Adjudication of Self-reported Symptomatic Stone Recurrence in the Prevention of Urinary Stones With Hydration Trial.

OBJECTIVE: To assess accuracy of self-reported stone events in a large clinical trial by adjudication against the weight of documentation for spontaneous stone passage or surgical intervention. METHODS: Participants in the Prevention of Urinary Stones with Hydration (PUSH) trial were randomized to a multi-component behavioral intervention or control arm to increase and maintain high fluid intake. The primary endpoint was urinary stone events including symptomatic stone passage or procedural intervention. An independent adjudication committee blinded to randomization assignments reviewed all events. Confirmed clinical stone events required typical stone symptoms and documentation of stone passage (eg, via photograph, clinical record) and/or surgical intervention. Events with typical symptoms and self-described stone passage but without objective documentation of passage were also considered as meeting the primary endpoint and classified separately as patient-reported passage. Non-events did not meet either criteria. RESULTS: At time of this blinded analysis, a total of 1658 participants were randomized and had a median follow-up of 19 months. Self-reported stone events (n = 217) were adjudicated by the committee as either confirmed clinical events (134; 61.8%), patient-reported passage (71; 32.7%), or non-events (12; 5.5%). Confirmed clinical events consisted of stone passage in 66/134 and procedural interventions in 68/134 (53 for symptoms and 15 without symptoms). CONCLUSION: Rigorous adjudication revealed that self-reported stone events in the PUSH trial overwhelmingly represented clinically documented passage, surgical intervention, and patient-reported passage outside healthcare settings, with only 5.5% failing to satisfy adjudication criteria. Similar adjudication and classification processes warrant consideration for implementation in future stone trials. CLINICAL TRIALS REGISTRATION: NCT03244189.

A Patient-Prioritized Research Agenda for Clinical Trials in Kidney Stone Disease.

PURPOSE: To ensure that research on kidney stones provides meaningful impact for the kidney stone community, patients and caregivers should be engaged as stakeholders in clinical trial design, starting at study inception. This project aimed to elicit, refine, and prioritize research ideas from kidney stone stakeholders to develop a patient-centered research agenda for clinical trials. MATERIALS AND METHODS: The Kidney Stone Engagement Core, a group of patients, caregivers, advocates, clinicians, and researchers, executed an iterative process of surveys and focus groups to elicit and refine research themes, which were then translated into research questions. A separate group of patients, caregivers, and clinicians prioritized these questions through parallel modified Delphi and crowd-sourced digital platforms. A research agenda was developed by the Kidney Stone Engagement Core based on the highest rated questions during a hybrid virtual/in-person capstone session. RESULTS: A total of 70 individuals (57 patients and caregivers, 13 researchers and clinicians) participated in the elicitation, 20 individuals (15 patients and caregivers, 5 researchers and clinicians) participated in refinement, and an additional 80 individuals (81 patients and caregivers, 9 researchers and clinicians) participated in prioritization. Key novel themes emerged from elicitation and refinement: ureteral stents, genetic evaluation, shared surgical decision-making, key subgroups, cumulative disease burden, genetic evaluation, and psychosocial support. Stakeholders generated 6 proposed trials from these themes focused on surveillance, surgical intervention, and medical prevention. CONCLUSIONS: Patients and caregivers valued comparative effectiveness kidney stone research that focused on individualized care, shared decision-making, and improvement of patient-reported experiences. This process provided actionable recommendations for future patient-centered clinical trials within kidney stone disease.

The Hydronephrosis Severity Index guides paediatric antenatal hydronephrosis management based on artificial intelligence applied to ultrasound images alone.

Antenatal hydronephrosis (HN) impacts up to 5% of pregnancies and requires close, frequent follow-up monitoring to determine who may benefit from surgical intervention. To create an automated HN Severity Index (HSI) that helps guide clinical decision-making directly from renal ultrasound images. We applied a deep learning model to paediatric renal ultrasound images to predict the need for surgical intervention based on the HSI. The model was developed and studied at four large quaternary free-standing paediatric hospitals in North America. We evaluated the degree to which HSI corresponded with surgical intervention at each hospital using area under the receiver-operator curve, area under the precision-recall curve, sensitivity, and specificity. HSI predicted subsequent surgical intervention with > 90% AUROC, > 90% sensitivity, and > 70% specificity in a test set of 202 patients from the same institution. At three external institutions, HSI corresponded with AUROCs ≥ 90%, sensitivities ≥ 80%, and specificities > 50%. It is possible to automatically and reliably assess HN severity directly from a single ultrasound. The HSI stratifies low- and high-risk HN patients thus helping to triage low-risk patients while maintaining very high sensitivity to surgical cases. HN severity can be predicted from a single patient ultrasound using a novel image-based artificial intelligence system.

Cross-modal Transfer Learning Based on an Improved CycleGAN Model for Accurate Kidney Segmentation in Ultrasound Images.

OBJECTIVE: Deep-learning algorithms have been widely applied in the field of automatic kidney ultrasound (US) image segmentation. However, obtaining a large number of accurate kidney labels clinically is very difficult and time-consuming. To solve this problem, we have proposed an efficient cross-modal transfer learning method to improve the performance of the segmentation network on a limited labeled kidney US dataset. METHODS: We aim to implement an improved image-to-image translation network called Seg-CycleGAN to generate accurate annotated kidney US data from labeled abdomen computed tomography images. The Seg-CycleGAN framework primarily consists of two structures: (i) a standard CycleGAN network to visually simulate kidney US from a publicly available labeled abdomen computed tomography dataset; (ii) and a segmentation network to ensure accurate kidney anatomical structures in US images. Based on the large number of simulated kidney US images and small number of real annotated kidney US images, we then aimed to employ a fine-tuning strategy to obtain better segmentation results. RESULTS: To validate the effectiveness of the proposed method, we tested this method on both normal and abnormal kidney US images. The experimental results showed that the proposed method achieved a segmentation accuracy of 0.8548 in dice similarity coefficient on all testing datasets and 0.7622 on the abnormal testing dataset. CONCLUSIONS: Compared with existing data augmentation and transfer learning methods, the proposed method improved the accuracy and generalization of the kidney US image segmentation network on a limited number of training datasets. It therefore has the potential to significantly reduce annotation costs in clinical settings.

The Evolving Role of Genetic Testing in Monogenic Kidney Stone Disease: Spotlight on Primary Hyperoxaluria.

PURPOSE: Multiple factors are thought to give rise to common, recurrent kidney stone disease, but for monogenic stone disorders a firm diagnosis is possible through genetic testing. The autosomal recessive primary hyperoxalurias (PH) are rare forms of monogenic kidney stone disease. All 3 types of PH are caused by inborn errors of glyoxylate metabolism in the liver, leading to hepatic oxalate overproduction and excessive renal urinary oxalate excretion. These conditions are characterized by kidney stones, nephrocalcinosis, progressive chronic kidney disease, and kidney failure. Systemic oxalosis, the extra-renal deposition of oxalate resulting in severe morbidity and mortality, occurs in chronic kidney disease when oxalate clearance by the kidneys declines. Novel small interfering RNA-based therapeutics targeting the liver to reduce urinary oxalate excretion have been approved, introducing precision medicine to treat primary hyperoxaluria type 1. The goal of this narrative review is to address the benefits and practicalities of genetic testing for suspected monogenic kidney stone disease and the critical roles of a multidisciplinary team. MATERIALS AND METHODS: We collated our procedures, education, training, and workflows to help other clinicians integrate genetic assessment into their diagnostic routines. RESULTS: In our experience, increased access to genetic testing facilitates early detection of PH and other monogenic causes of kidney stone disease so that individualized care can be instituted promptly. CONCLUSIONS: Alongside biochemical assessments, more widespread genetic testing may ensure more timely diagnoses so that patients with suspected monogenic kidney stone disease gain access to an expanded range of services and enrollment in clinical trials and registries.

Preoperative vs Postoperative Opioid Prescriptions and Prolonged Opioid Refills Among US Youths.

Importance: High-risk practices, including dispensing an opioid prescription before surgery when not recommended, remain poorly characterized among US youths and may contribute to new persistent opioid use. Objective: To characterize changes in preoperative, postoperative, and refill opioid prescriptions up to 180 days after surgery. Design, Setting, and Participants: This retrospective cohort study was performed using national claims data to determine opioid prescribing practices among a cohort of opioid-naive youths aged 11 to 20 years undergoing 22 inpatient and outpatient surgical procedures between 2015 and 2020. Statistical analysis was performed from June 2023 to April 2024. Main Outcomes and Measures: The primary outcome was the percentage of initial opioid prescriptions filled up to 14 days prior to vs 7 days after a procedure. Secondary outcomes included the likelihood of a refill up to 180 days after surgery, including refills at 91 to 180 days, as a proxy for new persistent opioid use, and the opioid quantity dispensed in the initial and refill prescriptions in morphine milligram equivalents (MME). Exposures included patient and prescriber characteristics. Multivariable logistic regression models were used to estimate the association between prescription timing and prolonged refills. Results: Among 100 026 opioid-naive youths (median [IQR] age, 16.0 [14.0-18.0] years) undergoing a surgical procedure, 46 951 (46.9%) filled an initial prescription, of which 7587 (16.2%) were dispensed 1 to 14 days before surgery. The mean quantity dispensed was 227 (95% CI, 225-229) MME; 6467 youths (13.8%) filled a second prescription (mean MME, 239 [95% CI, 231-246]) up to 30 days after surgery, and 1216 (3.0%) refilled a prescription 91 to 180 days after surgery. Preoperative prescriptions, increasing age, and procedures not typically associated with severe pain were most strongly associated with new persistent opioid use. Conclusions and Relevance: In this retrospective study of youths undergoing surgical procedures, of which, many are typically not painful enough to require opioid use, opioid dispensing declined, but approximately 1 in 6 prescriptions were filled before surgery, and 1 in 33 adolescents filled prescriptions 91 to 180 days after surgery, consistent with new persistent opioid use. These findings should be addressed by policymakers and communicated by professional societies to clinicians who prescribe opioids.

Using structured problem solving to promote fluid consumption in the prevention of urinary stones with hydration (PUSH) trial.

BACKGROUND: Structured Problem Solving (SPS) is a patient-centered approach to promoting behavior change that relies on productive collaboration between coaches and participants and reinforces participant autonomy. We aimed to describe the design, implementation, and assessment of SPS in the multicenter Prevention of Urinary Stones with Hydration (PUSH) randomized trial. METHODS: In the PUSH trial, individuals with a history of urinary stone disease and low urine output were randomized to control versus a multicomponent intervention including SPS that was designed to promote fluid consumption and thereby prevent recurrent stones. We provide details specifically about training and fidelity assessment of the SPS coaches. We report on implementation experiences related to SPS during the initial conduct of the trial. RESULTS: With training and fidelity assessment, coaches in the PUSH trial applied SPS to help participants overcome barriers to fluid consumption. In some cases, coaches faced implementation barriers such as variable participant engagement that required tailoring their work with specific participants. The coaches also faced challenges including balancing rapport with problem solving, and role clarity for the coaches. CONCLUSIONS: We adapted SPS to the setting of kidney stone prevention and overcame challenges in implementation, such as variable patient engagement. Tools from the PUSH trial may be useful to apply to other health behavior change settings in nephrology and other areas of clinical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03244189.

Postoperative Recovery of Quality-of-Life Following Ureteroscopy for Nephrolithiasis: The Impact on Pain Intensity and Interference and the Ability to Participate in Social Roles.

OBJECTIVE: To prospectively capture patient-reported outcomes to assess the recovery profile of ureteroscopy (URS). MATERIALS AND METHODS: Adults undergoing URS for renal/ureteral stones were eligible for inclusion (11/2020-8/2022). Patients prospectively completed PROMIS - Pain Intensity, - Pain Interference, and - Ability to participate in social roles and activities in-person preoperatively (POD 0) and via email on POD 1, 7, 14, and 30. Scores are reported as T-scores (normalized to U.S. population, mean=50) with a change of 5 (0.5 SD) considered clinically significant. RESULTS: One hundred and seventy-eight participants enrolled at POD 0 (POD 1 =87, POD 7 =83, POD 14 =70, POD30 =67). There was a worsening of quality of life from day 0 to day 1 and day 0 to 7. All dimensions then improved with an increase in scores from day 0 to day 14 and day 0 to day 30. On multivariable analysis, the presence of a preoperative ureteral stent (OR 0.14) and use of semirigid URS (OR 0.33) were associated with a reduced odds for severe pain interference at day 1. The use of semirigid URS (OR 0.20) was associated with a reduced odds for severe worsening in the ability to participate in social roles at day 1. CONCLUSION: Ability to participate in social roles declines immediately postoperatively, while pain intensity and interference sharply increase. There is a gradual improvement until POD 30. Findings suggest preoperative stents may influence postoperative recovery. Results offer meaningful insight to assist in counseling and setting expectation for patients postoperatively.

Surgeon, and Institution Characteristics Associated Surgical Preferences in the Pediatric KIDney Stone Care Improvement Network.

OBJECTIVE: To reveal barriers and opportunities to implement evidence for the management of pediatric kidney stone disease, we determined surgeon and institutional factors associated with preferences for the type of surgical intervention for kidney and ureteral stones. METHODS: We conducted a cross-sectional study of urologists participating in the Pediatric KIDney Stone Care Improvement Network (PKIDS) trial. Questionnaires ascertained strengths of urologists' preferences for types of surgery as well as characteristics of participating urologists and institutions. The outcome was the strength of preferences for ureteroscopy, shockwave lithotripsy, and percutaneous nephrolithotomy for four scenarios for which two alternative procedures are recommended by the AUA guidelines: (1) 2 cm kidney stone, (2) 9 mm proximal ureteral stone, (3) 1.5 cm lower pole kidney stone, (4) 1 cm nonlower pole kidney stone. Principal component analysis was performed to identify unique clusters of factors that explain surgical preferences. RESULTS: One hundred forty-eight urologists at 29 sites completed surveys. Stated preferences were highly skewed except for the choice between ureteroscopy and percutaneous nephrolithotomy for a 1.5 cm kidney stone. Shockwave lithotripsy ownership and local practice patterns most frequently associated with the strength of surgeons' preferences for the type of surgery. Principal component analysis revealed that three clusters of stone, patient, and heterogenous characteristics explained 30% of the variance in preferences. CONCLUSION: There is wide variation in the strengths of preferences for surgical interventions supported by current guidelines that are partially explained by surgeon and institutional characteristics. These results reveal opportunities to develop strategies for guidelines that consider real-world drivers of care.

Application of STREAM-URO and APPRAISE-AI reporting standards for artificial intelligence studies in pediatric urology: A case example with pediatric hydronephrosis.

INTRODUCTION: Artificial intelligence (AI) and machine learning (ML) in pediatric urology is gaining increased popularity and credibility. However, the literature lacks standardization in reporting and there are areas for methodological improvement, which incurs difficulty in comparison between studies and may ultimately hurt clinical implementation of these models. The "STandardized REporting of Applications of Machine learning in UROlogy" (STREAM-URO) framework provides methodological instructions to improve transparent reporting in urology and APPRAISE-AI in a critical appraisal tool which provides quantitative measures for the quality of AI studies. The adoption of these will allow urologists and developers to ensure consistency in reporting, improve comparison, develop better models, and hopefully inspire clinical translation. METHODS: In this article, we have applied STREAM-URO framework and APPRAISE-AI tool to the pediatric hydronephrosis literature. By doing this, we aim to describe best practices on ML reporting in urology with STREAM-URO and provide readers with a critical appraisal tool for ML quality with APPRAISE-AI. By applying these to the pediatric hydronephrosis literature, we provide some tutorial for other readers to employ these in developing and appraising ML models. We also present itemized recommendations for adequate reporting, and critically appraise the quality of ML in pediatric hydronephrosis insofar. We provide examples of strong reporting and highlight areas for improvement. RESULTS: There were 8 ML models applied to pediatric hydronephrosis. The 26-item STREAM-URO framework is provided in Appendix A and 24-item APPRAISE-AI tool is provided in Appendix B. Across the 8 studies, the median compliance with STREAM-URO was 67 % and overall study quality was moderate. The highest scoring APPRAISE-AI domains in pediatric hydronephrosis were clinical relevance and reporting quality, while the worst were methodological conduct, robustness of results, and reproducibility. CONCLUSIONS: If properly conducted and reported, ML has the potential to impact the care we provide to patients in pediatric urology. While AI is exciting, the paucity of strong evidence limits our ability to translate models to practice. The first step toward this goal is adequate reporting and ensuring high quality models, and STREAM-URO and APPRAISE-AI can facilitate better reporting and critical appraisal, respectively.

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.

A Systematic Scoping Review of Comparative Effectiveness Studies in Kidney Stone Disease.

OBJECTIVE: To review the status of comparative effectiveness studies for kidney stone disease with focus on study outcome, type, population, time trends, and patient-centered approaches. METHODS: A systematic scoping review was performed for articles published between January 1, 2005, and March 30, 2021, using keywords relevant to kidney stone disease. Studies published in English that compared two or more alternative methods for prevention, diagnosis, treatment, monitoring, or care delivery were included. Two reviewers independently reviewed abstracts and an arbitrator resolved discrepancies. Nine reviewers abstracted information from full-length studies. Descriptive statistics were summarized, and linear regression was performed to evaluate temporal trends of study characteristics. RESULTS: We reviewed 1773 abstracts and 707 full-length manuscripts focused on surgical intervention (440); medical expulsive therapy (MET) (152); analgesic control (80); and homeopathic, diagnostics, and/or prophylaxis (84). Randomized controlled trials were common across all outcome categories, including surgery (41.6%), MET (60.2%), analgesic control (81.3%), homeopathic (41.2%), diagnostic (47.6%), and prophylaxis (49.1%). Patient-reported outcomes were utilized in 71.7% and 95% of MET and analgesic control studies, respectively, but in the minority of all other study themes. Over time, meta-analyses and multicenter studies increased [P < .001]. CONCLUSION: Surgical and MET themes dominate published comparative literature in kidney stone disease. There is substantial variation in use of patient-reported outcomes across surgical themes. Multicentered studies and those generating higher level evidence have increased over time but opportunities exist to improve collaborative, high-quality, and patient-centered research in kidney stone disease.

Contribution of Hypersensitivity to Postureteroscopy Ureteral Stent Pain: Findings From Study to Enhance Understanding of Stent-associated Symptoms.

OBJECTIVE: To examine the relationships between preoperative hypersensitivity to pain and central sensitization, and postoperative ureteral stent pain after ureteroscopy (URS) for urinary stones. METHODS: Adults enrolled in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS) underwent quantitative sensory testing (QST) prior to URS and stent placement. Hypersensitivity to mechanical pain was assessed using a pressure algometer. Participants rated their pain intensity to pressure applied to the ipsilateral flank area and lower abdominal quadrant on the side of planned stent placement, and the contralateral forearm (control). Pressure pain thresholds were also assessed. Central sensitization was assessed by applying a pointed stimulator (pinprick) and calculating the temporal summation. Postoperative stent pain intensity and interference were assessed using PROMIS questionnaires. Data were analyzed using repeated-measures mixed-effects linear models. RESULTS: Among the 412 participants, the median age was 54.0years, and 46% were female. Higher preoperative pain ratings to 2 kg and 4 kg mechanical pressure to the ipsilateral flank and abdominal areas were associated with higher postoperative stent pain intensity with the stent in situ. Greater degree of central sensitization preoperatively, manifesting as higher temporal summation, was associated with higher postoperative pain intensity. Factors associated with preoperative hypersensitivity on QST included female sex, presence of chronic pain conditions, widespread pain, and depression. CONCLUSION: Hypersensitivity to pain and central sensitization preoperatively was associated with postoperative ureteral stent pain, suggesting a physiologic basis for stent symptom variation. QST may identify patients more likely to develop stent pain after URS and could inform selection for preventive and interventional strategies.

Role of Climate Change in Urologic Health: Kidney Stone Disease.

Kidney stones are rising in incidence and prevalence worldwide. Given the temperature dependence of kidney stone presentations, climate change is projected to further increase the burden of disease for individuals and society. PATIENT SUMMARY: This mini-review reports current knowledge on climate change in relation to kidney stone disease. Kidney stones are more common in patients living in parts of the world that are hotter and more humid. Kidney stone problems are also more common after periods of high heat, which have a greater impact on men than on women. As temperatures rise with climate change, it is likely that the occurrence of kidney stones and the costs associated with their diagnosis and treatment will increase as well.

Posterior urethral valves in patients with trisomy 21: Similar renal outcomes and rates of volitional voiding.

INTRODUCTION: Posterior urethral valves (PUV) occur in patients with Down Syndrome (DS) at a rate of 3-4%; far higher than the general population. Our understanding of the relationship between PUVs and DS is in its infancy, with the majority of the literature consisting of case reports. In this study, we present the largest known series of DS patients with PUVs. AIM: We hypothesized that patients with DS and PUVs would have worse functional bladder outcomes and renal outcomes when compared to PUV patients without DS. STUDY DESIGN: We queried our prospectively managed multi-institutional database of PUV patients from 1990 to 2021. We identified patients with a concomitant diagnosis of DS and PUV. In addition, we performed a systematic review of the literature describing the presentation of children with PUV and DS. Patient demographics, renal outcomes, voiding habits, surgical interventions, and radiologic images were aggregated and analyzed. RESULTS: Out of the 537 patients in our PUV database, we identified 18 patients with a concomitant diagnosis of PUV and DS, as well as 14 patients with a concomitant diagnosis of PUV and DS from the literature. DS and non-DS patients had a similar age at presentation, 31.5 days (2-731) and 17 (4-846), and length of follow up 6.32 years (2-11.2) and 6.98 (1-13). Both groups had similar nadir creatinines DS 0.43 (0.4-0.8), non-DS 0.31 (0.2-0.5) and similar rates of renal failure (DS 11.1% and non-DS 14.5%). With respect to bladder outcomes, a similar percentage of patients were volitionally voiding at last follow up (DS 72.2% and non-DS 72.3%). Our literature review corroborated these findings. CONCLUSIONS: Patients with DS and PUV have similar renal outcomes to other PUV patients in terms of renal function, progression to renal failure, and probability of volitional voiding with continence. Given the increased rate of PUVs in the DS population, physicians should have a high index of suspicion for PUV when patients with DS present with voiding dysfunction.