Faculty Bibliography

BACKGROUND:Primary hyperoxaluria (PH) is a family of three rare, autosomal recessive genetic disorders that can result in recurrent kidney stones, progressive chronic kidney disease (CKD), and kidney failure. PH prevalence is underestimated due to its varying presentation and lack of awareness; delays in diagnosis can lead to substantial burdens on the healthcare system. METHODS:This retrospective, observational claims analysis evaluated disease burden and cost of care in patients who had PH, PH with CKD, or CKD alone. Data from the Merative MarketScan Commercial Claims and Encounters databases and the Centers for Medicare and Medicaid Services Medicare Fee-for-Service Limited Data Set were assessed during the study period of January 1, 2017, to December 31, 2021. PH prevalence was calculated based on the sample population within each data source. RESULTS:The study sample included 326 patients who had PH; applying projection factors to the US population, an estimated 4500 patients had a diagnosis of PH in 2021. Among these patients, 37% were estimated to have PH with CKD (65% of whom had early CKD, 33% had advanced CKD, and 2% had stage reported as unknown). Patients who had CKD alone (n = 845) were matched with patients who had PH with CKD (n = 169). Patients who had PH with CKD were significantly more burdened with kidney stones (p < 0.01) than patients who had CKD alone. Higher rates of pharmacotherapy and medical treatments were observed in patients who had PH with CKD versus patients who had CKD alone. Median semi-annual total all-cause healthcare costs were greater in patients who had PH with CKD than in patients with CKD alone, regardless of CKD stage ($54,154 in patients who had PH with advanced CKD vs. $35,016 in patients with advanced CKD alone; $9,784 in patients who had PH with early CKD vs. $5,572 in patients with early CKD alone). CONCLUSIONS:CKD stage progression among patients who had PH is associated with increasing all-cause costs, suggesting that early diagnosis and treatment of PH to limit the progression to advanced CKD could represent an opportunity to alleviate not only PH symptoms, but also the healthcare cost burden.

BACKGROUND:Urinary stone disease with a clear genetic cause, monogenic stone disease (MSD), is increasingly recognized as a significant proportion of the total population. When MSD is suspected, genetic testing provides a firm diagnosis that can alter management and treatment. Here we present testing results from a large cohort with suspected MSD. METHODS:Subjects with features suggestive of MSD (early onset, family history, frequent stones, nephrocalcinosis [NC], and/or CKD) were recruited by the Rare Kidney Stone Consortium and genotyped for up to 160 known or candidate MSD genes via a targeted massively parallel sequencing (tMPS) panel. We compared clinical and biochemical features between genetically resolved MSD and unresolved individuals. RESULTS:Of 426 families (657 patients) enrolled, 145 (34%) were resolved with identified disease associated variants in 22 known MSD genes. Ninety-nine families were biallelic, 37 monoallelic, and 2 digenic. An additional 21 of the 231 screened family members were resolved. Genes identified in 10 or more families were: AGXT, HOGA1, SLC34A3, CYP24A1, SLC3A1, and CLCN5. Compared to the unresolved group, MSD probands had a lower baseline and last visit estimated glomerular filtration rate (eGFR), earlier age of stone presentation, and more stone events and procedures/year of life. The resolve rate was higher in those less than 16 years, and NC was seen earlier in the MSD group. Overall, NC was a risk factor for lower eGFR. Among the specific disorders, primary hyperoxaluria patients had the earliest age of stone and NC diagnosis, and as expected, the highest urinary oxalate level. CONCLUSIONS:Our study emphasizes the value of selecting patients enriched for factors associated with MSD, and comprehensive genetic testing to achieve a high yield of genetic diagnoses. Significant clinical and biochemical characteristics of MSD patients were defined. A definitive MSD diagnosis facilitates individualized management and strategies to delay disease progression in probands and affected family members.

OBJECTIVE:To evaluate urinalysis testing patterns within the Veterans Health Administration (VHA), estimate the proportion and likelihood of patients who completed a urinalysis to have microscopic hematuria (MH), and explore how urinalysis testing patterns may influence MH detection. METHODS:This was a retrospective cross-sectional study using VHA data. We identified adult patients without a known urologic cancer history who had at least 1 outpatient visit at any VHA site and at least 1 interpretable urinalysis performed in 2015. The factors associated with the number or urinalyses performed on each patient and associations with the presence of MH were investigated. RESULTS:Among 5,719,966 adults, 39% completed a urinalysis. Variation in the proportion of patients who completed urinalyses was highest by age, among patients with hypertension and diabetes, and by region. Of patients who underwent urinalysis and had no prior genitourinary cancer history, 54% did not have an interpretable urinalysis result. Among patients with at least one interpretable microscopic urinalysis, 37% had MH. This was more common among older patients, females, current smokers, and patients with more comorbidities. Variation in the likelihood of patients having MH remained after adjusting for multiple factors and when contextualized by urinalysis completion and interpretability patterns. CONCLUSION/CONCLUSIONS:The number of urinalyses performed in the VHA system is remarkably high. Detection of MH is influenced by the frequency of urinalysis testing and interpretability of results. The presence and detection of MH varies by factors which should be considered when adjudicating the need for further evaluation of MH.

RATIONALE & OBJECTIVE/OBJECTIVE:Despite national efforts, the uptake of home dialysis (peritoneal dialysis or home hemodialysis) remains low. Characteristics of the built environment may differentially impact home dialysis use. STUDY DESIGN/METHODS:Retrospective cohort study (2010-2019). SETTING & PARTICIPANTS/METHODS:1,103,695 adults (aged≥18 years) initiating dialysis in the US Renal Data System. EXPOSURE/METHODS:We examined 3 built environment domains based on residential ZIP code: (1) medically underserved areas (MUAs), defined as neighborhoods with limited primary care access; (2) distance to the nearest dialysis facility; and (3) distribution of housing characteristics (structure and overcrowding). OUTCOME/RESULTS:Uptake of home dialysis modalities at dialysis initiation. ANALYTICAL APPROACH/METHODS:We quantified associations between built environment characteristics and home dialysis initiation using multilevel logistic regression stratified by urbanicity type (urban, suburban, small-town, and rural). RESULTS:Among adults initiating dialysis, 40.8% lived in MUAs. Across ZIP codes, the mean percentage of overcrowded housing was 4.2% (SD, 4.7%), and the percentage of detached housing was 61.1% (SD, 21.1%); mean distance to the nearest dialysis facility was 5.5km (SD, 9.1km). Living in MUAs was associated with reduced home dialysis use only in urban (OR, 0.94; 95% CI, 0.91-0.96) and suburban (OR, 0.92; 95% CI, 0.89-0.94) areas. Similarly, housing overcrowding was associated with decreased home dialysis use only in urban (OR, 0.88; 95% CI, 0.86-0.89) and suburban (OR, 0.91; 95% CI, 0.90-0.93) areas. Longer distance to a dialysis facility was the most salient neighborhood factor associated with increased home dialysis use in small towns (OR, 1.14; 95% CI, 1.12-1.16) and rural areas (OR, 1.17; 95% CI, 1.15-1.19). LIMITATIONS/CONCLUSIONS:Housing characteristics were measured at the ZIP code level. CONCLUSIONS:Built environment characteristics associated with home dialysis uptake vary by urbanicity. Policies should address built environment barriers that are specific to urbanicity level. For example, increasing the frequency of dialysate delivery schedules could address housing space constraints in urban and suburban areas, and promoting home dialysis might be more effective for patients living far from dialysis centers in small-town and rural areas.

OBJECTIVES/UNASSIGNED:To review the different analgesic modalities and benefits of non-opioid pain management options as well as their evidence-based, established superiority, compared to opioid medications. MATERIALS/UNASSIGNED:We review the updated literature about pain management of renal colic, a prevalent and painful urologic condition. Prescribers must know the efficacy, safety and possible ramifications of analgesic selections. RESULTS/UNASSIGNED:Commonly prescribed medications in the United States (US) include non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids. In the context of the current epidemic of death from overdoses of opioids in the US, the frequency of opioid prescribing for renal colic is likely excessive, problematic and potentially remediable. We also present analgesic modalities revolving around interventions with peri-procedural pain management for ureteroscopy and percutaneous nephrolithotomy. After touching on the implications of misguided opioid use, especially in the context of kidney stone disease, and despite the evidence and consensus guidelines supporting NSAIDs in renal colic, current evidence has shown that many clinicians continue to prescribe opioids as first-line treatment. Finally, we highlight current efforts targeted at the reduction of opioid use and prescription in the setting of provider education and decision aids in curbing misguided opioid use in renal colic. CONCLUSIONS/UNASSIGNED:While the evidence against treating kidney stones with opioids is clear, more work is needed to shift current practices to reflect that renal colic is a non-opioid-requiring condition.

BACKGROUND:), can be self- or caregiver-administered at home with fixed-dosing for patients ≥ 12 years of age. This real-world study aimed to understand treatment preferences among individuals with PH1, highlighting challenges in administration of current treatments. METHODS:A cross-sectional web-based survey was conducted among U.S.-based adults (aged ≥ 18) diagnosed with PH1. The survey consisted of a 20-25 min questionnaire and was conducted from October to December 2023. RESULTS:The study participants (N = 39) included both male (N = 26) and female (N = 13) adults with PH1. Participants came from a range of community settings, including urban (46%), rural (39%), and suburban (15%); and were full- or part-time workers (56%) or students (41%). Most participants were on lumasiran therapy (95%) for an average of 1 year (range: 0.3-1.8 years). The survey revealed that the commonly reported factors important for treatment selection among participants living with PH1 were frequency of administration, treatment administrator, time required for treatment, and place of administration. The ability to self-administer was ranked as the top choice by most participants. Over half (56%) found quarterly injections easy or very easy. Similarly, 56-59% found home administration, whether self- or healthcare provider (HCP)-administered, easy or very easy. Nearly half (46%) considered injections at medical facilities challenging or very challenging. The majority indicated traveling > 15 min for injections would be burdensome (57%) and arranging appointments problematic (54%). When comparing administration methods, 72% preferred self-injection over HCP-administered injections. Regarding treatment regimens, 57% found it easy or very easy to receive monthly injections initially, before switching to quarterly. Additionally, 64% preferred a medication dosage that is not weight-based. While participants expressed a preference for less frequent treatments, 67% preferred self-injection at home over medical facility injections, and 67% preferred monthly injections at home over quarterly injections at a medical facility. CONCLUSIONS:This study shows that patients with PH1 value treatments that are convenient and fit their lifestyle.

PURPOSE/UNASSIGNED:Urine calcium excretion is greater after dinner and urine volumes are lower. The result is higher urine calcium concentrations, which may confer greater risk of stone formation, at night. We considered whether night-time administration - as compared with daytime administration - of thiazides would be more effective for stone prevention. MATERIALS AND METHODS/UNASSIGNED:We performed 12-hour urine collections in 7 patients taking 25 mg of chlorthalidone (CTD) and 10 patients taking 25 mg of hydrochlorothiazide (HCTZ). Participants completed urine collections at baseline, again after a week of morning medication administration, and again after a week of evening administration, all on repeated self-selected diets. RESULTS/UNASSIGNED:Chlorthalidone reduced urine calcium excretion for both 12-hour periods whether administered in the morning or in the evening: morning dosing lowered urine calcium from 130±70 mg/gram Cr at baseline, to 76±52 mg/gram Cr (P<0.02); evening dosing lowered it to 87±51 mg/gram Cr, which was not significant. On the other hand, HCTZ did not reduce urine calcium excretion regardless of the time of administration: mean 24-hour urine calcium excretion (UCa) was 124±38 mg/gram Cr at baseline and 106±40 mg/gram Cr when HCTZ was given in AM, and 117±54 mg/gram Cr when given in PM. CONCLUSION/UNASSIGNED:We conclude that the long-acting and more effective CTD is a preferable agent for stone prevention. Time of administration does not appear to be important, although morning administration may more effectively address higher post-dinner calcium excretion. The most commonly used thiazide (HCTZ) is shorter acting, frequently dosed once per day, but does not appear to reduce urine calcium excretion at this dose.

BACKGROUND:Identifying factors associated with uncomplicated and complicated opioid use is essential, especially with regard to safety concerns in impaired kidney function. Literature about opioid prescription and their potential complications in patients with different stages of chronic kidney disease (CKD) is scarce. This study describes opioid use and poisoning in hospitalized CKD patients. METHODS:The National Inpatient Database (NIS) was queried from 2016 to 2020 to identify which patients with known CKD stages were admitted with diagnoses of uncomplicated and complicated opioid use, and opioid poisoning. Patients with end-stage kidney disease receiving any form of renal replacement therapy were excluded. CKD1 served as a reference, and demographic and socio-economic characteristics were accounted for. Logistic regressions were performed to evaluate the relationship between CKD stages and each condition. RESULTS:The final cohort included 2,917,404 (14,587,017 weighted) CKD patients, of whom 1.763 ± 0.023% and 1.177 ± 0.016% had uncomplicated and complicated opioid use, respectively. Odds of uncomplicated use were lower with more advanced CKD stages. We observed an increase of complicated use with milder forms of CKD. No differences in odds of complicated opioid use were found when CKD4-5 patients were compared to CKD1. After adjustment, opioid use was found to be the main predictor of poisoning in hospitalized CKD patients. CONCLUSION/CONCLUSIONS:Prescribers appear to be more cautious in patients with advanced CKD, with lower odds of being on opioid analgesics in this group. Most CKD patients had higher odds of complicated use, and poisoning was essentially driven by complicated opioid use rather than CKD stage.

PURPOSE OF REVIEW/OBJECTIVE:Initiation of hemodialysis treatment with a thrice-weekly prescription is currently the standard of care irrespective of patients' residual kidney function (RKF), comorbidities, and preferences. RECENT FINDINGS/RESULTS:Each year ∼12 000 Veterans with advanced kidney disease progress to end-stage kidney disease (ESKD) requiring dialysis and comprise greater than 10% of the US incident ESKD population. Dialysis is costly and is associated with impaired health-related quality of life (HRQOL) and high mortality risk, especially in the first year of treatment. Evidence suggests an incremental dialysis transition using twice-weekly hemodialysis provides various benefits, including more dialysis-free time, longer RKF preservation, less vascular access damage, and lower patient burden. Pragmatic studies are needed to inform the efficacy and safety of incremental hemodialysis as a personalized dialysis regimen, and could inform its consideration as a conservation strategy during times of supply shortages. Broadly implementing twice-weekly hemodialysis could also potentially allow more Veterans to receive care within VA-based dialysis units. The VA IncHVets Trial is a pragmatic, multicenter, randomized controlled trial comparing the efficacy and safety of twice-weekly incremental vs. thrice-weekly hemodialysis among Veterans transitioning to ESKD. SUMMARY/CONCLUSIONS:Further research is needed to determine whether incremental hemodialysis is well tolerated, effective, and facilitates a more favorable transition to dialysis.