Muna T. Canales

25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men

Objective: To test the hypothesis that lower 25-hydroxyvitamin D [25(OH)D] levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline. Methods: We measured 25(OH)D and assessed cognitive function using the Modified Mini-Mental State Examination (3MS) and Trail Making Test Part B (Trails B) in a cohort of 1,604 men enrolled in the Osteoporotic Fractures in Men Study and followed them for an average of 4.6 years for changes in cognitive function. Results: In a model adjusted for age, season, and site, men with lower 25(OH)D levels seemed to have a higher odds of cognitive impairment, but the test for trend did not reach significance (impairment by 3MS: odds ratio [OR] 1.84, 95% confidence interval [CI] 0.81–4.19 for quartile [Q] 1; 1.41, 0.61–3.28 for Q2; and 1.18, 0.50–2.81 for Q3, compared with Q4 [referent group; p trend = 0.12]; and impairment by Trails B: OR 1.66, 95% CI 0.98–2.82 for Q1; 0.96, 0.54–1.69 for Q2; and 1.30, 0.76–2.22 for Q3, compared with Q4 [p trend = 0.12]). Adjustment for age and education further attenuated the relationships. There was a trend for an independent association between lower 25(OH)D levels and odds of cognitive decline by 3MS performance (multivariable OR 1.41, 95% CI 0.89–2.23 for Q1; 1.28, 0.84–1.95 for Q2; and 1.06, 0.70–1.62 for Q3, compared with Q4 [p = 0.10]), but no association with cognitive decline by Trails B. Conclusion: We found little evidence of independent associations between lower 25-hydroxyvitamin D level and baseline global and executive cognitive function or incident cognitive decline.

Foods With Added Fiber Lower Serum Creatinine Levels in Patients With Chronic Kidney Disease

OBJECTIVE To determine the effect of foods with added fiber on blood urea nitrogen (BUN) and serum creatinine concentrations in patients with chronic kidney disease (CKD). DESIGN Participants were enrolled in a 6-week single-blind crossover study. SETTING Free living with partial dietary intervention. PATIENTS Thirteen CKD patients with Modification of Diet in Renal Disease formula-based estimated glomerular filtration rate (eGFR) ≤50 mL/minute/1.73 m(2) at the time of screening (5 men, 8 women; mean age, 67.0 ± 14.8 years) completed the study. INTERVENTION Patients consumed control foods (cereal, cookies, and bars) providing 1.6 g/day fiber daily for 2 weeks, followed by similar foods providing 23 g/day fiber daily for 4 weeks, incorporated into their usual diets. MAIN OUTCOME The main outcome of the study was the determination of the impact of foods with added fiber on BUN and serum creatinine levels. RESULTS Consuming foods with added fiber resulted in a 10.6% decrease in mean BUN concentration (13.8 ± 2.0 to 12.1 ± 1.8 mmol/L or 38.5 ± 5.6 to 34.0 ± 5.1 mg/dL; P < .05). Serum creatinine level decreased from a baseline value of 216 ± 26 to 201 ± 23 mmol/L (2.44 ± 0.30 to 2.27 ± 0.26 mg/dL; P < .05) after 2 weeks of fiber-containing food consumption, and remained significantly lower at 195 ± 23 mmol/L (2.21 ± 0.26 mg/dL) after 4 weeks of the intervention (P < .05). Calculated eGFR increased from a baseline value of 29.6 ± 3.5 to 31.4 ± 3.8 mL/minute/1.73 m(2) at the end of 2 weeks, and remained higher at 32.5 ± 3.6 mL/minute/1.73 m(2) after 4 weeks of fiber intervention (P < .05). CONCLUSION We conclude that increasing fiber intake in CKD patients through the consumption of foods with added fiber may reduce serum creatinine levels and improve eGFR. Additional studies are warranted to confirm these findings and to determine whether the changes are due to direct effects on kidney function.

Renal function and sleep-disordered breathing in older men

BACKGROUND Sleep-disordered breathing (SDB) is common in severe chronic kidney disease (CKD) and may contribute to morbidity and mortality in this population. However, the association between mild to moderate CKD and likelihood of SDB is uncertain. METHODS We studied 2696 men >or=65 years (mean 73.0 +/- 5.5) enrolled in the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study who had serum creatinine (SCr) measured 3.4 years prior to overnight polysomnography (PSG). CKD was expressed as quartiles of estimated glomerular filtration rate (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD) formula. SDB was assessed using the respiratory disturbance index (RDI) with >or=4% oxygen desaturation. RESULTS Mean SCr was 0.99 +/- 0.20 mg/dl; 14.8% had eGFR <60 ml/min/1.73 m(2). Median RDI was 7.4 events/hour (inter-quartile range 2.6-15.8). Lower eGFR was not associated with higher mean RDI in the unadjusted model (P for trend = 0.180). There was evidence of an interaction between eGFR and age for the prediction of RDI; an association between lower eGFR and higher RDI was evident only among men <or=72 (median) years. Among this age group, however, the association was not statistically significant after further adjustment for body mass index (BMI) (P for trend = 0.278). CONCLUSIONS In this cohort of older community-dwelling men, reduced renal function was not associated with greater evidence of SDB, except among younger old men. However, this association was largely explained by higher BMI at lower eGFR. Further prospective study in younger populations is needed to clarify our findings.

Estimated GFR and Mortality in Older Men: Are All eGFR Formulae Equal?

Background: Recently, the first estimated glomerular filtration rate (eGFR) formula specifically developed for community-dwelling older adults, the Berlin Initiative Study Equation 2 (BIS2), was reported. To date, however, no study has examined the performance of the BIS2 to predict death in older adults as compared to equations used clinically and in research. Methods: We prospectively followed 2,994 community-dwelling men (age 76.4 ± 5.6) enrolled in the MrOS Sleep Study. We calculated baseline eGFR from serum creatinine and cystatin-C using the BIS2, Chronic Kidney Disease Epidemiology (CKD-EPIcr,cysc), CKD-EPIcysc and CKD-EPIcr equations. Analyses included Cox-proportional hazards regression and net reclassification improvement (NRI) for the outcomes of all-cause and cardiovascular death. Results: Follow-up time was 7.3 ± 1.9 years. By BIS2, 42 and 11% had eGFR <60 and <45, respectively, compared to CKD-EPIcr (23 and 6%), CKD-EPIcysc (36 and 13%) and CKD-EPIcr,cysc (28 and 8%). BIS2 eGFR <45 was associated with twofold higher rate of all-cause mortality when compared to eGFR ≥75 after multivariate adjustment (HR 2.1, 95% CI 1.5-2.8). Results were similar for CKD-EPIcr,cysc <45 (HR 2.1, 95% CI 1.6-2.7) and CKD-EPIcysc <45 (HR 2.1, 95% CI 1.7-2.7) and weaker for CKD-EPIcr <45 (HR 1.5, 95% CI 1.2-2.0). In NRI analyses, when compared to CKD-EPIcr,cysc, both BIS2 and CKD-EPIcr equations more often misclassified participants with respect to mortality. We found similar results for cardiovascular death. Conclusion: The BIS2 did not outperform and the CKD-EPIcr was inferior to the cystatin C-based CKD-EPI equations to predict death in this cohort of older men. Thus, the cystatin C-based CKD-EPI equations are the formulae of choice to predict death in community-dwelling older men.

Association of Sleep Disordered Breathing with Erectile Dysfunction in Community Dwelling Older Men.

Purpose: We investigated the association between sleep disordered breathing and erectile dysfunction in older men. Materials and Methods: We performed a cross‐sectional analysis of community dwelling men age 67 years or older enrolled in the Osteoporotic Fractures in Men Sleep Study. Participants underwent overnight polysomnography (2003 to 2005) and completed sexual health questionnaires (2005 to 2006). We defined sleep disordered breathing using the apnea‐hypopnea index or nocturnal hypoxemia. Erectile dysfunction was defined using the MMAS (Massachusetts Male Aging Study) scale and, in sexually active men, the International Index of Erectile Function. We used logistic regression to examine the association between sleep disordered breathing and erectile dysfunction. Results: Mean participant age was 76±5 years. Of the 2,676 men completing the MMAS, 70% had moderate to complete erectile dysfunction. Among 1,099 sexually active men completing the IIEF‐5 (5‐item International Index of Erectile Function), 26% had moderate to severe erectile dysfunction. A higher apnea‐hypopnea index was associated with greater odds of MMAS defined moderate to complete erectile dysfunction after adjusting for age and study site (OR 1.39, 95% CI 1.00–1.92 for severe sleep disordered breathing vs none, p trend=0.008), but not after further adjustment for body mass index, socioeconomic status and comorbidities (OR 1.05, 95% CI 0.75–1.49, p trend=0.452). Greater nocturnal hypoxemia was associated with increased odds of MMAS defined moderate to complete erectile dysfunction (unadjusted OR 1.36, 95% Cl 1.04–1.80 vs none) but this was attenuated after adjustment for age and study site (OR 1.24, 95% CI 0.92–1.66). Sleep disordered breathing was not associated with erectile dysfunction by 5‐item International Index of Erectile Function. Conclusions: In this cross‐sectional analysis in older men sleep disordered breathing was associated with higher odds of erectile dysfunction in unadjusted analyses that was largely explained by higher body mass index and increased comorbidity among men with sleep disordered breathing. Prospective studies accounting for obesity and multimorbidity would further clarify the association of sleep disordered breathing and erectile dysfunction.

Association of Increased Urinary Albumin with Risk of Incident Clinical Fracture and Rate of Hip Bone Loss: The Osteoporotic Fractures in Men Study.

Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community‐dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003–2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003–2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow‐up, 20.0% of men had an incident clinical fracture. In multivariate‐adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate‐adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (–1.8% more annualized loss than in men with ACR <30 mg/g; p < 0.001), but the limited prevalence of macroalbuminuria precluded reliable estimates of its fracture associations. In these community‐dwelling older men, we found no association between urine albumin levels and risk of incident clinical fracture, but found a borderline significant, positive association with rate of hip bone loss.

Sleep Apnea and Kidney Function Trajectory: Results From a 20-Year Longitudinal Study of Healthy Middle-Aged Adults

Study Objectives To determine whether sleep apnea, defined by polysomnography, accelerates kidney function decline in generally healthy adults not selected for sleep apnea or kidney disease. Methods We performed a retrospective cohort study in 855 participants from the Wisconsin Sleep Cohort Study, a large 20-year population-based study of sleep apnea, who had at least one polysomnogram and serial measurements of serum creatinine over time. Sleep apnea was defined as an apnea-hypopnea index ≥ 15 or positive airway pressure (PAP) use at baseline. We compared the slope of estimated glomerular filtration rate (eGFR) change and odds of rapid eGFR decline (>2.2 mL/minute/1.73 m2/year) for those with and without sleep apnea. Results The mean follow-up was 13.9 ± 3.4 years. The cohort was 50.4 ± 7.6 years, 55% male, and 97% white. The mean eGFR was 89.3 ± 13.8 mL/minute/1.73 m2 and 11% had sleep apnea. Overall, the mean eGFR change was -0.88 ± 1.12 mL/minute/1.73 m2/year. Compared with those without sleep apnea, participants with sleep apnea had a 0.2 mL/minute/1.73 m2/year slower eGFR decline though this was not statistically significant (95% CI [-0.06-0.45], p = .134). When we excluded those on PAP therapy (n = 17), eGFR decline was even slower among those with sleep apnea (0.36 mL/minute/1.73 m2/year slower, 95% CI [0.08-063], p = .012). Those with sleep apnea had lower odds of rapid eGFR decline but this was not statistically significant, even after excluding PAP users. Conclusion Among healthy middle-aged adults, the presence of sleep apnea at baseline did not accelerate kidney function decline compared with those without sleep apnea over time.

Evaluating Region of Interest Measurement Strategies to Characterize Upper Urinary Tract Stones on Computerized Tomography

Purpose: Computerized tomography imaging is regularly used to assess stone HU values as a surrogate for stone composition and fragility. Techniques for measuring HU values are unstandardized, leading to high variability. We investigated several region of interest measurement strategies to quantify this variability. Materials and Methods: Patients from an institutional database who underwent preoperative computerized tomography, surgical stone extraction and stone composition analysis were identified. HU measurements were made of each patient stone using transverse/coronal slices in the abdominal/bone windows with 4 region of interest techniques, including 1) the maximum diameter region of interest, 2) the maximum diameter region of interest at all stone inclusive slices, 3) 2 equal‐sized, nonoverlapping circular regions of interest and 4) 3 to 5 smaller nonoverlapping regions of interest randomly placed on the stone. Stones that were 80% or greater pure by composition were separately analyzed. Results: A total of 172 patients were included in study. Mean ± SD stone size was 19.3 ± 15.6 mm. On subtype analysis 51 stones were calcium oxalate monohydrate, 9 were calcium oxalate dihydrate, 7 were calcium phosphate hydroxyapatite/brushite and 16 were uric acid. Mean HU values in the abdominal window for all stones identified by region of interest techniques 1 to 4 were 457 ± 253, 351 ± 210, 581 ± 363 and 587 ± 329, respectively. The distribution of means significantly differed across region of interest techniques, planes and windows when considering all stones together (p <0.0001), stones with greater than 80% calcium oxalate dihydrate (p = 0.0113) and greater than 80% calcium oxalate monohydrate (p <0.0001), and uric acid stones (p <0.0001). Conclusions: HU values obtained to assess stone density vary depending on window, plane and region of interest technique. We recommend that clinicians select a single region of interest measurement technique and use it consistently to minimize interinstitutional variability.

Age, Body Mass Index, and Gender Predict 24-Hour Urine Parameters in Recurrent Idiopathic Calcium Oxalate Stone Formers.

INTRODUCTION AND OBJECTIVE Despite guidelines, routine 24-hour urine testing is completed in <10% of high-risk, recurrent stone formers. Using surrogates for metabolic testing, such as key patient characteristics, could obviate the cost and burden of this test while providing information needed for proper stone prevention counseling. METHODS We performed a retrospective study of 392 consecutive patients from 2007 to 2014 with ≥2 lifetime stone episodes, >70% calcium oxalate by mineral analysis, and ≥1 24-hour urine collection. We compared mean 24-hour urine values by age in decades. We used logistic regression and receiver operating characteristic (ROC) curve analysis to assess the predictive ability of age, gender, body mass index (BMI), and comorbidities to detect abnormal 24-hour urine parameters. RESULTS The mean age of the cohort was 51 ± 16 years. Older age was associated with greater urinary oxalate (p-trend <0.001), lower urinary uric acid (UA) (p-trend = 0.007), and lower urinary pH (p-trend <0.001). A nonlinear association was noted between age and urinary calcium or citrate (calcium peaked at 40-49 years, p = 0.03; citrate nadired at 18-29 years, p = 0.001). ROC analysis of age, gender, and BMI to predict 24-hour urine abnormalities performed the best for hyperuricosuria (area under the curve [AUC] 0.816), hyperoxaluria (AUC 0.737), and hypocitraturia (AUC 0.740). Including diabetes mellitus or hypertension did not improve AUC significantly. CONCLUSIONS In our recurrent calcium oxalate cohort, age significantly impacted urinary calcium, oxalate, citrate, and pH. Along with gender and BMI, age can be used to predict key 24-hour urine stone risk results. These data lay the foundation for a risk prediction tool, which could be a surrogate for 24-hour urine results in recurrent stone formers, who are unwilling or unable to complete metabolic testing. Further validation of these findings is needed in other stone populations.

Renal Function and Death in Older Women: Which eGFR Formula Should We Use?

Background. The Berlin Initiative Study (BIS) eGFR equations were developed specifically for aged populations, but their predictive validity compared to standard formulae is unknown in older women. Methods. In a prospective study of 1289 community-dwelling older women (mean age 79.5 years), we compared the performance of the BIS1 SCr-based equation to the CKD-EPIcr and the BIS2 SCr- and Scysc-based equation to the CKD-EPIcr,cysc to predict cardiovascular and all-cause mortality. Results. Prevalence of specific eGFR category (i.e., ≥75, 60–74, 45–59, and <45) according to eGFR equation was 12.3%, 38.4%, 37.3%, and 12.0% for BIS1; 48.3%, 27.8%, 16.2%, and 7.8% for CKD-EPIcr; 14.1%, 38.6%, 37.6%, and 9.6% for BIS2; and 33.5%, 33.4%, 22.0%, and 11.1% for CKD-EPIcr,cysc, respectively. Over 9 ± 4 years, 667 (51.8%) women died. For each equation, women with eGFR <45 were at increased risk of mortality compared to eGFR ≥75 [adjusted HR (95% CI): BIS1, 1.5 (1.1–2.0); CKD-EPIcr, 1.7 (1.3–2.2); BIS2, 2.0 (1.4–2.8); CKD-EPIcr,cysc, 1.8 (1.4–2.3); p-trend <0.01]. Net reclassification analyses found no material difference in discriminant ability between the BIS and CKD-EPI equations. Results were similar for cardiovascular death. Conclusions. Compared to CKD-EPI, BIS equations identified a greater proportion of older women as having CKD but performed similarly to predict mortality risk. Thus, the BIS equations should not replace CKD-EPI equations to predict risk of death in older women.