Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease.

SIGNIFICANCE STATEMENT: Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of ROD, but an up-to-date skeletal phenotype in CKD-associated acidosis has not been described. We comprehensively studied associations between acidosis and bone in patients with CKD using advanced methods to image the skeleton and analyze bone-tissue, along with biochemical testing. Cross-sectionally, acidosis was associated with higher markers of bone remodeling and female-specific impairments in cortical and trabecular bone quality. Prospectively, acidosis was associated with cortical expansion and trabecular microarchitectural deterioration. At the bone-tissue level, acidosis was associated with deficits in bone mineral content. Future work investigating acidosis correction on bone quality is warranted. BACKGROUND: Renal osteodystrophy is a state of impaired bone quality and strength. Metabolic acidosis (MA) is associated with alterations in bone quality including remodeling, microarchitecture, and mineralization. No studies in patients with CKD have provided a comprehensive multimodal skeletal phenotype of MA. We aim to describe the structure and makeup of bone in patients with MA in the setting of CKD using biochemistry, noninvasive imaging, and histomorphometry. METHODS: The retrospective cross-sectional analyses included 180 patients with CKD. MA was defined as bicarbonate ≤22 mEq/L. We evaluated circulating bone turnover markers and skeletal imaging with dual energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subset of 54 participants had follow-up. We assessed associations between baseline and change in bicarbonate with change in bone outcomes. Histomorphometry, microCT, and quantitative backscatter electron microscopy assessed bone biopsy outcomes in 22 participants. RESULTS: The mean age was 68±10 years, 54% of participants were male, and 55% were White. At baseline, acidotic subjects had higher markers of bone turnover, lower areal bone mineral density at the radius by dual energy x-ray absorptiometry, and lower cortical and trabecular volumetric bone mineral density and impaired trabecular microarchitecture. Over time, acidosis was associated with opposing cortical and trabecular effects: cortical expansion but trabecular deterioration. Bone-tissue analyses showed reduced tissue mineral density with increased heterogeneity of calcium distribution in acidotic participants. CONCLUSIONS: MA is associated with multiple impairments in bone quality. Future work should examine whether correction of acidosis improves bone quality and strength in patients with CKD.

Food Insecurity Is Associated With Urge Urinary Incontinence: An Analysis of the 2005-2010 National Health and Nutrition Examination Survey.

PURPOSE: Urge urinary incontinence is the involuntary leakage of urine associated with a sudden compelling urge to void. A previous study found an association between urge urinary incontinence and household income, indicating that social determinants of health may influence urge urinary incontinence. Food insecurity is a relevant social determinant of health, as a diet with bladder irritants may worsen urge urinary incontinence symptoms. This study aimed to investigate the association between urge urinary incontinence and food insecurity. MATERIALS AND METHODS: We collected data from the 2005-2010 cycles of the National Health and Nutrition Examination Survey, a nationally representative health survey administered by the Centers for Disease Control and Prevention. The association between urge urinary incontinence and food insecurity was analyzed using survey-weighed logistic regression with adjustments for demographic, socioeconomic status, behavioral, and medical comorbidities covariates. RESULTS: We included 14,847 participants with mean age 50.4±17.9 years; 22.4% of participants reported at least 1 episode of urge urinary incontinence. We found that participants who reported food insecurity had 55% greater odds of experiencing urge urinary incontinence compared to those who have not (OR=1.55, 95% CI=1.33-1.82, P < .001). When comparing diets, food-insecure participants reported significantly less intake of bladder irritants (caffeine and alcohol) compared to food-secure participants. When the sample was stratified by food insecurity status (yes vs no), consumption of caffeine did not differ by urge urinary incontinence status and consumption of alcohol was lower among participants with vs without urge urinary incontinence. CONCLUSIONS: Adults reporting food insecurity in the past year are significantly more likely to experience urge urinary incontinence than those who did not. Consumption of bladder irritants including caffeine and alcohol was significantly less in food-insecure compared to food-secure participants. When the sample was stratified by food insecurity status (yes vs no), consumption of caffeine did not differ by urge urinary incontinence status and consumption of alcohol was lower among participants with vs without urge urinary incontinence. These data indicate that diet alone does not drive the association between urge urinary incontinence and food insecurity. Instead, food insecurity may be a proxy for social inequity, perhaps the greatest driver of disease.

The relationship between fecal incontinence and food insecurity in United States women: an analysis of 2005-2010 National Health and Nutrition Examination Survey.

BACKGROUND: Fecal incontinence is a prevalent debilitating pelvic floor disorder characterized by the involuntary loss of stool. Fecal incontinence is known to be associated with constipation and loose stool, advancing age, chronic comorbidities, and previous anorectal trauma, among other biologic risk factors. The relationship between social determinants of health, such as food insecurity, and fecal incontinence is not well elucidated. OBJECTIVE: This study aimed to investigate the association between fecal incontinence and food insecurity using a nationally representative sample of US adult women. Our secondary aim was to examine the role of diet by assessing dietary differences between participants with and without fecal incontinence and between food-insecure women with and without fecal incontinence. STUDY DESIGN: This study analyzed data from the National Health and Nutrition Examination Survey, a nationally representative series of cross-sectional health surveys. Fecal incontinence was defined as accidental leakage of stool within the last 30 days. Food insecurity was assessed using the household food security measure created by the US Department of Agriculture. Dietary data from the National Health and Nutrition Examination Survey dietary interviews titled "Individual Foods, First Day" and "Individual Foods, Second Day," which estimate the foods and drinks consumed in the preceding 24 hours, were pooled. The association between fecal incontinence and food insecurity was analyzed using logistic regression after controlling for patient characteristics. RESULTS: Overall, 3216 women were included, representing nearly 130 million US women. Of these women, 10.9% had fecal incontinence. There was no significant difference in diet between women with and without fecal incontinence (p>0.05). Food-insecure women in the overall sample reported higher carbohydrate and sugar intake and lower fiber and alcohol intake (all P<.05). Among food-insecure women, those with fecal incontinence had higher calorie and total fats intake than those without fecal incontinence; there was no significant difference in other dietary components (p>0.05). There was a significant association between food insecurity and fecal incontinence, such that women with food insecurity had higher odds of fecal incontinence after adjusting for patient characteristics and diet (odds ratio, 1.76; 95% confidence interval, 1.17-2.66; P=.008). CONCLUSION: Food insecurity was associated with fecal incontinence even after accounting for diet. Understanding the role of social determinants of health in fecal incontinence symptomatology and treatment is important to potentially alleviate symptom burden and improve the quality of life in at-risk populations.

Associations between collagen X biomarker and linear growth velocity in a pediatric chronic kidney disease cohort.

BACKGROUND: Collagen X biomarker (CXM) is a novel biomarker of linear growth velocity. We investigated whether CXM correlated with measured growth velocity in children with impaired kidney function. METHODS: We used data from children aged 2 through 16 years old enrolled in the Chronic Kidney Disease in Children (CKiD) study. We assessed the association between CXM level and growth velocity based on height measurements obtained at study visits using linear regression models constructed separately by sex, with and without adjustment for CKD covariates. Linear mixed-effects models were used to capture the between-individual and within-individual CXM changes over time associated with concomitant changes in growth velocity from baseline through follow-up. RESULTS: A total of 967 serum samples from 209 participants were assayed for CXM. CXM correlated more strongly in females compared to male participants. After adjustment for growth velocity and CKD covariates, only proteinuria in male participants affected CXM levels. Finally, we quantified the between- and within-participant associations between CXM level and growth velocity. A between-participant increase of 24% and 15% in CXM level in females and males, respectively, correlated with a 1 cm/year higher growth velocity. Within an individual participant, on average, 28% and 13% increases in CXM values in females and males, respectively, correlated with a 1 cm/year change in measured growth. CONCLUSIONS: CXM measurement is potentially a valuable aid for monitoring growth in pediatric CKD. However, future research, including studies of CXM metabolism, is needed to clarify whether CXM can be a surrogate of growth in children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Reduced kidney function and hypertension in adolescents with low birth weight, NHANES 1999-2016.

BACKGROUND: Chronic kidney disease (CKD) is a major health problem, and the risk of CKD and hypertension in children born low birth weight (LBW) is under-recognized. We hypothesized that children born with LBW would have a higher prevalence of reduced kidney function and hypertension. METHODS: Using the National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study to evaluate whether LBW (< 2500 g), very low birth weight (VLBW < 1500 g), and large birth weight (BW) (> 4000 g) were associated with kidney disease using 4 different estimating equations. We used the Counahan-Barratt, updated Schwartz, CKiD-U25, and full age spectrum creatinine-based GFR estimating equations to evaluate associations between a history of LBW/VLBW/large BW and reduced kidney function (eGFR < 90 mL/min/1.73 m2) in children. We also assessed blood pressure (BP) using the old and new pediatric hypertension guidelines. RESULTS: Our analysis included 6336 children (age 12-15 years) in NHANES representing over 13 million US individuals. Using the updated Schwartz, the prevalence of reduced kidney function was 30.1% (25.2-35.6) for children born with LBW compared to 22.4% (20.5-24.3) in children with normal BW. Equations yielded different estimates of prevalence of reduced kidney function in LBW from 21.5% for Counahan-Barratt to 35.4% for CKiD-U25. Compared to those with normal BW, participants with LBW and VLBW had a 7.2 and 10.3% higher prevalence of elevated BP and a 2.4 and 14.6% higher prevalence of hypertension, respectively. CONCLUSIONS: Children born with LBW are at higher risk of reduced kidney function and hypertension than previously described. A higher resolution version of the Graphical abstract is available as Supplementary information.

Association of GSTM1 Deletion With Progression of CKD in Children: Findings From the Chronic Kidney Disease in Children (CKiD) Study.

RATIONALE & OBJECTIVE: Loss of function of the product of the GSTM1 gene has been implicated in rapid progression of adult chronic kidney disease (CKD). Its role in pediatric CKD has not been previously described. STUDY DESIGN: Secondary analysis of a prospective observational cohort examining the association between deletions in GSTM1 and progression of CKD. SETTING & PARTICIPANTS: We used data and samples from the prospective Chronic Kidney Disease in Children (CKiD) cohort aged 1-16 years at enrollment with CKD. EXPOSURE: We defined the exposure as fewer than 2 GSTM1 alleles on real-time polymerase chain reaction amplification. OUTCOME: The primary outcome was a composite of 50% decrease in estimated glomerular filtration rate (eGFR) or start of kidney replacement therapy. Secondary outcomes included remission of proteinuria in children with glomerular disease and cardiovascular complications. ANALYTICAL APPROACH: The primary analysis was by Cox proportional hazards model. Analysis was adjusted for age, sex, race, ethnicity, body mass index category, diagnosis category, and eGFR. RESULTS: The analysis included 674 children. Their mean age at most recent visit was 11.9 years; 61% were male, and 20% were Black. There were 241 occurrences of the primary outcome at the time of analysis. After adjustment for baseline characteristics, the risk of progression of CKD for exposed children was 1.94 (95% CI, 1.27-2.97). The effect size was similar with either 1 or 2 deletions (autosomal dominant inheritance). The relationships between number of functional GSTM1 alleles and prespecified secondary outcomes were not statistically significant after adjustment. LIMITATIONS: Missing data, especially for secondary outcomes, and relatively small sample size compared to genetic studies in adults. CONCLUSIONS: GSTM1 deletion is associated with more rapid progression of pediatric CKD after adjustment in this large prospective cohort. No statistically significant associations were seen with secondary outcomes. If replicated, these findings may inform development of interventions for CKD in children.

Female Sexual Dysfunction as Measured by Low Sexual Frequency is Associated With Lower Socioeconomic Status: An Analysis of the National Health and Nutrition Examination Survey (NHANES), 2007-2016.

BACKGROUND: Female sexual dysfunction (FSD) is a complex disorder of biopsychosocial etiology, and FSD symptoms affect more than 40% of adult women worldwide. AIM: In this cross-sectional study, we sought to investigate the association between FSD and socioeconomic status (SES) in a nationally representative female adult population. METHODS: Economic and sexual data for women aged 20-59 from the 2007-2016 National Health and Nutrition Examination Survey, a United States nationwide representative database, was analyzed. Poverty income ratio (PIR), a ratio of family income to poverty threshold, was used as a measure of SES, and low sexual frequency was used as a measure of FSD. The association between FSD and SES was analyzed using survey-weighted logistic regression after adjusting for relevant social and gynecologic covariates, such as marital status and history of pregnancy, as well as significant medical comorbidities. OUTCOMES: We found that FSD, as measured by low sexual frequency, was associated with lower SES. RESULTS: Among the 7,348 women of mean age 38.4 (IQR 29-47) included in the final analysis, 26.3% of participants reported sexual frequency of 0-11 times/year and 73.7% participants reported sexual frequency >11 times/year. Participants of PIR <2 were 92% more likely to report sexual frequency ≤11 times/year than those of PIR ≥2 after adjusting for demographics, social history, gynecologic history and significant medical conditions (OR = 1.92; 95% CI = 1.21-3.05; P < .006). CLINICAL IMPLICATIONS: The evaluation and treatment of FSD may benefit from a comprehensive approach that takes SES into account. STRENGTHS & LIMITATIONS: This study is limited by its cross-sectional design, but it is strengthened by a large, nationally representative sample with extensive, standardized data ascertainment. CONCLUSION: Lower SES and lower sexual frequency are directly correlated among female adults in the United States; future studies should focus on social determinants of health as risk factors for FSD. Kim JI, Zhu D, Davila J, et al. Female Sexual Dysfunction as Measured by Low Sexual Frequency is Associated With Lower Socioeconomic Status: An Analysis of the National Health and Nutrition Examination Survey (NHANES), 2007-2016. J Sex Med 2022;19:90-97.

Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19.

BACKGROUND: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). METHODS: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. RESULTS: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. CONCLUSIONS: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

Effects of long-term vitamin D and n-3 fatty acid supplementation on inflammatory and cardiac biomarkers in patients with type 2 diabetes: secondary analyses from a randomised controlled trial.

AIMS/HYPOTHESIS: Interventions that reduce inflammation may delay progression of microvascular and macrovascular complications in diabetes. We examined the effects of vitamin D3 and/or n-3 fatty acid supplementation vs placebo on 5 year changes in serum inflammatory and cardiac biomarkers in adults with type 2 diabetes. METHODS: This study reports pre-specified secondary outcomes of the Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease, in which 1312 US adults with type 2 diabetes and without known cardiovascular disease, malignancy, or end-stage kidney disease were randomised using computer-generated random numbers in blocks of eight to vitamin D3 (2000 IU/day) vs placebo and n-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]; 1 g/day) vs placebo in a 2 × 2 factorial design. Participants, examiners, and researchers assessing outcomes were blinded to intervention assignment. We measured serum IL-6, high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and after 2 and 5 years. RESULTS: A total of 333 participants were randomised to vitamin D3 and placebo n-3 fatty acids, 289 to n-3 fatty acids and placebo vitamin D3, 370 to vitamin D3 and n-3 fatty acids, and 320 to 2 placebos; 989 (75%) and 934 (71%) participants returned blood samples at 2 and 5 years, respectively. Participants had a mean age of 67.6 years (46% women). Overall, baseline geometric means of IL-6, hsCRP and NT-proBNP were 1.2 pg/ml, 1.9 mg/l and 262 ng/l, respectively. After 5 years, mean IL-6 and hsCRP remained within 6% of their baseline values while mean NT-proBNP increased by 55% overall. Compared with placebo, participants assigned to vitamin D3 had a 1.24-fold greater increase in NT-proBNP over 5 years (95% CI 1.09, 1.41; p = 0.003), while IL-6 and hsCRP did not have a significant difference in change. Comparing n-3 fatty acids with placebo, there was no significant difference in change in IL-6, hsCRP or NT-proBNP. No heterogeneity was observed in subgroup analyses accounting for baseline eGFR, urine albumin to creatinine ratio, initial biomarker concentration, 25-hydroxyvitamin D level or EPA+DHA index. CONCLUSIONS/INTERPRETATION: Among adults with type 2 diabetes, supplementation with vitamin D3 or n-3 fatty acids did not reduce IL-6, hsCRP or NT-proBNP over 5 years. TRIAL REGISTRATION: ClinicalTrials.gov NCT01684722 FUNDING: The study was funded by grant R01DK088762 from the National Institute of Diabetes and Digestive and Kidney Diseases. Graphical abstract.

Associations of Serum Calciprotein Particle Size and Transformation Time With Arterial Calcification, Arterial Stiffness, and Mortality in Incident Hemodialysis Patients.

RATIONALE & OBJECTIVE: Characteristics of the transformation of primary to secondary calciprotein particles (CPPs) in serum, including the size of secondary CPP (CPP2) aggregates and the time of transformation (T50), may be markers for arterial calcification in patients undergoing hemodialysis (HD). We examined the associations of CPP2 aggregate size and T50 with arterial calcification in incident HD patients. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Incident HD patients (n=402with available CPP2 measures and n=388with available T50 measures) from the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) Study PREDICTORS: Serum CPP2 size and T50 at baseline. OUTCOMES: Primary outcomes were baseline coronary artery and thoracic aorta calcifications. Exploratory outcomes included baseline arterial stiffness, measured by pulse wave velocity (PWV) and ankle brachial index, and longitudinally, repeat measures of PWV and all-cause mortality. ANALYTICAL APPROACH: Tobit regression, multiple linear regression, Poisson regression, linear mixed-effects regression, and Cox proportional hazards regression. RESULTS: Mean age was 55±13 years, 41% were women, 71% were Black, and 57% had diabetes mellitus. Baseline CPP2 size and T50 were correlated with baseline fetuin A level (r=-0.59 for CPP2 and 0.44 for T50; P<0.001 for both), but neither was associated with baseline measures of arterial calcification or arterial stiffness. Baseline CPP2 size and T50 were not associated with repeat measures of PWV. During a median follow-up of 3.5 (IQR, 1.7-6.2) years, larger CPP2 was associated with higher risk for mortality (HR, 1.17 [95% CI, 1.05-1.31] per 100nm larger CPP2 size) after adjusting for demographics and comorbid conditions, but there was no association between baseline T50 and risk for mortality. LIMITATIONS: Possible imprecision in assays, small sample size, limited generalizability to incident HD populations with different racial composition, and residual confounding. CONCLUSIONS: In incident HD patients, neither CPP2 size nor T50 was associated with prevalent arterial calcification and stiffness. Larger CPP2 was associated with risk for mortality, but this finding needs to be confirmed in future studies.

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States.

RATIONALE & OBJECTIVE: Underlying kidney disease is an emerging risk factor for more severe coronavirus disease 2019 (COVID-19) illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing chronic kidney disease (CKD) and investigated the association between the degree of underlying kidney disease and in-hospital outcomes. STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 4,264 critically ill patients with COVID-19 (143 patients with pre-existing kidney failure receiving maintenance dialysis; 521 patients with pre-existing non-dialysis-dependent CKD; and 3,600 patients without pre-existing CKD) admitted to intensive care units (ICUs) at 68 hospitals across the United States. PREDICTOR(S): Presence (vs absence) of pre-existing kidney disease. OUTCOME(S): In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/cardiac arrest, thromboembolic events, major bleeds, and acute liver injury (secondary). ANALYTICAL APPROACH: We used standardized differences to compare patient characteristics (values>0.10 indicate a meaningful difference between groups) and multivariable-adjusted Fine and Gray survival models to examine outcome associations. RESULTS: Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median of 4 [IQR, 2-9] days for maintenance dialysis patients; 7 [IQR, 3-10] days for non-dialysis-dependent CKD patients; and 7 [IQR, 4-10] days for patients without pre-existing CKD). More dialysis patients (25%) reported altered mental status than those with non-dialysis-dependent CKD (20%; standardized difference=0.12) and those without pre-existing CKD (12%; standardized difference=0.36). Half of dialysis and non-dialysis-dependent CKD patients died within 28 days of ICU admission versus 35% of patients without pre-existing CKD. Compared to patients without pre-existing CKD, dialysis patients had higher risk for 28-day in-hospital death (adjusted HR, 1.41 [95% CI, 1.09-1.81]), while patients with non-dialysis-dependent CKD had an intermediate risk (adjusted HR, 1.25 [95% CI, 1.08-1.44]). LIMITATIONS: Potential residual confounding. CONCLUSIONS: Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies in this vulnerable population.

Associations between Socioeconomic Status and Urge Urinary Incontinence: An Analysis of NHANES 2005 to 2016.

PURPOSE: Urge urinary incontinence significantly impacts quality of life. We investigated the association between urge urinary incontinence and socioeconomic status in a nationally representative adult population. MATERIALS AND METHODS: We analyzed the 2005 to 2016 NHANES (National Health and Nutrition Examination Survey), a United States population based, cross-sectional study. Urge urinary incontinence was determined by self-report of leaking urine before reaching the toilet. Socioeconomic status was represented by the poverty income ratio, which reflects the family income relative to poverty thresholds specific to that year and household size. Survey weighted logistic regression models were used to analyze the relationship between socioeconomic status and the poverty income ratio. Multiplicative terms were applied to test for interaction in prespecified subgroups of interest. RESULTS: A total of 25,553 participants were included in the final analysis, representing 180 million people in the United States. Of the participants 19.4% reported any urge urinary incontinence, 4.2% reported weekly urge urinary incontinence and 1.6% reported daily urge urinary incontinence. In the fully adjusted multivariable models those with a poverty income ratio less than 2.00 showed significantly higher odds of any urge urinary incontinence compared to the group with a poverty income ratio of 2.00 or greater (OR 1.17, 95% CI 1.05-1.30, p=0.003). There was increasing strength of association for weekly and daily urge urinary incontinence (OR 1.31, 95% CI 1.12-1.55, p <0.001, and OR 1.60, 95% CI 1.23-2.09, p=0.001, respectively). Individual interaction analyses revealed no significant effect of female gender, age greater than 50 years, body mass index 30 kg/m2 or greater, or less than a high school education on the association of urge urinary incontinence with the poverty income ratio. CONCLUSIONS: This study revealed a significant association between urge urinary incontinence and socioeconomic status after meaningful adjustment for covariates. Health care interventions targeting low socioeconomic status individuals with urge urinary incontinence are needed to address this disparity.

Vitamin D in chronic kidney disease: is there a role outside of PTH control?

PURPOSE OF REVIEW: Vitamin D deficiency is common in patients with kidney disease and many patients receive vitamin D supplementation. Several large, well-designed clinical trials have been published in the last few years evaluating the effects of vitamin D supplementation on important outcomes for patients with kidney disease including effects on cardiovascular disease, secondary hyperparathyroidism, and kidney disease progression. RECENT FINDINGS: Several negative trials have been published showing no effect of cholecalciferol supplementation on cardiovascular events, kidney disease progression, and albuminuria. Long-term supplementation does not appear to be associated with kidney stone disease. Vitamin D supplementation decreases parathyroid hormone (PTH) levels and high levels of 25-hydroxyvitamin D may be required for maximal suppression. SUMMARY: There appear to be no effects of vitamin D supplementation on noncalcemic outcomes including progression of kidney disease, albuminuria, or cardiovascular disease. The primary reason to use vitamin D in kidney disease remains to lower PTH levels.

Effects of Sodium Bicarbonate in CKD Stages 3 and 4: A Randomized, Placebo-Controlled, Multicenter Clinical Trial.

RATIONALE & OBJECTIVE: Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes. STUDY DESIGN: Multicenter, randomized, placebo-controlled, clinical trial. SETTING & PARTICIPANTS: 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY. INTERVENTION: Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n=74) or identical-appearing placebo (n=75). OUTCOMES: Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months. RESULTS: Mean baseline serum bicarbonate level was 24.0±2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3±11.2mL/min/1.73m2. Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4±2.2, 25.5±2.3, 25.6±2.6, and 24.4±2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P<0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P=0.1; and 10 repetitions P=0.07) or bone mineral density (P=0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P=0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups. LIMITATIONS: Initial mean serum bicarbonate level was in the normal range. CONCLUSIONS: Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function. FUNDING: National Institutes of Health grant. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01452412.

Community Racial Composition and Hospitalization Among Patients Receiving In-Center Hemodialysis.

RATIONALE & OBJECTIVE: Community racial composition has been shown to be associated with mortality in patients receiving maintenenance dialysis. It is unclear whether living in communities with predominantly Black residents is also associated with risk for hospitalization among patients receiving hemodialysis. STUDY DESIGN: Retrospective analysis of prospectively collected data from a cohort of patients receiving hemodialysis. SETTING & PARTICIPANTS: 4,567 patients treated in 154 dialysis facilities located in 127 unique zip codes and enrolled in US Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 5 (2010-2015). EXPOSURE: Tertile of percentage of Black residents within zip code of patients' dialysis facility, defined through a link to the American Community Survey. OUTCOME: Rate of hospitalizations during the study period. ANALYTIC APPROACH: Associations of patient-, facility-, and community-level variables with community's percentage of Black residents were assessed using analysis of variance, Kruskal-Wallis, or χ2/Fisher exact tests. Negative binomial regression was used to estimate the incidence rate ratio for hospitalizations between these communities, with and without adjustment for potential confounding variables. RESULTS: Mean age of study patients was 62.7 years. 53% were White, 27% were Black, and 45% were women. Median and threshold percentages of Black residents in zip codes in which dialysis facilities were located were 34.2% and≥14.4% for tertile 3 and 1.0% and≤1.8% for tertile 1, respectively. Compared with those in tertile 1 facilities, patients in tertile 3 facilities were more likely to be younger, be Black, live in urban communities with lower socioeconomic status, have a catheter as vascular access, and have fewer comorbid conditions. Patients dialyzing in communities with the highest tertile of Black residents experienced a higher adjusted rate of hospitalization (adjusted incidence rate ratio, 1.32; 95% CI, 1.12-1.56) compared with those treated in communities within the lowest tertile. LIMITATIONS: Potential residual confounding. CONCLUSIONS: The risk for hospitalization for patients receiving maintenance dialysis is higher among those treated in communities with a higher percentage of Black residents after adjustment for dialysis care, patient demographics, and comorbid conditions. Understanding the cause of this association should be a priority of future investigation.

Association between dietary zinc intake and abdominal aortic calcification in US adults.

BACKGROUND: In animal studies, zinc supplementation inhibited phosphate-induced arterial calcification. We tested the hypothesis that higher intake of dietary zinc was associated with lower abdominal aortic calcification (AAC) among adults in the USA. We also explored the associations of AAC with supplemental zinc intake, total zinc intake and serum zinc level. METHODS: We performed cross-sectional analyses of 2535 participants from the National Health and Nutrition Examination Survey 2013-14. Dietary and supplemental zinc intakes were obtained from two 24-h dietary recall interviews. Total zinc intake was the sum of dietary and supplemental zinc. AAC was measured using dual-energy X-ray absorptiometry in adults ≥40 years of age and quantified using the Kauppila score system. AAC scores were categorized into three groups: no AAC (AAC = 0, reference group), mild-moderate (AAC >0-≤6) and severe AAC (AAC >6). RESULTS: Dietary zinc intake (mean ± SE) was 10.5 ± 0.1 mg/day; 28% had AAC (20% mild-moderate and 8% severe), 17% had diabetes mellitus and 51% had hypertension. Higher intake of dietary zinc was associated with lower odds of having severe AAC. Per 1 mg/day higher intake of dietary zinc, the odds of having severe AAC were 8% lower [adjusted odds ratio 0.92 (95% confidence interval 0.86-0.98), P = 0.01] compared with those without AAC, after adjusting for demographics, comorbidities and laboratory measurements. Supplemental zinc intake, total zinc intake and serum zinc level were not associated with AAC. CONCLUSIONS: Higher intake of dietary zinc was independently associated with lower odds of having severe AAC among noninstitutionalized US adults.

Metabolic Acidosis 1 Year Following Kidney Transplantation and Subsequent Cardiovascular Events and Mortality: An Observational Cohort Study.

RATIONALE & OBJECTIVE: Recent studies suggest that metabolic acidosis is associated with mortality and graft failure in kidney transplant recipients. However, it is unknown whether serum bicarbonate (measured as total carbon dioxide [tCO2] in serum) levels predict cardiovascular events (CVEs) following kidney transplantation. STUDY DESIGN: Observational cohort study. SETTINGS & PARTICIPANTS: Single-center study of 2,128 kidney transplant recipients free of CVEs during the first 13.5 months following transplantation. PREDICTOR: tCO2 level at 1 year posttransplantation. OUTCOMES: Ischemic, arrhythmic, and heart failure CVEs and death from any cause. ANALYTICAL APPROACH: Independent associations were assessed using multivariable proportional hazards regression models. Restricted cubic spline Poisson models were used to explore nonlinear associations. Linear spline proportional hazards models were used to assess associations at different tCO2 levels. RESULTS: The prevalence of metabolic acidosis defined as tCO2 level < 24 mEq/L was 38.8% (n=826). There were 384 recipients with a CVE and 610 deaths during a median follow-up of 4.0 years. CVEs included 241 ischemic, 137 arrhythmic, and 150 heart failure events. tCO2 level < 20 mEq/L was associated with increased risk for CVEs (adjusted HR [aHR], 2.00; 95% CI, 1.29-3.10) compared to the reference category of tCO2 level of 24.0 to 25.9 mEq/L. This association was primarily due to ischemic CVEs (aHR, 2.28; 95% CI, 1.34-3.90). For every 1 mEq/L lower tCO2 level for those with tCO2 < 24 mEq/L, risks for all CVEs and ischemic events were 17% and 15% higher, respectively (aHR for all CVEs of 0.83 [95% CI, 0.74-0.94] and aHR for ischemic CVEs of 0.85 [95% CI, 0.74-0.99]). Notably, tCO2 level < 20 mEq/L, compared to tCO2 level of 24.0 to 25.9 mEq/L, was independently associated with all-cause mortality (aHR, 1.43; 95% CI, 1.02-2.02). For every 1-mEq/L lower tCO2 level for those with tCO2 < 24 mEq/L, there was 17% higher risk for death (aHR, 0.83; 95% CI, 0.75-0.92). LIMITATIONS: Single-center observational study. CONCLUSIONS: Metabolic acidosis is an independent risk factor for ischemic CVEs after kidney transplantation. It is unknown whether correction of acidosis improves outcomes in these patients.

The association of neighborhood racial mix and ED visit count in a cohort of patients on hemodialysis.

BACKGROUND: Neighborhood racial mix is associated with dialysis facility performance metrics and mortality outcomes in patients on hemodialysis. We explored the association of neighborhood racial mix with emergency department (ED) visits in patients receiving hemodialysis. METHODS: Using Looking Glass (Montefiore's clinical database) we identified a cohort of patients on hemodialysis with an index ED visit at any of 4 Montefiore Hospital locations, between January 2013 and December 2017 and followed it for number of ED visits through December of 2017 or dropout due to death. The racial mix data for the Bronx block group of each subject's residence was derived from the Census Bureau. We then used negative binomial regression to test the association of quintile of percent of Black residents per residential block group with ED visits in unadjusted and adjusted models. To adjust further for quality offered by local dialysis facilities, with the facility zip code as the locus, we used data from the "Dialysis Compare" website. RESULTS: Three thousand nine-hundred and eighteen subjects were identified and the median number of ED visits was 3 (interquartile range (IQR) 1-7) during the study period. Subjects living in the highest quintile of percent Black residents were older, more commonly female and had lower poverty rates and higher rates of high school diplomas. Unadjusted models showed a significant association between the highest quintiles of Black neighborhood residence and count of ED visits. Fully adjusted, stratified models revealed that among males, and Hispanic and White subjects, living in neighborhoods with the highest quintiles of Black residents was associated with significantly more ED visits (p-trend =0.001, 0.02, 0.01 respectively). No association was found between dialysis facility locations' quintile of Black residents and quality metrics. CONCLUSIONS: Living in a neighborhood with a higher percentage of Black residents is associated with a higher number of ED visits in males and non-Black patients on hemodialysis.

The Role of Vitamin D in CKD Stages 3 to 4: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Deficiency of 25-hydroxyvitamin D (25[OH]D) is common in patients with chronic kidney disease stages 3 and 4 and is associated with poor outcomes. However, the evaluation and management of vitamin D deficiency in nephrology remains controversial. This article reports on the proceedings from a "controversies conference" on vitamin D in chronic kidney disease that was sponsored by the National Kidney Foundation. The report outlines the deliberations of the 3 work groups that participated in the conference. Until newer measurement methods are widely used, the panel agreed that clinicians should classify 25(OH)D "adequacy" as concentrations > 20ng/mL without evidence of counter-regulatory hormone activity (ie, elevated parathyroid hormone). The panel also agreed that 25(OH)D concentrations < 15ng/mL should be treated irrespective of parathyroid hormone level. Patients with 25(OH)D concentrations between 15 and 20ng/mL may not require treatment if there is no evidence of counter-regulatory hormone activity. The panel agreed that nutritional vitamin D (cholecalciferol, ergocalciferol, or calcifediol) should be supplemented before giving activated vitamin D compounds. The compounds need further study evaluating important outcomes that observational studies have linked to low 25(OH)D levels, such as progression to end-stage kidney disease, infections, fracture rates, hospitalizations, and all-cause mortality. We urge further research funding in this field.