Association between circulating proprotein convertase subtilisin/kexin type 9 levels and prognosis in patients with severe chronic kidney disease

2018 ◽  
Vol 35 (4) ◽  
pp. 632-639 ◽  
Author(s):  
Laust Dupont Rasmussen ◽  
Morten Bøttcher ◽  
Per Ivarsen ◽  
Hanne Skou Jørgensen ◽  
Mette Nyegaard ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Coronary Artery ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Healthy Controls ◽  
Proprotein Convertase ◽  
Transplant Candidates

Abstract Background Chronic kidney disease is a risk factor for premature development of coronary atherosclerosis and mortality. A high level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently recognized cardiovascular risk factor and has become the target of effective inhibitory treatment. In 167 kidney transplantation candidates, we aimed to: (i) compare levels of PCSK9 with those of healthy controls, (ii) examine the association between levels of PCSK9 and low-density lipoprotein cholesterol (LDL-c) and the degree of coronary artery disease (CAD) and (iii) evaluate if levels of PCSK9 predict major adverse cardiac events (MACE) and mortality. Methods Kidney transplant candidates (n = 167) underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) before transplantation. MACE and mortality data were extracted from the Western Denmark Heart Registry, a review of patient records and patient interviews. A group of 79 healthy subjects were used as controls. Results Mean PCSK9 levels did not differ between healthy controls and kidney transplant candidates. In patients not receiving lipid-lowering therapy, PCSK9 correlated positively with LDL-c (rho = 0.24, P < 0.05). Mean PCSK9 was similar in patients with and without obstructive CAD at both CCTA and ICA. In a multiple regression analysis, PCSK9 was associated with neither LDL-c (β=−6.45, P = 0.44) nor coronary artery calcium score (β=2.17, P = 0.84). During a follow-up of 3.7 years, PCSK9 levels were not associated with either MACE or mortality. Conclusions The ability of PCSK9 levels to predict cardiovascular disease and prognosis does not seem to apply to a cohort of kidney transplant candidates.

LDL S-homocysteinylation decrease in chronic kidney disease patients undergone lipid lowering therapy

2012 ◽  
Vol 47 (1) ◽  
pp. 117-123 ◽  
Author(s):  
Angelo Zinellu ◽  
Salvatore Sotgia ◽  
Elisabetta Pisanu ◽  
Giacomina Loriga ◽  
Luca Deiana ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy

MANAGEMENT OF HYPERPARATHYROIDISM IN KIDNEY TRANSPLANTATION CANDIDATES: A NEED FOR CONSENSUS

2020 ◽  
Vol 26 (3) ◽  
pp. 299-304 ◽  
Author(s):  
Hubert Golingan ◽  
Shenae K. Samuels ◽  
Pauline Camacho ◽  
Darshana M. Dadhania ◽  
Fernando E. Pedraza-Taborda ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
American Association ◽  
The United States ◽  
Standards Of Care ◽  
Endocrine Surgery ◽  
Transplant Candidates

Objective: To assess the evolving standards of care for hyperparathyroidism in kidney transplant candidates. Methods: An 11-question, Institutional Review Board–approved survey was designed and reviewed by multiple institutions. The questionnaire was made available to the American Society of Transplantation's Kidney Pancreas Community of Practice membership via their online hub from April through July 2019. Results: Twenty percent (n = 41) of kidney transplant centers responded out of 202 programs in the United States. Forty-one percent (n = 17) of respondents believed medical literature supports the concept that a serum parathyroid hormone level greater than 800 pg/mL could endanger the survival of a transplanted kidney and therefore makes transplantation in an affected patient relatively or absolutely contraindicated. Sixty-six percent (n = 27) said they occasionally recommend parathyroidectomy for secondary hyperparathyroidism prior to transplantation, and 66% (n = 27) recommend parathyroidectomy after transplantation based on persistent, unsatisfactory posttransplantation parathyroid hormone levels. Forty-six percent (n = 19) prefer subtotal parathyroidectomy as their choice; 44% (n = 18) had no standard preference. Endocrine surgery and otolaryngology were the most common surgical specialties consulted to perform parathyroidectomy in kidney transplant candidates. The majority of respondents (71%, n = 29) do not involve endocrinologists in the management of kidney transplantation candidates. Conclusion: Our survey shows wide divergence of clinical practice in the area of surgical management of kidney transplantation candidates with hyperparathyroidism. We suggest that medical/surgical societies involved in the transplantation care spectrum convene a multidisciplinary group of experts to create a new section in the kidney transplantation guidelines addressing the collaborative management of parathyroid disease in transplantation candidates. Abbreviations: AACE = American Association of Clinical Endocrinologists; AAES = American Association of Endocrine Surgeons; AHNS = American Head and Neck Society; CKD = chronic kidney disease; CKD-MBD = chronic kidney disease–mineral and bone disorder; ESRD = end-stage renal disease; HPT = hyperparathyroidism; KDIGO = Kidney Disease Improving Global Outcomes; KT = kidney transplantation; KTC = kidney transplant candidate; PTH = parathyroid hormone; PTX = parathyroidectomy; US = ultrasonography

scholarly journals Plasma Nitration of High-Density and Low-Density Lipoproteins in Chronic Kidney Disease Patients Receiving Kidney Transplants

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Ahmed Bakillah ◽  
Fasika Tedla ◽  
Isabelle Ayoub ◽  
Devon John ◽  
Allen J. Norin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Sandwich Elisa ◽  
High Density ◽  
Hiv Protease ◽  
Lipid Lowering ◽  
Hiv Protease Inhibitors ◽  
Kidney Transplant Recipients

Background. Functional abnormalities of high-density lipoprotein (HDL) could contribute to cardiovascular disease in chronic kidney disease patients. We measured a validated marker of HDL dysfunction, nitrated apolipoprotein A-I, in kidney transplant recipients to test the hypothesis that a functioning kidney transplant reduces serum nitrated apoA-I concentrations.Methods. Concentrations of nitrated apoA-I and apoB were measured using indirect sandwich ELISA assays on sera collected from each transplant subject before transplantation and at 1, 3, and 12 months after transplantation. Patients were excluded if they have history of diabetes, treatment with lipid-lowering medications or HIV protease inhibitors, prednisone dose > 15 mg/day, nephrotic range proteinuria, serum creatinine > 1.5 mg/dL, or active inflammatory disease. Sera from 18 transplanted patients were analyzed. Four subjects were excluded due to insufficient data. Twelve and eight patients had creatinine < 1.5 mg/dL at 3 and 12 months after transplantation, respectively.Results. Nitrated apoA-I was significantly reduced at 12 months after transplantation (p=0.039). The decrease in apoA-I nitration was associated with significant reduction in myeloperoxidase (MPO) activity (p=0.047). In contrast to apoA-I, nitrated apoB was not affected after kidney transplantation.Conclusions. Patients with well-functioning grafts had significant reduction in nitrated apoA-I 12 months after kidney transplantation. Further studies are needed in a large cohort to determine if nitrated apoA-I can be used as a valuable marker for cardiovascular risk stratification in chronic kidney disease.

Intensive Lipid Lowering With Atorvastatin in Patients With Coronary Artery Disease, Diabetes, and Chronic Kidney Disease

2008 ◽  
Vol 83 (8) ◽  
pp. 870-879 ◽  
Author(s):  
James Shepherd ◽  
John J.P. Kastelein ◽  
Vera A. Bittner ◽  
Rafael Carmena ◽  
Prakash C. Deedwania ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Chronic Kidney Disease ◽  
Coronary Artery ◽  
Kidney Disease ◽  
Lipid Lowering ◽  
Artery Disease

Lipid disorders of patients with chronic kidney disease

2015 ◽  
Author(s):  
Alan G. Jardine ◽  
Rajan K. Patel
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Coronary Disease ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Strong Argument ◽  
Lowering Therapy ◽  
Coronary Events ◽  
Cv Disease

The risk of developing cardiovascular (CV) disease is increased in patients with chronic kidney disease (CKD) and although dyslipidaemia is a major contributory factor to the development of premature CV disease, the relationship is complex. Changes in lipid fractions are related to glomerular filtration rate and the presence and severity of proteinuria, diabetes, and other confounding factors. The spectrum of CV disease changes from lipid-dependent, atheromatous coronary disease in early CKD to lipid-independent, non-coronary disease, manifesting as heart failure, and sudden cardiac death in advanced and end-stage renal disease. Statin-based lipid-lowering therapy is proven to reduce coronary events across the spectrum of CKD. The relative reduction in overall CV events, however, diminishes as CKD progresses and the proportion of lipid-dependent coronary events declines. There is nevertheless a strong argument for the use of statin-based therapy across the spectrum of CKD. The argument is particularly strong for those patients with progressive renal disease who will eventually require transplantation, in whom preventive therapy should start as early as possible. The SHARP study established the benefits and endorses the use of lipid-lowering therapy in CKD 3-4 but uncertainty about the value of initiation of statin therapy in CKD 5 remains. There is, however, no rationale for stopping agents started earlier in the course of the illness for compelling indications, particularly in those who will ultimately be transplanted. The place of high-density lipoprotein-cholesterol raising and triglyceride lowering therapy needs to be assessed in trials. Modifying dyslipidaemia in CKD has demonstrated that lipid-dependent atheromatous cardiovascular disease is only one component of the burden of CV disease in CKD patients, that this is proportionately less in advanced CKD, and that modification of lipid profiles is only one part of CV risk management.

MO445BRAIN AND GUT AXIS IN CHRONIC KIDNEY DISEASE: FOCUS ON SPECIFIC BIOMARKERS, AND TIGHT JUNCTION PROTEINS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Leah Hernandez ◽  
Liam Ward ◽  
Thomas Ebert ◽  
Samsul Arefin ◽  
Olof Heimbürger ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tight Junction ◽  
Kidney Transplant ◽  
Subcutaneous Fat ◽  
Intestinal Barrier ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Tight Junction Proteins ◽  
Junction Proteins

Abstract Background and Aims Chronic kidney disease (CKD) is a progressive systemic disease that affect the microvascular permeability of the blood-brain barrier (BBB) and intestinal barrier leading to increased morbidity, mortality and central nervous system symptoms. In this study we examined the relationship of blood brain and intestinal barrier dysfunction in relation to uraemic environment and increased risk of developing neurologic complications and mortality. In addition, potential proteins conferring the junctional communications were assessed. Method The study included serum samples from 216 prevalent haemodialysis (HD), 80 peritoneal dialysis (PD) and 80 healthy subjects. Permeability of the BBB was evaluated by measuring serum concentrations for brain-specific biomarkers S100B, NSE (neuron specific enolase), BDNF (brain-derived neurotrophic factor), GFAP (glial fibrillary acidic protein) using ELISA. TMAO (trimethylamine-N-Oxide) as a surrogate of gut generated uraemic toxins was analysed by mass spectrophotometry. Subcutaneous fat tissues with identified microvessels from 10 kidney transplant recipients and 11 donors were examined for expression of tight junction proteins claudin-5, occludin and JAM-1 (junction adhesion molecule-1) by immunohistochemical staining. Results HD and PD groups showed elevated cholesterol, triglyceride, creatinine, hsCRP and lower BMI, and P-albumin compared to healthy controls. BDNF serum concentrations were lower in both HD (14.0 ng/mL, IQR 8.7-19.2) and PD (17.9 ng/mL, IQR 14.4-23.4) vs controls (20.2 ng/mL, IQR 16.7-25.7). Similarly, S100B serum concentrations were lower in both HD (31.6 pg/mL, IQR 9.4-186) and PD (49.4 pg/mL, IQR 9.8-118) vs control (87.3 pg/mL, IQR 13.3-749). Conversely, NSE serum concentrations were higher in both HD (5.3 ng/mL, IQR 4.4-6.6) and PD (4.0 ng/mL, IQR 3.6-4.7) vs controls (3.5 ng/mL, IQR 2.9-4.3). Finally, TMAO serum concentration were also higher in both HD (6.4 ng/μL, IQR 4.0-11.2) and PD (3.8 ng/μL, IQR 2.2-6.3) vs controls (0.4 ng/μL, IQR 0.3-0.6). No significant sex differences in biomarker concentration were found, except for TMAO in healthy controls. Immunohistochemistry studies of endothelial tight junction proteins in microvessels, within the subcutaneous fat tissues, showed reduced expression of claudin-5 (5%), occludin (6%) and JAM-1 (5%) in kidney transplant patients vs donors (7%, 8% and 8%, respectively), and ongoing studies are indicating a trend for altered expression of tight junction proteins after ex vivo stimulation with TMAO. Conclusion We report that CKD5 patients showed disruption of BBB and intestinal barrier resulting in altered circulating serum levels of brain-specific biomarkers, secondary to a disruption in the tight junction protein markers in microvasculature of adipose tissue. These findings imply that it is important to continuously monitor cognitive function(s) in CKD. Further studies are needed to assess direct effect of TMAO on tight junction proteins which confer vascular permeability.

Abstract P370: Risk Factors for Progression of Coronary Artery Calcification in Patients with Chronic Kidney Disease

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Joshua D Bundy ◽  
Lawrence J Appel ◽  
Matthew Budoff ◽  
Jing Chen ◽  
Alan S Go ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Coronary Artery ◽  
Kidney Disease ◽  
Cystatin C ◽  
Coronary Artery Calcification ◽  
Lipid Lowering ◽  
Cvd Risk Factors ◽  
Cvd Risk

Introduction: Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and predicts the risk of cardiovascular disease (CVD). Risk factors for the progression of CAC in patients with CKD have not been well studied. Hypothesis: We assessed the hypothesis that several established and novel CVD risk factors are associated with progression of CAC among patients with CKD. Methods: In a random subsample of 1,123 participants from the Chronic Renal Insufficiency Cohort (CRIC) Study, CAC was measured at baseline and the follow-up visit using electron beam computed tomography (CT) or multidetector CT. CAC progression was defined as an increase of Agatston score ≥100 units during follow-up. Multiple logistic regression and mixed-effects regression models were used to assess risk factors for progression of CAC. Results: Over an average of 3-year follow-up, 332 (29.6%) participants developed CAC progression. After adjusting for age, sex, race, clinical site, total cholesterol, HDL-cholesterol, systolic blood pressure, antihypertensive treatment, diabetes, and current smoking in the multivariable models, history of CVD (odds ratio [OR] 1.53, 95% CI 1.09-2.15, p=0.02), lipid-lowering treatment (OR 1.81, 95% CI 1.28-2.55, p<0.001), higher serum phosphate (OR 1.37, 95% CI 1.17-1.61, p<0.001), hemoglobin A1c (OR 1.32, 95% CI 1.10-1.58, p=0.002), and cystatin C (OR 1.24, 95% CI 1.06-1.45, p=0.007), and lower estimated-glomerular filtration rate (eGFR) (OR 1.32, 95% CI 1.10-1.56, p=0.002) were associated with CAC progression. In addition, lower physical activity, lipid-lowering treatment, body-mass index, LDL-cholesterol, lower serum calcium, phosphate, total parathyroid hormone, fibrinogen, interleukin-6, tumor necrosis factor-α, fibroblast growth factor-23, lower eGFR, cystatin C, and 24-hour urine albumin were associated with square root transformed change in CAC score from baseline in multiple-adjusted models. These findings persisted after additional adjustment for baseline CAC score. Conclusions: In conclusion, these data suggest that reduced kidney function, calcium and phosphate metabolic disorders and inflammation, in addition to established CVD risk factors, might play a role in CAC progression among patients with CKD.

Lipid-Lowering Therapy in Persons With Chronic Kidney Disease

2012 ◽  
Vol 157 (4) ◽  
pp. 251 ◽  
Author(s):  
Ashish Upadhyay ◽  
Amy Earley ◽  
Jenny L. Lamont ◽  
Shana Haynes ◽  
Christoph Wanner ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy

scholarly journals Impact of age on cardiovascular drug use in patients with chronic kidney disease

2019 ◽  
Vol 13 (2) ◽  
pp. 199-207
Author(s):  
Cédric Villain ◽  
Sophie Liabeuf ◽  
Marie Metzger ◽  
Christian Combe ◽  
Denis Fouque ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Oral Anticoagulants ◽  
Antiplatelet Agents ◽  
Older Age ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Antithrombotic Drugs ◽  
Ras Blockers

Abstract Background Elderly patients with chronic kidney disease (CKD) are often excluded from clinical trials; this may affect their use of essential drugs for cardiovascular complications. We sought to assess the impact of age on cardiovascular drug use in elderly patients with CKD. Methods We used baseline data from the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort including 3033 adult patients with CKD Stages 3 and 4. We studied the use of recommended drugs for coronary artery disease (CAD), stroke and atrial fibrillation by age, after adjusting for socio-demographic and clinical conditions. Results The patients’ mean age was 66.8 years (mean estimated glomerular filtration rate 32.9 mL/min/1.73 m2). The prevalence of CAD was 24.5% [81.3% receiving antiplatelet agents, 75.6% renin–angiotensin system (RAS) blockers, 65.4% β-blockers and 81.3% lipid-lowering therapy], that of stroke 10.0% (88.8% receiving antithrombotic drugs) and that of atrial fibrillation 11.1% (69.5% receiving oral anticoagulants). Compared with patients aged &lt;65 years, older age (≥65 years) was associated with greater use of antithrombotic drugs in stroke [adjusted odds ratio (aOR) (95% confidence interval) = 2.83 (1.04–7.73) for patients aged (75–84 years)] and less use of RAS blockers [aOR = 0.39 (0.16–0.89) for patients aged ≥85 years], β-blockers [aOR = 0.31 (0.19–0.53) for patients aged 75–84 years] and lipid-lowering therapy [aOR = 0.39 (0.15–1.02) for patients aged ≥85 years, P for trend = 0.01] in CAD. Older age was not associated with less use of antiplatelet agents in CAD or oral anticoagulants in atrial fibrillation. Conclusions In patients with CKD, older age per se was not associated with the underuse of antithrombotic drugs but was for other major drugs, with a potential impact on cardiovascular outcomes.

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