Fruit and Vegetable Intake Patterns, Kidney Failure, and Mortality in Adults with and without Chronic Kidney Disease in the United States.

BACKGROUND: Fruits and vegetables (F&Vs) are vital components of healthy diets but may be restricted in CKD to avoid high potassium intake. We previously generated F&V patterns for patients in the National Health and Nutrition Examination Survey (NHANES) and demonstrated increased prevalence of the Overall Low Intake pattern in patients with CKD. OBJECTIVE: To evaluate the association of F&V patterns (Overall Low Intake, High Unprocessed, Moderate Processed, High Ultra-Processed) with risk of kidney failure and its composite with death. METHODS: Adults in NHANES III with valid dietary data and longitudinal follow up for kidney failure and death were included. F&V patterns were identified using 24 hour dietary recalls and latent class analysis, yielding 4 patterns. Cox models were used to evaluate the prospective association between each pattern and hazard of kidney failure or a composite of kidney failure or death over up to 20 years. Models were adjusted for demographics and select comorbidities and weighted for the complex survey design. Secondary analyses evaluated serum carotenoids as objective biomarkers of F&V intake. RESULTS: Among 16,726 eligible participants in NHANES III, F&V consumption consistent with the High Ultra-Processed pattern associated with highest risk for kidney failure, but attenuated with adjustment for kidney function. The High Unprocessed pattern associated with the lowest adjusted risk for death or kidney failure combined (HR 0.73; 95% CI 0.65, 0.81 relative to Overall Low Intake). High serum carotenoids were associated with lower risk of death or kidney failure combined (HR 0.57; 95% CI 0.49, 0.65 for quartile 4 versus quartile 1). Results were similar in patients with CKD at baseline. CONCLUSIONS: Higher intake of unprocessed F&Vs associate with better outcomes in the general population and patients with CKD. Results emphasize the need to safely improve F&V intake in CKD.

Prevalence of Cognitive Impairment and Relationships with Other Factors in Patients with End Stage Kidney Disease Receiving Hemodialysis.

Despite recommendations, cognitive screening in patients with end stage kidney disease (ESKD) rarely happens, leading to underestimates of cognitive impairment (CI) prevalence and missed opportunities for intervention. We aimed to describe CI prevalence and associated factors in 100 patients receiving in-center hemodialysis aged 50 years and older. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA). Descriptive analysis techniques characterized the sample and estimated mean scores. Non-parametric and parametric tests explored relationships among MoCA scores and other patient factors. Of the 100 patients, 32% had normal cognitive function, 56% mild CI, and 12% moderate CI. Age, income, and education level significantly corelated with cognitive function in our sample. Identifying clinical factors and appropriate follow up for abnormal screening are crucial next steps in managing cognitive impairment in patients with ESKD receiving in-center hemodialysis.

Humoral immunity trends in a hemodialysis cohort following SARS-CoV-2 mRNA booster: A cohort study.

Background and Aims: Patients with end stage kidney disease on hemodialysis are vulnerable to SARS-CoV-2 infection. Current guidelines recommend boosters of SARS-CoV-2 mRNA-based vaccines. The long-term humoral response of hemodialysis patients infected with SARS-CoV-2 after receiving a booster of SARS-CoV-2 mRNA-based vaccines has been incompletely characterized. Here, we determined the long-term humoral response of hemodialysis patients to two and three doses of the Pfizer BioNTech (BNT162b2) mRNA SARS-CoV-2 vaccine and investigated the effect of postbooster SARS-CoV-2 infection on antibody levels over time. Methods: Samples were collected on a monthly basis and tested for anti-SARS-CoV-2 antibodies against anti-spike S1 domain. Thirty-five hemodialysis patients were enrolled in the original study and 27 of these received a booster. Patients were followed up to 6 months after the first two doses and an additional 7 months after the third BNT162b2 dose. Results are presented as the internationally harmonized binding antibody units (BAU/mL). Results: Antibody level significantly increased from prebooster to 2 weeks postbooster, with a median [25th, 75th percentile] rise from 52.72 [28.55, 184.7] to 6216 [3806, 11,730] BAU/mL in the total population. Of patients with a negative or borderline detectable antibody level 6 months after vaccination who received a third dose, 89% developed positive antibody levels 2 weeks postbooster. Postbooster antibody levels declined an average rate of 29% per month in infection-naïve patients. Antibody levels spiked in patients infected with SARS-CoV-2 after receiving a booster but declined rapidly. No patients infected postbooster required hospitalization. Conclusions: A third dose of BNT162b2 restores antibody levels to high levels in dialysis patients but levels decline over time. A third dose did not necessarily prevent infection, but no patients suffered severe infection or required hospitalization. SARS-CoV-2 recovered patients appear to have a blunted rise in antibody levels after a third dose. Although patients infected with SARS-CoV-2 postbooster had an immediate spike in antibody levels, these declined over time.

Longitudinal Pilot Evaluation of the Gut Microbiota Comparing Patients With and Without Chronic Kidney Disease.

OBJECTIVE: The gut microbiota contributes to metabolic diseases, such as diabetes and hypertension, but is poorly characterized in chronic kidney disease (CKD). DESIGN AND METHODS: We enrolled 24 adults within household pairs, in which at least one member had self-reported kidney disease, diabetes, or hypertension. CKD was classified based on estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine-albumin-to-creatinine ratio of ≥ 30 mg/g. Participants collected stool and dietary recalls seasonally over a year. Gut microbiota was characterized using 16s rRNA and metagenomic sequencing. RESULTS: Ten participants had CKD (42%) with a median (interquartile range) estimated glomerular filtration rate of 49 (44, 54) mL/min/1.73 m2. By 16s rRNA sequencing, there was moderate to high intraclass correlation (ICC = 0.63) for seasonal alpha diversity (Shannon index) within individuals and modest differences by season (P < .01). ICC was lower with metagenomics, which has resolution at the species level (ICC = 0.26). There were no differences in alpha or beta diversity by CKD with either method. Among 79 genera, Frisingicoccus, Tuzzerella, Faecalitalea, and Lachnoclostridium had lower abundance in CKD, while Collinsella, Lachnospiraceae_ND3007, Veillonella, and Erysipelotrichaceae_UCG_003 were more abundant in CKD (each nominal P < .05) using 16s rRNA sequencing. Higher Collinsella and Veillonella and lower Lachnoclostridium in CKD were also identified by metagenomics. By metagenomics, Coprococcus catus and Bacteroides stercoris were more and less abundant in CKD, respectively, at false discovery rate corrected P = .02. CONCLUSIONS: We identified candidate taxa in the gut microbiota associated with CKD. High ICC in individuals with modest seasonal impacts implies that follow-up studies may use less frequent sampling.

Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study.

OBJECTIVE: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age. METHODS: Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival. RESULTS: Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P=0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P=0.11), percentage predicted peak Vo2 for age and sex (74±18% [n=91] versus 72±18% [n=84]; P=0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P=0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P=0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P=0.01), but had similar rates of other complications. CONCLUSIONS: By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo2, complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT0245531.

Patterns of Fruit and Vegetable Intake in Adults With and Without Chronic Kidney Disease in the United States.

OBJECTIVE: To characterize patterns of fruit and vegetable (F&V) intake in US adults with and without chronic kidney disease (CKD). METHODS: We used 24-hour dietary recall data from multiple cycles of the National Health and Nutrition Examination Survey spanning 3 groups from 1988 to 2018 (1988-1994; 2003-2010; 2011-2018). We categorized F&Vs based on food processing and phytochemical content. We assessed patterns of F&Vs using latent class analysis and compared intake patterns across the 3 temporal cohorts and CKD status using weighted multinomial logistic regression. RESULTS: Four similar patterns of F&Vs emerged in each cycle: Overall Low Intake, High Unprocessed, High Ultra-Processed, and Moderate Processed F&Vs. The Overall Low Intake pattern was most prevalent in all cohorts and CKD groups. After adjustment for demographic variables and selected health conditions, participants with compared to without CKD were more likely to be classified as Overall Low Intake in each cohort, although this was not significant in the National Health and Nutrition Examination Survey 2011-2018. CONCLUSIONS: Low consumption of F&Vs was more common in patients with CKD. Longitudinal studies are needed to determine if low intake is a risk factor for, or response to, CKD.

Perceptions of Caregiving Experience, Level of Burden, and Sense of Well-Being Among Caregivers of Patients Receiving In-Center Hemodialysis.

Family caregivers are essential to the well-being of patients receiving hemodialysis. Yet poor understanding of caregivers' most pressing needs and factors that adversely affect caregivers impede targeted intervention development. To address this gap, 46 caregivers (38 female, 28 White, 21 spouses/partners, mean age 54 years) of patients from seven hemodialysis centers completed surveys and semi-structured interviews via telephone. Most caregivers denied depressive symptoms and negative impact of caregiving on their self-esteem, but reported adverse effects on their health, schedule, and finances. Greater acknowledgment of the important role of family caregivers, assistance with instrumental activities of daily living, transportation, and resources for education and emotional support may address their most pressing challenges. Age, race, and relationship to the patient influenced caregiver perspectives. Interventions to support these invaluable members of the health care team are warranted.

Long-term humoral immunity decline in hemodialysis patients following severe acute respiratory syndrome coronavirus 2 vaccination: A cohort study.

Background and Aims: Dialysis patients are extremely vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with high rates of hospitalization and mortality rates. In January 2021, the University of Virginia Dialysis Program initiated a program-wide vaccination campaign to administer the Pfizer BioNTech messenger RNA SARS-CoV-2 (BNT162b2) vaccine. The aim of this study was to characterize the long-term time-dependent decline in humoral immunity in hemodialysis patients. Methods: A prospective cohort study measuring serial monthly semiquantitative IgG antibody levels to the SARS-CoV-2 spike protein receptor binding domain in fully vaccinated in-center hemodialysis patients. Samples were collected monthly and tested for anti-SARS-CoV-2 antibodies against the anti-spike S1 domain for 2-6 months post full vaccination. Results were presented as internationally harmonized binding antibody units (BAU/ml). To analyze the change in antibody levels over time, a linear mixed model with random intercept and random slope was used for longitudinal antibody levels. A multivariable model was used to estimate the slope of antibody levels by adjusting for selected patient characteristics. Based on the estimated intercepts and slopes for each subject from the unadjusted model, 10-month antibody levels were projected. Results: The mean baseline antibody level was 647.59 BAU/ml and 87.88% (29/33) of patients were considered qualitatively positive. Two patients were negative at baseline and an additional two had borderline results. Patient antibody levels declined at an adjusted average rate of 31% per month. At 6 months postvaccination, 40% of patients remaining in the cohort possessed either negative or borderline IgG antibody levels. Projecting future antibody levels suggests that 65% of the cohort will progress to borderline or negative antibody levels at 10 months post full vaccination. Conclusion: The long-term vaccine response following vaccination with the BNT162b2 in hemodialysis patients was characterized. Our data add to the limited pool of data in this patient population and emphasize the critical need for vaccine boosters.

Urine tricarboxylic acid cycle signatures of early-stage diabetic kidney disease.

INTRODUCTION: Urine tricarboxylic acid (TCA) cycle organic anions (OAs) are elevated in diabetes and may be biomarkers for diabetic kidney disease (DKD) progression. OBJECTIVES: We assessed associations of 10 urine TCA cycle OAs with estimated glomerular filtration rate (eGFR) and eGFR slope. METHODS: This study is ancillary to the Simultaneous Risk Factor Control Using Telehealth to SlOw Progression of Diabetic Kidney Disease (STOP-DKD) Trial-a randomized trial of pharmacist-led medication and behavior management in 281 patients with early to moderate DKD at Duke from 2014 to 2015. We used linear mixed models to assess associations of urine TCA cycle OAs with outcomes and modelled TCA cycle OAs as: (1) the average of z-scores for each OA; and (2) principal component (PC) scores derived by principal component analysis (PCA). Untargeted urine metabolomics were added for additional discovery. RESULTS: Among 132 participants with 24 h urine samples (50% men; 58% Black; mean age 64 years [SD 9]; mean eGFR 74 ml/min/1.73m2 [SD 21] and median urine albumin-to-creatinine [UACR] 20 mg/g [IQR 8-95]), PCA identified 3 OA metabolite PCs. Malate, fumarate, pyruvate, α-ketoglutarate, lactate, succinate and citrate/isocitrate loaded positively on PC1; methylsuccinate, ethylmalonate and succinate loaded positively on PC2; and methylmalonate, ethylmalonate and citrate/isocitrate loaded negatively on PC3. Over a median follow-up of 1.8 years (IQR, 1.2 to 2.2), higher average OA z-score was strongly associated with higher eGFR after covariate adjustment (p = 0.01), but not with eGFR slope (p = 0.9). Higher PC3, but not other PCs, was associated with lower eGFR (p < 0.001). Conditional random forests and smooth clipped absolute deviation models confirmed methylmalonate, citrate/isocitrate, and ethylmalonate, and added lactate as top ranked metabolites in models of baseline eGFR (R-squared 0.32 and 0.33, respectively). Untargeted urine metabolites confirmed association of urine TCA cycle OAs with kidney function. CONCLUSION: Thus, lower urine TCA cycle OAs, most notably lower methylmalonate, ethylmalonate and citrate/isocitrate, are potential indicators of kidney impairment in early stage DKD.

Retraction Note: Development and In Vitro-In Vivo Characterization of Chronomodulated Pulsatile Delivery Formulation of Terbutaline Sulphate by Box-Behnken Statistical Design.

This article has been retracted by the journal because the editors have clear evidence that the scientific findings in this article are unreliable.