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.

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.

Quality of life impact and recovery after ureteroscopy and stent insertion: insights from daily surveys in STENTS.

BACKGROUND: Our objective was to describe day-to-day evolution and variations in patient-reported stent-associated symptoms (SAS) in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS), a prospective multicenter observational cohort study, using multiple instruments with conceptual overlap in various domains. METHODS: In a nested cohort of the STENTS study, the initial 40 participants having unilateral ureteroscopy (URS) and stent placement underwent daily assessment of self-reported measures using the Brief Pain Inventory short form, Patient-Reported Outcome Measurement Information System measures for pain severity and pain interference, the Urinary Score of the Ureteral Stent Symptom Questionnaire, and Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index. Pain intensity, pain interference, urinary symptoms, and bother were obtained preoperatively, daily until stent removal, and at postoperative day (POD) 30. RESULTS: The median age was 44 years (IQR 29,58), and 53% were female. The size of the dominant stone was 7.5 mm (IQR 5,11), and 50% were located in the kidney. There was consistency among instruments assessing similar concepts. Pain intensity and urinary symptoms increased from baseline to POD 1 with apparent peaks in the first 2 days, remained elevated with stent in situ, and varied widely among individuals. Interference due to pain, and bother due to urinary symptoms, likewise demonstrated high individual variability. CONCLUSIONS: This first study investigating daily SAS allows for a more in-depth look at the lived experience after URS and the impact on quality of life. Different instruments measuring pain intensity, pain interference, and urinary symptoms produced consistent assessments of patients' experiences. The overall daily stability of pain and urinary symptoms after URS was also marked by high patient-level variation, suggesting an opportunity to identify characteristics associated with severe SAS after URS.

Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in chronic kidney disease.

Due to multiple compensating mechanisms, the serum bicarbonate concentration is a relatively insensitive marker of acid-base status; especially in chronic kidney disease (CKD). This is a major drawback that impairs the ability to diagnose acid excess or monitor alkali therapy. We postulated that it is more logical to measure the compensatory defense mechanism(s) rather than the defended parameter, which remains normal if the compensation is successful. Therefore, a retrospective cross-sectional study was performed in 1733 stone formers along with a prospective cross-sectional study of 22 individuals with normal kidney function and 50 patients in different stages of CKD. While serum bicarbonate was flat and did not fall below the reference range until near CKD stage 5, citrate excretion (24-hour urinary citrate excretion rate; urinary citrate-to-creatinine ratio, in the retrospective analysis, and spot urinary citrate-to-creatinine ratio in the prospective study) progressively and significantly declined starting from CKD stage 2. Following an acute acid load in 25 participants with a wide range of estimated glomerular filtration rates, the urinary citrate-to-creatinine ratio inversely and significantly associated with acid accumulation, whereas serum bicarbonate did not. We compared changes in serum bicarbonate and urinary citrate-to-creatinine ratio in response to alkali therapy in patients with CKD stage 3 or 4 started on potassium citrate in our kidney stone database. With alkali therapy, there was no change in serum bicarbonate, but the urinary citrate-to-creatinine ratio rose consistently in all patients adherent to potassium citrate therapy. Thus, the urinary citrate-to-creatinine ratio (the defense mechanism) is a potential easily implementable, pragmatic, and a superior parameter to serum bicarbonate (the defended entity) to assess acid-base status, and monitor alkali therapy. Additional studies are needed before a clinical test can be devised.

Disparities in Kidney Stone Disease: A Scoping Review.

PURPOSE: We reviewed the available evidence regarding health disparities in kidney stone disease to identify knowledge gaps in this area. MATERIALS AND METHODS: A literature search was conducted using PubMed®, Embase® and Scopus® limited to articles published in English from 1971 to 2020. Articles were selected based on their relevance to disparities in kidney stone disease among adults in the United States. RESULTS: Several large epidemiological studies suggest disproportionate increases in incidence and prevalence of kidney stone disease among women as well as Black and Hispanic individuals in the United States, whereas other studies of comparable size do not report racial and ethnic demographics. Numerous articles describe disparities in imaging utilization, metabolic workup completion, analgesia, surgical intervention, stone burden at presentation, surgical complications, followup, and quality of life based on race, ethnicity, socioeconomic status and place of residence. Differences in urinary parameters based on race, ethnicity and socioeconomic status may be explained by both dietary and physiological factors. All articles assessed had substantial risk of selection bias and confounding. CONCLUSIONS: Health disparities are present in many aspects of kidney stone disease. Further research should focus not only on characterization of these disparities but also on interventions to reduce or eliminate them.

Prevention of Urinary Stones With Hydration (PUSH): Design and Rationale of a Clinical Trial.

RATIONALE & OBJECTIVE: Although maintaining high fluid intake is an effective low-risk intervention for the secondary prevention of urinary stone disease, many patients with stones do not increase their fluid intake. STUDY DESIGN: We describe the rationale and design of the Prevention of Urinary Stones With Hydration (PUSH) Study, a randomized trial of a multicomponent behavioral intervention program to increase and maintain high fluid intake. Participants are randomly assigned (1:1 ratio) to the intervention or control arm. The target sample size is 1,642 participants. SETTING & PARTICIPANTS: Adults and adolescents 12 years and older with a symptomatic stone history and low urine volume are eligible. Exclusion criteria include infectious or monogenic causes of urinary stone disease and comorbid conditions precluding increased fluid intake. INTERVENTIONS: All participants receive usual care and a smart water bottle with smartphone application. Participants in the intervention arm receive a fluid intake prescription and an adaptive program of behavioral interventions, including financial incentives, structured problem solving, and other automated adherence interventions. Control arm participants receive guideline-based fluid instructions. OUTCOMES: The primary end point is recurrence of a symptomatic stone during 24 months of follow-up. Secondary end points include changes in radiographic stone burden, 24-hour urine output, and urinary symptoms. LIMITATIONS: Periodic 24-hour urine volumes may not fully reflect daily behavior. CONCLUSIONS: With its highly novel features, the PUSH Study will address an important health care problem. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03244189.

Uric acid stone disease: lessons from recent human physiologic studies.

PURPOSE OF REVIEW: An overly acidic urine resulting in supersaturation of urine with respect to uric acid is the major mechanism responsible for uric acid nephrolithiasis. The present review summarizes findings from recent human physiologic studies examining the pathophysiology and reversibility of low urine pH in uric acid stone formers. RECENT FINDINGS: Epidemiologic and metabolic studies have confirmed an increase in the prevalence of uric acid nephrolithiasis and reported its association with several features of the metabolic syndrome including dyslipidemia, hyperglycemia, hepatic steatosis, and greater visceral adiposity. Physiologic studies in uric acid stone formers have identified diet-independent excessive net acid excretion and concomitant reduction in urinary buffering from impaired renal ammoniagenesis as the two causes underlying the greater aciduria. Administration of the insulin sensitizer pioglitazone to uric acid stone formers reduced the acid load presented to the kidney and enhanced ammoniagenesis and ammonium excretion, resulting in significantly higher urine pH. SUMMARY: Recent human physiologic studies have identified greater acid excretion and reduced urinary buffering by ammonia as two culprits of aciduria in uric acid nephrolithiasis that can be reversed by pioglitazone, raising new questions regarding the origin of the aciduria and opening the door to pathophysiology-based treatment of uric acid stones.

Increased production and reduced urinary buffering of acid in uric acid stone formers is ameliorated by pioglitazone.

Idiopathic uric acid nephrolithiasis is characterized by an overly acidic urine pH caused by the combination of increased acid production and inadequate buffering of urinary protons by ammonia. A large proportion of uric acid stone formers exhibit features of the metabolic syndrome. We previously demonstrated that thiazolidinediones improved the urinary biochemical profile in an animal model of the metabolic syndrome. In this proof-of-concept study, we examined whether the thiazolidinedione pioglitazone can also ameliorate the overly acidic urine in uric acid stone formers. Thirty-six adults with idiopathic uric acid nephrolithiasis were randomized to pioglitazone 30 mg/day or matching placebo for 24 weeks. At baseline and study end, participants underwent collection of blood and 24-hour urine in an inpatient research unit while consuming a fixed metabolic diet, followed by assessment of the ammoniagenic response to an acute oral acid load. Twenty-eight participants completed the study. Pioglitazone treatment improved features of the metabolic syndrome. Pioglitazone also reduced net acid excretion and increased urine pH (5.37 to 5.59), the proportion of net acid excreted as ammonium, and ammonium excretion in response to an acute acid load, whereas these parameters were unchanged with placebo. Treatment of patients with idiopathic uric acid nephrolithiasis with pioglitazone for 24 weeks led to a reduction in the acid load presented to the kidney and a more robust ammoniagenesis and ammonium excretion, resulting in significantly higher urine pH. Future studies should consider the impact of this targeted therapy on uric acid stone formation.

Citrate therapy for calcium phosphate stones.

PURPOSE OF REVIEW: Calcium phosphate (CaP) stones represent an increasingly encountered form of recurrent nephrolithiasis, but current prophylactic medical regimens are suboptimal. Although hypocitraturia is a well-described risk factor for CaP stones, strategies that enhance citrate excretion have not consistently been effective at reducing CaP saturation and stone recurrence. This review summarizes the role of citrate therapy in CaP nephrolithiasis. RECENT FINDINGS: Citrate in urine inhibits CaP stone formation through multiple mechanisms, including the formation of soluble citrate-calcium complexes, and inhibition of CaP nucleation, crystal growth and crystal aggregation. Recent in-vitro studies demonstrate that citrate delays CaP crystal growth through distinct inhibitory mechanisms that depend on supersaturation and citrate concentration. The impact of pharmacological provision of citrate on CaP saturation depends on the accompanying cation: Potassium citrate imparts a significant alkali load that enhances citraturia and reduces calciuria, but could worsen urine pH elevation. Conversely, citric acid administration results in minimal citraturia and alteration in CaP saturation. SUMMARY: Citrate, starting at very low urinary concentrations, can significantly retard CaP crystal growth in vitro through diverse mechanisms. Clinically, the net impact on CaP stone formation of providing an alkali load during pharmacological delivery of citrate into the urinary environment remains to be determined.

The Differential Effects of Human Immunodeficiency Virus and Hepatitis C Virus on Bone Microarchitecture and Fracture Risk.

Background: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected individuals have a significantly greater osteoporotic fracture risk than HIV-monoinfected persons, despite the fact that HIV/HCV coinfection has not been associated with lower bone mineral density (BMD) than HIV or HCV alone. To evaluate if changes in bone microarchitecture, measured by trabecular bone score (TBS), could explain these differences, we performed a prospective, cross-sectional cohort study of virologically suppressed HIV-infected subjects, untreated HCV-infected subjects, HIV/HCV-coinfected subjects, and uninfected controls. Methods: We enrolled 532 male subjects: 57 HIV/HCV coinfected, 174 HIV infected, 123 HCV infected, and 178 controls. We conducted analysis of covariance comparing BMD and TBS between groups, controlling for age, race, body mass index, and smoking. We used linear regression to evaluate predictors of BMD and TBS and evaluated the effects of severity of HCV infection and tenofovir disoproxil fumarate use. Results: Despite both infections being associated with decreased BMD, only HCV, but not HIV, was associated with lower TBS score. Also, HIV/HCV-coinfected subjects had lower TBS scores than HIV-monoinfected, HCV-monoinfected, and uninfected subjects. Neither the use of TDF or HCV viremia nor the severity of HCV liver disease was associated with lower TBS. Conclusions: HCV infection is associated with microarchitectural changes at the lumbar spine as assessed by the low TBS score, suggesting that microstructural abnormalities underlie some of the higher fracture risk in HCV infection. TBS might improve fracture risk prediction in HCV infection.

Impact of Potassium Citrate vs Citric Acid on Urinary Stone Risk in Calcium Phosphate Stone Formers.

PURPOSE: To our knowledge no medication has been shown to be effective for preventing recurrent calcium phosphate urinary stones. Potassium citrate may protect against calcium phosphate stones by enhancing urine citrate excretion and lowering urine calcium but it raises urine pH, which increases calcium phosphate saturation and may negate the beneficial effects. Citric acid can potentially raise urine citrate but not pH and, thus, it may be a useful countermeasure against calcium phosphate stones. We assessed whether these 2 agents could significantly alter urine composition and reduce calcium phosphate saturation. MATERIALS AND METHODS: In a crossover metabolic study 13 recurrent calcium phosphate stone formers without hypercalciuria were evaluated at the end of 3, 1-week study phases during which they consumed a fixed metabolic diet and received assigned study medications, including citric acid 30 mEq twice daily, potassium citrate 20 mEq twice daily or matching placebo. We collected 24-hour urine specimens to perform urine chemistry studies and calculate calcium phosphate saturation indexes. RESULTS: Urine parameters did not significantly differ between the citric acid and placebo phases. Potassium citrate significantly increased urine pH, potassium and citrate compared to citric acid and placebo (p <0.01) with a trend toward lower urine calcium (p = 0.062). Brushite saturation was increased by potassium citrate when calculated by the relative supersaturation ratio but not by the saturation index. CONCLUSIONS: Citric acid at a dose of 60 mEq per day did not significantly alter urine composition in calcium phosphate stone formers. The long-term impact of potassium citrate on calcium phosphate stone recurrence needs to be studied further.

Association of serum magnesium with all-cause mortality in patients with and without chronic kidney disease in the Dallas Heart Study.

Background: Low serum magnesium (SMg) has been linked to increased mortality and cardiovascular disease (CVD) in the general population. We examined whether this association is similar in participants with versus without prevalent chronic kidney disease (CKD) in the multiethnic Dallas Heart Study (DHS) cohort. Methods: SMg was analyzed as a continuous variable and divided into tertiles. Study outcomes were all-cause death, cardiovascular (CV) death or event, and CVD surrogate markers, evaluated using multivariable Cox regression models adjusted for demographics, comorbidity, anthropometric and biochemical parameters including albumin, phosphorus and parathyroid hormone, and diuretic use. Median follow-up was 12.3 years (11.9-12.8, 25th percentile-75th percentile). Results: Among 3551 participants, 306 (8.6%) had prevalent CKD. Mean SMg was 2.08 ± 0.19 mg/dL (0.85 ± 0.08 mM, mean ± SD) in the CKD and 2.07 ± 0.18 mg/dL (0.85 ± 0.07 mM) in the non-CKD subgroups. During the follow-up period, 329 all-cause deaths and 306 CV deaths or events occurred. In a fully adjusted model, every 0.2 mg/dL decrease in SMg was associated with ∼20-40% increased hazard for all-cause death in both CKD and non-CKD subgroups. In CKD participants, the lowest SMg tertile was also independently associated with all-cause death (adjusted hazard ratio 2.31; 95% confidence interval 1.23-4.36 versus 1.15; 0.55-2.41; for low versus high tertile, respectively). Conclusions: Low SMg levels (1.4-1.9 mg/dL; 0.58-0.78 mM) were independently associated with all-cause death in patients with prevalent CKD in the DHS cohort. Randomized clinical trials are important to determine whether Mg supplementation affects survival in CKD patients.

Relationship between Urinary Calcium and Bone Mineral Density in Patients with Calcium Nephrolithiasis.

PURPOSE: Calcium nephrolithiasis is associated with an increased risk of osteoporosis and fracture. Hypercalciuria has been assumed to be pathogenic for bone loss in kidney stone formers, although this association was shown in small cross-sectional studies. We explored the association of urine calcium with bone mineral density in kidney stone formers. MATERIALS AND METHODS: We retrospectively studied bone mineral density in kidney stone formers. Excluded were subjects with hypercalcemia, chronic bowel disease, primary hyperparathyroidism, distal renal tubular acidosis or endogenous creatinine clearance less than 40 ml per minute. We included 250 males and 182 females subdivided into 145 who were estrogen treated and postmenopausal, and 37 who were nonestrogen treated and postmenopausal. We assessed the association of lumbar spine and femoral neck bone mineral density with 24-hour urine calcium on random and restricted diets, and while fasting using univariable and multivariable models adjusting for body mass index, urine sodium and sulfate. RESULTS: On multivariable analysis no significant association was found between urine calcium on a random or a restricted diet, or during fasting conditions and femoral neck or lumbar spine bone mineral density in men and estrogen treated women. In estrogen untreated women lumbar spine bone mineral density inversely correlated with urine calcium on the restricted diet (r = -0.38, p = 0.04 and adjusted r = -0.45, p = 0.02) and in the fasting state (r = -0.42, p = 0.05). CONCLUSIONS: Unlike in previous small cross-sectional studies we found no significant relationship between urine calcium and bone mineral density in a large group of calcium kidney stone formers. However, a significant inverse relationship was found in estrogen untreated kidney stone formers only. This study suggests that mechanism(s) other than hypercalciuria explain the lower bone mineral density and the higher fracture risk in patients who are kidney stone formers. It also highlights the role of estrogen on bone integrity.

Temporal Changes in Kidney Stone Composition and in Risk Factors Predisposing to Stone Formation.

PURPOSE: The prevalence of kidney stones has increased globally in recent decades. However, studies investigating the association between temporal changes in the risk of stone formation and stone types are scarce. We investigated temporal changes in stone composition, and demographic, serum and urinary parameters of kidney stone formers from 1980 to 2015. MATERIALS AND METHODS: We retrospectively analyzed the records of 1,516 patients diagnosed with either calcium or uric acid stones at an initial visit to a university kidney stone clinic from 1980 to 2015. RESULTS: From 1980 to 2015, the proportion of uric acid stones in all stone formers increased from 7% to 14%. While age and body mass index increased with time in both uric acid and calcium stone formers, uric acid stone formers were consistently older and had a higher body mass index and lower urinary pH than calcium stone formers. The proportion of females with stones has increased over time but the increase in female gender was more prominent among calcium stone formers. Urinary pH, phosphorus, oxalate and sodium increased with time in calcium stone formers but remained unchanged in uric acid stone formers. After accounting for various parameters of stone risk, the strongest clinical discriminant of uric acid vs calcium stones was urinary pH. Limitations of this study include the retrospective single center design and the available number of patients with stone analysis. CONCLUSIONS: From 1980 to 2015, the proportion of uric acid stones increased significantly. With time, there were proportionately more female calcium stone formers but not uric acid stone formers. Urinary pH is the most prominent factor distinguishing uric acid from calcium stones.

Longitudinal changes in serum 25-hydroxyvitamin D in the Dallas Heart Study.

CONTEXT: While the prevalence of vitamin D deficiency is well described in various populations, limited data are available regarding longitudinal variation in serum 25-hydroxyvitamin D concentrations. OBJECTIVES: To evaluate the temporal trends in serum 25(OH)D, prevalence of vitamin D deficiency and factors influencing these trends. PARTICIPANTS, DESIGN AND SETTING: Adults enrolled in the Dallas Heart Study, a longitudinal, probability-based, multiethnic, population study in Dallas, Texas, USA. MAIN OUTCOME MEASURES: Prevalence of vitamin D deficiency and predictors of change in serum 25(OH)D. RESULTS: A total of 2045 participants had serum 25(OH)D measured on two occasions (2000-2002 and 2007-2009) at a median interval of 7 years. Serum 25(OH)D decreased (42.7-39.4 nmol/L, P<.001) and the prevalence of vitamin D deficiency [25(OH)D <50 nmol/L] increased significantly (60.6%-66.4%, P<.0001) despite vitamin D supplementation increasing over the interval (7.2%-23.0%; P<.0001). In a multivariable model adjusting for sex, race, BMI, age, season of blood draw, smoking and exercise, a greater decline in serum 25(OH)D was noted in men compared with women (-8.0 vs -3.5 nmol/L, P<.0001), in participants of Hispanic ethnicity vs White and Black ethnicity (P<.0001), in nonobese vs obese participants (-7.2 vs -4.0 nmol/L, P=.005) and in nonusers vs users of vitamin D supplements (-5.7 vs -1.7 nmol/L, P=.032). CONCLUSIONS: Despite increased vitamin D supplementation, serum 25(OH)D decreased in an ethnically diverse cohort of Dallas County residents between 2000-2002 and 2007-2009. Features most predictive of a decline in serum 25(OH)D include male sex, Hispanic ethnicity and weight gain.

Effect of acute hyperinsulinemia on magnesium homeostasis in humans.

BACKGROUND: Insulin may influence magnesium homeostasis through multiple mechanisms. Acutely, it stimulates the shift of magnesium from plasma into red blood cells and platelets, and in vitro, it stimulates the activity of the TRPM6 channel, a key regulator of renal magnesium reabsorption. We investigated the impact of hyperinsulinemia on magnesium handling in participants with a wide range of insulin sensitivity. METHOD: Forty-seven participants were recruited, including 34 nondiabetic controls and 13 with type 2 diabetes mellitus. After stabilization under fixed metabolic diet, participants underwent hyperinsulinemic-euglycemic clamp. Serum and urine samples were collected before and during hyperinsulinemia. Change in serum magnesium, urinary magnesium to creatinine (Mg2+ :Cr) ratio, fractional excretion of urinary magnesium (FEMg2+ ), and estimated transcellular shift of magnesium were compared before and during hyperinsulinemia. RESULTS: Hyperinsulinemia led to a small but statistically significant decrease in serum magnesium, and to a shift of magnesium into the intracellular compartment. Hyperinsulinemia did not significantly alter urinary magnesium to creatinine ratio or fractional excretion of urinary magnesium in the overall population, although a small but statistically significant decline in these parameters occurred in participants with diabetes. There was no significant correlation between change in fractional excretion of urinary magnesium and body mass index or insulin sensitivity measured as glucose disposal rate. CONCLUSIONS: In human participants, acute hyperinsulinemia stimulates the shift of magnesium into cells with minimal alteration in renal magnesium reabsorption, except in diabetic patients who experienced a small decline in fractional excretion of urinary magnesium. The magnitude of magnesium shift into the intracellular compartment in response to insulin does not correlate with that of insulin-stimulated glucose entry into cells.

Adiponectin protects against incident hypertension independent of body fat distribution: observations from the Dallas Heart Study.

BACKGROUND: Excess adipose tissue has been implicated in the pathogenesis of insulin resistance and atherosclerosis and is a key risk factor for blood pressure (BP) elevation. However, circulating levels of adiponectin, a protein produced by adipose tissue and widely implicated in the pathogenesis of insulin resistance and atherosclerosis, are inversely proportional to adiposity. The relationship between adiponectin and incident hypertension has not been determined in the general US population. METHODS: Normotensive participants (n = 1233) enrolled in the Dallas Heart Study, a multiethnic, probability-based population sample of Dallas County adults were followed for median of 7 years. Retroperitoneal, intraperitoneal, visceral, and subcutaneous adipose tissue were measured at baseline by magnetic resonance imaging. Liver fat content was measured by 1 H-magnetic resonance spectroscopy. Relative risk regression was used to determine the association of adiponectin with incident hypertension after adjustment for age, race, sex, BMI, smoking, diabetes, baseline systolic BP, total cholesterol, and regional fat depot. RESULTS: Of the 1233 study participants (median age 40 years, 40% black, and 56% women), 391 (32%) had developed hypertension over a median follow-up of 7 years. Adiponectin levels were associated with reduced risk of incident hypertension (RR 0.81, 95% CI [0.68-0.96]) in the fully adjusted model, which included liver fat. Similar results were observed after adjustment for subcutaneous or visceral fat depots when tested individually or simultaneously in the model. CONCLUSION: Our study suggested a protective role of adiponectin against incident hypertension independent of body fat distribution.

Skeletal Fluorosis Due to Fluorocarbon Inhalation from an Air Dust Cleaner.

Skeletal fluorosis (SF) is an osteosclerotic metabolic bone disorder caused by excessive ingestion or inhalation of fluoride. SF is extremely rare in developed countries. We report a case of SF due to inhalational abuse from a fluoride-containing air dust cleaner. A 33-year-old man with no past medical history presented with progressively worsening low back pain for 2 years. Physical examination was notable for loss of lumbar lordosis and tenderness over the lumbar spine. Radiographs were notable for uniform generalized osteosclerosis in the long bones, entire spine, rib cage, and pelvic bones, and loss of the normal lumbar curvature. DXA scan showed Z-scores of +10.7 at the lumbar spine, +6.5 at the total hip, and +1.0 at the 1/3 radius. Laboratory studies were notable for elevated serum alkaline phosphatase (334 U/L, ref: 40-129 U/L) compared to a normal value 3 years prior, suggesting acquired osteosclerosis. Serum fluoride concentration returned elevated (2.8 mg/L, ref: 0.0-0.2 mg/L). Initially, the source of fluoride excess could not be identified. At a follow-up visit, he was found inhaling from a can of an air duster hidden in an inner pocket. He admitted "huffing" 2-7 cans weekly from a fluorocarbon-containing air dust cleaner for the past 3 years to achieve a euphoric feeling, explaining the source of his SF. Fluoride inhalation can be a potential source for SF, and should be suspected in patients with acquired osteosclerosis, as inhalant abuse is increasingly practiced in many countries.