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  • 1
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    25-Hydroxyvitamin D Deficiency and Inflammation and Their Association with Hemoglobin Levels in Chronic Kidney Disease
    S. Karger AG ; 2009
    In:  American Journal of Nephrology Vol. 30, No. 1 ( 2009), p. 64-72
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 30, No. 1 ( 2009), p. 64-72
    Abstract: 〈 i 〉 Background/Aims: 〈 /i 〉 There is limited information about the association of anemia with 25-hydroxyvitamin D [25(OH)D] deficiency and inflammation in the setting of decreased kidney function in the general population. 〈 i 〉 Methods: 〈 /i 〉 We examined the association that anemia has with 25(OH)D deficiency and inflammation among 16,301 participants in the Third National Health and Nutrition Examination Survey (NHANES III). Measures of kidney function were estimated glomerular filtration rate (GFR) by using the Modification of Diet in Renal Disease equation. 〈 i 〉 Results: 〈 /i 〉 The age-adjusted prevalence of anemia (hemoglobin 〈 12 g/dl) at an estimated GFR of 59–30 ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 was 17% increasing to 56% for those participants with an estimated GFR 〈 30 ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 , while the age-adjusted prevalence of elevated C-reactive protein (CRP 〉 0.21 mg/dl) and reduced 25(OH)D ( 〈 20 ng/ml) was 50 and 30%, respectively. After adjusting for demographics, comorbidities and laboratory results, 25(OH)D 〈 20 ng/ml (OR: 1.17; 95% CI: 1.03–1.32; p = 0.014) and log CRP (OR: 3.63; 95% CI: 2.4–5.48 per unit increase of log CRP; p 〈 0.0001) were associated with hemoglobin levels 〈 12 g/dl. 〈 i 〉 Conclusion: 〈 /i 〉 This study provides evidence that lower 25(OH)D and higher CRP levels are independently associated with lower hemoglobin concentrations in kidney disease subjects not requiring dialysis.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000202632
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
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  • 2
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    Association between Dietary Sodium and Potassium Intake with Chronic Kidney Disease in US Adults: A Cross-Sectional Study
    S. Karger AG ; 2013
    In:  American Journal of Nephrology Vol. 37, No. 6 ( 2013), p. 526-533
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 37, No. 6 ( 2013), p. 526-533
    Abstract: 〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 Clinical guidelines recommend a diet low in sodium and high in potassium to reduce blood pressure and cardiovascular events. Little is known about the relationship between dietary sodium and potassium intake and chronic kidney disease (CKD). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 13,917 participants from the National Health and Nutrition Examination Survey (2001-2006) were examined. Sodium and potassium intake were calculated from 24-hour recall and evaluated in quartiles. CKD was defined as estimated glomerular filtration rate (eGFR) 〈 60 ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 or eGFR ≥60 ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 with albuminuria ( 〉 30 mg/g creatinine). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The mean (SE) age and eGFR of participants were 45.0 ± 0.4 years and 88.0 ± 0.60 ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 , respectively. 2,333 (14.2%) had CKD: 1,146 (7.3%) had an eGFR 〈 60 ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 and 1,514 (8.4%) had an eGFR ≥60 ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 and albuminuria. After adjustment for age, sex, race, BMI, diabetes, hypertension, cardiovascular disease and congestive heart failure, subjects in the highest quartile of sodium intake had lower odds of CKD compared to subjects in the lowest quartile (adjusted OR: 0.79; 95% CI: 0.66-0.96; p 〈 0.016). Compared to the highest quartile, the odds of CKD increased 44% for participants in the lowest quartile of potassium intake (adjusted OR: 1.44; 95% CI: 1.16-1.79; p = 0.0011). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Higher intake of sodium and potassium is associated with lower odds of CKD among US adults. These results should be corroborated through longitudinal studies and clinical trials designed specifically to examine the effects of dietary sodium and potassium intake on kidney disease and its progression.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000351178
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
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  • 3
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    Fibroblast Growth Factor 23 Trajectories in Chronic Hemodialysis Patients: Lessons from the HEMO Study
    S. Karger AG ; 2019
    In:  American Journal of Nephrology Vol. 49, No. 4 ( 2019), p. 263-270
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 49, No. 4 ( 2019), p. 263-270
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Long-term patterns of fibroblast growth factor 23 (FGF23) are poorly characterized among dialysis patients. 〈 b 〉 〈 i 〉 Objectives: 〈 /i 〉 〈 /b 〉 To identify different FGF23 trajectories and determine clinical factors that predict distinct FGF23 trajectories and whether FGF23 trajectories differ in regard to their associations with all-cause mortality among prevalent hemodialysis patients. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The HEMO study was a randomized multicenter study evaluating the effects of high-dose vs. standard-dose and high-flux vs. low-flux hemodialysis on mortality. We measured intact FGF23 levels in stored serum samples at baseline and annually among 919 HEMO participants and identified FGF23 trajectories using group-based modeling. Logistic regression determined predictors of trajectories. Cox regression models evaluated the association between trajectory and all-cause mortality. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We identified 5 distinct FGF23 trajectory groups during the initial 24 months: low stable, low increasing, elevated increasing, elevated decreasing, and elevated stable. In multivariable models, diabetes, high dose dialysis, no venous catheter, low serum calcium, phosphorus, and interleukin-6, no vitamin D analog use, and greater residual kidney function were associated with the low stable trajectory group compared to the elevated stable group. High flux dialysis, no venous catheter, and low serum phosphorus and 25-hydroxyvitamin D were associated with the elevated decreasing trajectory group compared to the elevated stable group. After full adjustment, the low stable trajectory group was associated with reduced mortality (hazard ratio [HR] 0.61; 95% CI ­0.41–0.91) compared to the elevated stable trajectory group. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 We identified 5 distinct FGF23 trajectories over 24 months among HEMO study participants including a decreasing trajectory. The low stable FGF23 trajectory was associated with a reduced HR of all-cause mortality.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000497445
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
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  • 4
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    Low Body Mass Index and Dyslipidemia in Dialysis Patients Linked to Elevated Plasma Fibroblast Growth Factor 23
    S. Karger AG ; 2013
    In:  American Journal of Nephrology Vol. 37, No. 3 ( 2013), p. 183-190
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 37, No. 3 ( 2013), p. 183-190
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Fibroblast growth factor 23 (FGF23) has been associated with death in dialysis patients. Since FGF23 shares structural features with FGF19 subfamily members that exert hormonal control of fat mass, we hypothesized that high circulating FGF23 concentrations would be associated with the development of a uremic lipid profile and lower body mass index (BMI). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 This study was conducted among 654 patients receiving chronic hemodialysis. C-terminal FGF23 concentrations were measured in stored plasma samples. Linear regression was used to examine the cross-sectional associations of plasma FGF23 concentrations with BMI, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides. Cox proportional hazard models were used to examine the association between FGF23 concentrations and all-cause mortality. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Participants had a mean age of 60 ± 11 years and a median (IQR) FGF23 concentration of 4,212 (1,411-13,816) RU/ml. An increase per SD in log 〈 sub 〉 10 〈 /sub 〉 FGF23 was associated with lower BMI (β = -1.11; p = 0.008), TC (β = -6.46; p = 0.02), LDL-C (β = -4.73; p = 0.04) and HDL-C (β = -2.14; p = 0.03); after adjusting for age, gender, race, cardiovascular risk factors, serum albumin, markers of mineral metabolism, and use of lipid-lowering drugs. The association of FGF23 with death was attenuated after adjustment for HDL-C (HR of highest quartile 1.53, 95% CI 1.06-2.20 compared to lowest quartile). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 These results indicate that higher plasma FGF23 levels are associated with lower BMI and dyslipidemia in dialysis patients. The association between FGF23 and death may be mediated through unexplored metabolic risk factors unrelated to mineral metabolism.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000346941
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
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  • 5
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    Mineral Metabolites, Angiotensin II Inhibition and Outcomes in Advanced Chronic Kidney Disease
    S. Karger AG ; 2015
    In:  American Journal of Nephrology Vol. 42, No. 5 ( 2015), p. 361-368
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 42, No. 5 ( 2015), p. 361-368
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Evidence suggests that the renin-angiotensin-aldosterone system (RAAS) interacts with the vitamin D-fibroblast growth factor 23-Klotho axis. We investigated whether circulating mineral metabolism markers modify outcomes in response to RAAS inhibition in subjects with advanced chronic kidney disease (CKD). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 In this retrospective cohort study, we analyzed the association of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use with all-cause mortality and dialysis initiation among 1,753 subjects (1,099 CKD, estimated glomerular filtration rate 18 ± 6 ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 and 654 end-stage renal disease [ESRD]) from the Homocysteine in Kidney and End Stage Renal Disease (HOST) study. A propensity score analysis accounted for indication bias and Cox regression models adjusted for mineral metabolism markers. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Mean follow-up was 3.2 years; 714 (41%) subjects died and 615 (56%) initiated dialysis. In adjusted analyses, all subjects treated with ACEI/ARB had a significantly lower hazard of death (hazards ratio (HR) 0.81, 95% CI 0.70-0.95, p = 0.007). Those with CKD not on dialysis and treated with ACEI/ARB trended toward a lower hazard of dialysis initiation (HR 0.86, 95% CI 0.73-1.01, p = 0.06). The association with mortality did not differ by level of mineral metabolism marker (p for interaction 〉 0.16); however, the relationship with dialysis initiation differed according to the median serum phosphorus level (p for interaction 〈 0.001). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 RAAS inhibition was associated with decreased all-cause mortality independent of disordered mineral metabolism among mostly male HOST subjects with advanced CKD and ESRD. However, among those with CKD not requiring dialysis, the renoprotection associated with RAAS inhibition was attenuated by higher serum phosphorus levels. Further studies are needed to confirm this association.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000441684
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
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  • 6
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    Effect of Sodium Zirconium Cyclosilicate on Serum Potassium and Bicarbonate in Patients with Hyperkalemia and Metabolic Acidosis Associated with Chronic Kidney Disease: Rationale and Design of the NEUTRALIZE Study
    S. Karger AG ; 2022
    In:  Nephron Vol. 146, No. 6 ( 2022), p. 599-609
    Details
    In: Nephron, S. Karger AG, Vol. 146, No. 6 ( 2022), p. 599-609
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Sodium zirconium cyclosilicate (SZC) is a selective potassium (K 〈 sup 〉 + 〈 /sup 〉 ) binder for hyperkalemia management that provides rapid and sustained correction of hyperkalemia. The NEUTRALIZE study is investigating whether SZC, in addition to correcting hyperkalemia and maintaining normal serum K 〈 sup 〉 + 〈 /sup 〉 , can provide sustained increases in serum bicarbonate (HCO 〈 sub 〉 3 〈 /sub 〉 〈 sup 〉 − 〈 /sup 〉 ) in patients with hyperkalemia and metabolic acidosis associated with chronic kidney disease (CKD). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 This is a prospective, randomized, double-blind, placebo-controlled phase 3b study of US adults with stage 3–5 CKD not on dialysis with hyperkalemia (K 〈 sup 〉 + 〈 /sup 〉 & #x3e;5.0–≤5.9 mmol/L) and low-serum HCO 〈 sub 〉 3 〈 /sub 〉 〈 sup 〉 − 〈 /sup 〉 (16–20 mmol/L). In the open-label correction phase, all eligible patients receive SZC 10 g three times daily for up to 48 h. Patients who achieve normokalemia (K 〈 sup 〉 + 〈 /sup 〉 ≥3.5–≤5.0 mmol/L) are then randomized 1:1 to once-daily SZC 10 g or placebo for a 4-week, double-blind, placebo-controlled maintenance phase. The primary endpoint is the proportion of patients with normokalemia at the end of treatment (EOT) without rescue therapy for hyperkalemia. Key secondary endpoints include mean change in serum HCO 〈 sub 〉 3 〈 /sub 〉 〈 sup 〉 − 〈 /sup 〉 , the proportion of patients with an increase in serum HCO 〈 sub 〉 3 〈 /sub 〉 〈 sup 〉 − 〈 /sup 〉 of ≥2 or ≥3 mmol/L without rescue therapy for metabolic acidosis, and the proportion of patients with serum HCO 〈 sub 〉 3 〈 /sub 〉 〈 sup 〉 − 〈 /sup 〉 ≥22 mmol/L at EOT. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 NEUTRALIZE will establish whether SZC can provide sustained increases in serum HCO 〈 sub 〉 3 〈 /sub 〉 〈 sup 〉 − 〈 /sup 〉 while lowering serum K 〈 sup 〉 + 〈 /sup 〉 in patients with hyperkalemia and CKD-associated metabolic acidosis and may provide insights on the mechanism(s) underlying the increased serum HCO 〈 sub 〉 3 〈 /sub 〉 〈 sup 〉 − 〈 /sup 〉 with SZC treatment.
    Type of Medium: Online Resource
    ISSN: 1660-8151 , 2235-3186
    URL: Article
    DOI: 10.1159/000523911
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
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  • 7
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    Serum Bicarbonate Is Associated with Heart Failure in the Multi-Ethnic Study of Atherosclerosis
    S. Karger AG ; 2017
    In:  American Journal of Nephrology Vol. 45, No. 2 ( 2017), p. 118-126
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 45, No. 2 ( 2017), p. 118-126
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Low serum bicarbonate concentrations are associated with mortality and kidney disease progression. Data regarding associations between bicarbonate and cardiovascular disease (CVD) are scarce. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We performed a cohort study of 6,229 adult participants from the Multi-Ethnic Study of Atherosclerosis, a community-based cohort free of CVD at baseline. Serum bicarbonate was measured at baseline. Cardiovascular outcomes were defined as: (1) subclinical CVD (left ventricular mass [LVM] and aortic pulse pressure [PP] measured at baseline), (2) incident atherosclerotic cardiovascular events (CVE; composite of myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death, and stroke death), and (3) incident heart failure. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 During a median (interquartile range) follow-up of 8.5 (7.7-8.6) years, 331 (5.3%) participants had an incident CVE and 174 (2.8%) developed incident heart failure. We stratified analyses by use of diuretics because we observed a significant interaction between diuretic use and bicarbonate with study outcomes. Among diuretic nonusers, with adjustment, bicarbonate ≥25 mEq/L was associated with an estimated 3.0 g greater LVM (95% CI 0.5-5.0) and 1.0 mm Hg higher aortic PP (95% CI 0.4-2.0) compared to bicarbonate 23-24 mEq/L. Each 1 mEq/L of bicarbonate increase was associated with a 13% higher risk of incident heart failure (hazards ratio 1.13, 95% CI 1.01-2.11). Among diuretic users, higher bicarbonate was not associated with CVD. Bicarbonate was not associated with incident atherosclerotic CVE irrespective of diuretic use. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Among nonusers of diuretics in a large community-based study, higher serum bicarbonate concentrations are associated with subclinical CVD and new heart failure.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000454783
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
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  • 8
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    Racial/Ethnic Differences in Barriers to Kidney Transplant Evaluation among Hemodialysis Patients
    S. Karger AG ; 2018
    In:  American Journal of Nephrology Vol. 47, No. 1 ( 2018), p. 1-7
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 47, No. 1 ( 2018), p. 1-7
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Only a small percentage of dialysis patients receive a transplant and this is particularly the case for racial/ethnic minorities. Our objective was to identify barriers to initial transplant evaluation in our dialysis centers. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We conducted a survey of adult hemodialysis patients from 4 dialysis units in the Denver Metro area in 2016. Participants completed an 11-item survey with demographic information and questions regarding time on dialysis, if a provider ever spoke to them about transplant, and whether they had been evaluated for a transplant. Reasons for not having an evaluation were explored. Descriptive statistics, chi-square analyses, and multivariate analyses were used to examine the responses. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 A total of 167 patients completed the survey (response rate 63.9%). The majority of participants were male and were Hispanic (49%) or Non-Hispanic black (31.7%). Of these, 140 patients (84.0%) reported discussing kidney transplantation with their doctor but only 53% reported having a transplant evaluation. After adjustment for age, gender, and time on dialysis, significantly fewer blacks reported having an evaluation than Non-Hispanic whites or Hispanics (43.4 vs. 57.7% [whites] and 59.7% [Hispanics] , 〈 i 〉 p 〈 /i 〉  = 0.03). The most frequent responses of the patients who had not been evaluated were the following: not referred by their provider (46%), did not know how to proceed (43.4%), or did not understand the benefits (39.5%) or transplant process (38.2%). Compared to Non-Hispanic whites, blacks and Hispanics reported less understanding of the benefits and process of transplant. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Timely referral by providers and improved kidney transplantation education may reduce disparities in access to kidney transplantation.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000484484
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
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