilical construction in patients with bladder exstrophy (BE) can result in a flat or unnatural appearing scar. Three techniques for NU, the full thickness skin graft (FTSG), Rhomboid, and S-Flap, have demonstrated excellent short term reliability and safety; medium and long term aesthetic outcomes of these techniques are unknown. We hypothesized that a sample of adults with no knowledge of BE or NU would select a preferred technique when evaluating photos of NU in children 1-5 years following surgery. METHODS: A standardized survey was created to compare the cosmesis of the 3 NU techniques 1-5 years post operatively (Figure 1). Deidentified photos were obtained from prospectively consented patients enrolled in the Multi-Institutional Bladder Exstrophy Consortium (MIBEC). Photos from patients undergoing unrelated surgical procedures were included as controls. Surveys were administered anonymously through a REDCap database with recruitment through Amazon Mechanical Turk. Survey respondents, adults 18 years of age or older, rated the 3 NU techniques according to a 5 point Likert-scale with 1 being “appears very unnatural” and 5 being “appears very natural.” Descriptive statistics and analysis of variance (ANOVA) were utilized to evaluate respondent data; p-value thresholds were adjusted for multiple pairwise comparison. RESULTS: A total of 313 surveys were analyzed. Respondents rated control umbilici highest followed by the Rhomboid and FTSG NU techniques (Table 1). A statistically significant variance between the sample means was identified (p<0.001). Pairwise comparison showed significant variance between all but the Rhomboid and FTSG groups (Table 1). CONCLUSIONS: Of the NU techniques evaluated, the aesthetics of the Rhomboid and FTSG techniques were preferred over the S-Flap. Source of Funding: Internal © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e792-e793 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Susan Jarosz More articles by this author Ted Lee More articles by this author Jen Frazier More articles by this author Aseem Shukla More articles by this author Dana Weiss More articles by this author Travis Groth More articles by this author Joseph Borer More articles by this author Douglas Canning More articles by this author John Kryger More articles by this author Michael Mitchell More articles by this author Elizabeth Roth More articles by this author Expand All Advertisement Loading ...

This is the first, large scale, prospectively collected data on the hemodynamic evolution post-transplant in the absence of rejection. RAP greater than 10 mmHg and PCWP pressure greater than 15mmHg are significant markers of early graft loss and mortality and may warrant increased monitoring and modified treatment strategies.

Genetic variants in the alpha myosin heavy chain gene (MYH6; a‐MHC) are significantly enriched in Hypoplastic Left Heart Syndrome (HLHS), an anatomically and clinically severe form of Congenital Heart Disease (CHD). HLHS is characterized by atresia/stenosis of the aortic and mitral valves, and severe hypoplasia of the left ventricle and aorta. A novel variant resulting in an arginine to proline change (R443P) in the head domain of MYH6 was found to segregate with disease in a multigenerational family affected with HLHS and other forms of CHD.a‐MHC is a contractile protein that is important in the developing heart. After birth a‐MHC is located mainly in the atria, while the beta isoform (b‐MHC), which is encoded by the MYH7 gene, is mainly located in the ventricles Variants in both isoforms have been previously associated with hypertrophic and dilated cardiomyopathy, a leading cause of sudden cardiac death in children and adults, as well as CHD. . The two isoforms have ~92% amino acid homology, yet have distinct functional characteristics. At the cellular level, more is known about how variants in MYH7 cause disease because the majority of the b‐MHC protein has been crystallized, while crystal structures have not been solved for any portions of the human a‐MHC protein.The MUHS SMART team submitted two amino acid sequences from the MYH6 gene to I‐TASSER, a bioinformatics method for predicting three‐dimensional protein structure, in order to study the effect of the MYH6 R443P variant on protein structure and function. The first submission contained the wild‐type amino acid sequence, while the second contained the R443P variant. The predicted protein structures were 3‐D printed in order to visualize any structural differences between the wild‐type and variant. I‐TASSER results did not show a significant change in secondary structure but did predict altered ligand binding in the variant protein compared to wild‐type. The electrostatic interface changed from a positively charged, polar amino acid (arginine) to one with a neutral, non‐reactive side chain (proline).The R443P variant occurs within the helix O domain, which lies between the actin binding domain and the ATP binding region, and contains subdomains responsible for binding numerous other proteins, as well as, hydrolyzing ATP during contraction. Normal function of myosin during each contraction of the heart requires that interactions with this region occur at the appropriate place and time. We hypothesize that altered binding properties of myosin heavy chain could lead to altered contractility, affecting the maximum shortening velocity and force during muscle contraction in the developing heart. Future research will focus on the mechanism that this variant has on the functionality of these domains as well as drug targeting therapies as a means to correct or remediate the impact of variants such as R443P.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Purpose The standard for monitoring for rejection (ACR and AMR) following heart transplantation in pediatric and adult patients is endomyocardial biopsy (EMB). However, EMB is imperfect. A growing body of evidence suggests that quantification of donor specific cell-free DNA (cfDNA) may serve as an appropriate biomarker for the non-invasive surveillance for rejection. We designed a multi-center prospective blinded study to investigate the value of the donor fraction (DF), the ratio of donor specific cfDNA to total cfDNA, in the non-invasive detection of rejection following heart transplantation. Methods 241 heart transplant patients, age at transplant 8 days to 73 years (146 <18 years 95>18 years), were recruited from seven heart transplant sites. All patients were followed longitudinally for at least one year. 824 blood samples were paired with biopsies, underwent a stringent QC step, and were analyzed to determine the DF-cfDNA (myTAIHEART, TAI Diagnostics, Wauwatosa, WI). All downstream sample processing was handled by researchers blinded to clinical parameters. Logistic regression for modeling and the standard receiver operating characteristic (ROC) curve was calculated, and repeated measures analysis using generalized linear modeling with patients as clusters was used. Results By ROC analysis a threshold of DF-cfDNA could be determined which ruled out the presence of either ACR > 0R (n=15) or pAMR >0 (n=8) (p=0.03, see figure). By repeated measures analysis in ACR: DF-cfDNA in 0R (n=48) was different from 1R/2R/3R (n=15) (p=0.02). In AMR: DF-cfDNA pAMR 0 (n=702) was different from pAMR 1 (n=25) (p=0.04) or pAMR 2 (n=22) (p=0.04). Conclusion Accurate determination of DF-cfDNA is a promising non-invasive diagnostic strategy for ruling out the presence of ACR and AMR in both adult and pediatric heart transplant recipients.

Purpose A growing body of evidence suggests that quantification of total cell-free DNA (TcfDNA) may serve as an appropriate biomarker for risk for in several clinical scenarios. We designed a multi-center prospective blinded study to investigate the value of TcfDNA in non-invasive clinical monitoring following heart transplantation, DTRT. Methods 241 heart transplant patients, age at transplant 8 days to 73 years (146 <18 years 95>18 years), were recruited from seven heart transplant sites producing 2537 samples. 134 patients were enrolled prior to transplant and 107 were enrolled within 30 months following transplant. All patients were followed longitudinally for at least one year. 2537 samples were analyzed to determine the TcfDNA (myTAI-Total cfDNA, TAI Diagnostics, Wauwatosa, WI). All downstream sample processing was handled by researchers blinded to clinical parameters. Logistic regression for modeling and the standard receiver operating characteristic (ROC) curve was calculated, and repeated measures analysis using generalized linear modeling with patients as clusters was used. Results By ROC analysis a threshold of TcfDNA ng/ml plasma could be determined (33.6 ng/ml) that was highly predictive of death within 30 days, p<0.0001 (see figure). By repeated measures analysis, 44 samples associated with death within 30 days had a median TcfDNA of 73.93 (5.17-777.08) ng/ml plasma vs 8.31 (0.07-1395.80) ng/ml plasma in 1444 samples taken from healthy patients who did not die within 30 days of sample draw, p=0.004. Conclusion Elevation of TcfDNA strongly correlates with risk for near term death in both adult and pediatric heart transplant recipients and precise measurement of TcfDNA may be useful as a trend monitor for effectiveness of clinical care.

Heart transplantation is an accepted therapy for children with end-stage heart disease with average survival of 15-20 years. The highest risk for graft loss remains in the first 60 days post transplantation despite several advances in the care of these patients. Measurement of percent donor fraction (DF) cell-free DNA (cfDNA) allows for extremely sensitive monitoring of graft injury and may be useful early after heart transplant to detect patients at risk for graft failure or death.

Donor Fraction (DF) of cell-free DNA in transplant recipients has been correlated with rejection and allograft injury. Treatment of rejection results in a decrease in DF levels. Little is known about the clinical significance of rebound of, or increase in, DF following initial decrease associated with rejection treatment.

To determine the threshold of elevation of circulating donor fraction (DF) of cell free DNA (cfDNA) that will give an accurate predictive model for ISHLT grade 2 or higher cellular heart allograft rejection. Clinical and demographic factors as well as quantification of donor fraction and total (t-) cfDNA will contribute to the predictive model.

Donor fraction cell free DNA (DF cfDNA) was investigated as a marker for cardiac injury in cardiac transplant recipients. We hypothesized that injury from routine biopsy (bx) would produce a detectable rise in circulating DF cfDNA.

You have accessJournal of UrologyPediatrics1 Apr 2016V7-04 MULTI-INSTITUTIONAL BLADDER EXSTROPHY CONSORTIUM: TECHNICAL STANDARDIZATION OF DISTAL EPISPADIAS REPAIR IN A BOY John Ward, David Chu, Jason Van Batavia, Aseem Shukla, Dana Weiss, Joseph Borer, Evalynn Vasquez, John Kryger, Travis Groth, Michael Mitchell, and Douglas Canning John WardJohn Ward More articles by this author , David ChuDavid Chu More articles by this author , Jason Van BataviaJason Van Batavia More articles by this author , Aseem ShuklaAseem Shukla More articles by this author , Dana WeissDana Weiss More articles by this author , Joseph BorerJoseph Borer More articles by this author , Evalynn VasquezEvalynn Vasquez More articles by this author , John KrygerJohn Kryger More articles by this author , Travis GrothTravis Groth More articles by this author , Michael MitchellMichael Mitchell More articles by this author , and Douglas CanningDouglas Canning More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.561AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Distal male epispadias is a relatively rare entity in the spectrum of exstrophy-epispadias complex. We present a video of a recent distal male epispadias repair that includes skin closure with a rotational skin flap as described by Salle. Preoperative videourodynamics had demonstrated a marginally continent bladder neck, but otherwise normal bladder function. METHODS Technique was male epispadias repair without osteotomy performed at 9 months of life. No pelvic diastasis was present. High-definition video recording was used for real-time local and remote observation and future teaching, analysis, and review as part of the Multi-Institutional Bladder Exstrophy Consortium (MIBEC). RESULTS Our video demonstrates the repair of a mid-shaft distal male epispadias. The penis was initially degloved with a dorsal incision that circumscribes the urethral plate. The corpus spongiosum was then carefully separated off the corpora cavernosal bodies ventrally before moving dorsally. The proximal extent of dissection was the penopubic junction. The corpus spongiosum with dorsal urethral plate was isolated on a vessel loop. Distally, glans wings were made. The glans was never completely disassembled from the corpora cavernosal bodies. A urethroplasty was performed over an 8F urethral stent, and then replaced with a 6F stent that was sutured in place. Next, the neo-urethra and neo-meatus were advanced distally and the urethral plate situated more ventrally. Glansplasty was performed followed by reapproximation of corpora cavernosal bodies dorsally over the urethra without significant medial rotation. Finally, a ventral transverse island penile shaft skin flap was rotated 270 degrees counterclockwise around the penis using the technique of Salle to form a lateral-lying suture line. Three months later the meatus appeared orthotopic and the repair had healed well, with the exception of a small noticeable scar at the location of the suture line of the Salle skin flap (Figure 1). CONCLUSIONS Distal male epispadias repair can be performed effectively in the setting of MIBEC. High-quality video recording of such rare repairs can aid in future teaching and review. The Salle skin closure offers promise to avoid a dorsal penile shaft scar but requires long-term outcomes. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e723 Advertisement Copyright & Permissions© 2016MetricsAuthor Information John Ward More articles by this author David Chu More articles by this author Jason Van Batavia More articles by this author Aseem Shukla More articles by this author Dana Weiss More articles by this author Joseph Borer More articles by this author Evalynn Vasquez More articles by this author John Kryger More articles by this author Travis Groth More articles by this author Michael Mitchell More articles by this author Douglas Canning More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Circulating donor specific cell free-DNA (cf-DNA) can be isolated from recipient plasma and may be a stable biomarker for cellular injury. We designed a blinded prospective pilot study to test the accuracy of a targeted method of detection and quantification of donor specific cf-DNA in heart transplant recipients.

CF-DNA has been shown to correlate with rejection in heart and renal transplant (Tx) pts. We developed a rapid, highly sensitive quantitative approach to measure total CF-DNA. We herein seek to evaluate total CF-DNA as a biomarker for cellular injury and as a step in assay refinement.

You have accessJournal of UrologyPediatrics: Congenital Anomalies - Kidney & Ureter1 Apr 2011455 ANALYSIS OF THE WHOLE URINARY PROTEOME OF STABLE INFANTS WITH GRADE 4 URETEROPELVIC JUNCTION OBSTRUCTION: A FORGOTTEN MAJORITY Hrair-George Mesrobian, Michael Mitchell, Travis Groth, William See, Brian Halligan, Shama Mirza, and Bassam Wakim Hrair-George MesrobianHrair-George Mesrobian Milwaukee, WI More articles by this author , Michael MitchellMichael Mitchell Milwaukee, WI More articles by this author , Travis GrothTravis Groth Milwaukee, WI More articles by this author , William SeeWilliam See Milwaukee, WI More articles by this author , Brian HalliganBrian Halligan Milwaukee, WI More articles by this author , Shama MirzaShama Mirza Milwaukee, WI More articles by this author , and Bassam WakimBassam Wakim Milwaukee, WI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.547AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The management of newborns and infants with unilateral grade 4 ureteropelvic junction obstruction (UPJO) is dictated by its natural history as it unfolds over time. Attention has focused appropriately over progression, which can be observed in approximately 30%, and these patients clearly benefit from surgery. In another 10–30%, there is spontaneous resolution. In the remaining patients, management is in question and indefinite follow up is required because of the inability of current technology to predict outcomes. This communication reports the results of urinary proteome analysis in this latter patient population, the forgotten majority. METHODS Bladder urine specimens were obtained from 21 healthy infants-with normal maternal/fetal ultrasound- and 25 with grade 4 unilateral UPJO. All patients had > 40% ipsilateral individual kidney function by renal scanning and the antero-posterior diameter of the hydronephrotic kidney ranged from 1.6–3.9 cms at presentation. Over a 3 year follow up period, the disease progressed in 5 (20%) and resolved in 1 (4%) and remains stable in the majority (76%). All urinary specimens were prepared using standard methods and subjected to LC/MS/MS analysis. The normalized data were annotated utilizing the Ingenuity Pathways Analysis knowledge platform (IPA; www.Ingenuity. com)and compared to age matched normals. RESULTS In the stable UPJO group (76%), 35 and 47 candidate biomarker proteins were respectively identified by comparing the urinary proteomes to age matched controls (1–6 and 7–12 months). More importantly, a number of essential biologic functions were perturbed (Fig 1l72 illustration for 1–6 months age group). In addition, analysis uncovered production of reactive oxygen species, most prominent in the 7–12 months age group. CONCLUSIONS The urinary proteomes from the bladder in patients with stable grade 4 UPJO (by imaging criteria) are significantly perturbed at birth and appear to undergo change-relative to normal- throughout the first year of life. The imminent discovery of surrogate urinary biomarkers may result in reconsideration of the watchful waiting strategy during this critical period of renal maturation and development in infancy. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e185 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hrair-George Mesrobian Milwaukee, WI More articles by this author Michael Mitchell Milwaukee, WI More articles by this author Travis Groth Milwaukee, WI More articles by this author William See Milwaukee, WI More articles by this author Brian Halligan Milwaukee, WI More articles by this author Shama Mirza Milwaukee, WI More articles by this author Bassam Wakim Milwaukee, WI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...