Imaging fibrosis in pediatric kidney transplantation: A pilot study.

2023

e14540

05/2023

1399-3046

BACKGROUND: Noninvasive alternatives to biopsy for assessment of interstitial fibrosis and tubular atrophy (IFTA), the major determinant of kidney transplant failure, remain profoundly limited. Elastography is a noninvasive technique that propagates shear waves across tissues to measure their stiffness. We aimed to test utility of elastography for early detection of IFTA in pediatric kidney allografts.

METHODS: We compared ultrasound (USE) and MR elastography (MRE) stiffness measurements, performed on pediatric transplant recipients referred for clinically indicated biopsies, and healthy controls.

RESULTS: Ten transplant recipients (median age 16 years) and eight controls (median age 16.5 years) were enrolled. Three transplant recipients had "stable" allografts and seven had Banff Grade 1 IFTA. Median time from transplantation to biopsy was 12 months. Mean estimated glomerular filtration rate was 61.5 mL/min/1.73m by creatinine-cystatin-C CKiD equation at time of biopsy. Mean stiffness, calculated through one-way ANOVA, was higher for IFTA allografts (23.4 kPa USE/5.6 kPa MRE) than stable allografts (13.7 kPa USE/4.4 kPa MRE) and controls (9.1 kPa USE/3.6 kPa MRE). Pearson's coefficient between USE and MRE stiffness values was strong (r = .97). AUC for fibrosis prediction in transplanted kidneys was high for both modalities (0.91 USE and 0.89 MRE), although statistically nonsignificant (p > .05). Stiffness cut-off values for USE and MRE were 13.8 kPa and 4.6 kPa, respectively. Both values yielded a sensitivity of 100% but USE specificity (72%) was slightly higher than MRE (67%).

CONCLUSION: Elastography shows potential for detection of low-grade IFTA in allografts although a larger sample is imperative for clinical validation.

10.1111/petr.14540

Pediatr Transplant

37166372

Risk of Acute Kidney Injury Following Contrast-enhanced CT in a Cohort of 10 407 Children and Adolescents.

2023

e210816

04/2023

1527-1315

Background Previous studies have challenged the concept of contrast material-induced acute kidney injury (AKI) in adults; however, limited data exist for children and adolescents. Purpose To calculate the incidence and determine the risks of AKI in patients who received intravenous iodinated contrast media for CT. Materials and Methods This retrospective study was performed at a children's hospital from January 2008 to January 2018 and included patients aged 0-17 years in whom serum creatinine levels were measured within 48 hours before and after CT with or without contrast media. The incidence of AKI was measured according to the AKI Network guidelines. A subgroup analysis with propensity score matching of cases with control patients was performed. Differences before and after stratification based on estimated glomerular filtration rate (eGFR) were explored. Adjusted risk models were developed using log-binomial generalized estimating equations to estimate relative risk (RR). Results From a total of 54 000 CT scans, 19 377 scans from 10 407 patients (median age, 8.5 years; IQR, 3-14; 5869 boys, 4538 girls) were included in the analysis. Incidence rate of AKI for the entire sample was 1.5%; it was 1.4% (123 of 8844) in the group that underwent contrast-enhanced CT and 1.6% (171 of 10 533) in the group that did not ( = .18). In the contrast-enhanced CT group, AKI incidence was higher in the group with eGFR of at least 60 mL/min/1.73 m and in the group with eGFR lower than 60 mL/min/1.73 m (1.3% and 8.5%, respectively; < .001) compared with the noncontrast group (0.1% and 2.7%, respectively; < .001). Age was found to be a protective factor against AKI, with an RR of 0.96 (95% CI: 0.94, 0.99; = .01), and contrast media increased risk in the subgroup analysis, with an RR of 2.19 (95% CI: 1.11, 4.35; = .02). Conclusion The overall incidence of acute kidney injury after contrast-enhanced CT in children and adolescents was very low, and exposure to contrast media did not increase the risk consistently for acute kidney injury among different groups and analyses. © RSNA, 2022 See also the editorial by McDonald in this issue.

10.1148/radiol.210816

Radiology

36472537

Primary ablation versus urinary diversion in posterior urethral valve: Systematic review and meta-analysis.

2023

02/2023

1873-4898

PURPOSE: To determine differences in long-term kidney and bladder outcomes in boys with posterior urethral valves (PUV) managed by a primary valve ablation or primary urinary diversion.

MATERIALS AND METHODS: A systematic search was performed in March 2021. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed measures included kidney outcomes (chronic kidney disease, end-stage renal disease, kidney function) and bladder outcomes. Odds ratios (OR) and mean difference (MD) with 95% confidence interval (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analysis and meta-regression were performed according to study design, and potential covariates were assessed with subgroup analysis. The systematic review was prospectively registered on PROSPERO (CRD42021243967).

RESULTS: Thirty unique studies describing 1547 boys with PUV were included in this synthesis. Overall effect estimates demonstrate that patients undergoing primary diversion have significantly increased odds of developing renal insufficiency [OR 0.60, 95% CI 0.44, 0.80; p < 0.001]. However, when adjusting for baseline kidney function between intervention groups, there was no significant difference in long term kidney outcomes [p = 0.09, 0.35], or the development of bladder dysfunction or requiring clean-intermittent catheterization with primary ablation rather than diversion [OR 0.89, 95% CI 0.49, 1.59; p = 0.68].

CONCLUSIONS: Current low-quality evidence suggests that medium-term kidney outcomes in children are similar between primary ablation and primary diversion after adjusting for baseline kidney function, while bladder outcomes are highly heterogenous. Further research with covariate control is warranted to investigate sources of heterogeneity.

LEVEL OF EVIDENCE: Level III.

10.1016/j.jpurol.2023.02.008

J Pediatr Urol

36906479

Deep learning imaging features derived from kidney ultrasounds predict chronic kidney disease progression in children with posterior urethral valves.

2022

07/2022

1432-198X

BACKGROUND: We sought to use deep learning to extract anatomic features from postnatal kidney ultrasounds and evaluate their performance in predicting the risk and timing of chronic kidney disease (CKD) progression for boys with posterior urethral valves (PUV). We hypothesized that these features would predict CKD progression better than clinical characteristics such as nadir creatinine alone.

METHODS: We performed a retrospective cohort study of boys with PUV treated at two pediatric health systems from 1990 to 2021. Features of kidneys were extracted from initial postnatal kidney ultrasound images using a deep learning model. Three time-to-event prediction models were built using random survival forests. The Imaging Model included deep learning imaging features, the Clinical Model included clinical data, and the Ensemble Model combined imaging features and clinical data. Separate models were built to include time-dependent clinical data that were available at 6 months, 1 year, 3 years, and 5 years.

RESULTS: Two-hundred and twenty-five patients were included in the analysis. All models performed well with C-indices of 0.7 or greater. The Clinical Model outperformed the Imaging Model at all time points with nadir creatinine driving the performance of the Clinical Model. Combining the 6-month Imaging Model (C-index 0.7; 95% confidence interval [CI] 0.6, 0.79) with the 6-month Clinical Model (C-index 0.79; 95% CI 0.71, 0.86) resulted in a 6-month Ensemble Model that performed better (C-index 0.82; 95% CI 0.77, 0.88) than either model alone.

CONCLUSIONS: Deep learning imaging features extracted from initial postnatal kidney ultrasounds may improve early prediction of CKD progression among children with PUV. A higher resolution version of the Graphical abstract is available as Supplementary information.

10.1007/s00467-022-05677-0

Pediatr Nephrol

35867160

Pre-versus postnatal presentation of posterior urethral valves: a multi-institutional experience.

2022

350-356

09/2022

1464-410X

OBJECTIVE: To compare the outcomes of pre- vs postnatally diagnosed posterior urethral valves (PUV) at two large paediatric centres in North America to ascertain if the prenatal diagnosis of PUV is associated with better outcomes.

PATIENTS AND METHODS: All boys with PUV were identified at two large paediatric institutions in North America between 2000 and 2020 (The Hospital for Sick Children [SickKids, SK] and Children's Hospital of Philadelphia [CHOP]). Baseline characteristics and outcome measures were compared between those diagnosed pre- vs postnatally. Main outcomes of interest included progression of chronic kidney disease (CKD), the need for renal replacement therapy (RRT), and bladder function compromise, as determined by need for clean intermittent catheterisation (CIC). Time-to-event analyses were completed when possible.

RESULTS: During the study period, 152 boys with PUV were treated at the SK (39% prenatal) and 216 were treated at the CHOP (71% prenatal). At the SK, there was no difference between the pre- and postnatal groups in the proportion of boys who required RRT, progressed to CKD Stage ≥3, or who were managed with CIC when comparing the timing of diagnosis. The time to event for RRT and CIC was significantly younger for prenatally detected PUV. At the CHOP, significantly more prenatal boys required RRT; however, there was no significant difference in the age this outcome was reached. The proportion of boys managed with CIC was not different but the time to event was significantly earlier in the prenatal group.

CONCLUSION: This study represents the largest multi-institutional series of boys with PUV and failed to identify any difference in the outcomes of pre- vs postnatal detection of PUV. A multidisciplinary approach with standardisation of the treatment pathways will help in understanding the true impact of prenatal/early detection on outcomes of PUV.

10.1111/bju.15708

BJU Int

35142035

Pre-versus postnatal presentation of posterior urethral valves: a multi-institutional experience.

2022

350-356

09/2022

1464-410X

OBJECTIVE: To compare the outcomes of pre- vs postnatally diagnosed posterior urethral valves (PUV) at two large paediatric centres in North America to ascertain if the prenatal diagnosis of PUV is associated with better outcomes.

PATIENTS AND METHODS: All boys with PUV were identified at two large paediatric institutions in North America between 2000 and 2020 (The Hospital for Sick Children [SickKids, SK] and Children's Hospital of Philadelphia [CHOP]). Baseline characteristics and outcome measures were compared between those diagnosed pre- vs postnatally. Main outcomes of interest included progression of chronic kidney disease (CKD), the need for renal replacement therapy (RRT), and bladder function compromise, as determined by need for clean intermittent catheterisation (CIC). Time-to-event analyses were completed when possible.

RESULTS: During the study period, 152 boys with PUV were treated at the SK (39% prenatal) and 216 were treated at the CHOP (71% prenatal). At the SK, there was no difference between the pre- and postnatal groups in the proportion of boys who required RRT, progressed to CKD Stage ≥3, or who were managed with CIC when comparing the timing of diagnosis. The time to event for RRT and CIC was significantly younger for prenatally detected PUV. At the CHOP, significantly more prenatal boys required RRT; however, there was no significant difference in the age this outcome was reached. The proportion of boys managed with CIC was not different but the time to event was significantly earlier in the prenatal group.

CONCLUSION: This study represents the largest multi-institutional series of boys with PUV and failed to identify any difference in the outcomes of pre- vs postnatal detection of PUV. A multidisciplinary approach with standardisation of the treatment pathways will help in understanding the true impact of prenatal/early detection on outcomes of PUV.

10.1111/bju.15708

BJU Int

35142035

Pre-versus postnatal presentation of posterior urethral valves: a multi-institutional experience.

2022

350-356

12/2022

1464-410X

OBJECTIVE: To compare the outcomes of pre- vs postnatally diagnosed posterior urethral valves (PUV) at two large paediatric centres in North America to ascertain if the prenatal diagnosis of PUV is associated with better outcomes.

PATIENTS AND METHODS: All boys with PUV were identified at two large paediatric institutions in North America between 2000 and 2020 (The Hospital for Sick Children [SickKids, SK] and Children's Hospital of Philadelphia [CHOP]). Baseline characteristics and outcome measures were compared between those diagnosed pre- vs postnatally. Main outcomes of interest included progression of chronic kidney disease (CKD), the need for renal replacement therapy (RRT), and bladder function compromise, as determined by need for clean intermittent catheterisation (CIC). Time-to-event analyses were completed when possible.

RESULTS: During the study period, 152 boys with PUV were treated at the SK (39% prenatal) and 216 were treated at the CHOP (71% prenatal). At the SK, there was no difference between the pre- and postnatal groups in the proportion of boys who required RRT, progressed to CKD Stage ≥3, or who were managed with CIC when comparing the timing of diagnosis. The time to event for RRT and CIC was significantly younger for prenatally detected PUV. At the CHOP, significantly more prenatal boys required RRT; however, there was no significant difference in the age this outcome was reached. The proportion of boys managed with CIC was not different but the time to event was significantly earlier in the prenatal group.

CONCLUSION: This study represents the largest multi-institutional series of boys with PUV and failed to identify any difference in the outcomes of pre- vs postnatal detection of PUV. A multidisciplinary approach with standardisation of the treatment pathways will help in understanding the true impact of prenatal/early detection on outcomes of PUV.

10.1111/bju.15708

BJU Int

35142035

Potential benefits of functional magnetic resonance urography (fMRU) over MAG3 renal scan in children with obstructive uropathy.

2021

2021 Jul 10

1873-4898

<p><strong>INTRODUCTION: </strong>Functional renal imaging, most commonly with MAG3 nuclear medicine renal scan, is recommended in the evaluation of children with urinary tract dilation (UTD) suspected of obstructive uropathy. Alternatively, renal function can be evaluated with functional Magnetic Resonance Urography (fMRU), which has superior anatomic detail. However, there are not enough data comparing both methods' equivalency. In this study, we compare the functional and obstruction parameters of fMRU and MAG3 in a pediatric cohort presenting with obstructive uropathy.</p>

<p><strong>STUDY DESIGN: </strong>This is an IRB-approved retrospective review of all children undergoing fMRU at a single, free-standing children's hospital between May 2008 and September 2017. Patients who also underwent a MAG3 renal scan within 6 months and who had no interval surgical intervention were included in the study. Bladder catheterization was performed prior to both imaging studies.</p>

<p><strong>RESULTS: </strong>735 children had 988 fMRU studies performed during the study period. 37 unique patients (13 girls and 24 boys) with median age of 6 months (range: 2 mo-19&nbsp;y) were included in the final sample. Median time interval between studies was 70 days (range 6-179 days). The majority of participants (26/37, 70.3%) presented with UTD P3 and had diagnosis of uretero-pelvic junction obstruction (UPJO) in 21/37. Differential renal function (DRF) was used to group 10 fMRU and 9 MAG3 patients as normal; 9 fMRU and 11 MAG3 as mild; 11 fMRU and 6 MAG3 as moderate; and 7 fMRU and 6 MAG3 as severe; Wilcoxon signed-rank test (p&nbsp;=&nbsp;0.5106). Results were similar for DRF among patients with and without duplex kidneys. In the analysis of obstruction, using reference standard T½ MAG3&nbsp;≥&nbsp;20&nbsp;min, a greater or equal than 6&nbsp;min renal transit time (RTT) from fMRU showed a specificity of 94%, a sensitivity of 62%, and an AUC of 0.827.</p>

<p><strong>DISCUSSION AND CONCLUSIONS: </strong>The differential renal function determined by MAG3 and fMRU in children was not statistically different, therefore we concluded that it was similar and potentially equivalent. Better correlation was shown in patients who had normal split kidney function. While the tests are clinically equivalent, the variability of DRF within each clinical category (i.e., normal, mild, moderate, severe) is not surprising, because MAG3 does not clearly differentiate the dilated collecting system from the functional parenchymal tissue, while fMRU does. Using MAG3 as the gold standard, fMRU was 94.74% specific and 5% more sensitive in detecting UPJO with a RTT of 6min vs. 8min.</p>

10.1016/j.jpurol.2021.07.005

J Pediatr Urol

34426090

State-of-the-Art Renal Imaging in Children.

2020

2020 Jan 08

1098-4275

<p>Imaging modalities for diagnosing kidney and urinary tract disorders in children have developed rapidly over the last decade largely because of advancement of modern technology. General pediatricians and neonatologists are often the front line in detecting renal anomalies. There is a lack of knowledge of the applicability, indications, and nephrotoxic risks of novel renal imaging modalities. Here we describe the clinical impact of congenital anomalies of the kidneys and urinary tract and describe pediatric-specific renal imaging techniques by providing a practical guideline for the diagnosis of kidney and urinary tract disorders.</p>

10.1542/peds.2019-0829

Pediatrics

31915193

Risk factors for recurrent urinary tract infection and renal scarring.

2015

e13-21

07/2015

1098-4275

<p><strong>OBJECTIVES: </strong>To identify risk factors for recurrent urinary tract infection (UTI) and renal scarring in children who have had 1 or 2 febrile or symptomatic UTIs and received no antimicrobial prophylaxis.</p>

<p><strong>METHODS: </strong>This 2-year, multisite prospective cohort study included 305 children aged 2 to 71 months with vesicoureteral reflux (VUR) receiving placebo in the RIVUR (Randomized Intervention for Vesicoureteral Reflux) study and 195 children with no VUR observed in the CUTIE (Careful Urinary Tract Infection Evaluation) study. Primary exposure was presence of VUR; secondary exposures included bladder and bowel dysfunction (BBD), age, and race. Outcomes were recurrent febrile or symptomatic urinary tract infection (F/SUTI) and renal scarring.</p>

<p><strong>RESULTS: </strong>Children with VUR had higher 2-year rates of recurrent F/SUTI (Kaplan-Meier estimate 25.4% compared with 17.3% for VUR and no VUR, respectively). Other factors associated with recurrent F/SUTI included presence of BBD at baseline (adjusted hazard ratio: 2.07 [95% confidence interval (CI): 1.09-3.93]) and presence of renal scarring on the baseline (99m)Tc-labeled dimercaptosuccinic acid scan (adjusted hazard ratio: 2.88 [95% CI: 1.22-6.80]). Children with BBD and any degree of VUR had the highest risk of recurrent F/SUTI (56%). At the end of the 2-year follow-up period, 8 (5.6%) children in the no VUR group and 24 (10.2%) in the VUR group had renal scars, but the difference was not statistically significant (adjusted odds ratio: 2.05 [95% CI: 0.86-4.87]).</p>

<p><strong>CONCLUSIONS: </strong>VUR and BBD are risk factors for recurrent UTI, especially when they appear in combination. Strategies for preventing recurrent UTI include antimicrobial prophylaxis and treatment of BBD.</p>

10.1542/peds.2015-0409

Pediatrics

26055855