Browsing by Author "Moorthi, Ranjani"
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Item 4438 Twenty-four-hour Urinary Sodium Excretion Estimated from a Spot Urine Sample May Be Used as an Indicator of Intake in CKD Patients(Cambridge University Press, 2020-07-29) Lobene, Andrea; Stremke, Elizabeth; Moorthi, Ranjani; Moe, Sharon; Hill Gallant, Kathleen M.; Medicine, School of MedicineOBJECTIVES/GOALS: Sodium (Na) intake can elevate blood pressure and is a factor in developing chronic kidney disease (CKD). Twenty-four-hour urinary Na (24hUNa) is the gold standard for assessing Na intake but is burdensome. Validated equations estimate 24hUNa (e24hUNa) from a spot urine sample, but these estimations are not validated against a known Na intake in CKD. METHODS/STUDY POPULATION: The current study is a secondary analysis of a 9-day controlled feeding study in moderate CKD patients matched to healthy adults. Only CKD patients were used for the current analyses (n = 8). Participants consumed a controlled diet for 9 days, providing ~2400 mg Na/d as determined by inductively coupled plasma optical emission spectroscopy (ICP). On days 7 and 8, participants collected all urine in an inpatient setting, beginning with a fasting sample on day 7. Urine sample mineral analyses were performed by ICP and urinary creatinine by the Jaffe reaction. The day 7 fasting urine sample was used to calculate e24hUNa using 6 published equations. Log-transformed Na intake, measured 24hUNa, and e24hUNa were compared by repeated-measures ANOVA with planned contrasts using SAS. RESULTS/ANTICIPATED RESULTS: Fifty percent of the CKD patients (n = 4) were female; 63% (n = 5) were white, and 37% (n = 3) were black. On average, participants were aged 56.6 ± 13.8 y with a BMI of 31.7 ± 9.4 kg/m2 and eGFR of 40.7 ± 7.9 mL/min. Based on actual food intake, average Na intake on day 7 was 2024 ± 388 mg. Average measured 24hUNa was 2529 ± 1334 mg. The main ANOVA was significant (p = 0.02). Results from the planned contrasts found that e24hUNa from the SALTED cohort, an equation developed specifically for CKD patients, was significantly higher than both Na intake (p<0.001) and measured 24hUNa (p = 0.007). For the remaining 5 equations, e24hUNa was not significantly different from measured 24hUNa nor dietary Na intake. DISCUSSION/SIGNIFICANCE OF IMPACT : Our results suggest that e24hUNa calculated using most published equations may provide a reliable and low-burden method of assessing dietary Na intake in moderate CKD patients. These findings should be confirmed in larger samples. Additional studies are needed to validate or dispute the use of the SALTED equation for estimating Na intake.Item Analytical validity of a genotyping assay for use with personalized antihypertensive and chronic kidney disease therapy(Wolters Kluwer, 2019-01) Collins, Kimberly; Pratt, Victoria; Stansberry, Wesley; Medeiros, Elizabeth; Kannegolla, Karthik; Swart, Marelize; Skaar, Todd C.; Chapman, Arlene; Decker, Brian; Moorthi, Ranjani; Eadon, Michael; Medicine, School of MedicineHypertension and chronic kidney disease are inextricably linked. Hypertension is a well-recognized contributor to chronic kidney disease progression and, in turn, renal disease potentiates hypertension. A generalized approach to drug selection and dosage has not proven effective in managing these conditions, in part, because patients with heterogeneous kidney disease and hypertension etiologies are frequently grouped according to functional or severity classifications. Genetic testing may serve as an important tool in the armamentarium of clinicians who embrace precision medicine. Increasing scientific evidence has supported the utilization of genomic information to select efficacious antihypertensive therapy and understand hereditary contributors to chronic kidney disease progression. Given the wide array of antihypertensive agents available and diversity of genetic renal disease predictors, a panel-based approach to genotyping may be an efficient and economic means of establishing an individualized blood pressure response profile for patients with various forms of chronic kidney disease and hypertension. In this manuscript, we discuss the validation process of a Clinical Laboratory Improvement Amendments (CLIA)-approved genetic test to relay information on 72 genetic variants associated with kidney disease progression and hypertension therapy. These genomic-based interventions, in addition to routine clinical data, may help inform physicians to provide personalized therapy.Item CHRONIC KIDNEY DISEASE, MUSCLE WEAKNESS, AND MOBILITY LIMITATION(Oxford University Press, 2019-11) Latham-Mintus, Kenzie; Doshi, Simit; Moorthi, Ranjani; Medicine, School of MedicineObjectives: Chronic kidney disease (CKD) is associated with increased mobility limitation. Prior research has documented that peripheral nerve abnormalities occur early in CKD and progressively worsen. Loss of balance, impaired muscle strength, and slow gait predispose older adults to falls and frailty. However, the current literature is limited by a lack of nationally representative data that includes objective measures of kidney disease and physical functioning. Thus, this research examines whether CKD is associated with muscle strength, balance, gait, and self-reported mobility limitations. Methods: Data come from the 2016 Health and Retirement Study (HRS). Estimated GFR, a measure of kidney functioning derived from creatinine levels in the blood, was used to classify CKD (i.e, eGFR<45 or Stage 3b CKD). Logistic and linear regression models were generated to examine the association of CKD with physical functioning, net of demographic characteristics (i.e., age, sex, race, and education) and comorbidities (i.e., obesity, pain, and number of diagnosed medical conditions). Results: In unadjusted models, CKD was significantly associated (p<0.05) with more mobility limitations, slower walking speeds, stronger grip strengths, and non-participation in balance tests. After adjusting for covariates, CKD (β=-1.43, p=0.01) was negatively associated with grip strength. In sex-stratified models, CKD was associated with slower walking speeds among men, whereas CKD was associated with more mobility limitations among women. Discussion: In a nationally representative sample of older adults, CKD was associated with poorer physical functioning on multiple measures. After adjusting for demographic characteristics and comorbidities, CKD was associated with increased muscle weakness.Item DIFFERENTIAL EFFECTS OF VARYING DOSES OF DIETARY NITRATE ON MUSCLE FUNCTION AND BLOOD PRESSURE IN OLDER SUBJECTS(Oxford University Press, 2019-11) Coggan, Andrew R.; Gallardo, Edgar; Gray, Derrick A.; Hoffman, Richard; Moorthi, Ranjani; Kinesiology, School of Physical Education and Tourism ManagementWe have recently demonstrated that dietary nitrate, a source of nitric oxide via the enterosalivary pathway, can improve muscle contractile function in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. We therefore performed a randomized, double-blind, crossover study to determine the effects of ingesting 3.3 mL/kg of beetroot juice (BRJ) containing 0, 212, or 425 µmol/kg of nitrate in six healthy older (age 69±3 y) subjects. Maximal knee extensor speed (Vmax) and power (Pmax) were measured 2 h after BRJ ingestion using isokinetic dynamometry; blood pressure was monitored periodically throughout each study. Mean arterial pressure (in mmHg) was lower (P<0.05) after the high (80±4) vs. the low (84±3) or placebo (88±2) doses. Vmax (in rad/s), however, was higher (P<0.05) after the low dose (11.7±0.8), but not the high dose (10.8±1.0), compared to the placebo (10.5±1.0). Pmax (in W/kg) also tended to be higher (P=0.11) in the low (3.9±0.5) compared to the placebo (3.7±0.5) or high (3.7±0.5) trials. Five out of six subjects achieved a higher Vmax and Pmax after the low vs. the high dose. We conclude that dietary nitrate has differential effects on muscle function and blood pressure in older individuals. A high dose of nitrate intake further lowers blood pressure but does not enhance muscle contractility as much as a lower dose. Supported by Indiana University Purdue University Indianapolis and by the NIA (R21 AG053606).Item Initiation of Dialysis Is Associated With Impaired Cardiovascular Functional Capacity.(AHA, 2022-07-19) Arroyo, Eliott; Umukoro, Peter E.; Burney, Heather N.; Li, Yang; Li, Xiaochun; Lane, Kathleen A.; Sher, S. Jawad; Lu, Tzong-Shi; Moe, Sharon M.; Moorthi, Ranjani; Coggan, Andrew R.; McGregor, Gordon; Hiemstra, Thomas F.; Zehnder, Daniel; Lim, Kenneth; Kinesiology, School of Health and Human SciencesBackground The transition to dialysis period carries a substantial increased cardiovascular risk in patients with chronic kidney disease. Despite this, alterations in cardiovascular functional capacity during this transition are largely unknown. The present study therefore sought to assess ventilatory exercise response measures in patients within 1 year of initiating dialysis. Methods and Results We conducted a cross-sectional study of 241 patients with chronic kidney disease stage 5 from the CAPER (Cardiopulmonary Exercise Testing in Renal Failure) study and from the intradialytic low-frequency electrical muscle stimulation pilot randomized controlled trial cohorts. Patients underwent cardiopulmonary exercise testing and echocardiography. Of the 241 patients (age, 48.9 [15.0] years; 154 [63.9%] men), 42 were predialytic (mean estimated glomerular filtration rate, 14 mL·min·1.73 m), 54 had a dialysis vintage ≤12 months, and 145 had a dialysis vintage >12 months. Dialysis vintage ≤12 months exhibited a significantly impaired cardiovascular functional capacity, as assessed by oxygen uptake at peak exercise (18.7 [5.8] mL·min·kg) compared with predialysis (22.7 [5.2] mL·min·kg; <0.001). Dialysis vintage ≤12 months also exhibited reduced peak workload, impaired peak heart rate, reduced circulatory power, and increased left ventricular mass index (<0.05 for all) compared with predialysis. After excluding those with prior kidney transplant, dialysis vintage >12 months exhibited a lower oxygen uptake at peak exercise (17.0 [4.9] mL·min·kg) compared with dialysis vintage ≤12 months (18.9 [5.9] mL·min·kg; =0.033). Conclusions Initiating dialysis is associated with a significant impairment in oxygen uptake at peak exercise and overall decrements in ventilatory and hemodynamic exercise responses that predispose patients to functional dependence. The magnitude of these changes is comparable to the differences between low-risk New York Heart Association class I and higher-risk New York Heart Association class II to IV heart failure.Item Relationship between klotho and physical function in healthy aging(Springer, 2023-11-30) Arroyo, Eliott; Leber, Cecilia A.; Burney, Heather N.; Narayanan, Gayatri; Moorthi, Ranjani; Avin, Keith G.; Warden , Stuart J.; Moe, Sharon M.; Lim, Kenneth; Medicine, School of MedicineEpidemiological studies have reported a strong association between circulating Klotho and physical function; however, the cohorts were comprised of older adults with multiple comorbidities. Herein, we examined the relationship between Klotho and physical function in a community-based cohort of healthy adults. In this cross-sectional study, serum Klotho was measured in 80 adults who visited the Musculoskeletal Function, Imaging, and Tissue Resource Core of the Indiana Center for Musculoskeletal Health. Participants (n = 20, 10 [50%] men per group) were chosen into four age groups: 20–34, 35–49, 50–64, and ≥ 65 years, and were further grouped based on performance (low vs. high) on grip strength and chair stand tests. Klotho levels were lower in the ≥ 65 years group (703.0 [189.3] pg/mL; p = 0.022) and the 50–64 years group (722.6 [190.5] pg/mL; p = 0.045) compared to 20–34 years (916.1 [284.8] pg/mL). No differences were observed in Klotho between the low and high performers. The ≥ 65 years group walked a shorter distance during the 6-min walk test (6MWT) compared to 20–34 years (p = 0.005). Klotho was correlated with age (p < 0.001), body fat (p = 0.037), and 6MWT distance (p = 0.022). Klotho levels decline as early as the fifth decade of life, potentially before the onset of age-related impairment in exercise capacity.