Local adaptation, plasticity, and evolved resistance to hypoxic cold stress in high-altitude deer mice.

A fundamental question in evolutionary biology concerns the relative contributions of phenotypic plasticity vs. local adaptation (genotypic specialization) in enabling wide-ranging species to inhabit diverse environmental conditions. Here we conduct a long-term hypoxia acclimation experiment to assess the relative roles of local adaptation and plasticity in enabling highland and lowland deer mice ( Peromyscus maniculatus ) to sustain aerobic thermogenesis at progressively increasing elevations. We assessed the relative physiological performance capacities of highland and lowland natives as they were exposed to progressive, stepwise increases in hypoxia, simulating the gradual ascent from sea level to an elevation of 6000 m. The final elevation of 6000 m far exceeds the highest attainable elevations within the species' range, and therefore tests the animals' ability to tolerate levels of hypoxia that surpass the prevailing conditions within their current distributional limits. Our results demonstrate that highland natives exhibit superior thermogenic capacities at the most severe levels of hypoxia, suggesting that the species' broad fundamental niche and its ability to inhabit such a broad range of elevational zones is attributable to a combination of genetically based local adaptation and plasticity. Transcriptomic and physiological measurements identify evolved changes in the acclimation response to hypoxia that contribute to the enhanced thermogenic capacity of highland natives. SIGNIFICANCE STATEMENT: In species that are distributed across steep environmental gradients, the ability to inhabit a broad range of conditions may be attributable to local adaptation and/or a generalized acclimatization capacity (phenotypic plasticity). By experimentally acclimating highland and lowland deer mice ( Peromyscus maniculatus ) to progressively increasing levels of hypoxia during a simulated ascent to 6000 m, we assessed the relative roles of evolved and plastic changes in thermogenic capacity. At especially severe levels of hypoxia, the superior thermogenic performance of highland natives relative to lowland conspecifics suggests that the broad fundamental niche of deer mice is largely attributable to local adaptation to different elevational zones, including evolved plasticity in gene expression and respiratory traits.

Patient Characteristics, Management, and Outcomes in a Novel Cohort of Primary Hyperparathyroidism.

Context: Primary hyperparathyroidism (PHPT) increases the risk of bone loss, debilitating fractures, kidney stones, impaired renal function, and neurocognitive symptoms. Studies describing the natural history of PHPT have been limited to small samples, single institutions, or specific populations. Objective: We assessed the natural history of PHPT through a large, diverse national cohort from an electronic health record dataset representing more than 100 million patients. Methods: The TriNetX database was queried for adult patients with PHPT. We extracted demographics, comorbidities, and longitudinal biochemistries. Primary outcomes included major osteoporotic fracture (MOF) and chronic kidney disease (CKD). Outcomes were stratified by treatment strategy (surgical parathyroidectomy [PTX] vs nonsurgical) and age. Results: Among 50 958 patients with PHPT, 26.5% were treated surgically at a median of 0.3 years postdiagnosis. At diagnosis, median age was 65 years, 74.0% were female, and median calcium level was 10.9 mg/dL. Black and older patients underwent PTX less frequently than White and younger patients. MOF 10-year incidence was 5.20% (PTX) and 7.91% (nonsurgical), with median 1.7-year delay with PTX compared to nonsurgical. PTX-associated MOF absolute risk reduction was 0.83% (age < 65 years) and 3.33% (age ≥ 65 years). CKD 10-year incidence was 21.2% (PTX) and 33.6% (nonsurgical), with median 1.9-year delay with PTX. PTX-associated CKD absolute risk reduction was 12.2% (age < 65 years) and 9.5% (age ≥ 65 years). Conclusion: We report 1 of the largest, representative, population-based natural histories of PHPT with different management strategies. A minority of patients underwent PTX, especially in older age. Patients managed surgically had lower incidence of fracture and CKD, and older patients experienced differential benefit.

Extreme High-Elevation Mammal Surveys Reveal Unexpectedly High Upper Range Limits of Andean Mice.

AbstractIn the world's highest mountain ranges, uncertainty about the upper elevational range limits of alpine animals represents a critical knowledge gap regarding the environmental limits of life and presents a problem for detecting range shifts in response to climate change. Here we report results of mountaineering mammal surveys in the Central Andes, which led to the discovery of multiple species of mice living at extreme elevations that far surpass previously assumed range limits for mammals. We livetrapped small mammals from ecologically diverse sites spanning >6,700 m of vertical relief, from the desert coast of northern Chile to the summits of the highest volcanoes in the Andes. We used molecular sequence data and whole-genome sequence data to confirm the identities of species that represent new elevational records and to test hypotheses regarding species limits. These discoveries contribute to a new appreciation of the environmental limits of vertebrate life.

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.

Genomic insights into the mystery of mouse mummies on the summits of Atacama volcanoes.

Our understanding of the limits of animal life is continually revised by scientific exploration of extreme environments. Here we report the discovery of mummified cadavers of leaf-eared mice, Phyllotis vaccarum, from the summits of three different Andean volcanoes at elevations 6,029-6,233 m above sea level in the Puna de Atacama in Chile and Argentina. Such extreme elevations were previously assumed to be completely uninhabitable by mammals. In combination with a live-captured specimen of the same species from the nearby summit of Volcán Llullaillaco (6,739 m)1, the summit mummies represent the highest altitude physical records of mammals in the world. We also report a chromosome-level genome assembly for P. vaccarum that, in combination with a whole-genome re-sequencing analysis and radiocarbon dating analysis, provides insights into the provenance and antiquity of the summit mice. Radiocarbon data indicate that the most ancient of the mummies are, at most, a few centuries old. Genomic polymorphism data revealed a high degree of continuity between the summit mice and conspecifics from lower elevations in the surrounding Altiplano. Genomic data also revealed equal numbers of males and females among the summit mice and evidence of close kinship between some individuals from the same summits. These findings bolster evidence for resident populations of Phyllotis at elevations >6,000 m and challenge assumptions about the environmental limits of vertebrate life and the physiological tolerances of small mammals.

Extreme high-elevation mammal surveys reveal unexpectedly high upper range limits of Andean mice.

In the world's highest mountain ranges, uncertainty about the upper elevational range limits of alpine animals represents a critical knowledge gap regarding the environmental limits of life and presents a problem for detecting range shifts in response to climate change. Here we report results of mountaineering mammal surveys in the Central Andes, which led to the discovery of multiple species of mice living at extreme elevations that far surpass previously assumed range limits for mammals. We live-trapped small mammals from ecologically diverse sites spanning >6700 m of vertical relief, from the desert coast of northern Chile to the summits of the highest volcanoes in the Andes. We used molecular sequence data and whole-genome sequence data to confirm the identities of species that represent new elevational records and to test hypotheses regarding species limits. These discoveries contribute to a new appreciation of the environmental limits of vertebrate life.

Dietary crude oil exposure during sex differentiation skewed adult sex ratio towards males in the zebrafish.

Dietary crude oil exposure has detrimental morpho-physiological effects in fishes, including endocrine disruption. However, little is known about how it influences sex differentiation and its potential for skewing sex ratios of populations. Appropriate sex ratio is important for maintaining effective population size and structure. Deviations of these ratios can compromise population growth and maintenance and may induce changes in a species' evolutionary trajectory. We assessed the potential of dietary exposure to crude oil (6.5, 11.4, and 17.5 mg/kg food) to alter sex differentiation in the zebrafish (Danio rerio) (20-35 days post fertilization (dpf)) and subsequently skew the adult (90 dpf) sex ratio. Multiple health- and fitness-related phenotypic traits (i.e., body mass and length, condition factor, heart rate, oxygen consumption, and their capacity to cope with hypoxia) were also assessed to better understand the effects of dietary crude oil exposure. We showed that dietary exposure to crude oil during the process of sex differentiation skewed sex ratio towards males (up to 0.34:1 female to male ratio in the highest oil concentration). Remarkably, this effect occurred independently of affecting physiological variables and female gonad characteristics, thus highlighting just how subtle the effects of dietary crude oil exposure can be. Our results suggest that, although fish were in an apparently healthy state during experimentation, sex ratio was still impacted, potentially compromising the resilience of the population. Therefore, considering how complex chemical mixtures affect organisms at several levels (molecular-individual) in experimental designs is warranted to better understand the implications of the exposures and the hazards that populations face in the wild.

Patients' Experiences With the Removal of a Ureteral Stent: Insights From In-depth Interviews With Participants in the USDRN STENTS Qualitative Cohort Study.

OBJECTIVE: To describe the experiences of patients undergoing stent removal in the USDRN Study to Enhance Understanding of Stent-Associated Symptoms (STENTS), a prospective, observational cohort study of patients with short-term ureteral stent placement post-ureteroscopy. METHODS: We conducted a qualitative descriptive study using in-depth interviews. Participants reflected on (1) painful or bothersome aspects of stent removal, (2) symptoms immediately after removal, and (3) symptoms in the days following removal. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. RESULTS: The 38 participants interviewed were aged 13-77 years, 55% female, and 95% White. Interviews were conducted 7-30 days after stent removal. Almost all participants (n = 31) described that they experienced either pain or discomfort during stent removal, but for most (n = 25) pain was of short duration. Many participants (n = 21) described anticipatory anxiety related to the procedure, and several (n = 11) discussed discomfort arising from lack of privacy or feeling exposed. Interactions with medical providers often helped put participants at ease, but also increased discomfort for some. Following stent removal, several participants described lingering pain and/or urinary symptoms, but these largely resolved within 24 hours. A few participants described symptoms persisting for more than a day post stent removal. CONCLUSION: These findings on patients' experiences during and shortly after ureteral stent removal, particularly the psychological distress they experienced, identify opportunities for improvement in patient care. Clear communication from providers about what to expect with the removal procedure, and the possibility of delayed pain, may help patients adapt to discomfort.

The Patient Voice: Stent Experiences After Ureteroscopy-Insights from In-Depth Interviews with Participants in the USDRN STENTS Nested Qualitative Cohort Study.

Purpose: Ureteral stents are commonly used after ureteroscopy and cause significant discomfort, yet qualitative perspectives on patients' stent experiences remain unknown. We describe psychological, functional, and interpersonal effects of post-ureteroscopy stents and whether additional patient-reported assessments may be needed. Materials and Methods: Using a qualitative descriptive study design, we conducted in-depth interviews with a nested cohort of participants in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS). Participants shared their symptoms with a post-ureteroscopy stent and described symptom bother and impact on daily activities. All interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. During analysis, participants' experiences with interference in daily activities were categorized into three groups based on their impact: minimal, moderate, and substantial. Results: All 39 participants experienced pain, although descriptions varied and differentiated between feelings of pain vs discomfort. Almost all experienced urinary symptoms. Only a few reported other physical symptoms, although several psychological aspects were identified. In the areas of sleep, mood, life enjoyment, work, exercise, activities of daily living, driving, childcare, and leisure/social activities, the stent had little impact on daily living among participants placed in the minimal group (n = 12) and far greater impact for participants in the substantial group (n = 8). For patients in the moderate group (n = 19), some daily activities were moderately or substantially affected, whereas other activities were minimally affected. Conclusions: Counseling to better prepare patients for the impact of stent-associated symptoms may help mitigate symptom burden. While existing instruments adequately cover most symptoms, additional assessments for other domains, particularly psychological factors, may be needed.

Risk Factors for Increased Stent-associated Symptoms Following Ureteroscopy for Urinary Stones: Results From STENTS.

PURPOSE: The STudy to Enhance uNderstanding of sTent-associated Symptoms sought to identify risk factors for pain and urinary symptoms, as well as how these symptoms interfere with daily activities after ureteroscopy for stone treatment. MATERIALS AND METHODS: This prospective observational cohort study enrolled patients aged ≥12 years undergoing ureteroscopy with ureteral stent for stone treatment at 4 clinical centers. Participants reported symptoms at baseline; on postoperative days 1, 3, 5; at stent removal; and day 30 post-stent removal. Outcomes of pain intensity, pain interference, urinary symptoms, and bother were captured with multiple instruments. Multivariable analyses using mixed-effects linear regression models were identified characteristics associated with increased stent-associated symptoms. RESULTS: A total of 424 participants were enrolled. Mean age was 49 years (SD 17); 47% were female. Participants experienced a marked increase in stent-associated symptoms on postoperative day 1. While pain intensity decreased ∼50% from postoperative day 1 to postoperative day 5, interference due to pain remained persistently elevated. In multivariable analysis, older age was associated with lower pain intensity (P = .004). Having chronic pain conditions (P < .001), prior severe stent pain (P = .021), and depressive symptoms at baseline (P < .001) were each associated with higher pain intensity. Neither sex, stone location, ureteral access sheath use, nor stent characteristics were drivers of stent-associated symptoms. CONCLUSIONS: In this multicenter cohort, interference persisted even as pain intensity decreased. Patient factors (eg, age, depression) rather than surgical factors were associated with symptom intensity. These findings provide a foundation for patient-centered care and highlight potential targets for efforts to mitigate the burden of stent-associated symptoms.

Type 4 renal tubular acidosis and uric acid nephrolithiasis: two faces of the same coin?

PURPOSE OF REVIEW: The present review summarizes findings of recent studies examining the epidemiology, pathophysiology, and treatment of type 4 renal tubular acidosis (RTA) and uric acid nephrolithiasis, two conditions characterized by an abnormally acidic urine. RECENT FINDINGS: Both type 4 RTA and uric acid nephrolithiasis disproportionately occur in patients with type 2 diabetes and/or chronic kidney disease. Biochemically, both conditions are associated with reduced renal ammonium excretion resulting in impaired urinary buffering and low urine pH. Reduced ammoniagenesis is postulated to result from hyperkalemia in type 4 RTA and from insulin resistance and fat accumulation in the renal proximal tubule in uric acid nephrolithiasis. The typical biochemical findings of hyperkalemia and systemic acidosis of type 4 RTA are rarely reported in uric acid stone formers. Additional clinical differences between the two conditions include findings of higher urinary uric acid excretion and consequent urinary uric acid supersaturation in uric acid stone formers but not in type 4 RTA. SUMMARY: Type 4 RTA and uric acid nephrolithiasis share several epidemiological, clinical, and biochemical features. Although both conditions may be manifestations of diabetes mellitus and thus have a large at-risk population, the means to the shared biochemical finding of overly acidic urine are different. This difference in pathophysiology may explain the dissimilarity in the prevalence of kidney stone formation.

Bone health outcomes in post-lung transplant patients with cystic fibrosis.

BACKGROUND: Osteoporosis is a common comorbidity in patients with cystic fibrosis (CF). Although lung transplantation (LTx) improves quality of life of CF patients, there is little research examining long-term bone health outcomes following LTx in these patients. METHODS: Data were collected on 59 patients who underwent LTx between 2006 and 2019, including 30 with CF and 29 without CF. We compared baseline characteristics, long-term bone mineral density (BMD) trends, and fracture incidence between the two patient populations, and examined factors associated with post-LTx fractures in CF patients. RESULTS: Compared with non-CF patients, patients with CF were younger, had lower body mass index, and lower baseline BMD Z-scores at the lumbar spine, femoral neck, and total hip (all p<0.001). BMD at all sites declined in both groups in the first year post-LTx. In subsequent years, CF patients exhibited better BMD recovery relative to pre-transplantation, but continued to have lower BMD post-LTx. Post-transplant fractures occurred in 30% and 34% of CF and non-CF patients, respectively. CF patients who developed fractures after LTx had significantly lower BMD and lower pre-transplantation percent predicted forced expiratory volume in one second (FEV1%). CONCLUSIONS: Although CF patients exhibit better BMD recovery following LTx compared to their non-CF counterparts, CF patients start with significantly lower pre-LTx BMD and experience a similarly high rate of post-LTx fractures. These findings highlight the unique contribution of the CF disease process to bone health, as well as a clear need for better prevention and treatment of osteoporosis in CF patients before and after LTx.

Evolution and molecular basis of a novel allosteric property of crocodilian hemoglobin.

The extraordinary breath-hold diving capacity of crocodilians has been ascribed to a unique mode of allosterically regulating hemoglobin (Hb)-oxygenation in circulating red blood cells. We investigated the origin and mechanistic basis of this novel biochemical phenomenon by performing directed mutagenesis experiments on resurrected ancestral Hbs. Comparisons of Hb function between the common ancestor of archosaurs (the group that includes crocodilians and birds) and the last common ancestor of modern crocodilians revealed that regulation of Hb-O2 affinity via allosteric binding of bicarbonate ions represents a croc-specific innovation that evolved in combination with the loss of allosteric regulation by ATP binding. Mutagenesis experiments revealed that evolution of the novel allosteric function in crocodilians and the concomitant loss of ancestral function were not mechanistically coupled and were caused by different sets of substitutions. The gain of bicarbonate sensitivity in crocodilian Hb involved the direct effect of few amino acid substitutions at key sites in combination with indirect effects of numerous other substitutions at structurally disparate sites. Such indirect interaction effects suggest that evolution of the novel protein function was conditional on neutral mutations that produced no adaptive benefit when they first arose but that contributed to a permissive background for subsequent function-altering mutations at other sites. Due to the context dependence of causative substitutions, the unique allosteric properties of crocodilian Hb cannot be easily transplanted into divergent homologs of other species.

Evaluation of an association between RANKL and OPG with bone disease in people with cystic fibrosis.

BACKGROUND: As people with Cystic Fibrosis (CF) live longer, extra-pulmonary complications such as CF-related bone disease (CFBD) are becoming increasingly important. The etiology of CFBD is poorly understood but is likely multifactorial. Bones undergo continuous remodeling via pathways including RANK (receptor activator of NF-κB)/sRANKL (soluble ligand)/OPG (osteoprotegerin). We sought to examine the association between sRANKL (stimulant of osteoclastogenesis) and OPG levels (inhibitor of osteoclast formation) and CFBD to investigate their potential utility as biomarkers of bone turnover in people with CF. METHODS: We evaluated sRANKL and OPG in plasma from people with CF and healthy controls (HC) and compared levels in those with CF to bone mineral density results. We used univariable and multivariable analysis to account for factors that may impact sRANKL and OPG. RESULTS: We found a higher median [IQR] sRANKL 10,896pg/mL [5,781-24,243] CF; 2,406pg.mL [659.50-5,042] HC; p= 0.0009), lower OPG 56.68pg/mL [36.28-124.70] CF; 583.20pg/mL [421.30-675.10] HC; p < 0.0001), and higher RANKL/OPG in people with CF no BD than in HC (p < 0.0001). Furthermore, we found a higher RANKL/OPG ratio 407.50pg/mL [214.40-602.60] CFBD; 177.70pg/mL [131.50-239.70] CF no BD; p = 0.007) in people with CFBD versus CF without bone disease. This difference persisted after adjusting for variables thought to impact bone health. CONCLUSIONS: The current screening recommendations of imaging for CFBD may miss important markers of bone turnover such as the RANKL/OPG ratio. These findings support the investigation of therapies that modulate the RANK/RANKL/OPG pathway as potential therapeutic targets for bone disease in CF.

Alkali Citrate Content of Common Over-the-Counter and Medical Food Supplements.

Objective: Potassium citrate effectively decreases kidney stone recurrence, but it is costly and associated with side effects. While several over-the-counter supplements and medical foods purport to provide sufficient citrate to prevent recurrent stones, corroborating data on their actual citrate content is limited. Materials and Methods: Nine common nonprescription products were purchased online. Reported citrate content was obtained from packaging, promotional materials, or ingredient labels. Using a single serving of each product, actual citrate, sodium, potassium, calcium, magnesium, and oxalate content was measured using spectrophotometry and chromatography. Total alkali citrate, cost, and amounts of each component per 10 mEq of alkali citrate were also calculated. Results: Nearly all products contained more citrate than advertised, except for Litholyte® powder, Litholyte® Coffee, and Horbäach® potassium citrate. Per serving, Moonstone® powder, LithoBalance™, and KSP tabs™ contained the most citrate (means of 63.9, 33.5, and 26.9 mEq, respectively). Moonstone and LithoBalance had the greatest discrepancy between total citrate and alkali citrate (15.7 and 11.8 mEq per serving, respectively). NOW® potassium citrate was least expensive ($0.04/10 mEq alkali citrate). KSP tabs delivered the most daily sodium (mean 158 mg/10 mEq alkali citrate, Litholyte Coffee provided the most potassium (mean of 13 mEq/10 mEq alkali citrate), and Kidney COP® provided the most calcium (mean 147 mg/10 mEq alkali citrate). Conclusion: Some common over-the-counter products contain sufficient alkali to potentially promote a citraturic response; Moonstone provides the most alkali citrate, but at a higher cost than other products. Sodium, potassium, and calcium from these products must also be considered in daily consumption.

Romosozumab-aqqg in the Treatment of Osteoporosis in a Patient With Hypophosphatasia.

Hypophosphatasia is a rare, inherited condition that causes osteomalacia and recurrent fractures. Therapeutic options for osteoporosis in patients with hypophosphatasia are limited because of concerns for a greater likelihood of atypical femoral fractures with antiresorptive agents. We report here the case of a patient with hypophosphatasia and osteoporosis who was treated with romosozumab-aqqg (Romo). An 81-year-old woman presented for management of osteoporosis with multiple fractures. She experienced a decline in bone mineral density over 20 years despite sequential osteoporosis treatment with oral bisphosphonates, hormone replacement therapy, teriparatide, and denosumab. Hypophosphatasia was suspected because of low serum alkaline phosphatase levels and was confirmed by genetic testing. After diagnosing hypophosphatasia, bone mineral density continued to decline and a trial of Romo was begun. After 1 year of Romo therapy, bone mineral density improved by 21%, and 10% at the lumbar spine and total hip, respectively. These changes were substantially greater than what she had experienced with prior teriparatide therapy. Blood alkaline phosphatase remained low on Romo. To our knowledge, this is the first report of a patient with hypophosphatasia and osteoporosis treated with Romo. In our patient, Romo did not significantly impact serum alkaline phosphatase, but improved bone mineral density significantly. In conclusion, Romo is a potential treatment option for osteoporosis in patients with hypophosphatasia for whom limited alternatives exist.

Preclinical and Clinical Evidence of Effect of Acid on Bone Health.

Acid can have ill effect on bone health in the absence of frank clinical acidosis but affecting the bone mioneral matrix and bone cells via complex pathways botyh ascute;y and chronically. While the reaction of bone to an acid load is conserved in evolution and is adaptive, the capacity can be overwhelmed resulting in dire consequences. The preclinical an clincl evidence of the acdi effect on bone is very convincing and the clinical evidence in both association and interventiopn studies are also quite credible, The adverse effects of acid on bone is underappreoicated, under-investigated, and the potential benefits of alkali therapy is not generrally known.

Associations of Obesity and Neighborhood Factors With Urinary Stone Parameters.

INTRODUCTION: Obesity is associated with kidney stone disease, but it is unknown whether this association differs by SES. This study assessed the extent to which obesity and neighborhood characteristics jointly contribute to urinary risk factors for kidney stone disease. METHODS: This was a retrospective analysis of adult patients with kidney stone disease evaluated with 24-hour urine collection (2001-2020). Neighborhood-level socioeconomic data were obtained for a principal component analysis, which identified 3 linearly independent factors. Associations between these factors and 24-hour urine measurements were assessed using linear regression as well as groupings of 24-hour urine results using multivariable logistic regression. Finally, multiplicative interactions were assessed testing effect modification by obesity, and analyses stratified by obesity were performed. Analyses were performed in 2021. RESULTS: In total, 1,264 patients met the study criteria. Factors retained on principal component analysis represented SES, family structure, and housing characteristics. On linear regression, there was a significant inverse correlation between SES and 24-hour urine sodium (p=0.0002). On multivariable logistic regression, obesity was associated with increased odds of multiple stone risk factors (OR=1.61; 95% CI=1.15, 2.26) and multiple dietary factors (OR=1.33; 95% CI=1.06, 1.67). No significant and consistent multiplicative interactions were observed between obesity and quartiles of neighborhood SES, family structure, or housing characteristics. CONCLUSIONS: Obesity was associated with the presence of multiple stone risk factors and multiple dietary factors; however, the strength and magnitude of these associations did not vary significantly by neighborhood SES, family structure, and housing characteristics.