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1.
BMJ Open ; 13(5): e071309, 2023 05 25.
Article in English | MEDLINE | ID: mdl-37230521

ABSTRACT

INTRODUCTION: Patients with kidney failure receiving chronic haemodialysis have elevated risk of arrhythmias potentially increasing the likelihood of sudden cardiac death, stroke and hospitalisation. The DIALIZE study (NCT03303521) demonstrated that sodium zirconium cyclosilicate (SZC) was an efficacious and well-tolerated treatment for predialysis hyperkalaemia in patients undergoing haemodialysis. The DIALIZE-Outcomes study evaluates the effect of SZC on sudden cardiac death and arrhythmia-related cardiovascular outcomes in patients receiving chronic haemodialysis with recurrent hyperkalaemia. METHODS AND ANALYSIS: International, multicentre, randomised, double-blind, placebo-controlled study conducted at 357 study sites across 25 countries. Adults (≥18 years) receiving chronic haemodialysis three times per week with recurrent predialysis serum potassium (K+) ≥5.5 mmol/L post long interdialytic interval (LIDI) are eligible. Patients (~2800) will be randomised 1:1 to SZC or placebo, starting at 5 g orally once daily on non-dialysis days and titrated weekly in 5 g increments (maximum 15 g) to target predialysis serum K+ 4.0-5.0 mmol/L post LIDI. The primary objective is to evaluate efficacy of SZC versus placebo in reducing occurrence of the primary composite endpoint of sudden cardiac death, stroke or arrhythmia-related hospitalisation, intervention or emergency department visit. Secondary endpoints include efficacy of SZC versus placebo in maintaining normokalaemia (serum K+ 4.0-5.5 mmol/L post LIDI) at the 12-month visit, preventing severe hyperkalaemia (serum K+ ≥6.5 mmol/L post LIDI) at the 12-month visit and reducing the incidence of individual cardiovascular outcomes. Safety of SZC will be evaluated. The study is event driven, with participants remaining in the study until 770 primary endpoint events have occurred. Average time in the study is expected to be ~25 months. ETHICS AND DISSEMINATION: Approval was obtained from the relevant institutional review board/independent ethics committee from each participating site (approving bodies in supplementary information). The results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: EudraCT 2020-005561-14 and clinicaltrials.gov identifier NCT04847232.


Subject(s)
Hyperkalemia , Stroke , Adult , Humans , Hyperkalemia/drug therapy , Hyperkalemia/etiology , Potassium , Renal Dialysis/adverse effects , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/therapy , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Stroke/complications , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
2.
Int J Nephrol ; 2022: 6304571, 2022.
Article in English | MEDLINE | ID: mdl-35531468

ABSTRACT

Background: Evidence of longitudinal serum potassium (sK+) concentrations in hyperkalemic hemodialysis patients is sparse. Objective: These post hoc analyses of the placebo arm of the phase 3b DIALIZE study (NCT03303521) explored the course of hyperkalemia in hemodialysis patients receiving placebo. Methods: In DIALIZE, 196 patients receiving hemodialysis three times weekly were randomized to placebo or sodium zirconium cyclosilicate 5 g starting dose once daily on nondialysis days for 8 weeks. In these post hoc analyses of placebo patients overall (n = 86) and by predialysis sK+ subgroups at randomization <5.5 mmol/L, 5.5 to <6.0 mmol/L, 6.0 to <6.5 mmol/L, and ≥6.5 mmol/L, we assessed mean predialysis sK+ concentration by visit and the proportions of patients with mean predialysis sK+ ranges of 4.0-5.0 and 4.0-5.5 mmol/L by visit. Results: In placebo patients, the mean predialysis sK+ concentration at randomization was 5.9 mmol/L, and 5.8 mmol/L at the end of the study (day 57). For placebo patients overall and across all predialysis sK+ subgroups, the mean predialysis sK+ concentration remained ≥5.0 mmol/L for all visits over 8 weeks. Overall, 7-21% and 27-62% of placebo patients had predialysis sK+ ranges of 4.0-5.0 and 4.0-5.5 mmol/L, respectively, at any visit. The proportions of placebo patients with either predialysis sK+ range were greatest for those who were least hyperkalemic (<5.5 mmol/L) and generally decreased with increasing predialysis sK+ concentration. Conclusions: Patients receiving placebo and hemodialysis maintained high predialysis sK+ concentrations over 8 weeks following a hyperkalemic event. Most placebo patients remained hyperkalemic and may be at continued risk of adverse events.

4.
J Am Soc Nephrol ; 33(4): 850-866, 2022 04.
Article in English | MEDLINE | ID: mdl-35361724

ABSTRACT

BACKGROUND: Concerns regarding cardiovascular safety with current treatments for anemia in patients with dialysis-dependent (DD)-CKD have encouraged the development of alternatives. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis by increasing endogenous erythropoietin and iron availability. METHODS: In this open-label phase 3 study, patients with DD-CKD and anemia were randomized 1:1 to oral roxadustat three times weekly or parenteral epoetin alfa per local clinic practice. Initial roxadustat dose depended on erythropoiesis-stimulating agent dose at screening for patients already on them and was weight-based for those not on them. The primary efficacy end point was mean hemoglobin change from baseline averaged over weeks 28‒52 for roxadustat versus epoetin alfa, regardless of rescue therapy use, tested for noninferiority (margin, -0.75 g/dl). Adverse events (AEs) were assessed. RESULTS: Among 2133 patients randomized (n=1068 roxadustat, n=1065 epoetin alfa), mean age was 54.0 years, and 89.1% and 10.8% were on hemodialysis and peritoneal dialysis, respectively. Mean (95% confidence interval) hemoglobin change from baseline was 0.77 (0.69 to 0.85) g/dl with roxadustat and 0.68 (0.60 to 0.76) g/dl with epoetin alfa, demonstrating noninferiority (least squares mean difference [95% CI], 0.09 [0.01 to 0.18]; P<0.001). The proportion of patients experiencing ≥1 AE and ≥1 serious AE was 85.0% and 57.6% with roxadustat and 84.5% and 57.5% with epoetin alfa, respectively. CONCLUSIONS: Roxadustat effectively increased hemoglobin in patients with DD-CKD, with an AE profile comparable to epoetin alfa. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis. CLINICALTRIALS: gov Identifier: NCT02174731.


Subject(s)
Anemia , Renal Insufficiency, Chronic , Anemia/drug therapy , Anemia/etiology , Epoetin Alfa/therapeutic use , Glycine/analogs & derivatives , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases , Isoquinolines , Middle Aged , Renal Dialysis , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/therapy
5.
J Patient Exp ; 9: 23743735221092629, 2022.
Article in English | MEDLINE | ID: mdl-35425851

ABSTRACT

Anemia in chronic kidney disease (CKD) is associated with reduced health-related quality of life and physical functioning. This study investigated knowledge and awareness of anemia in patients with CKD in the United States (US) through an online, quantitative survey administered to patients aged ≥18 years with self-reported CKD, with or without anemia. Of 446 patients included, 255 (57.2%) were diagnosed with anemia and 191 (42.8%) were in the non-anemia cohort. In patients with anemia, 71.0% were aware of the relationship between CKD and anemia versus 52.9% in the non-anemia cohort. In the anemia cohort, 46.3% of patients were aware of their hemoglobin level, versus 27.2% in the non-anemia cohort. Despite 67.4% of patients with anemia believing their condition was well/very well managed, only 50% reported being informed about different treatments without prompting healthcare providers. In the US, patients with anemia and CKD perceived that anemia had a negative impact on physical health and emotional wellbeing. Results emphasize a lack of disease awareness, suggesting patients would benefit from further education on anemia in CKD.

6.
BMC Nephrol ; 23(1): 59, 2022 02 08.
Article in English | MEDLINE | ID: mdl-35135481

ABSTRACT

BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an effective and well-tolerated treatment for hyperkalemia in maintenance hemodialysis patients. In post-hoc analyses of the phase 3b DIALIZE study, we examined the spectrum of potassium responses to SZC. METHODS: Post-hoc analyses with SZC and placebo included: the number of long interdialytic interval (LIDI) visits during the 4-week evaluation period where patients attained pre-dialysis serum potassium (sK+) concentrations of 4.0-5.0 and 4.0-5.5 mmol/L; potassium gradient (the difference between pre-dialysis sK+ and dialysate potassium) at days 36, 43, 50, and 57, and change from baseline to the end of treatment (EOT) using categories of potassium gradient (1 to < 2, 2 to < 3, 3 to < 4, and ≥ 4 mmol/L). RESULTS: A greater proportion of patients achieved the ranges of pre-dialysis sK+ concentration with SZC versus placebo for ≥1, ≥ 2, ≥ 3, and 4 LIDI visits over 4 weeks; 23.7 and 48.5% of patients in the SZC group achieved pre-dialysis sK+ concentrations of 4.0-5.0 and 4.0-5.5 mmol/L, respectively, at all 4 LIDI visits. Baseline mean potassium gradient was similar with SZC and placebo. At day 57, mean (standard deviation) potassium gradient was 2.78 (0.08) mmol/L with SZC and 3.52 (0.08) mmol/L with placebo; mean difference (95% confidence interval) was - 0.74 mmol/L (- 0.97 to - 0.52). A greater reduction in potassium gradient category from baseline towards lower-risk categories at EOT was observed with SZC versus placebo. CONCLUSIONS: These analyses expand our knowledge of the spectrum of potassium responses with SZC in hyperkalemic hemodialysis patients. TRIAL REGISTRATION: NCT03303521 .


Subject(s)
Hyperkalemia/blood , Hyperkalemia/drug therapy , Ion Exchange Resins/therapeutic use , Potassium/blood , Silicates/therapeutic use , Dialysis Solutions/analysis , Double-Blind Method , Female , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged , Potassium/analysis , Renal Dialysis
9.
Int J Nephrol Renovasc Dis ; 14: 53-64, 2021.
Article in English | MEDLINE | ID: mdl-33654421

ABSTRACT

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD) that may reduce patients' health-related quality of life (HRQoL). This study explored the experience and knowledge of patients with CKD, with and without anemia, in China. METHODS: A quantitative online survey was administered to 500 consenting Chinese patient volunteers aged ≥18 years with self-reported CKD, with or without anemia, between August 29, and September 17, 2018. Patients with cancer were excluded. The 27-question survey explored knowledge of anemia, HRQoL, anemia management, and interactions with healthcare providers. RESULTS: Of 456 evaluable patients, 148 (32.5%) reported having anemia and 262 (57.5%) did not. Knowledge of anemia and its symptoms varied, and approximately half of all patients did not know their hemoglobin level. Patients with anemia expressed an adverse impact of anemia on HRQoL, most commonly lack of energy (65.5%), sadness/depression (54.1%), and feeling ill (50.0%). The most frequently reported treatments among these patients were dietary advice (68.9%), iron supplements (63.5%), and oral medications (53.4%). Although 89.2% of patients with anemia trusted their healthcare providers above other information sources, only 29.0% reported seeking information from them; this was despite 92.6% reporting wanting further information and support about managing conditions like anemia. CONCLUSION: Our findings suggest that patients with CKD, both with and without anemia, would benefit from increased awareness of anemia and more in-depth discussions with healthcare providers in order to facilitate better management of CKD and optimization of treatment plans.

10.
J Am Soc Nephrol ; 32(3): 737-755, 2021 03.
Article in English | MEDLINE | ID: mdl-33568383

ABSTRACT

BACKGROUND: Current anemia therapies for patients with non-dialysis-dependent CKD may require injection and medical visits. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis and improves iron homeostasis. METHODS: In this double-blind phase 3 study, we randomized patients with non-dialysis-dependent CKD stages 3-5 and hemoglobin <10.0 g/dl (1:1) to thrice-weekly 70-mg oral roxadustat or placebo. Doses were titrated throughout the study based on hemoglobin levels. The primary efficacy end point was mean change from baseline in hemoglobin averaged over weeks 28-52 versus placebo, irrespective of rescue therapy use. We assessed patients for adverse events. RESULTS: The study included 2781 patients, 1393 who received roxadustat and 1388 who received placebo. Mean baseline hemoglobin was 9.1 g/dl for both groups. The mean change in hemoglobin from baseline was 1.75 g/dl (95% confidence interval [95% CI], 1.68 to 1.81) with roxadustat versus 0.40 g/dl (95% CI, 0.33 to 0.47) with placebo, (P<0.001). Among 411 patients with baseline elevated high-sensitivity C-reactive protein, mean change in hemoglobin from baseline was 1.75 g/dl (95% CI, 1.58 to 1.92) with roxadustat versus 0.62 g/dl (95% CI, 0.44 to 0.80) with placebo, (P<0.001). Roxadustat reduced the risk of red blood cell transfusion by 63% (hazard ratio, 0.37; 95% CI, 0.30 to 0.44). The most common adverse events with roxadustat and placebo, respectively, were ESKD (21.0% versus 20.5%), urinary tract infection (12.8% versus 8.0%), pneumonia (11.9% versus 9.4%), and hypertension (11.5% versus 9.1%). CONCLUSIONS: Roxadustat effectively increased hemoglobin in patients with non-dialysis-dependent CKD and reduced the need for red blood cell transfusion, with an adverse event profile comparable to that of placebo. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With CKD, Not on Dialysis, NCT02174627.


Subject(s)
Anemia/drug therapy , Anemia/etiology , Glycine/analogs & derivatives , Hematinics/therapeutic use , Isoquinolines/therapeutic use , Prolyl-Hydroxylase Inhibitors/therapeutic use , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Aged , Anemia/blood , Double-Blind Method , Endpoint Determination , Female , Glycine/adverse effects , Glycine/therapeutic use , Hematinics/adverse effects , Hemoglobins/metabolism , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Isoquinolines/adverse effects , Male , Middle Aged , Prolyl-Hydroxylase Inhibitors/adverse effects , Renal Insufficiency, Chronic/blood , Safety
11.
J Am Soc Nephrol ; 30(9): 1723-1733, 2019 09.
Article in English | MEDLINE | ID: mdl-31201218

ABSTRACT

BACKGROUND: Patients with ESRD have minimal renal potassium excretion and, despite hemodialysis, often have persistent predialysis hyperkalemia. The DIALIZE study (NCT03303521) evaluated sodium zirconium cyclosilicate (SZC) in the management of hyperkalemia in hemodialysis patients. METHODS: In the DIALIZE study, a double-blind, placebo-controlled, phase 3b multicenter study, we randomized adults with ESRD who were managed by three-times weekly hemodialysis and had predialysis hyperkalemia to receive placebo or SZC 5 g once daily on non-dialysis days, and titrated towards maintaining normokalemia over 4 weeks, in 5 g increments to a maximum of 15 g. The primary efficacy outcome was proportion of patients during the 4-week stable-dose evaluation period who maintained predialysis serum potassium of 4.0-5.0 mmol/L during at least three of four hemodialysis treatments after the long interdialytic interval and did not require urgent rescue therapy to reduce serum potassium. RESULTS: In total, 196 patients (mean [standard deviation (SD)] age =58.1 [13.7] years old) were randomized to sodium zirconium cyclosilicate or placebo. Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001). Rescue therapy to reduce serum potassium during the treatment period was required by 2.1% of patients taking sodium zirconium cyclosilicate versus 5.1% taking placebo. Serious adverse events occurred in 7% and 8% of patients in sodium zirconium cyclosilicate and placebo groups, respectively. The two groups displayed comparable interdialytic weight gain. There were few episodes of hypokalemia. CONCLUSIONS: Sodium zirconium cyclosilicate is an effective and well-tolerated treatment for predialysis hyperkalemia in patients with ESRD undergoing adequate hemodialysis.


Subject(s)
Hyperkalemia/drug therapy , Ion Exchange Resins/therapeutic use , Kidney Failure, Chronic/complications , Silicates/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Hyperkalemia/etiology , Hyperkalemia/prevention & control , Ion Exchange Resins/adverse effects , Kidney Failure, Chronic/therapy , Male , Middle Aged , Potassium/blood , Renal Dialysis , Silicates/adverse effects , Young Adult
12.
Eur Heart J ; 40(11): 880-886, 2019 03 14.
Article in English | MEDLINE | ID: mdl-28431138

ABSTRACT

Although cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis. Several factors contribute to both the paucity of trials and the apparent lack of observed treatment effect in completed studies. Challenges associated with conducting trials in this population include patient heterogeneity, complexity of renal pathophysiology and its interaction with cardiovascular disease, and competing risks for death. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), an international organization of academic cardiovascular and renal clinical trialists, held a meeting of regulators and experts in nephrology, cardiology, and clinical trial methodology. The group identified several research priorities, summarized in this paper, that should be pursued to advance the field towards achieving improved cardiovascular outcomes for these patients. Cardiovascular and renal clinical trialists must partner to address the uncertainties in the field through collaborative research and design clinical trials that reflect the specific needs of the chronic and end-stage kidney disease populations, with the shared goal of generating robust evidence to guide the management of cardiovascular disease in patients with kidney disease.


Subject(s)
Cardiovascular Diseases/complications , Cardiovascular Diseases/therapy , Kidney Failure, Chronic/therapy , Renal Insufficiency, Chronic/complications , Cardiovascular Diseases/epidemiology , Cardiovascular System/physiopathology , Clinical Trials as Topic , Creatinine/blood , Humans , Interdisciplinary Placement/methods , Kidney/physiopathology , Patient Care Management/methods , Patient Selection , Renal Dialysis/methods , Renal Insufficiency, Chronic/epidemiology , Research Design/trends
14.
Eur J Sport Sci ; 17(2): 179-187, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27683969

ABSTRACT

The aim of this study was to examine the metabolic demand and extent of muscle damage of eccentric cycling targeting knee flexor (FLEX) and knee extensor (EXT) muscles. METHODS: Eight sedentary men (23.3 ± 0.7 y) underwent two eccentric cycling sessions (EXT and FLEX) of 30 min each, at 60% of the maximum power output. Oxygen consumption (VO2), heart rate (HR) and rated perceived exertion (RPE) were measured during cycling. Countermovement and squat jumps (CMJ and SJ), muscle flexibility, muscle soreness and pain pressure threshold (PPT) of knee extensor and flexor muscles were measured before, immediately after and 1-4 days after cycling. RESULTS: FLEX showed greater VO2 (+23%), HR (+14%) and RPE (+18%) than EXT. CMJ and SJ performance decreased similarly after cycling. Muscle soreness increased more after EXT than FLEX and PPT decreased in knee extensor muscles after EXT and decreased in knee flexor muscles after FLEX. Greater loss of muscle flexibility in knee flexor muscles after FLEX was observed. CONCLUSION: Eccentric cycling of knee flexor muscles is metabolically more demanding than that of knee extensors, however muscle damage induced is similar. Knee flexors experienced greater loss of muscle flexibility possibly due to increased muscle stiffness following eccentric contractions.


Subject(s)
Athletic Injuries/physiopathology , Bicycling/physiology , Knee/physiology , Muscle, Skeletal/injuries , Muscle, Skeletal/physiopathology , Range of Motion, Articular/physiology , Adult , Humans , Male , Random Allocation , Young Adult
16.
Nephrol Dial Transplant ; 29(4): 864-72, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24516231

ABSTRACT

BACKGROUND: Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD). METHODS: We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium HumanMethylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate. RESULTS: The mean eGFR slope was 2.2 (1.4) and -5.1 (1.2) mL/min/1.73 m(2) in the stable kidney function group and the rapid progression group, respectively. CpG islands in NPHP4, IQSEC1 and TCF3 were hypermethylated to a larger extent in subjects with stable kidney function (P-values of 7.8E-05 to 9.5E-05). These genes are involved in pathways known to promote the epithelial to mesenchymal transition and renal fibrosis. Other CKD-related genes that were differentially methylated are NOS3, NFKBIL2, CLU, NFKBIB, TGFB3 and TGFBI, which are involved in oxidative stress and inflammatory pathways (P-values of 4.5E-03 to 0.046). Pathway analysis using Ingenuity Pathway Analysis showed that gene networks related to cell signaling, carbohydrate metabolism and human behavior are epigenetically regulated in CKD. CONCLUSIONS: Epigenetic modifications may be important in determining the rate of loss of kidney function in patients with established CKD.


Subject(s)
DNA Methylation/genetics , Epigenesis, Genetic , Glomerular Filtration Rate , Renal Insufficiency, Chronic/genetics , Adult , Aged , Disease Progression , Epithelial-Mesenchymal Transition , Female , Humans , Male , Middle Aged , Prognosis , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/physiopathology , Young Adult
17.
Obesity (Silver Spring) ; 22(5): 1359-66, 2014 May.
Article in English | MEDLINE | ID: mdl-24415732

ABSTRACT

OBJECTIVE: The race-specific association of inflammation with adiposity and muscle mass in subjects with chronic kidney disease (CKD) was examined. METHODS: Plasma concentration of interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, tumor necrosis factor (TNF)-α, TGF-ß, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin was measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Bioelectric impedance analysis was used to determine body fat mass (BFM) and fat-free mass (FFM). RESULTS: Plasma levels of hs-CRP, fibrinogen, IL-1RA, IL-6, and TNF-α increased and serum albumin decreased across the quartiles of body mass index. In multivariable analysis, BFM and FFM were positively associated with hs-CRP, fibrinogen, IL-1ß, IL-1RA, and IL-6. One standard deviation (SD) increase in BFM and FFM was associated with 0.36 (95% confidence interval [CI] = 0.33, 0.39) and 0.26 (95% CI = 0.22, 0.30) SD increase in log-transformed hs-CRP, respectively (P < 0.001). Race stratified analysis showed that the association between biomarkers and BFM and FFM differed by race, with Caucasians, demonstrating a stronger association with markers of inflammation than African Americans. CONCLUSIONS: BFA and FFM are positively associated with markers of inflammation in patients with CKD. Race stratified analysis showed that Caucasians have a stronger association with markers of inflammation compared to African Americans.


Subject(s)
Adiposity , Black or African American , Inflammation/ethnology , Kidney Failure, Chronic/ethnology , White People , Adult , Aged , Biomarkers/blood , Body Mass Index , C-Reactive Protein/metabolism , Cohort Studies , Cross-Sectional Studies , Electric Impedance , Fibrinogen/metabolism , Humans , Inflammation/blood , Interleukin 1 Receptor Antagonist Protein/blood , Interleukin-10/blood , Interleukin-1beta/blood , Interleukin-6/blood , Kidney Failure, Chronic/blood , Linear Models , Middle Aged , Multivariate Analysis , Serum Albumin , Socioeconomic Factors , Transforming Growth Factor beta/blood , Tumor Necrosis Factor-alpha/blood
18.
Clin J Am Soc Nephrol ; 7(12): 1938-46, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23024164

ABSTRACT

BACKGROUND AND OBJECTIVES: Increased risk of mortality in patients with CKD has been attributed to inflammation. However, the association between kidney function, albuminuria, and biomarkers of inflammation has not been examined in a large cohort of CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study measured the plasma levels of IL-1ß, IL-1 receptor antagonist (IL-1RA), IL-6, TNF-α, TGF-ß, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin in 3939 participants enrolled in the Chronic Renal Insufficiency Cohort study between June 2003 and September 2008. An inflammation score was established based on plasma levels of IL-1ß, IL-6, TNF-α, hs-CRP, and fibrinogen. Estimated GFR (eGFR) and serum cystatin C were used as measures of kidney function. Albuminuria was quantitated by urine albumin to creatinine ratio (UACR). RESULTS: Plasma levels of IL-1ß, IL-1RA, IL-6, TNF-α, hs-CRP, and fibrinogen were higher among participants with lower levels of eGFR. Inflammation score was higher among those with lower eGFR and higher UACR. In regression analysis adjusted for multiple covariates, eGFR, cystatin C, and UACR were strongly associated with fibrinogen, serum albumin, IL-6, and TNF-α. Each unit increase in eGFR, cystatin C, and UACR was associated with a -1.2% (95% confidence interval, -1.4, -1), 64.9% (56.8, 73.3) and 0.6% (0.4, 0.8) change in IL-6, respectively (P<0.001). CONCLUSIONS: Biomarkers of inflammation were inversely associated with measures of kidney function and positively with albuminuria.


Subject(s)
Albuminuria/urine , Cytokines/blood , Inflammation/blood , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/physiopathology , Aged , Albuminuria/complications , Biomarkers/blood , C-Reactive Protein/metabolism , Cohort Studies , Confidence Intervals , Creatinine/urine , Cystatin C/blood , Female , Fibrinogen/metabolism , Glomerular Filtration Rate , Humans , Inflammation/complications , Interleukin 1 Receptor Antagonist Protein/blood , Interleukin-1beta/blood , Interleukin-6/blood , Male , Middle Aged , Multivariate Analysis , Renal Insufficiency, Chronic/complications , Serum Albumin/metabolism , Statistics, Nonparametric , Transforming Growth Factor beta/blood , Tumor Necrosis Factor-alpha/blood
19.
Semin Vasc Surg ; 25(2): 82-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22817857

ABSTRACT

Foot complications are common in patients with diabetes, however, chronic kidney disease has emerged as an independent risk factor for development of foot lesions in the diabetic population. Apart from peripheral arterial disease, infection, and neuropathy, which are classic factors contributing to development of foot lesions, skin disorders specific to renal failure, impaired wound healing from uremia, and psychosocial issues offer further compounded risk. Consequently, there are high ulceration and amputation rates that are associated with increased morbidity and mortality. In recent studies, foot-care programs with a multidisciplinary approach within dialysis units have demonstrated improved outcomes.


Subject(s)
Diabetic Foot/therapy , Diabetic Nephropathies/epidemiology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency/epidemiology , Amputation, Surgical , Combined Modality Therapy , Comorbidity , Diabetic Foot/epidemiology , Humans , Limb Salvage , Risk Assessment , Risk Factors , Treatment Outcome , Wound Healing
20.
Am J Cardiovasc Drugs ; 12(3): 165-78, 2012 Jun 01.
Article in English | MEDLINE | ID: mdl-22583147

ABSTRACT

Hispanics are the fastest growing ethnic minority in the USA. Among Hispanics, lack of hypertension awareness and lack of effective blood pressure (BP) control are problematic, as are higher incidence rates of hypertension-related co-morbidities compared with non-Hispanic populations. Moreover, there are currently no hypertension treatment guidelines that address the unique characteristics of this ethnic group. This article discusses ethnic differences in hypertension and cardiovascular risk factors and reviews the literature on the efficacy of antihypertensive agents in Hispanic patients, with a focus on the role of renin-angiotensin-aldosterone system (RAAS) inhibition in the management of hypertension in these patients. Hypertension in Hispanic patients can be challenging to manage, in part because this population has a higher prevalence of obesity, diabetes, and metabolic syndrome compared with non-Hispanic whites. The presence of these co-morbidities suggests that RAAS-inhibitor-based therapies may be particularly beneficial in this population. However, few studies have evaluated the efficacy of antihypertensive treatments in Hispanic patients. Two outcomes studies in hypertensive patients have shown the benefits of treating Hispanic patients with antihypertensive therapy and included RAAS inhibitors as part of the treatment regimen. In addition, BP-lowering trials have shown the antihypertensive efficacy of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and direct renin inhibitors, although data on the latter are more limited. Additional studies are needed to more thoroughly evaluate the effects of RAAS inhibitors (and other drug classes) on outcomes and BP lowering in the Hispanic hypertensive population.


Subject(s)
Antihypertensive Agents/therapeutic use , Hispanic or Latino/statistics & numerical data , Hypertension/drug therapy , Blood Pressure/drug effects , Health Knowledge, Attitudes, Practice , Humans , Hypertension/epidemiology , Hypertension/ethnology , Outcome Assessment, Health Care , Practice Guidelines as Topic , Renin-Angiotensin System/drug effects , Risk Factors , United States/epidemiology
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