The yield of genetic testing in management of nephrolithiasis.

OBJECTIVE: To describe the yield and indications for performing genetic testing in patients with nephrolithiasis. Genetic testing for nephrolithiasis is becoming more accessible and rapid due to technologic advances. This study aimed to determine the diagnostic yield of genetic testing in a cohort of high-risk stone formers and to identify 24-hour urine characteristics to prompt genetic screening. MATERIALS AND METHODS: We retrospectively identified patients who underwent genetic testing for nephrolithiasis from 2020-22 at a single institution using a custom PerkinElmer™ genomics panel for nephrolithiasis. We compared characteristics of patients with and without genetic abnormalities. We used receiver operator characteristic (ROC) analysis to identify candidate thresholds for genetic testing. RESULTS: Fourteen of 36 patients (39%) who underwent genetic testing had identifiable mutations. Five patients (14%) had known pathogenic mutations, including genes for primary hyperoxaluria (PH2 and PH3), cystinuria, and enamel renal syndrome. The remaining mutations were variants of uncertain significance. Of the 14 patients with identified mutations, only 6 had concordant 24-hour urine abnormalities, including 3/5 with known pathogenic mutations. In patients with urine oxalate ≥40mg/day, 3/29 (10.3%) had PH2 or PH3. ROC analysis showed that an oxalate threshold of ≥80mg/day may have promising screening characteristics. CONCLUSIONS: Genetic testing for nephrolithiasis remains controversial due to unknown yield and the time and energy required to discuss results with patients. This preliminary report describes the yield and identifies clinical factors and a potential cut-off that may assist clinicians in deciding when genetic profiling should be pursued.

Renal Autotransplantation: Association Between Preoperative Disease Duration and Surgical Outcomes.

OBJECTIVE: To determine whether early versus delayed autotransplantation are associated with adverse outcomes in patients undergoing renal autotransplantation. METHODS: Patients who underwent renal autotransplantation from June 2012 to September 2022 were divided into 2 groups based on timing of autotransplant in relation to initial intervention or diagnosis (early cohort: ≤1-year; delayed cohort: >1-year). Primary outcomes were perioperative complications, aborted surgery, renal function (glomerular filtration rate [GFR]), and postoperative complications at most recent follow-up. RESULTS: Autotransplantation patients (N = 72) were predominantly female (68%) and White (54%), with a median age of 49 years. Ninety percentage of patients had undergone previous interventions, including stenting (40%) and nephrostomy tubes (49%), primarily for obstruction (64%). Early versus delayed cohorts had median preoperative disease durations of 143 (IQR 83-222) versus 673 days (IQR 529-1703, P <.001), with similar median follow-up times (879 vs 818 days, P = .8). Groups were similar in demographics and comorbidities. There were no significant differences in rates of aborted surgery (15% vs 4.2%, P = .3), perioperative complications (15% vs 17%, P > .9), long-term complications (49% vs 48%, P > .9), or changes in GFR (median change +3 vs +4, P = .7). Outcomes were comparable across preoperative disease durations ranging from 6 to 24 months. These findings were confirmed following adjustments for sex, body mass index, American Society of Anesthesiologists classification, race, preoperative creatinine levels, laterality, gastroesophageal reflux disease, diabetes, hypertension, nephrolithiasis, hyperlipidemia, history of colon surgery, urologic surgery, abdominal surgery, and prior interventions in separate logistic models. CONCLUSION: Disease duration before autotransplantation does not influence outcomes, offering reassurance for clinical decision-making in complex cases.

Case presentation and review of renal autotransplantation for nutcracker syndrome.

Nutcracker Syndrome (NCS) is characterized by entrapment of the left renal vein, leading hematuria, flank pain, and proteinuria. We evaluated the efficacy of renal autotransplantation as a curative treatment for NCS through a review and case report. 55 patients from 18 studies were analyzed, with a combined 91% success rate of symptom resolution or improvement post-autotransplantation. In our case report, a 25-year-old man with severe NCS received laparoscopic nephrectomy and autotransplant, resulting in symptom resolution at 3.1 years follow up. Further research should confirm these findings and refine patient selection criteria and surgical techniques.

Voided volume may not impact stone outcomes: Review of a large institutional nephrolithiasis cohort.

Background: Urologic guidelines universally recommend increasing fluid intake for kidney stone prevention. Increased voided volume is thought to help reduce stone recurrence and severity, but supporting evidence is limited. Patients and Methods: Nephrolithiasis outcomes and 24-h urine data for patients from the Registry for Stones of the Kidney and Ureter (ReSKU), a registry of nephrolithiasis patients collected between 2015 and 2020, were retrospectively analysed. Outcome was stone events, either an office visit where a patient reports symptomatic passage of stones or surgery for stone removal. Results: We identified 450 stone patients with 24-h urine and kidney stone outcome data. There was no significant difference in 24-h voided volume between patients with one stone event and patients with two or more stone events. On multivariable logistic regression, after controlling for age, gender, BMI, and 24-h sodium and creatinine per kilogram, no significant associations were found between voided volume and stone events. There was a statistically significant negative correlation noted between voided volume and stone events in calcium oxalate dihydrate stone formers (Spearman R = -0.42, p = 0.04), but not others. Conclusions: Twenty-four-hour voided volume was not associated with stone events in a large institutional cohort, and subset analysis reveals that some stone formers may benefit more from increased voided volume than others; identifying such patients represents a novel precision medicine opportunity.

Ultrasound-Only Percutaneous Nephrolithotomy Is Safe and Effective Compared to Fluoroscopy-Directed Percutaneous Nephrolithotomy.

Introduction: Outcomes after ultrasound-only percutaneous nephrolithotomy (PCNL), in which no fluoroscopy is used, are not well known. The goal of this study was to compare outcomes of ultrasound-only and fluoroscopy-directed PCNL. Materials and Methods: Prospectively collected data from the Registry for Stones of the Kidney and Ureter database were reviewed for all patients who underwent PCNL at one academic center from 2015 to 2021. Primary outcomes were complications and stone-free rates (no residual fragments ≥3 mm). Results: Of the 141 patients who underwent ultrasound-only PCNL and 147 who underwent fluoroscopy-directed PCNL, there was no difference in complication rates (15% vs 16%, p = 0.87) or stone-free status (71% vs 65%, p = 0.72), respectively. After adjusting for body mass index, American Society of Anesthesiologists (ASA), stone size, and stone complexity by Guy score, ultrasound-only PCNL was not associated with any increased odds of complications (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.3-1.6, p = 0.41) or residual stone fragments ≥3 mm (OR 1.0, 95% CI 0.5-1.9, p = 0.972) compared with fluoroscopy-directed PCNL. Ultrasound-only PCNL was associated with shorter operative time (median 99.5 vs 126 minutes, p < 0.001), and the use of ultrasound remained a significant predictor of short operative time (<100 minutes) after controlling for supine positioning, stone size, and stone complexity by Guy score (OR 2.31, 95% CI 1.01-5.29, p = 0.048). Patients in the ultrasound-only group were spared a mean radiation exposure dose of 10 mGy per procedure. Conclusions: Ultrasound-only PCNL is safe and achieves similar stone-free rates compared with fluoroscopy-directed PCNL with the added benefit of avoidance of radiation.

Association between obstructive sleep apnea and 24-h urine chemistry risk factors for urinary stone disease.

The effect of obstructive sleep apnea (OSA) on 24-h urine parameters and resultant kidney stone risk is unknown. We sought to compare urinary lithogenic risk factors among patients with kidney stone disease with and without OSA. We performed a retrospective cohort study of adult patients with nephrolithiasis undergoing both polysomnography and 24-h urine analysis. Measures of acid load including gastrointestinal alkali absorption, urinary titratable acid, and net acid excretion were calculated from 24-h urine. We performed univariable comparisons of 24-h urine parameters between those with and without OSA and fit a multivariable linear regression model adjusting for age, sex, and BMI. Overall, there were 127 patients who underwent both polysomnography and a 24-h urine analysis from 2006 to 2018. There were 109 (86%) patients with OSA and 18 (14%) without. Patients with OSA were more commonly male, had greater BMI and had higher rates of hypertension. Patients with OSA had significantly higher levels of 24-h urinary oxalate, uric acid, sodium, potassium, phosphorous, chloride, and sulfate; higher supersaturation of uric acid; higher titratable acid, and net acid excretion; and lower urinary pH and supersaturation of calcium phosphate (p < 0.05). The difference in urinary pH and titratable acid, but not net acid excretion, remained significant when adjusting for BMI, age, and gender (both p = 0.02). OSA is associated with changes in urinary analytes that promote kidney stone formation, similar to those observed with obesity. After accounting for BMI, OSA is independently associated with lower urine pH and increased urinary titratable acid.

Maternal family history of urolithiasis is associated with earlier age of onset of stone disease.

PURPOSE: To evaluate the impact of detailed family history on the severity of disease and age of onset in patients with urolithiasis. METHODS: Prospectively collected data from a single institution between October 2015 and December 2020 were analyzed. Our primary endpoint was the number of patients experiencing at least one recurrent stone during the follow-up period. RESULTS: Of 1566 patients analyzed, 603 (39%) reported at least one family member with a history of stones. The percentage of patients experiencing at least one recurrent stone event was higher in patients with a family history of stones (38%) compared to those without a family history of stones (28%) over a median follow-up period of 8 months (p = 0.001). On multivariate analysis, the presence of any family history of urolithiasis increased risk of recurrent stone events (odds ratio [OR] 1.62, p < 0.001). The presence of both a first- and a second-degree relative with urolithiasis was associated with higher odds for a recurrent stone event (OR 2.17; p = 0.003) and a younger age of onset for stones, (OR 3.32; < 0.001). A maternal-side relative with stones conferred a higher odds ratio for younger age of first onset of stones (OR 2.93; p < 0.001). CONCLUSION: Any family history of kidney stone disease imparts an increased risk of recurrent stone event and an earlier age of onset for urolithiasis. The presence of both first- and second-degree relatives or a maternal-side relative with kidney stones may be a predictor for an earlier age of onset for urolithiasis.

Machine Learning Models to Predict 24 Hour Urinary Abnormalities for Kidney Stone Disease.

OBJECTIVE: To help guide empiric therapy for kidney stone disease, we sought to demonstrate the feasibility of predicting 24-hour urine abnormalities using machine learning methods. METHODS: We trained a machine learning model (XGBoost [XG]) to predict 24-hour urine abnormalities from electronic health record-derived data (n = 1314). The machine learning model was compared to a logistic regression model [LR]. Additionally, an ensemble (EN) model combining both XG and LR models was evaluated as well. Models predicted binary 24-hour urine values for volume, sodium, oxalate, calcium, uric acid, and citrate; as well as a multiclass prediction of pH. We evaluated performance using area under the receiver operating curve (AUC-ROC) and identified predictors for each model. RESULTS: The XG model was able to discriminate 24-hour urine abnormalities with fair performance, comparable to LR. The XG model most accurately predicted abnormalities of urine volume (accuracy = 98%, AUC-ROC = 0.59), uric acid (69%, 0.73) and elevated urine sodium (71%, 0.79). The LR model outperformed the XG model alone in prediction of abnormalities of urinary pH (AUC-ROC of 0.66 vs 0.57) and citrate (0.69 vs 0.64). The EN model most accurately predicted abnormalities of oxalate (accuracy = 65%, ROC-AUC = 0.70) and citrate (65%, 0.69) with overall similar predictive performance to either XG or LR alone. Body mass index, age, and gender were the three most important features for training the models for all outcomes. CONCLUSION: Urine chemistry prediction for kidney stone disease appears to be feasible with machine learning methods. Further optimization of the performance could facilitate dietary or pharmacologic prevention.

Proton pump inhibitors use and risk of incident nephrolithiasis.

Proton pump inhibitors (PPIs) are widely prescribed medications that have effects on both enteric and urinary solute handling with an unknown effect on risk of nephrolithiasis. Our objectives were to examine the association between PPI exposure and incident nephrolithiasis and to determine its effect on 24H urine chemistry. We performed a single-center retrospective study on patients diagnosed with gastroesophageal reflux disease (GERD) without a history of kidney stones. Exposure to PPIs was abstracted, and then subsequent kidney stone diagnoses were identified. Multivariable Cox models with time-varying covariates were used to estimate the hazard of PPI use on incident nephrolithiasis. We used multivariable linear regression to analyze a subset of patients who went through 24-h urine analysis. We identified n = 55,765 PPI-naïve GERD patients without prior kidney stone diagnoses of whom 40,866 (73.2%) were exposed to PPI over a median of 3 year follow up. On multivariable analysis, PPI use was associated with higher risk of incident kidney stone diagnoses (HR 1.19, 95% CI 1.06-1.34). Among 593 patients with GERD with 24-H urine data, the PPI-exposed group (n = 307) had significantly lower mean urinary citrate (mean 3.0 vs 3.4 mmol, p = 0.029) and urinary magnesium (mean 3.6 vs 4.3 mmol, p < 0.001) on multivariable analyses. Exposure to PPIs is associated with an increased risk of kidney stones among patients with GERD. Hypomagnesemia and hypocitraturia associated with PPI exposure may contribute to kidney stone risk.

Association Between Surgical Volume and Survival Among Patients With Variant Histologies of Bladder Cancer.

OBJECTIVE: To examine the relationship between hospital volume and the management of bladder cancer variant histology. Variant histologies of bladder cancer are rare which limits the ability for providers to develop expertise however there is a clear hospital and/or surgeon-volume relationship for management of rare or complex surgical and/or medical diseases. METHODS: We queried the National Cancer Database from 2004-2016 for all cases of bladder cancer, identifying cases of variant histology. Our primary outcome was overall survival while secondary outcomes included identifying treatment patterns. Hospitals were stratified into those that managed ≤2, >2-4, >4-6, and ≥6 cases per year of variant histology. RESULTS: We identified 23,284 patients with bladder cancer of variant histology who were treated at 1301 hospitals. Few institutions had high volume experience with this disease: 18.5% (n = 241) treated >2 patients annually and 5.7% (n = 76) treated >4 cases annually. Hospital volume positively correlated with utilization of early radical cystectomy (RC) in non-muscle invasive disease and neoadjuvant chemotherapy in muscle-invasive disease. On multivariable analysis, increased hospital volume was associated with improved survival. After stratifying by sub-type, hospital volume continued to be associated with improved survival for squamous, small cell, and sarcomatoid cancers. CONCLUSION: Management of variant histology urothelial carcinoma at high-volume centers is associated with improved overall survival. The mechanisms of this are multifactorial, and future research should focus on improvement opportunities for low-volume hospitals, centralization of care, and/or increased access to care at high-volume centers.

Machine Learning Prediction of Kidney Stone Composition Using Electronic Health Record-Derived Features.

Objectives: To assess the accuracy of machine learning models in predicting kidney stone composition using variables extracted from the electronic health record (EHR). Materials and Methods: We identified kidney stone patients (n = 1296) with both stone composition and 24-hour (24H) urine testing. We trained machine learning models (XGBoost [XG] and logistic regression [LR]) to predict stone composition using 24H urine data and EHR-derived demographic and comorbidity data. Models predicted either binary (calcium vs noncalcium stone) or multiclass (calcium oxalate, uric acid, hydroxyapatite, or other) stone types. We evaluated performance using area under the receiver operating curve (ROC-AUC) and accuracy and identified predictors for each task. Results: For discriminating binary stone composition, XG outperformed LR with higher accuracy (91% vs 71%) with ROC-AUC of 0.80 for both models. Top predictors used by these models were supersaturations of uric acid and calcium phosphate, and urinary ammonium. For multiclass classification, LR outperformed XG with higher accuracy (0.64 vs 0.56) and ROC-AUC (0.79 vs 0.59), and urine pH had the highest predictive utility. Overall, 24H urine analyte data contributed more to the models' predictions of stone composition than EHR-derived variables. Conclusion: Machine learning models can predict calcium stone composition. LR outperforms XG in multiclass stone classification. Demographic and comorbidity data are predictive of stone composition; however, including 24H urine data improves performance. Further optimization of performance could lead to earlier directed medical therapy for kidney stone patients.

The Impact of Hospital Volume on Short-term and Long-term Outcomes for Patients Undergoing Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

OBJECTIVES: To examine the effect of hospital volume on short and long-term outcomes for radical nephroureterectomy (RNUx). Upper tract urothelial carcinoma is a rare malignancy that few surgeons have experience with. The hospital volume-outcome relationship has been well established for other cancers but not RNUx. METHODS: The National Cancer Database was queried for all cases of upper tract urothelial carcinoma that underwent RNUx from 2004 to 2016. Average annual hospital volume for radical nephroureterectomy was stratified into tertiles. The upper tertile, defined as 6 or more RNUx per year, was considered high volume while low volume was less than 6 RNUx per year. Kaplan-Meier and Cox proportional hazards regression were used to identify independent predictors of overall survival, and logistic regression was used to identify predictors of perioperative outcomes. RESULTS: We identified 37,479 RNUx performed across 1290 hospitals. There were no differences in baseline health or cancer staging between patients who presented at low- versus high-volume centers. Both peri-operative survival (30- and 90-day mortality) and long-term overall survival were improved in patients treated at high-volume centers. On multivariable survival analysis, treatment at a high-volume center was associated with improved hazards of survival. This relationship for long-term survival remained consistent on landmark analysis where patients who died within 90 days of surgery were removed. CONCLUSIONS: Treatment at a high-volume hospital was associated not only with improved short-term perioperative outcomes but also with improved overall long-term survival. The mechanism behind this is likely multifactorial with surgeon volume, and ancillary support services all playing critical roles.

Association of Chronic Kidney Disease Stage with 24-Hour Urine Values Among Patients with Nephrolithiasis.

Introduction: Nephrolithiasis is a known risk factor for chronic kidney disease (CKD); however, it is unknown how CKD affects urinary parameters related to stone risk. The purpose of this study was to assess the relationship of diminishing glomerular filtration rate (GFR) and kidney stone-related 24-hour urine (24H urine) composition. Materials and Methods: A single-institution retrospective review of patients (n = 2057) who underwent 24H urine analysis was performed. The serum creatinine within 1 year of the first 24H urine was used to determine estimated GFR and stratify patients by CKD stage. We performed analysis of variance and multivariable linear regression to assess the relationship of GFR and urinary analytes. Results: Among all patients, there were 184 (8.9%), 1537 (74.7%), 245 (11.9%), 70 (3.4%), 17 (0.8%), and 4 (0.2%) in CKD stage I, II, IIIa, IIIb, IV, and V groups, respectively. On analysis of 24H urine composition, as CKD increased, changes in urinary parameters protective against crystallization included decreased calcium and uric acid (UA) (P < 0.001). In addition, parameters favoring crystallization included decreased citrate and magnesium (P = 0.002 and P < 0.001, respectively). The net effect with increasing GFR was decreasing supersaturation of calcium oxalate and phosphate. On linear regression, urinary excretion of calcium, oxalate, citrate, UA, phosphate, and ammonia all decreased with decreasing GFR (all P < 0.05). Conclusions: Higher CKD stage was associated with changes in urinary analytes that both promoted and inhibited stone formation, with the net effect of decreasing calcium oxalate and phosphate supersaturation. These patients may benefit from medical therapy that targets improving urinary citrate instead of lowering calcium or UA.

Nephrolithiasis and Elevated Urinary Ammonium: A Matched Comparative Study.

OBJECTIVE: To describe the associations between elevated urinary ammonium and clinical characteristics of kidney stone formers. A 24-hour urine test is recommended in high-risk patients to identify urinary abnormalities and select interventions to reduce the recurrence risk. While elevations in urine ammonium may be seen in acidosis, diarrhea, high protein diets or due to pathogenic bacteria, the clinical characteristics of these patients have not been previously described. METHODS: We retrospectively identified adult patients with kidney stone disease who completed a 24-hour urine at our institution between 2006 and 2017. Patients with elevated urinary ammonium were identified (n = 121) and matched 1:1 by age and sex to controls for an overall cohort of n = 242. Differences in medical and surgical history, 24-hour urine analytes and stone composition were compared. RESULTS: Among 3625 24-hour urine studies screened, 7.1% of patients showed high urinary ammonium. In our study cohort, patients with elevated urinary ammonium also showed higher urine volume, oxalate, calcium, uric acid, sodium, chloride, and sulfate. Clinically, these patients had higher body mass index, and more often had a history of recurrent urinary tract infections, diabetes, gout, bowel resection, and urinary reconstruction history. Struvite stones tended to be more common in the elevated ammonium group vs control (n = 7 vs 1, P = .07). CONCLUSION: Elevated urinary ammonium among kidney stone patients is relatively uncommon. However, these patients have higher rates of comorbid metabolic conditions, urinary tract infections, and bowel surgery. This finding should prompt further review of the patient's history and may help direct prevention strategies.

A Phase I Trial of Intravesical Cabazitaxel, Gemcitabine and Cisplatin for the Treatment of Nonmuscle Invasive bacillus Calmette-Guérin Unresponsive or Recurrent/Relapsing Urothelial Carcinoma of the Bladder.

PURPOSE: For patients with bacillus Calmette-Guérin unresponsive or recurrent/relapsing nonmuscle invasive bladder cancer, multi-agent intravesical trials have been limited. In this study we investigate the safety of intravesical cabazitaxel, gemcitabine and cisplatin in the salvage setting. MATERIALS AND METHODS: This was a dose escalation, drug escalation trial for patients with bacillus Calmette-Guérin unresponsive or recurrent/relapsing nonmuscle invasive bladder cancer who declined or were ineligible for radical cystectomy. All patients underwent a 6-week induction regimen of sequentially administered cabazitaxel, gemcitabine and cisplatin. Complete response was defined as no cancer on post-induction transurethral bladder tumor resection and negative urine cytology, while partial response allowed for positive cytology. Responders continued with maintenance cabazitaxel and gemcitabine monthly for the first year and bimonthly for the second year. RESULTS: A total of 18 patients were enrolled. Mean age was 71 years, median followup was 27.8 months (range 16.3 to 46.9) and mean number of previous rounds of intravesical therapies before trial enrollment was 3.7. Nine patients (50%) had received intravesical chemotherapy after bacillus Calmette-Guérin and 7 (39%) were previously treated in a phase I clinical trial setting. At enrollment 6 (33%) subjects had T1 disease and 13 (72%) had carcinoma in situ. There were no dose limiting toxicities. Initial partial and complete response rates were 94% and 89%, respectively. At 1 year recurrence-free survival was 0.83 (range 0.57 to 0.94) and at 2 years estimated recurrence-free survival was 0.64 (0.32 to 0.84). CONCLUSIONS: In this high risk and highly pretreated cohort of bacillus Calmette-Guérin unresponsive or recurrent/relapsing nonmuscle invasive bladder cancer cases combination intravesical cabazitaxel, gemcitabine and cisplatin was a well tolerated and potentially effective regimen.

Linking 24-h urines to clinical phenotypes: what alternatives does the future bring?

PURPOSE OF REVIEW: The 24-h urine test is recommended as part of the metabolic evaluation for patients with nephrolithiasis to guide preventive interventions. However, this test may be challenging to interpret and has limits in its predictive ability. In this review, we summarize and discuss the most recent research on the opportunities and challenges for utilizing urinary biomarkers for kidney stone prevention. RECENT FINDINGS: Contemporary studies utilizing the 24-h urine test have improved our understanding of how to better administer testing and interpret test results. Beyond the standard panel of 24-h urine parameters, recent applications of proteomics and metabolomics have identified protein and metabolic profiles of stone formers. These profiles can be assayed in future studies as potential biomarkers for risk stratification and prediction. Broad collaborative efforts to create large datasets and biobanks from kidney stone formers will be invaluable for kidney stone research. SUMMARY: Recent advances in our understanding of kidney stone risk have opened opportunities to improve metabolic testing for kidney stone formers. These strategies do not appear to be mutually exclusive of 24-h urine testing but instead complementary in their approach. Finally, large clinical datasets hold promise to be leveraged to identify new avenues for stone prevention.

Urological In-Flight Medical Events on Commercial Airlines.

PURPOSE: In-flight medical events are rare but may cause significant distress as access to care is limited. There is a paucity of data on in-flight urological medical events. We describe urological in-flight medical emergencies and report clinical and flight outcomes. MATERIALS AND METHODS: We reviewed all in-flight urological medical emergencies between 2015 and 2017 from MedAire®, a ground based medical support center that provides remote medical advisory services to approximately 35% of commercial airline passenger traffic worldwide. Our primary end point was the incidence rates of in-flight urological medical events. We also characterized the types of in-flight medical emergencies, in-flight management and their impact on flight status. Statistical analyses included Student's t-tests, chi-square analysis and analysis of variance. RESULTS: We identified 1,368 (1%) urological in-flight medical emergencies from a total of 138,612 in-flight medical emergencies, with an incidence of 0.5 per million passengers. The most common in-flight medical emergencies were lower urinary tract symptoms (35%), urinary retention (30%) and flank pain (21%). Among in-flight medical emergencies 883 (60%) resolved in flight, 273 (28%) required on-arrival medical evaluation and 21 (1.5%) resulted in flight diversions. Of the flight diversions the majority were due to urinary retention (12, 57%) and less commonly flank pain (6, 28%) and testicular/abdominal pain (3, 15%). CONCLUSIONS: The most common causes of urological in-flight medical emergencies are lower urinary tract symptoms, urinary retention and renal colic, the majority of which resolved in flight. These data are useful for informing flight personnel and emergency kit equipment needs to minimize the impact of these events when they occur.