Contribution of thick ascending limb and distal convoluted tubule to glucose-induced hypercalciuria in healthy controls.

Carbohydrates increase kidney stone risk and increase urine calcium and magnesium. We hypothesize that the effects of glucose as an allosteric modulator of calcium-sensing receptors may mediate this effect. Six healthy subjects were on a low-sodium diet before consuming 100 g of glucose beverage. Timed fasting (3) and postglucose (6) urine and blood samples were collected every 30 min. Urine composition and serum markers were measured and microvesicular abundance of tubular transport proteins (NHE3, NKCC2, NCC, and TRPV5) were quantified. Postglucose, serum glucose, and insulin rose rapidly with a parallel increase in calcium and magnesium excretion and no change in fractional excretion of sodium. Both serum parathyroid hormone (PTH) and urine TRPV5 fell in the postglucose periods. The rise in the calcium and magnesium excretion likely occurred primarily in the thick ascending limb where they are both under control of the calcium-sensing receptor. The fall in PTH and TRPV5 support the role of glucose as an allosteric modulator of calcium-sensing receptor.NEW & NOTEWORTHY Sugar increases urine calcium and magnesium as well as kidney stone and bone disease risk. Our study provided new insights into the underlying mechanism as we gave healthy subjects an oral glucose load and used newer tools such as fractional excretion of lithium, serum parathyroid hormone, and microvesicular abundance of tubular transport proteins to characterize the mechanism and identify the thick ascending limb with possible calcium-sensing receptor mediation as a likely contributor to this mechanism.

Metabolomic profiles and pathogenesis of nephrolithiasis.

PURPOSE OF REVIEW: Kidney stone disease is caused by supersaturation of urine with certain metabolites and minerals. The urine composition of stone formers has been measured to prevent stone recurrence, specifically calcium, uric acid, oxalate, ammonia, citrate. However, these minerals and metabolites have proven to be unreliable in predicting stone recurrence. Metabolomics using high throughput technologies in well defined patient cohorts can identify metabolites that may provide insight into the pathogenesis of stones as well as offer possibilities in therapeutics. RECENT FINDINGS: Techniques including 1H-NMR, and liquid chromatography paired with tandem mass spectroscopy have identified multiple possible metabolites involved in stone formation. Compared to formers of calcium oxalate stones, healthy controls had higher levels of hippuric acid as well as metabolites involved in caffeine metabolism. Both the gut and urine microbiome may contribute to the altered metabolome of stone formers. SUMMARY: Although metabolomics has offered several potential metabolites that may be protective against or promote stone formation, the mechanisms behind these metabolomic profiles and their clinical significance requires further investigation.

Clinical Effectiveness of Calcium Oxalate Stone Treatments.

INTRODUCTION: Lowering kidney stone risk and urine calcium oxalate supersaturation is a primary clinical focus for kidney stone prevention and can be achieved with multiple strategies. Common strategies include advice to increase fluid intake, restrict dietary sodium, or prescribing a thiazide-type diuretic. We investigated how physicians make these decisions in real-world practice and evaluate their efficacy based on 24-h urine collections. METHODS: We reviewed medical charts for 203 kidney stone formers with idiopathic calcium stones from University of Chicago Kidney Stone Clinic between 2005 and 2020. Patients had three 24-h urines before an initial pre-treatment clinic visit and one follow-up 24-h urine. We analyzed changes in urine composition based on treatment advice using t tests and ANOVA. RESULTS: Patients who received advice to increase fluid intake had lower urine volume at baseline (1.5 vs. 2.5 L/day, p < 0.001) and larger increase in urine volume at follow-up (0.6 vs. 0.1 L/day, p < 0.001) compared to those who did not receive the advice. Patients who were advised to restrict dietary sodium had a higher urine sodium at baseline (208 vs. 139 mEq/day, p < 0.001), a larger reduction in urine sodium (-28 vs. 13 mEq/day, p = 0.002), and larger reduction in urine calcium (-74 vs. -28 mg/day, p = 0.005) compared with those not advised to restrict dietary sodium. Patients started on a thiazide had a higher baseline urine calcium (281 vs. 213 mg/day) and larger reduction in urine calcium (-83 vs. -9 mg/day, p < 0.001) compared with patients not started on a thiazide. In combination, thiazide prescriptions with dietary sodium restriction reduced urine calcium by 99 mg/day and reduced calcium oxalate supersaturation from 8.0 to 5.5 and calcium phosphate supersaturation from 1.4 to 1.0. CONCLUSION: Providers use 24-h urine data to guide treatment strategy decisions. These strategies achieved the intended effects on urine composition and lowered kidney stone risk.

What treatments reduce kidney stone risk in patients with bowel disease?

We examined how physicians made therapeutic choices to decrease stone risk in patients with bowel disease without colon resection, many of whom have enteric hyperoxaluria (EH), at a single clinic. We analyzed clinic records and 24-h urine collections before and after the first clinic visit, among 100 stone formers with bowel disease. We used multivariate linear regression and t tests to compare effects of fluid intake, alkali supplementation, and oxalate-focused interventions on urine characteristics. Patients advised to increase fluid intake had lower initial urine volumes (L/day; 1.3 ± 0.5 vs. 1.7 ± 0.7) and increased volume more than those not so advised (0.7 ± 0.6 vs. 0.3 ± 0.6 p = 0.03; intervention vs. non-intervention). Calcium oxalate supersaturation (CaOx SS) fell (95% CI -4.3 to -0.8). Alkali supplementation increased urine pH (0.34 ± 0.53 vs. 0.22 ± 0.55, p = 0.26) and urine citrate (mg/d; 83 ± 256 vs. 98 ± 166, p = 0.74). Patients advised to reduce oxalate (mg/day) absorption had higher urine oxalate at baseline (88 ± 44 vs. 50 ± 26) which was unchanged on follow-up (88 (baseline) vs. 91 (follow-up), p = 0.90). Neither alkali (95% CI -1.4 to 2.1) nor oxalate-focused advice (95% CI -1.2 to 2.3) lowered CaOx SS. Physicians chose treatments based on baseline urine characteristics. Advice to increase fluid intake increased urine volume and decreased CaOx SS. Alkali and oxalate interventions were ineffective.

Evidence for abnormal linkage between urine oxalate and citrate excretion in human kidney stone formers.

BACKGROUND: Animal models have demonstrated an interactive relationship between the epithelial anion exchanger SLC26A6 and transporter NaDC-1 that regulates citrate and oxalate homeostasis. This relationship is a potential mechanism to protect against kidney stones as higher urine oxalate is accompanied by higher urine citrate but it has not been explored in humans. METHODS: We examined 24-h urine data on 13,155 kidney stone forming patients (SF) from separate datasets at the University of Chicago and Litholink, a national laboratory, and 143 non-kidney stone forming participants (NSF) to examine this relationship in humans. We used multivariate linear regression models to examine the association between oxalate and citrate in all study participants and separately in SF and NSF. RESULTS: Higher urinary oxalate was associated with higher urinary citrate in both SF and NSF. In NSF, the multivariate adjusted urine citrate excretion was 3.0 (1.5-4.6) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol). In SF, the multivariate adjusted urine citrate excretion was 0.3 (0.2-0.4) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol). CONCLUSIONS: Higher urinary oxalate excretion was associated with higher urinary citrate excretion and this effect was larger in non-kidney stone forming participants compared with those who form kidney stones.

Sex Differences of Kidney Stone Urine Risk Factors after Roux-en-Y Gastric Bypass.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) is a bariatric surgical procedure that is associated with higher risk of kidney stones after surgery. We examined urine composition in 18 men and women before and after RYGB to examine differences in kidney stone risk. METHODS: Three 24-h urine collections were performed before and 1 year after RYGB. We analyzed mean urinary values for pre- and post-RYGB collections and compared men and women. RESULTS: Seven men and eleven women completed pre- and post-RYGB urine collections. Pre-RYGB, men had higher calcium oxalate supersaturation (CaOx SS) (7.0 vs. 5.0, p = 0.04) compared with women. Post-RYGB, women had higher urine CaOx SS (13.1 vs. 4.6, p = 0.002), calcium phosphate supersaturation (1.04 vs. 0.59, p = 0.05), and lower urine volumes (1.7 vs. 2.7L, p < 0.001) compared with men. DISCUSSION/CONCLUSION: There are important differences in urine composition by sex that may contribute to higher kidney stone risk in women after RYGB compared with men.

Bisphosphonates and management of kidney stones and bone disease.

PURPOSE OF REVIEW: Kidney stones are strongly associated with low bone density and bone fracture. Clinical management focuses on prevention of kidney stones and bone fracture. We reviewed literature of kidney stones and bone disease with a special focus on updates in therapeutic strategies. We will review the literature regarding dietary management, supplements, and medications and emphasize the recent studies on bisphosphonates and kidney stone management. RECENT FINDINGS: Bisphosphonate medications are commonly used in management of low bone density. Previous studies showed that they reduce urinary calcium. A recent large prospective study found that bisphosphonates may reduce the risk of kidney stones in individuals who have low bone density. In addition to lowering urinary calcium, a recent study found that bisphosphonates may act as an inhibitor in the urinary space. SUMMARY: There are multiple dietary and pharmacologic strategies that can be considered for kidney stones and bone disease, such as low salt and normal calcium diet, as well as thiazides, alkali, and bisphosphonate medications. Bisphosphonates may have an important role in reducing bone resorption and reducing overall risk of kidney stone and bone disease.

Risk Factors for Kidney Stone Formation following Bariatric Surgery.

Kidney stones are painful, common, and increasing in incidence. Obesity and bariatric surgery rates are also on the rise in the United States. Although bariatric surgery is associated with improvements in metabolic outcomes, malabsorptive bariatric surgery procedures are also associated with increased risk of kidney stones. Restrictive bariatric surgeries have not been associated with kidney-stone risk. Higher risk of kidney stones after malabsorptive procedures is associated with postsurgical changes in urine composition, including high urine oxalate, low urine citrate, and low urine volume. Certain dietary recommendations after surgery may help mitigate these urine changes and reduce risk of kidney stones. Understanding risk of kidney stones after surgery is essential to improving patient outcomes after bariatric surgery.

Menopause and Risk of Kidney Stones.

PURPOSE: Metabolic changes due to menopause may alter urine composition and kidney stone risk but results of prior work on this association have been mixed. We examined menopause and the risk of incident kidney stones, and changes in 24-hour urine composition in the NHS (Nurses' Health Study) II. MATERIALS AND METHODS: Using multivariate adjusted Cox proportional hazards models we prospectively analyzed 108,639 NHS II participants who provided information on menopause and kidney stones. We also analyzed 24-hour urine collections from 658 participants who performed a collection while premenopausal and a repeat collection after menopause. RESULTS: During 22 years of followup there were 3,456 incident kidney stones. The multivariate adjusted relative risk of an incident kidney stone in postmenopausal participants compared with premenopause was 1.27 (95% CI 1.08-1.46). On stratified analysis compared with premenopause the multivariate adjusted relative risk of natural and surgically induced menopause was 1.27 (95% CI 1.09-1.48) and 1.43 (95% CI 1.19-1.73), respectively. Among the 74,505 postmenopausal participants there was a total of 1,041 incident stone events. Compared with no hormone therapy neither current nor past use was significantly associated with kidney stone risk. Compared with premenopause the postmenopausal urine collections had lower mean calcium, citrate, phosphorus and uric acid, and higher mean volume. CONCLUSIONS: Postmenopausal status is associated with a higher risk of incident kidney stones. Natural menopause and surgical menopause are independently associated with higher risk. There are small but significant differences in urine composition between premenopausal and postmenopausal urine collections.

Relative Supersaturation of 24-Hour Urine and Likelihood of Kidney Stones.

PURPOSE: The relative supersaturation of calcium oxalate, calcium phosphate and uric acid is used clinically in kidney stone prevention. The magnitude of the association between relative supersaturation and stone risk requires further quantification. MATERIALS AND METHODS: We performed a cross-sectional study using 24-hour urine collections from the NHS (Nurses' Health Study) I and II, and HPFS (Health Professionals Follow-up Study) cohorts to quantify the association between the relative supersaturation of calcium oxalate, calcium phosphate and uric acid, and the likelihood of stone formation. RESULTS: The OR of being a stone former was 5.85 (95% CI 3.40-10.04) in NHS I, 6.38 (95% CI 3.72-11.0) in NHS II and 6.95 (95% CI 3.56-13.6) in HPFS for the highest category of calcium oxalate relative supersaturation compared with less than 1.0. The OR of being a stone former was 1.86 (95% CI 0.94-3.71) in NHS I, 4.37 (95% CI 2.68-7.10) in NHS II and 3.59 (95% CI 2.04-6.31) in HPFS for the highest category of calcium phosphate relative supersaturation compared with less than 1.0. For uric acid relative supersaturation the OR of being a stone former was 4.30 (95% CI 2.34-7.90) in NHS I and 2.74 (95% CI 1.71-4.40) in NHS II for the highest relative supersaturation category compared with less than 1.0. In HPFS the uric acid relative supersaturation was not significantly associated with the likelihood of stone formation. CONCLUSIONS: The likelihood of being a stone former increases with higher relative supersaturation of calcium oxalate and calcium phosphate in men and women, and with higher relative supersaturation of uric acid in women.

Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. RESULTS: We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). CONCLUSIONS: Low bone density is an independent risk factor for incident kidney stone and is associated with higher 24-hour urine calcium excretion. Among participants with low bone density, bisphosphonate use was associated with lower risk of incident kidney stone but was not independently associated with 24-hour urine calcium excretion.

Insights Into Nephrolithiasis From the Nurses' Health Studies.

OBJECTIVES: To review the contributions of the Nurses' Health Study (NHS) I and NHS II to understanding the role of dietary factors, beverages, body size, and urinary factors in the development of kidney stones. METHODS: We conducted a review of kidney stone-related publications of NHS I and NHS II between 1976 and 2016. RESULTS: Studies using NHS I and NHS II data have demonstrated the importance of many factors in kidney stone formation and were the first to report that higher dietary calcium was associated with a lower risk of incident kidney stones in women. Data from these cohorts were instrumental in emphasizing that nephrolithiasis is a systemic disease and suggesting that a kidney stone or shared risk factors may lead to hypertension, diabetes, and cardiovascular disease. CONCLUSIONS: Findings from the NHSs have changed the scientific understanding and the clinical practice of stone prevention and have been incorporated into widely consulted textbooks and the American Urological Association Medical Management of Kidney Stones guidelines.

"Ms. B changes doctors": using a comic and patient transition packet to engineer patient-oriented clinic handoffs (EPOCH).

BACKGROUND: Few patient-centered interventions exist to improve year-end residency clinic handoffs. AIM: Our purpose was to assess the impact of a patient-centered transition packet and comic on clinic handoff outcomes. SETTING: The study was conducted at an academic medicine residency clinic. PARTICIPANTS: Participants were patients undergoing resident clinic handoff 2011-2013 PROGRAM DESCRIPTION: Two months before the 2012 handoff, patients received a "transition packet" incorporating patient-identified solutions (i.e., a new primary care provider (PCP) welcome letter with photo, certificate of recognition, and visit preparation tool). In 2013, a comic was incorporated to stress the importance of follow-up. PROGRAM EVALUATION: Patients were interviewed by phone with response rates of 32 % in 2011, 43 % in 2012 and 36 % in 2013. Most patients who were interviewed were aware of the handoff post-packet (95 %). With the comic, more patients recalled receiving the packet (44 % 2012 vs. 64 % 2013, p< 0.001) and correctly identified their new PCP (77 % 2012 vs. 98 % 2013, p< 0.001). Among patients recalling the packet, most (70 % 2012; 65 % 2013) agreed it helped them establish rapport. Both years, fewer patients missed their first new PCP visit (43 % in 2011, 31 % in 2012 and 26 % in 2013, p< 0.001). DISCUSSION: A patient-centered transition packet helped prepare patients for clinic handoffs. The comic was associated with increased packet recall and improved follow-up rates.

Results of an enhanced clinic handoff and resident education on resident patient ownership and patient safety.

PURPOSE: Although internal medicine resident clinic handoffs present risks for patients, few interventions exist. The authors evaluated an enhanced handoff. METHOD: In 2011, the authors formalized a handoff protocol including a standardized sign-out process, resident education, improved scheduling, and time to establish care through telephone visits. The authors surveyed 25 residents in 2011 and 19 in 2010 regarding their perceptions and performed chart audits to examine patient outcomes. RESULTS: Compared with 2010, residents in 2011 reported longer handoffs (>20 minutes, 52% versus 6%, P<.01), more verbal handoffs (80% versus 38%, P<.01), more patients aware of the handoff (100% versus 74%, P=.01), less discomfort with paperwork for patients not yet seen (40% versus 74%, P=.03), and more ownership of patients before the first visit (56% versus 26%, P=.05). In 2011, more patients saw their correct primary care provider (82% versus 44%, P<.01), and more tests were followed up appropriately (67% versus 46%, P=.02). The authors detected in 2011 a trend for patients to be seen the month their physician intended (40% versus 33%, P=.06) and a trend toward fewer acute (hospital and emergency department) visits three months post handoff (20% versus 26%, P=.06). CONCLUSIONS: Enhancing clinic handoffs can improve the handoff process, increase the likelihood of patients seeing the correct primary care provider within the target time frame, reduce missed tests, and possibly reduce acute visits.

Outcomes for resident-identified high-risk patients and resident perspectives of year-end continuity clinic handoffs.

BACKGROUND: Many patients nationwide change their primary care physician (PCP) when internal medicine (IM) residents graduate. Few studies have examined this handoff. OBJECTIVE: To assess patient outcomes and resident perspectives after the year-end continuity clinic handoff DESIGN: Retrospective cohort PARTICIPANTS: Patients who underwent a year-end clinic handoff in July 2010 and a comparison group of all other resident clinic patients from 2009-2011. PGY2 IM residents surveyed from 2010-2011. MEASUREMENTS: Percent of high-risk patients after the clinic handoff scheduled for an appointment, who saw their assigned PCP, lost to follow-up, or had an acute visit (ED or hospitalization). Perceptions of PGY2 IM residents surveyed after receiving a clinic handoff. RESULTS: Thirty graduating residents identified 258 high-risk patients. While nearly all patients (97 %) were scheduled, 29 % missed or cancelled their first new PCP visit. Only 44 % of patients saw the correct PCP and six months later, one-fifth were lost to follow-up. Patients not seen by a new PCP after the handoff were less likely to have appropriate follow-up for pending tests (0 % vs. 63 %, P<0.001). A higher mean no show rate (NSR) was observed among patients who missed their first new PCP visit (22 % vs. 16 % NSR, p<0.001) and those lost to follow-up (21 % vs. 17 % NSR, p=0.019). While 47 % of residents worried about missing important data during the handoff, 47 % reported that they do not perceive patients as "theirs" until they are seen by them in clinic. CONCLUSIONS: While most patients were scheduled for appointments after a clinic handoff, many did not see the correct resident and one-fifth were lost to follow-up. Patients who miss appointments are especially at risk of poor clinic handoff outcomes. Future efforts should improve patient attendance to their first new PCP visit and increase PCP ownership.

Problems after discharge and understanding of communication with their primary care physicians among hospitalized seniors: a mixed methods study.

BACKGROUND: Communication and coordination with primary care physicians (PCPs) is recommended to ensure safe care transitions for hospitalized older patients. Understanding patient experiences of problems after discharge can help clinical teams design more patient-centered care transitions. OBJECTIVE: To report older patients' experiences with problems after hospital discharge and investigate whether PCPs were aware of their hospitalization. DESIGN: Prospective mixed methods study. SETTING: Single academic medical center. PATIENTS: Hospitalized patients and PCPs. MEASUREMENTS: Telephone interviews of frail, older general medical patients conducted 2 weeks after discharge to elicit patient problems after discharge, such as: (1) obtaining medications, or follow-up appointments; and (2) perceptions of hospital physician communication with their PCP. For each patient interviewed, their PCP was faxed a survey 2 weeks after discharge to assess awareness of hospitalization. RESULTS: Forty-two percent (27) of patients reported 42 different post-discharge problems. The most frequently reported problems were difficulty with follow-up appointments or tests (12). Other reported problems included readmission and return to the Emergency Department (10), problems with medications (8), not-prepared for discharge (8), and hospital complications or questions (4). Thirty percent of PCPs were unaware of patient hospitalization. Patients were twice as likely to report a problem if their PCP was unaware of the hospitalization (31% PCP aware, vs. 67% PCP not aware; P < 0.05). CONCLUSION: This study suggests that many frail, older patients reported problems after discharge and were twice as likely to do so when the patient's PCP was not aware of the hospitalization. Systematic interventions to improve communication with PCPs during patient hospitalization are needed.