Browsing by Author "Shafi, Tariq"

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    A Metabolomics Approach to Identify Metabolites Associated With Mortality in Patients Receiving Maintenance Hemodialysis
    (Elsevier, 2024-06-29) Al Awadhi, Solaf; Myint, Leslie; Guallar, Eliseo; Clish, Clary B.; Wulczyn, Kendra E.; Kalim, Sahir; Thadhani, Ravi; Segev, Dorry L.; McAdams DeMarco, Mara; Moe, Sharon M.; Moorthi, Ranjani N.; Hostetter, Thomas H.; Himmelfarb, Jonathan; Meyer, Timothy W.; Powe, Neil R.; Tonelli, Marcello; Rhee, Eugene P.; Shafi, Tariq; Medicine, School of Medicine
    Introduction: Uremic toxins contributing to increased risk of death remain largely unknown. We used untargeted metabolomics to identify plasma metabolites associated with mortality in patients receiving maintenance hemodialysis. Methods: We measured metabolites in serum samples from 522 Longitudinal US/Canada Incident Dialysis (LUCID) study participants. We assessed the association between metabolites and 1-year mortality, adjusting for age, sex, race, cardiovascular disease, diabetes, body mass index, serum albumin, Kt/Vurea, dialysis duration, and country. We modeled these associations using limma, a metabolite-wise linear model with empirical Bayesian inference, and 2 machine learning (ML) models: Least absolute shrinkage and selection operator (LASSO) and random forest (RF). We accounted for multiple testing using a false discovery rate (pFDR) adjustment. We defined significant mortality-metabolite associations as pFDR < 0.1 in the limma model and metabolites of at least medium importance in both ML models. Results: The mean age of the participants was 64 years, the mean dialysis duration was 35 days, and there were 44 deaths (8.4%) during a 1-year follow-up period. Two metabolites were significantly associated with 1-year mortality. Quinolinate levels (a kynurenine pathway metabolite) were 1.72-fold higher in patients who died within year 1 compared with those who did not (pFDR, 0.009), wheras mesaconate levels (an emerging immunometabolite) were 1.57-fold higher (pFDR, 0.002). An additional 42 metabolites had high importance as per LASSO, 46 per RF, and 9 per both ML models but were not significant per limma. Conclusion: Quinolinate and mesaconate were significantly associated with a 1-year risk of death in incident patients receiving maintenance hemodialysis. External validation of our findings is needed.
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    Plasma metabolites and physical function in patients undergoing hemodialysis
    (Springer Nature, 2024-04-10) Moorthi, Ranjani N.; Moe, Sharon M.; O’Connell, Thomas; Dickinson, Stephanie; Kalim, Sahir; Thadhani, Ravi; Clish, Clary B.; Shafi, Tariq; Rhee, Eugene P.; Avin, Keith G.; Medicine, School of Medicine
    Impaired physical function contributes to falls, fractures, and mortality among patients undergoing dialysis. Using a metabolomic approach, we identified metabolite alterations and effect size-based composite scores for constructs of impaired gait speed and grip strength. 108 participants incident to dialysis had targeted plasma metabolomics via liquid chromatography-mass spectrometry and physical function assessed (i.e., 4 m walk, handgrip strength). Physical function measures were categorized as above/ below median, with grip utilizing sex-based medians. To develop composite scores, metabolites were identified via Wilcoxon uncorrected p < 0.05 and effect size > 0.40. Receiver operating characteristic analyses tested whether scores differentiated between above/below function groups. Participants were 54% male, 77% Black and 53 ± 14 y with dialysis vintage of 101 ± 50 days. Median (IQR) grip strength was 35.5 (11.1) kg (males) and 20 (8.4) kg (females); median gait speed was 0.82 (0.34) m/s. Of 246 measured metabolites, composite scores were composed of 22 and 12 metabolites for grip strength and gait speed, respectively. Area under the curve for metabolite composite was 0.88 (gait) and 0.911 (grip). Composite scores of physical function performed better than clinical parameters alone in patients on dialysis. These results provide potential pathways for interventions and needed validation in an independent cohort.
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    Prevalence and Persistence of Uremic Symptoms in Incident Dialysis Patients
    (ASN, 2020-02-01) Rhee, Eugene P.; Guallar, Eliseo; Hwang, Seungyoung; Kim, Noori; Tonelli, Marcello; Moe, Sharon M.; Himmelfarb, Jonathan; Thadhani, Ravi I.; Powe, Neil R.; Shafi, Tariq; Medicine, School of Medicine
    Background Uremic symptoms are major contributors to the poor quality of life among patients on dialysis, but whether their prevalence or intensity has changed over time is unknown. Methods We examined responses to validated questionnaires in two incident dialysis cohort studies, the Choices for Health Outcomes in Caring for ESRD (CHOICE) study (N=926, 1995–1998) and the Longitudinal United States/Canada Incident Dialysis (LUCID) study (N=428, 2011–2017). We determined the prevalence and severity of uremic symptoms—anorexia, nausea/vomiting, pruritus, sleepiness, difficulty concentrating, fatigue, and pain—in both cohorts. Results In CHOICE and LUCID, respectively, mean age of the participants was 58 and 60 years, 53% and 60% were male, and 28% and 32% were black. In both cohorts, 54% of the participants had diabetes. Median time from dialysis initiation to the symptoms questionnaires was 45 days for CHOICE and 77 days for LUCID. Uremic symptom prevalence in CHOICE did not change from baseline to 1-year follow-up and was similar across CHOICE and LUCID. Baseline symptom prevalence in CHOICE and LUCID was as follows: anorexia (44%, 44%, respectively), nausea/vomiting (36%, 43%), pruritus (72%, 63%), sleepiness (86%, 68%), difficulty concentrating (55%, 57%), fatigue (89%, 77%), and pain (82%, 79%). In both cohorts, >80% of patients had three or more symptoms and >50% had five or more symptoms. The correlation between individual symptoms was low (ρ<0.5 for all comparisons). In CHOICE, no clinical or laboratory parameter was strongly associated with multiple symptoms. Conclusions The burden of uremic symptoms among patients on dialysis is substantial and has not changed in the past 15 years. Improving quality of life will require identification of the factors that underlie the pathogenesis of uremic symptoms and better ways of removing the toxins that are responsible.