Distinguishing characteristics of pediatric patients with primary hyperoxaluria type 1 in PEDSnet.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism that causes oxalate deposition, leading to recurrent calcium oxalate kidney stones, chronic kidney disease and systemic oxalosis, which produces a broad range of serious life-threatening complications. Patients with PH1 have delayed diagnosis due to the rarity of the disease and the overlap with early-onset kidney stone disease not due to primary hyperoxaluria. OBJECTIVE: The objective of this study was to determine the clinical features of individuals <21 years of age with PH1 that precede its diagnosis. We hypothesized that a parsimonious set of features could be identified that differentiate patients with PH1 from patients with non-primary hyperoxaluria-associated causes of early-onset kidney stone disease. STUDY DESIGN: We determined the association between clinical characteristics and PH1 diagnosis in a case-control study conducted between 2009 and 2021 in PEDSnet, a clinical research network of eight US pediatric health systems. Each patient with genetically confirmed PH1 was matched by sex and PEDSnet institution to up to 4 control patients with kidney stones without PH of any type. We obtained patient characteristics and diagnostic test results occurring before to less than 6 months after study entrance from a centralized database query and from manual chart review. Differences were examined using standardized differences and multivariable regression. RESULTS: The study sample included 37 patients with PH1 and 147 controls. Patients with PH1 were younger at diagnosis (median age of 3 vs 13.5 years); 75 % of children with PH1 were less than 8 years-old. Patients with PH1 were more likely to have combinations of nephrocalcinosis on ultrasound or CT (43 % vs 3 %), lower eGFR at diagnosis (median = 52 mL/min/1.73 m2 vs 114 mL/min/1.73 m2), and have normal mobility. Patients with PH1 had higher proportion of calcium oxalate monohydrate kidney stones than controls (median = 100 % vs 10 %). There were no differences in diagnosis of failure to thrive, stone size, or echocardiography results. CONCLUSIONS: Children with PH1 are characterized by presentation before adolescence, nephrocalcinosis, decreased eGFR at diagnosis, and calcium oxalate monohydrate stone composition. If externally validated, these characteristics could facilitate earlier diagnosis and treatment of children with PH1.

Robotic retroperitoneal lymph node dissection for paratesticular rhabdomyosarcoma in adolescents: a case series.

Robotic assisted (RA) retroperitoneal lymph node dissection (RPLND) has grown in popularity as it offers decreased morbidity and faster recovery compared to the open technique. Proponents of open surgery raised concerns about the oncological fidelity of the RA approach for testicular tumors where complete resection is needed. In boys > 10 years with paratesticular rhabdomyosarcoma (RMS), RPLND is indicated for staging purposes only. In this population, the RA technique should provide its benefits without concerns for oncological compromise. We present an analysis of RA-RPLND for boys with paratesticular RMS. We queried our institution's prospectively collected database of pediatric robotic cases for patients undergoing RA-RPLND post-radical orchiectomy for paratesticular mass, confirmed by pathology as RMS. Demographic, surgical, follow-up, and oncological outcomes were evaluated between 2017 and 2023. Five patients underwent RA-RPLND for paratesticular RMS. The median age was 16.1 years (15-17), with median OR time of 456 min (357-508). No conversions to open occurred. Inpatient median total opioid use was 1.8 (0.4-2.7) morphine equivalent/kg. The median lymph node yield was 27 (8-44) and post-op length of stay was 3 days (2-5). The median time to initiating adjuvant chemotherapy was 10.5 days (7-13). One patient had complications: pneumothorax attributed to central line placement and chyle leak that resolved in 1 week with dietary restriction. Our series demonstrates the feasibility, safety, and efficacy of the RA approach for RPLND in pediatric patients with paratesticular RMS. This is the most extensive case series currently in the literature and the only one exclusively done for paratesticular RMS.

The real world experience of pediatric primary hyperoxaluria patients in the PEDSnet clinical research network.

The rarity of primary hyperoxaluria (PH) challenges our understanding of the disease. The purpose of our study was to describe the course of clinical care in a United States cohort of PH pediatric patients, highlighting health service utilization. We performed a retrospective cohort study of PH patients < 18 years old in the PEDSnet clinical research network from 2009 to 2021. Outcomes queried included diagnostic imaging and testing related to known organ involvement of PH, surgical and medical interventions specific to PH-related renal disease, and select PH-related hospital service utilization. Outcomes were evaluated relative to cohort entrance date (CED), defined as date of first PH-related diagnostic code. Thirty-three patients were identified: 23 with PH type 1; 4 with PH type 2; 6 with PH type 3. Median age at CED was 5.0 years (IQR 1.4, 9.3 years) with the majority being non-Hispanic white (73%) males (70%). Median follow-up between CED and most recent encounter was 5.1 years (IQR 1.2, 6.8). Nephrology and Urology were the most common specialties involved in care, with low utilization of other sub-specialties (12%-36%). Most patients (82%) had diagnostic imaging used to evaluate kidney stones; 11 (33%) had studies of extra-renal involvement. Stone surgery was performed in 15 (46%) patients. Four patients (12%) required dialysis, begun in all prior to CED; four patients required renal or renal/liver transplant.    Conclusion: In this large cohort of U.S. PH children, patients required heavy health care utilization with room for improvement in involving multi-disciplinary specialists. What is Known: • Primary hyperoxaluria (PH) is rare with significant implications on patient health. Typical involvement includes the kidneys; however, extra-renal manifestations occur. • Most large population studies describe clinical manifestations and involve registries. What is New: • We report the clinical journey, particularly related to diagnostic studies, interventions, multispecialty involvement, and hospital utilization, of a large cohort of PH pediatric patients in the PEDSnet clinical research network. • There are missed opportunities, particularly in that of specialty care, that could help in the diagnosis, treatment, and even prevention of known clinical manifestations.

A Case of Multicystic Dysplastic Kidney Presenting as a Single Midline Pelvic Cyst.

We present an unusual case of a female neonate presenting with a single midline pelvic cyst. Prenatal imaging was suggestive of multicystic dysplastic kidney (MCDK), but postnatal imaging was atypical for this diagnosis given the location and singular cyst noted. The patient ultimately underwent surgical exploration and was diagnosed with an ectopic MCDK. Ectopic MCDK should be considered in the differential diagnosis of unilocular cystic pelvic lesions identified in the perinatal period.

Ureteral Stent Placement Prior to Definitive Stone Treatment Is Associated With Higher Postoperative Emergency Department Visits and Opioid Prescriptions for Youth Having Ureteroscopy or Shock Wave Lithotripsy.

PURPOSE: Little is known about the impact of ureteral stents on youth having stone surgery. We evaluated the association of ureteral stent placement before or concurrent with ureteroscopy and shock wave lithotripsy with emergency department visits and opioid prescriptions among pediatric patients. MATERIALS AND METHODS: We conducted a retrospective cohort study of individuals aged 0-24 years who underwent ureteroscopy or shock wave lithotripsy from 2009-2021 at 6 hospitals in PEDSnet, a research network that aggregates electronic health record data from children's health systems in the United States. The exposure, primary ureteral stent placement, was defined as a stent placed concurrent with or within 60 days before ureteroscopy or shock wave lithotripsy. Associations between primary stent placement and stone-related ED visits and opioid prescriptions within 120 days of the index procedure were evaluated with mixed-effects Poisson regression. RESULTS: Two-thousand ninety-three patients (60% female; median age 15 years, IQR 11-17) had 2,477 surgical episodes; 2,144 were ureteroscopy and 333 were shock wave lithotripsy. Primary stents were placed in 1,698 (79%) ureteroscopy episodes and 33 (10%) shock wave lithotripsy episodes. Ureteral stents were associated with a 33% higher rate of emergency department visits (IRR 1.33; 95% CI 1.02-1.73) and a 30% higher rate of opioid prescriptions (IRR 1.30; 95% CI 1.10-1.53). The magnitudes of both associations were greater for shock wave lithotripsy. Results were similar for age <18 and were lost when restricted to concurrent stent placement. CONCLUSIONS: Primary ureteral stent placement was associated with more frequent emergency department visits and opioid prescriptions, driven by pre-stenting. These results support elucidating situations where stents are not necessary for youth with nephrolithiasis.

Robotic upper tract surgery in infants 6 months or less: is there enough space?

Robot-assisted laparoscopic surgery (RALS) has recently been described in children < 1 year old. However, little data exist on robotic utilization in infants ≤ 6 months old, likely due to concerns for limited intraabdominal space and decreased distance between ports in this cohort. We hypothesized that the robotic approach can be successfully used for infants ≤ 6 months old. A prospectively collected database of patients undergoing urologic robotic surgery at our institution was reviewed. Patients ≤ 6 months and ≥ 4 kg were included. Patient demographics, intraoperative details, hospital length of stay, and complications were reviewed. Descriptive statistics were performed. Twelve patients ≤ 6 months old underwent urologic robotic surgery by three surgeons at our institution (2013-2019): pyeloplasty (6), ureteroureterostomy (4), heminephrectomy (1), and nephrectomy (1). Median age at surgery was 4.75 months (IQR 4, 6). Median weight was 7.09 kg (IQR 6.33, 7.78). Median console time was 105 min (IQR 86, 123). For all procedures, 8-mm robotic arm ports were used. No procedures were converted to open. Median post-operative hospital stay was 24 h (IQR). Febrile UTI was the only complication occurring within 30 days of surgery (n = 4, 33%; 7-20 days, Clavien grade 2). For those undergoing pyeloplasty or ureteroureterostomy (n = 10), postoperative ultrasound showed improved (n = 9) or stable hydronephrosis (n = 1). At a median follow-up of 19.73 months (IQR 4.27, 38.32), no patient required an unplanned secondary intervention. Robotic upper urinary tract surgery is feasible and safe in patients ≤ 6 months of age and can be performed successfully with the same technique as for older children.

Does a standardized operative approach in cloacal reconstruction allow for preservation of a patent urethra?

BACKGROUND: Cloacal malformations are recognized as a particularly challenging congenital condition to manage and they present with a wide spectrum of anatomical configurations making surgical repair very complicated. Urethral necrosis or urethral loss is a known and devastating complication of cloacal repair. The surgical repair of these malformations has evolved over time and historically only common channel (CC) length was measured. More recently, it has been advocated that the urethral length and the CC are both important in determining surgical repair. The purpose of our study is to evaluate if this surgical approach allows for preservation of a patent urethra. METHODS: A prospective database of all cloaca patients maintained with IRB approval (IRB# STUDY00000721) was retrospectively reviewed. We included any girl with cloacal malformation who underwent primary repair at our institution between May 2014 and December 2019. Standardized preop evaluation with endoscopy and 3-dimentional imaging to assess urethral length and CC length. These measurements were used to determine operative approach. Girls with CC < 1 cm undergo posterior sagittal anorectoplasty and introitoplasty (PSARP + I), those with CC measuring 1-3 cm and urethra > 1.5 cm undergo total urogenital mobilization (TUM) and those with CC > 3 cm or urethra < 1.5 cm undergo urogenital separation (UGS). Postoperative urethral patency was determined at the time of cystoscopy and exam under anesthesia (EUA) 4-6 weeks postoperatively by visualizing a viable and healthy urethra that is catheterizable. RESULTS: A total of 59 patients met inclusion criteria with a median age of 11.6 months. Four girls underwent PSARP + I, 19 girls had a TUM and 36 girls underwent a UGS. All of the girls who had PSARP +I (n = 4) or TUM (n = 19) had a viable and patent urethra that was catheterizable at the cystoscopy and EUA 4-6 weeks postoperatively. Of the 36 girls who had UGS, all but 2 (5.6%) had a viable and patent urethra that catheterized without problems. Overall, 97% of girls in this cohort had a patent urethra after cloacal repair using this surgical protocol. CONCLUSIONS: The use of a standard protocol that considers urethral and common channel length for cloacal repairs results in a viable and patent urethra in 97% of patients. LEVEL OF EVIDENCE: Level II.

Prediction of kidney failure in children with chronic kidney disease and obstructive uropathy.

BACKGROUND: Obstructive uropathy (OU) is a leading cause of pediatric kidney injury. Accurate prediction of kidney disease progression may improve clinical outcomes. We aimed to examine discrimination and accuracy of a validated kidney failure risk equation (KFRE), previously developed in adults, in children with OU. METHODS: We identified 118 children with OU and an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 in the Chronic Kidney Disease in Children study, a national, longitudinal, observational cohort. Each patient's 5-year risk of kidney failure was estimated using baseline data and published parameters for the 4- and 8-variable KFREs. Discriminative ability of the KFRE was estimated using the C statistic for time-to-event analysis. Sensitivity and specificity were evaluated across varying risk thresholds. RESULTS: Among the 118 children, 100 (85%) were boys, with median baseline age of 10 years (interquartile range, 6-14). Median eGFR was 42 mL/min/1.73m 2 (32-53), with a median follow-up duration of 4.5 years (2.7-7.2); 23 patients (19.5%) developed kidney failure within 5 years. The 4-variable KFRE discriminated kidney failure risk with a C statistic of 0.75 (95% CI, 0.68-0.82). A 4-variable risk threshold of ≥ 30% yielded 82.6% sensitivity and 75.0% specificity. Results were similar using the 8-variable KFRE. CONCLUSIONS: In children with OU, the KFRE discriminated the 5-year risk of kidney failure at C statistic values lower than previously published in adults but comparable with suboptimal values reported in the overall CKiD population. The 8-variable equation did not improve model discrimination or accuracy, suggesting the need for continued research into additional, disease-specific markers.

Surgical outcomes are equivalent after pure laparoscopic and robotic-assisted pyeloplasty for ureteropelvic junction obstruction.

INTRODUCTION: Minimally invasive (robotic and pure laparoscopic) pyeloplasty has been increasingly used for treatment of ureteropelvic junction obstruction (UPJO). However, few large-scale studies have compared these two modalities directly. METHODS: We performed a retrospective single-center review of all patients who underwent pure laparoscopic (LP) or robotic pyeloplasty (RALP) between 2007 and 2018. Patients were excluded if the initial surgery at our institution was a redo pyeloplasty or if they lacked follow-up information. Outcomes of interest included operative time, length of stay, and complication rates, including rates of secondary procedures. We compared these outcomes between groups using Student's t test for continuous variables and a Chi-square for categorical variables. RESULTS: A total of 282 patients were identified. Forty-eight were excluded based on study criteria; therefore, our total study cohort was 234 patients: 119 RALP and 115 LP cases. Overall mean postoperative follow-up time was 20.8 months, with no significant differences between groups. Mean operative time was shorter in the LP group when compared the RALP group (3 h 7 min vs. 3 h 41 min, p < 0.001). There were no significant differences between groups in length of stay (1.22 days vs 1.50 days, p = 0.095). Complications occurred in 52 patients (22.2% of overall cohort) with no difference in incidence between groups. Twenty-five patients (14 in the RALP group and 11 in the LP group) underwent unplanned secondary procedures; 19 of these patients (9 in the RALP group and 10 in the LP group) needed a procedure to address secondary obstruction. CONCLUSION: We demonstrated no significant differences between RALP and LP in regards to complication rates. Surgeons performing RALP and LP have the potential to offer the same level of care for the surgical management of UPJO, especially in countries where robotic technology may not be readily available.

Anatomic factors predict urinary continence in patient with anorectal malformation.

It has been described that patients with more complex anorectal malformations (ARM), lower sacral ratios and spinal anomalies have poorer rates of fecal and urinary continence. While the ARM subtype has been shown to be an independent predictor of fecal continence, it is not well understood how each of these anatomic factors impact urinary continence. The purpose of this study was to identify anatomic factors associated with urinary continence in children born with ARM. We performed a retrospective review of a large prospectively collected database of children with ARM. Inclusion criteria included diagnosis of ARM, age >4 years, available lateral sacral ratio measurement and presence of spinal MRI. Any child with incomplete or absent continence data was excluded. Continence was defined as voiding per urethra volitionally, dry between voids and ≤1 urinary accident per week. Bivariable tests of association and log-binomial regression models were used to examine association between anatomic factors and urinary continence. A total of 434 patients were included in the study. 57.8% (n = 251) were male. Median age was 8.4 years (IQR 6.0-12.3). With regards to severity of ARM, 20.3% (n = 88) were complex, 23.3% (n = 101) were moderate and 56.5% (n = 245) were simple. Lateral sacral ratio included 11.1% (n = 48) that were <0.4, 36.2% (n = 157) 0.4-0.7 and 52.8% (n = 229) > 0.7. Spine status was found to be myelomeningocele in 4.4% (n = 19), low conus or tethered cord in 34.8% (n = 151) and normal or fatty filum in 60.8% (n = 264). Overall 62.2% were continent. ARM severity, lateral sacral ratio and spine status were each independent predictors of urinary continence on univariate and multivariable analysis. We conclude that in children born with ARM, the severity of ARM, lateral sacral ratio and spine status each independently predict urinary continence. These results allow us to better understand these complex patients and their ability to develop urinary continence. This is crucial in enabling proper patient and family counseling and thus, setting appropriate expectations.

Trans IL-6 signaling does not appear to play a role in renal scarring after urinary tract infection.

INTRODUCTION: While inflammation is an important innate defense mechanism against infection, it can also lead to local tissue damage. The trans signaling pathway of interleukin (IL)-6 is a known mediator of inflammation. We hypothesized that the trans IL-6 signaling pathway is associated with the development of post febrile urinary tract infection (UTI) renal scarring. OBJECTIVE: To compare soluble regulators of trans IL-6 signaling between patients with a history of febrile UTI who do or do not have renal scarring. STUDY DESIGN: After IRB-approval, we collected urine samples in pediatric patients with a history of febrile (≥38 °C) UTI (urine culture >50 K uropathogen) with documented presence or absence of renal scarring on imaging. Samples were collected at a time when patients were not actively infected. Enzyme-linked immunosorbent assays were performed on samples for markers of trans IL-6 signaling: IL-6, soluble (s) IL-6 receptor (R), and soluble (s)gp130, a buffer in trans IL-6 signaling. Values were normalized to urine creatinine. Results were analyzed by t-test or Mann-Whitney U. Spearman rank correlation was used. A p-value of <0.05 was considered significant. RESULTS: A total of 50 urines from patients with a history of febrile UTI were collected: 23 with and 27 without scarring. There was no difference between groups regarding age or gender. There was no significant difference in urine IL-6, sIL-6R, or sgp130 between those with and without scarring (Figure). While IL-6 values significantly correlated with sIL-6R and sgp130 in those without renal scarring, IL-6 did not correlate with sgp130 in those with scarring. Ratios of IL-6 to sgp130 and sIL-6R to sgp130 were not different between groups. DISCUSSION: The inflammatory response generated in response to infection is believed to be largely responsible for the development of renal scarring after UTI. IL-6 is a cytokine known to be induced during UTI with a pro-inflammatory pathway, known as trans signaling. This study investigated for differences in markers of trans IL-6 signaling between patients with a history of febrile UTI with and without renal scarring. There was no significant difference between the absolute values or ratio of these markers between groups. CONCLUSIONS: Markers of trans IL-6 signaling are not different between individuals with a history of febrile UTI with and without renal scarring in the non-acute setting.

Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy.

BACKGROUND: Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. METHODS: Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. RESULTS: In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). CONCLUSIONS: In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.

Impact of successful pediatric ureteropelvic junction obstruction surgery on urinary HIP/PAP and BD-1 levels.

INTRODUCTION: In the pediatric patient whose ureteropelvic junction obstruction (UPJO) is not always symptomatic, imaging is the most common means of detecting surgical success. There is interest, however, in other means of post-operative monitoring. A panel of antimicrobial peptides (AMPs) has been previously found to be elevated in UPJO, but the impact of surgical correction on these AMPs is unknown. OBJECTIVE: To determine if elevated levels of candidate urinary AMP biomarkers of urinary tract obstruction decrease following UPJO repair. STUDY DESIGN: Pediatric patients undergoing surgical correction of an UPJO were recruited for participation. Bladder urine from uninfected consenting/assenting patients was collected immediately prior to surgery and then at least 6 months afterward. Based on prior studies demonstrating significant elevation of beta defensin 1 (BD-1), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in patients with UPJO versus control patients, we performed enzyme-linked immunosorbent assays on these four AMPs to compare their expression before and after surgical intervention. If found to significantly decrease, AMP levels were compared to healthy controls. AMP levels were normalized to urine creatinine. Results were analyzed with paired t test or Wilcoxon test using Graphpad software. Correlation was calculated using Pearson or Spearman correlation. A p-value of <0.05 was considered significant. RESULTS: 13 UPJO patients were included in this study; 9 were male (69%). Age at surgery was a median of 4.3 years (average 6.1, range 0.4-18.4 years). Follow-up urine samples were collected a median of 27.4 months after surgery (average 27.4; range 7.8-45.3 months). All 13 patients had clinical improvement and/or signs of improved hydronephrosis on post-operative imaging. HIP/PAP and BD-1 significantly decreased in post-surgical samples compared to pre-surgical samples (p = 0.02 and 0.01, respectively); NGAL and LL-37 did not significantly change. Overall, HIP/PAP decreased in 12 patients (92%) and BD-1 decreased in 11 patients (85%). BD-1 levels after successful repair were not different from healthy controls (p = 0.06). DISCUSSION: Urinary biomarkers of obstruction should detect significant obstructive pathology as well as reflect its resolution. This would enable their use in post-operative monitoring and augment current methods of determining successful surgical outcome through imaging. CONCLUSIONS: The AMPs HIP/PAP and BD-1 are significantly elevated in UPJO but then significantly decrease after pyeloplasty, with BD-1 returning to healthy control levels. As a result, these AMPs could serve as markers of successful surgical intervention.

Krt5+ urothelial cells are developmental and tissue repair progenitors in the kidney.

Congenital urinary tract obstruction (UTO) is the leading cause of chronic kidney disease in children; however, current management strategies do not safeguard against progression to end-stage renal disease, highlighting the need for interventions to limit or reverse obstructive nephropathy. Experimental UTO triggers renal urothelial remodeling that culminates in the redistribution of basal keratin 5-positive (Krt5+) renal urothelial cells (RUCs) and the generation of uroplakin-positive (Upk)+ RUCs that synthesize a protective apical urothelial plaque. The cellular source of Upk+ RUCs is currently unknown, limiting the development of strategies to promote renal urothelial remodeling as a therapeutic approach. In the present study, we traced the origins of adult Upk+ RUCs during normal development and in response to UTO. Fate mapping analysis demonstrated that adult Upk+ RUCs derive from embryonic and neonatal Krt5+ RUCs, whereas Krt5+ RUCs lose this progenitor capacity and become lineage restricted by postnatal day 14. However, in response to UTO, postnatal day 14-labeled adult Krt5+ RUCs break their lineage restriction and robustly differentiate into Upk+ RUCs. Thus, Krt5+ RUCs drive renal urothelial formation during normal ontogeny and after UTO by differentiating into Upk+ RUCs in a temporally restricted manner.

Analysis of the Ribonuclease A Superfamily of Antimicrobial Peptides in Patients Undergoing Chronic Peritoneal Dialysis.

Infectious peritonitis is a common complication in patients undergoing chronic peritoneal dialysis (PD), limiting the duration of PD as a modality for renal replacement therapy and increasing patient morbidity and mortality. Antimicrobial peptides (AMPs) serve critical roles in mucosal defense, but their expression and activity during peritonitis are poorly understood. We hypothesized that AMPs belonging to the Ribonuclease (RNase) A Superfamily are present in peritoneal fluid and increase during peritonitis in patients undergoing chronic PD. In the absence of peritonitis, we detected RNase 3, RNase 6, and RNase 7 in cell-free supernatants and viable cells obtained from peritoneal fluid of chronic PD patients. The cellular sources of these RNases were eosinophils (RNase 3), macrophages (RNase 6), and mesothelial cells (RNase 7). During peritonitis, RNase 3 increased 55-fold and RNase 7 levels increased 3-fold on average, whereas RNase 6 levels were unchanged. The areas under the receiver-operating characteristic curves for RNase 3 and RNase 7 were 0.99 (95% confidence interval (CI): 0.96-1.0) and 0.79 (95% CI: 0.64-0.93), respectively, indicating their potential as biomarkers of peritonitis. Discrete omental reservoirs of these RNases were evident in patients with end stage kidney disease prior to PD initiation, and omental RNase 3 reactive cells increased in patients undergoing PD with a history of peritonitis. We propose that constitutive and inducible pools of antimicrobial RNases form a network to shield the peritoneal cavity from microbial invasion in patients undergoing chronic PD.

Common clinical markers predict end-stage renal disease in children with obstructive uropathy.

BACKGROUND: Obstructive uropathy (OU) is a common cause of end-stage renal disease (ESRD) in children. Children who escape the newborn period with mild-to-moderate chronic kidney disease (CKD) continue to be at increased risk. The predictive ability of clinically available markers throughout childhood is poorly defined. METHODS: Patients with OU were identified in the Chronic Kidney Disease in Children Study. The primary outcome of interest was renal replacement therapy (RRT) (cases). Controls were age matched and defined as patients within the OU cohort who did not require RRT during study follow-up. RESULTS: In total, 27 cases and 41 age-matched controls were identified. Median age at baseline and age at outcome measurement were 10 vs. 16 years, respectively. First available glomerular filtration rate (GFR) (36.9 vs. 53.5 mL/min per 1.73 m2), urine protein/creatinine (Cr) (0.40 vs. 0.22 mg/mg) and microalbumin/Cr (0.58 vs. 0.03 mg/mg), and serum CO2 (20 vs. 22 mmol/L) and hemoglobin (12.4 vs. 13.2 g/dL) differed significantly between cases and controls, respectively. GFR declined 3.07 mL/min per 1.73 m2/year faster in cases compared to that in controls (p < 0.0001). Urine protein/Cr and microalbumin/Cr increased by 0.16 and 0.11 per year more in cases compared to those in controls, respectively (p ≤ 0.001 for both). Serum phosphate increased by 0.11 mg/dL and serum albumin and hemoglobin decreased by 0.04 (g/dL) and 0.14 (g/dL) per year more for cases compared to those for controls, respectively (p < 0.05 for all). CONCLUSIONS: Age-specific baseline and longitudinal measures of readily available clinical measures predict progression to ESRD in children with mild-to-moderate CKD from OU.

Impact on Patient Care of a Multidisciplinary Center Specializing in Colorectal and Pelvic Reconstruction.

Aim of the study: Many patients with an anorectal malformation (ARM) or pelvic anomaly have associated urologic or gynecologic problems. We hypothesized that our multidisciplinary center, which integrates pediatric colorectal, urologic, gynecologic and GI motility services, could impact a patient's anesthetic exposures and hospital visits. Methods: We tabulated during 2015 anesthetic/surgical events, endotracheal intubations, and clinic/hospital visits for all patients having a combined procedure. Main results: Eighty two patients underwent 132 combined procedures (Table 1). The median age at intervention was 3 years [0.2-17], and length of follow up was 25 months [7-31]. The number of procedures in patients who underwent combined surgery was lower as compared to if they had been done independently [1(1-5) vs. 3(2-7) (p < 0.001)]. Intubations were also lower [1[1-3] vs. 2[1-6]; p < 0.001]. Hospital length of stay was significantly lower for the combined procedures vs. the theoretical individual procedures [8 days [3-20] vs. 10 days [4-16]] p < 0.05. Post-operative clinic visits were fewer when combined visits were coordinated as compared to the theoretical individual clinic visits (urology, gynecology, and colorectal) [1[1-4] vs. 2[1-6]; p = < 0.001]. Conclusions: Patients with anorectal and pelvic malformations are likely to have many medical or surgical interventions during their lifetime. A multidisciplinary approach can reduce surgical interventions, anesthetic procedures, endotracheal intubations, and hospital/outpatient visits.

Interleukin-6/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection.

The signaling networks regulating antimicrobial activity during urinary tract infection (UTI) are incompletely understood. Interleukin-6 (IL-6) levels increase with UTI severity, but the specific contributions of IL-6 to host immunity against bacterial uropathogens are unknown. To clarify this we tested whether IL-6 activates the Stat3 transcription factor, to drive a program of antimicrobial peptide gene expression in infected urothelium during UTI. Transurethral inoculation of uropathogenic Escherichia coli led to IL-6 secretion, urothelial Stat3 phosphorylation, and activation of antimicrobial peptide transcription, in a Toll-like receptor 4-dependent manner in a murine model of cystitis. Recombinant IL-6 elicited Stat3 phosphorylation in primary urothelial cells in vitro, and systemic IL-6 administration promoted urothelial Stat3 phosphorylation and antimicrobial peptide expression in vivo. IL-6 deficiency led to decreased urothelial Stat3 phosphorylation and antimicrobial peptide mRNA expression following UTI, a finding mirrored by conditional Stat3 deletion. Deficiency in IL-6 or Stat3 was associated with increased formation of intracellular bacterial communities, and exogenous IL-6 reversed this phenotype in IL-6 knockout mice. Moreover, chronic IL-6 depletion led to increased renal bacterial burden and severe pyelonephritis in C3H/HeOuJ mice. Thus, IL-6/Stat3 signaling drives a transcriptional program of antimicrobial gene expression in infected urothelium, with key roles in limiting epithelial invasion and ascending infection.

Image of the Month: Clinical Features in a Newborn with Covered Cloacal Exstrophy.

Cloacal exstrophy is the most severe type of anorectal malformations that belongs to the bladder-exstrophy-epispadias complex of genitourinary malformations. Interestingly, its variant, the covered cloacal exstrophy, is often missed. The clinical findings of this variant may include an imperforate anus, low lying umbilicus, thick pubic bone, and pubic diastasis but with an intact abdominal wall. We present an interesting case of covered cloacal exstrophy with a side-by-side duplicated bladder and discuss important considerations for the time of colostomy creation in the newborn period.