Julia B Lewis

Vanderbilt University, Нашвилл, Michigan, United States

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Publications (60)480.41 Total impact

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    ABSTRACT: In this manuscript, nephrologist-investigators from one of five Clinical Center Networks of the Systolic Blood Pressure Intervention Trial (SPRINT) provide background information and context on the intensity of anti-hypertensive therapy in conjunction with the release of detailed results from SPRINT's primary analysis. The authors highlight published evidence on the safety and efficacy of differing intensities of anti-hypertensive therapy in mild to moderate CKD, where SPRINT will help to inform practice, as well as where gaps in evidence will remain. The authors also challenge the nephrology community to renew its attention and efforts on hypertension clinical care and research.
    No preview · Article · Nov 2015 · Journal of the American Society of Nephrology

  • No preview · Article · Sep 2015 · American Journal of Kidney Diseases
  • Julia B. Lewis
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    ABSTRACT: A technical expert panel (TEP) was convened to evaluate all available literature in the area of bone and mineral metabolism and advise the Centers for Medicare and Medicaid services on the creation and collection of quality measures. The proposed quality measures were evaluated for importance, usability, feasibility, and scientific acceptability. All are important parameters to avoid unintended harmful consequences of a quality measure causing harm to patients or to the delivery of their health care. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Aug 2015 · Seminars in Dialysis
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    ABSTRACT: Ferric citrate is a novel phosphate binder that allows the simultaneous treatment of hyperphosphatemia and iron deficiency in patients being treated for end-stage renal disease with hemodialysis (HD). Multiple clinical trials in HD patients have uniformly and consistently demonstrated the efficacy of the drug in controlling hyperphosphatemia with a good safety profile, leading the US Food and Drug Administration in 2014 to approve its use for that indication. A concurrent beneficial effect, while using ferric citrate as a phosphate binder, is its salutary effect in HD patients with iron deficiency being treated with an erythropoietin-stimulating agent (ESA) in restoring iron that becomes available for reversing chronic kidney disease (CKD)-related anemia. Ferric citrate has also been shown in several studies to diminish the need for intravenous iron treatment and to reduce the requirement for ESA. Ferric citrate is thus a preferred phosphate binder that helps resolve CKD-related mineral bone disease and iron-deficiency anemia.
    No preview · Article · Jun 2015 · Therapeutic Advances in Chronic Disease
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    ABSTRACT: Low serum bicarbonate level has been reported to be an independent predictor of kidney function decline and mortality in patients with chronic kidney disease. Mechanisms underlying low serum bicarbonate levels may differ in patients with and without diabetes. We aimed to specifically investigate the association of serum bicarbonate level with kidney disease progression and cardiovascular outcome in a cohort of patients with type 2 diabetes and nephropathy. Post hoc analysis of 2 multicenter randomized controlled trials. 2,628 adults with type 2 diabetes and nephropathy. Serum bicarbonate level. Incidence of: (1) end-stage renal disease (ESRD), (2) ESRD or doubling of serum creatinine level, (3) all-cause mortality, (4) cardiovascular events (fatal/nonfatal stroke/myocardial infarction), and (5) heart failure. Serum bicarbonate was measured at baseline as total carbon dioxide. Associations of baseline serum bicarbonate level with end points were investigated using Cox regression models. Serum bicarbonate levels were studied as a continuous variable and stratified in quartiles. Follow-up was 2.8±1.0 (SD) years. Cox regression analyses showed that serum bicarbonate level had inverse associations with incident ESRD (HR, 0.91; 95% CI, 0.89-0.93; P<0.001) and incidence of the combined end point of ESRD or serum creatinine doubling (HR, 0.94; 95% CI, 0.92-0.96; P<0.001). These associations were independent of age, sex, and cardiovascular risk factors, but disappeared after adjustment for baseline estimated glomerular filtration rate (all P>0.05). Analysis of bicarbonate quartiles showed similar results for the quartile with the lowest bicarbonate (≤21 mEq/L) versus the quartile with normal bicarbonate levels (24-26 mEq/L). There was no association of bicarbonate level with cardiovascular events and heart failure. Post hoc analysis and single measurement of serum bicarbonate. In this cohort of patients with type 2 diabetes with nephropathy, serum bicarbonate level associations with kidney disease end points were not retained after adjustment for estimated glomerular filtration rate, which is in contrast to results of earlier studies in nondiabetic populations. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · American Journal of Kidney Diseases
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    ABSTRACT: Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Maintenance dialysis patients with serum phosphorus levels ≥6.0mg/dL after washout of prior phosphate binders. 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04±1.99 [SD] vs -2.18±2.25mg/dL, respectively; P=0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95mg/dL; P=0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1±399.8 vs -152.7±392.1pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Open-label study, few peritoneal dialysis patients. Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · American Journal of Kidney Diseases
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    ABSTRACT: Hyperphosphatemia is common in end-stage renal disease and associates with mortality. Phosphate binders reduce serum phosphorus levels; however, adherence is often poor. This pilot study aims to assess patients' self-motivation to adhere to phosphate binders, its association with phosphorus control, and potential differences by race. Cross sectional design. Subjects were enrolled from one academic medical center dialysis practice from July to November 2012. Self-motivation to adhere to phosphate binders was assessed with the autonomous regulation (AR) scale (range: 1-7) and self-reported medication adherence with the Morisky Medication Adherence Scale. Linear regression models adjusting for age, sex, health literacy, and medication adherence were applied to determine associations with serum phosphorus level, including any evidence of interaction by race. Among 100 participants, mean age was 51 years (±15 years), 53% were male, 72% were non-white, 89% received hemodialysis, and mean serum phosphorus level was 5.7 ± 1.6 mg/dL. More than half (57%) reported the maximum AR score (7). Higher AR scores were noted in those reporting better health overall (P = .001) and those with higher health literacy (P = .01). AR score correlated with better medication adherence (r = 0.22; P = .02), and medication adherence was negatively associated with serum phosphorus (r = -0.40; P < .001). In subgroup analysis among non-whites, higher AR scores correlated with lower serum phosphorus (high vs lower AR score: 5.55 [1.5] vs 6.96 [2.2]; P = .01). Associations between AR score (β 95% confidence interval: -0.37 [-0.73 to -0.01]; P = .04), medication adherence (β 95% confidence interval: -0.25 [-0.42 to -0.07]; P = .01), and serum phosphorus persisted in adjusted analyses. Self-motivation was associated with phosphate binder adherence and phosphorus control, and this differed by race. Additional research is needed to determine if personalized, culturally sensitive strategies to understand and overcome motivational barriers may optimize mineral bone health in end-stage renal disease. Published by Elsevier Inc.
    Full-text · Article · Apr 2015 · Journal of Renal Nutrition
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    ABSTRACT: Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0-28.9] versus 26.8 [13.4-47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023-9695] versus 6954 [2664-12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders. Copyright © 2015 by the American Society of Nephrology.
    No preview · Article · Mar 2015 · Journal of the American Society of Nephrology
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    ABSTRACT: Background/aims: Pyridoxamine dihydrochloride (Pyridorin™) blocks pathogenic oxidative pathways in the progression of diabetic nephropathy. The pyridoxamine pilot study was designed to test entry criteria and outcomes. Subjects had SCr 1.3-3.5 mg/dl, protein-to-creatinine ≥1,200 mg/g and used a surrogate outcome of ΔSCr over 52 weeks. Subjects had to be on a maximally tolerated dose of ACE/ARB for 3 months; stable other antihypertensive doses for 2 months; stable diuretic dose for 2 weeks, and BP ≤160/90 mm Hg; or enter a Pharmaco-Stabilization Phase (PSP). This pilot failed to detect an effect on ΔSCr in intent-to-treat analysis. Methods: We queried the locked clinical trial database for subgroups in which there was a treatment effect. Results: Subjects not requiring PSP and those with entry SCr <2.0 mg/dl had a treatment effect. Subjects entering PSP required more changes in antihypertensive medications and experienced larger ΔSCr over 52 weeks. PSP subjects with BP >140/90 mm Hg had no treatment effect, but those ≤140/90 mm Hg did. Conclusion: Time required for acute effects of ACE/ARB to stabilize is unknown, but these data suggest >3 months. Thus, subjects in the pivotal trial must be on ACE/ARB for 6 months. Frequent antihypertensive adjustment could engender SCr changes unrelated to CKD progression. Thus, we will require subjects to have BP ≤150/90 mm Hg and on stable antihypertensives for 26 weeks, or ≤140/90 mm Hg and on stable antihypertensives for 13 weeks. Since ΔSCr over 52 weeks is limited as a surrogate outcome, the pivotal trial uses a time-to-event analysis of baseline SCr to at least a 50% increase in SCr or ESRD as the primary outcome. This substantial ΔSCr is protected from noise and is clinically relevant. The pyridoxamine pilot provided critical information to inform the design of PIONEER-CSG-17, which we conducted under the SPA agreement with FDA.
    No preview · Article · Dec 2014
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    ABSTRACT: Background: Ferric citrate (FC) is a new phosphorus binder shown to increase serum iron stores while reducing intravenous iron and erythropoiesis-stimulating agent usage. Such reductions could lower hospitalization rates and associated costs. Methods: Hospitalizations during a Phase III trial were compared between FC and active control (AC). Hospitalization costs were estimated using the 2013 US Renal Data System Annual Data Report. Results: 34.6% of FC patients were hospitalized at least once versus 45.6% of the AC group (risk reduction 24.2%; p = 0.02). There were 181 unique hospitalizations in the FC group versus 239 in the AC group, for a difference of 58 hospitalizations. Total potential savings was US$ 867,622 in hospitalization costs in the FC group. If the hospitalization reduction in our study was applied to the general end-stage renal disease population, this could translate into a savings of US$ 3002/patient/year. Conclusions: Patients receiving FC experienced fewer hospitalizations with the potential for significant savings.
    No preview · Article · Dec 2014 · Expert Review of Pharmacoeconomics & Outcomes Research
  • Anna Burgner · Julia B Lewis

    No preview · Article · Sep 2014 · Nature Reviews Nephrology
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    ABSTRACT: Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of -2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.
    No preview · Article · Jul 2014 · Journal of the American Society of Nephrology
  • Kausik Umanath · Anna Burgner · Julia B Lewis · Jamie P Dwyer

    No preview · Article · Apr 2014 · American Journal of Kidney Diseases
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    ABSTRACT: Bilirubin, a potent endogenous antioxidant, was found to protect against development of diabetic nephropathy (DN) in rodents. In humans, cross-sectional studies found an inverse relation between bilirubin and DN. We prospectively investigated whether bilirubin is associated with progression of DN towards end-stage renal disease (ESRD). To this end, we performed a post-hoc analysis in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial with independent replication in the Irbesartan Diabetic Nephropathy Trial (IDNT). Subjects with type 2 diabetes and nephropathy with ALT, AST, and bilirubin levels <1.5 times the ULN were included. The renal endpoint was defined as the composite of confirmed doubling of serum creatinine (DSCR) or ESRD. Bilirubin was inversely associated with the renal endpoint in RENAAL independent of age, gender, race, BMI, smoking, total cholesterol, diastolic blood pressure, HbA1c, treatment, eGFR, ACR, and AST. These results were confirmed in IDNT. In conclusion, we found an independent inverse association of bilirubin with progression of nephropathy in RENAAL and IDNT. These data suggest a protective effect of bilirubin against progression of nephropathy in type 2 diabetes. The well-established role of bilirubin as an antioxidant is a potential explanation for our findings.
    Full-text · Article · Mar 2014 · Diabetes
  • Kausik Umanath · Julia B Lewis · Jamie P Dwyer
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    ABSTRACT: Hypertension is a common problem among patients with glomerular disease and CKD. Optimal blood pressure targets for these patients have been the source of much debate. Careful review of the available data supports a blood pressure target of less than 140/90 mmHg. Consideration for a lower goal of less than 130/80 mmHg should be given for patients with heavy proteinuria. Renin-angiotensin system inhibitors should be used as the cornerstone of therapy for all patients with glomerular disease and CKD.
    No preview · Article · Mar 2014 · Advances in chronic kidney disease
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    ABSTRACT: BACKGROUND: Most dialysis patients require phosphate binders to control hyperphosphatemia. Ferric citrate has been tested in phase 2 trials as a phosphate binder. This trial was designed as a dose-response and efficacy trial. STUDY DESIGN: Prospective, phase 3, multicenter, open-label, randomized clinical trial. SETTING & PARTICIPANTS: 151 participants with hyperphosphatemia on maintenance hemodialysis therapy. INTERVENTION: Fixed dose of ferric citrate taken orally as a phosphate binder for up to 28 days (1, 6, or 8 g/d in 51, 52, and 48 participants, respectively). OUTCOMES: Primary outcome is dose-response of ferric citrate on serum phosphorus level; secondary outcomes are safety and tolerability. MEASUREMENTS: Serum chemistry tests including phosphorus, safety data. RESULTS: 151 participants received at least one dose of ferric citrate. Mean baseline phosphorus levels were 7.3 ± 1.7 (SD) mg/dL in the 1-g/d group, 7.6 ± 1.7 mg/dL in the 6-g/d group, and 7.5 ± 1.6 mg/dL in the 8-g/d group. Phosphorus levels decreased in a dose-dependent manner (mean change at end of treatment, -0.1 ± 1.3 mg/dL in the 1-g/d group, -1.9 ± 1.7 mg/dL in the 6-g/d group, and -2.1 ± 2.0 mg/dL in the 8-g/d group). The mean difference in reduction in phosphorus levels between the 6- and 1-g/d groups was 1.3 mg/dL (95% CI, 0.69 to 1.9; P < 0.001), between the 8- and 1-g/d groups was 1.5 mg/dL (95% CI, 0.86 to 2.1; P < 0.001), and between the 8- and 6-g/d groups was 0.21 mg/dL (95% CI, -0.39 to 0.81; P = 0.5). The most common adverse event was stool discoloration. LIMITATIONS: Sample size and duration confirm efficacy, but limit our ability to confirm safety. CONCLUSIONS: Ferric citrate is efficacious as a phosphate binder in a dose-dependent manner. A phase 3 trial is ongoing to confirm safety and efficacy.
    No preview · Article · Jan 2013 · American Journal of Kidney Diseases
  • Jamie P Dwyer · Julia B Lewis
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    ABSTRACT: Diabetic nephropathy (DN) refers to the structural and functional changes in the kidneys of patients with diabetes mellitus (type 1 or 2). A subset of patients with presumed DN may not have overt proteinuria as a prerequisite to renal failure, contrary to the classical paradigm. No animal model fully recapitulates the human subset. All studies on this subject are observational and most lack biopsy data. Many mechanisms have been postulated, including use of renin-angiotensin system agents, recurrent bouts of acute kidney injury, genetic predisposition, and renal lesions other than DN. A well-designed biopsy study and a series of intervention trials are needed to fully understand this entity.
    No preview · Article · Jan 2013 · The Medical clinics of North America
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    ABSTRACT: Ferric citrate (KRX-0502; Keryx Biopharmaceuticals, Inc., NY, USA) is a novel phosphate-binding agent presently in Phase III clinical development. Ferric citrate dissociates in the bowel lumen releasing the ferric ion to precipitate with dietary phosphorus, which is then excreted in the stool. Studies to date have shown the agent to be efficacious and safe with only mild gastrointestinal side effects. Absorption of either component of the agent (ferric iron or citrate) has the potential to be of benefit for patients with end-stage renal disease. An ongoing Phase III trial is confirming the safety and efficacy of ferric citrate as a phosphate binder in dialysis patients.
    No preview · Article · Jan 2013 · Expert Review of Endocrinology & Metabolism
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    ABSTRACT: Chronic kidney disease associated mineral and bone disorders arise as a result of aberrant bone mineral metabolism in patients with advancing levels of renal dysfunction and end-stage renal disease. One of the cornerstones of treatment is the use of phosphate-binding agents. We describe the rationale and study design for a clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder. This trial is a three-period, international, multicenter, randomized, controlled clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder, consisting of a 2-week washout period, a 52-week safety assessment period in which subjects are randomized to ferric citrate or active control, and a 4-week efficacy assessment period in which subjects randomized to ferric citrate in the safety assessment period are randomized to ferric citrate or placebo. Eligible subjects include end-stage renal disease patients who have been treated with thrice-weekly hemodialysis or peritoneal dialysis for at least 3 months in dialysis clinics in the United States and Israel. Primary outcome measure will be the effect of ferric citrate vs. placebo on the change in serum phosphorus. Safety assessments will be performed by monitoring adverse events, concomitant medication use, and sequential blood chemistries (including iron parameters, phosphorus, and calcium). This three-period trial will assess the efficacy of ferric citrate as a phosphate binder. If proven safe and efficacious, ferric citrate will likely provide an additional phosphate binder to treat chronic kidney disease associated mineral and bone disorders.
    No preview · Article · Jun 2012 · Hemodialysis International
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    ABSTRACT: OBJECTIVES: Clinical decision support (CDS), such as computerized alerts, improves prescribing in the setting of acute kidney injury (AKI), but considerable opportunity remains to improve patient safety. The authors sought to determine whether pharmacy surveillance of AKI patients could detect and prevent medication errors that are not corrected by automated interventions. METHODS: The authors conducted a randomized clinical trial among 396 patients admitted to an academic, tertiary care hospital between June 1, 2010 and August 31, 2010 with an acute 0.5 mg/dl change in serum creatinine over 48 hours and a nephrotoxic or renally cleared medication order. Patients randomly assigned to the intervention group received surveillance from a clinical pharmacist using a web-based surveillance tool to monitor drug prescribing and kidney function trends. CDS alerting and standard pharmacy services were active in both study arms. Outcome measures included blinded adjudication of potential adverse drug events (pADEs), adverse drug events (ADEs) and time to provider modification or discontinuation of targeted nephrotoxic or renally cleared medications. RESULTS: Potential ADEs or ADEs occurred for 104 (8.0%) of control and 99 (7.1%) of intervention patient-medication pairs (p=0.4). Additionally, the time to provider modification or discontinuation of targeted nephrotoxic or renally cleared medications did not differ between control and intervention patients (33.4 hrs vs. 30.3 hrs, p=0.3). CONCLUSIONS: Pharmacy surveillance had no incremental benefit over previously implemented CDS alerts.
    Full-text · Article · Jun 2012 · Applied Clinical Informatics