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Ckd, trial and diabetes

Pablo Antonio Ureña-Torres, Mario Cozzolino, Jordi Bover
Secondary hyperparathyroidism (SHPT) is one of the most frequent and deleterious complication of chronic kidney disease (CKD). SHPT is also one of the principal components of the now called CKD-mineral and bone disorders (MBD) syndrome. It is usually prevented and treated by vitamin D derivatives. However, the rationale for the prescription of vitamin D sterols in those patients is still a matter of hotly debates, mainly because of unsatisfactory results from numerous observational and not well-controlled studies...
March 12, 2018: Néphrologie & Thérapeutique
Julio Rosenstock, Vlado Perkovic, John H Alexander, Mark E Cooper, Nikolaus Marx, Michael J Pencina, Robert D Toto, Christoph Wanner, Bernard Zinman, David Baanstra, Egon Pfarr, Michaela Mattheus, Uli C Broedl, Hans-Juergen Woerle, Jyothis T George, Maximilian von Eynatten, Darren K McGuire
BACKGROUND: Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA® trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk. METHODS: CARMELINA® is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events...
March 14, 2018: Cardiovascular Diabetology
Fen Chen, Shulin Li, Dong Sun
Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) has recently been utilized as a noninvasive tool for evaluating renal oxygenation. Several methods have been proposed for analyzing BOLD images. Regional ROI selection is the earliest and most widely used method for BOLD analysis. In the last 20 years, many investigators have used this method to evaluate cortical and medullary oxygenation in patients with ischemic nephropathy, hypertensive nephropathy, diabetic nephropathy, chronic kidney disease (CKD), acute kidney injury and renal allograft rejection...
March 8, 2018: Kidney & Blood Pressure Research
S Pilemann-Lyberg, M Lindhardt, Frederik Persson, S Andersen, P Rossing
AIMS: Uric acid (UA) is a risk factor for CKD. We evaluated UA in relation to change in GFR in patients with type 1 diabetes. METHODS: Post hoc analysis of a trial of losartan in diabetic nephropathy, mean follow-up 3 years (IQR 1.5-3.5). UA was measured at baseline. Primary end-point was change in measured GFR. UA was tested in a linear regression model adjusted for known progression factors (gender, HbA1c , systolic blood pressure, cholesterol, baseline GFR and baseline urinary albumin excretion rate (UAER))...
February 15, 2018: Journal of Diabetes and its Complications
Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Maria Dolores Sanchez-Niño, Lara Valiño-Rivas, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease...
March 9, 2018: Nephrology, Dialysis, Transplantation
Ramón C Hermida, Diana E Ayala, Artemio Mojón, José R Fernández
This trial investigated whether therapy with the entire daily dose of ≥1 hypertension medications at bedtime exerts a greater reduction in the risk of incident chronic kidney disease (CKD) than therapy with all medications upon awakening. We conducted a prospective, open-label, blinded endpoint trial of 2078 hypertensive patients without CKD (1017 men/1061 women, 53.6 ± 13.7 years of age) randomized to ingest all their prescribed hypertension medications upon awakening (n = 1041) or the entire daily dose of ≥1 of those medications at bedtime (n = 1037)...
March 12, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Jose Kuzhively, Bettina Tahsin, Peter Hart, Leon Fogelfeld
AIM: Evaluate legacy effect on renal outcomes after the end of a multifactorial-multidisciplinary intervention in patients with advanced diabetic nephropathy (ADN trial) CKD 3-4. METHODS: A retrospective electronic review was conducted of 72 patients who completed the ADN trial ESRD-free with subsequent follow-up of two years or until ESRD development. RESULTS: At baseline, reflecting ADN trial end, 38 post-intervention and 34 post-control patients were similar except for lower HbA1c, SBP and age in the post-intervention group...
February 10, 2018: Journal of Diabetes and its Complications
Ambreen Gul, Philip Zager
PURPOSE OF REVIEW: Multiple experimental and clinical studies have identified pathways by which uric acid may facilitate the development and progression of chronic kidney disease (CKD) in people with diabetes. However, it remains uncertain if the association of uric acid with CKD represents a pathogenic effect or merely reflects renal impairment. RECENT FINDINGS: In contrast to many published reports, a recent Mendelian randomization study did not identify a causal link between uric acid and CKD in people with type 1 diabetes...
March 1, 2018: Current Diabetes Reports
Andrew A House
Heart failure and chronic kidney disease have increasing incidence and prevalence owing in part to the aging population and increasing rates of hypertension, diabetes, and other cardiovascular and kidney disease risk factors. The presence of one condition also has a strong influence on the other, leading to greater risks for hospitalization, morbidity, and death, as well as very high health care costs. Despite the frequent coexistence of heart failure and chronic kidney disease, many of the pivotal randomized trials that guide the management of heart failure have excluded patients with more advanced stages of chronic kidney disease...
February 23, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Naila Rabbani, Paul J Thornalley
Advanced glycation end products (AGEs) are stable posttranslational modifications of proteins formed by the spontaneous reaction with glucose and related metabolites. Important AGEs quantitatively are methylglyoxal (MG)-derived hydroimidazolone MG-H1, Nε -carboxymethyl-lysine (CML), and glucosepane. They contribute to the development of chronic kidney disease (CKD). Cellular proteolysis of AGE-modified proteins forms AGE free adducts, glycated amino acids, which are cleared by the kidneys and excreted in urine...
February 22, 2018: Kidney International
Marinaldo Pacífico Cavalcanti Neto, Jailane de Souza Aquino, Larissa de Fátima Romão da Silva, Ruanniere de Oliveira Silva, Keyth Sulamitta de Lima Guimarães, Yohana de Oliveira, Evandro Leite de Souza, Marciane Magnani, Hubert Vidal, José Luiz de Brito Alves
The gut microbiota plays an important role in host metabolism and its dysregulation have been related to cardiometabolic disorders (CMD), such as type 2 diabetes mellitus (T2D), dyslipidemia and arterial hypertension, as well as to chronic kidney diseases (CKD). The implication of the gut microbiota on systemic disorders has been associated with changes in its composition (dysbiosis) as a result of the oxidative unbalance in the body. This alteration may be the result of the adoption of unhealthy lifestyle behavior, including lack of physical activity and fat- or sugar-rich diets, which are largely associated with increased incidence of CMD and CKD...
February 2, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Hiddo J L Heerspink, Dennis L Andress, George Bakris, John J Brennan, Ricardo Correa-Rotter, Jyotirmoy Dey, Fan-Fan Hou, Dalane W Kitzman, Donald Kohan, Hirofumi Makino, John McMurray, Vlado Perkovic, Sheldon Tobe, Melissa Wigderson, Hans-Henrik Parving, Dick de Zeeuw
AIMS: People with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin-to-creatinine ratio (UACR) with a large variability between patients. We are assessing its effect on renal outcomes in the Study of Diabetic Nephropathy with atrasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit...
February 6, 2018: Diabetes, Obesity & Metabolism
Melanie P Chin, George L Bakris, Geoffrey A Block, Glenn M Chertow, Angie Goldsberry, Lesley A Inker, Hiddo J L Heerspink, Megan O'Grady, Pablo E Pergola, Christoph Wanner, David G Warnock, Colin J Meyer
BACKGROUND: Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4...
2018: American Journal of Nephrology
Michael Mauer, Alessandro Doria
BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) in the western world. Current treatment methods, with better control of glycemia and blood pressure, including renin-angiotensin system blockade (RASB), appear to have slowed the DN progression rate but have not substantially decreased the annual incidence of new DN ESRD cases. Thus, new treatment targets are needed. SUMMARY: Higher levels of serum uric acid (UA) are associated with increased risk of the clinical manifestations of DN in persons with types 1 and 2 diabetes...
2018: Contributions to Nephrology
Claire C J Dekkers, David C Wheeler, C David Sjöström, Bergur V Stefansson, Valerie Cain, Hiddo J L Heerspink
Background: The sodium-glucose co-transporter 2 inhibitor dapagliflozin decreases haemoglobin A1c (HbA1c), body weight, blood pressure (BP) and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes. The efficacy and safety of this drug have not been properly defined in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease (CKD). Methods: In a pooled analysis of 11 phase 3 randomized controlled clinical trials, we determined least square mean changes in HbA1c, body weight, BP, estimated glomerular filtration rate (eGFR) and UACR over 102 weeks in patients with type 2 diabetes and an eGFR between 12 to less than 45 mL/min/1...
January 23, 2018: Nephrology, Dialysis, Transplantation
Alan J Garber, Martin J Abrahamson, Joshua I Barzilay, Lawrence Blonde, Zachary T Bloomgarden, Michael A Bush, Samuel Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Vivian A Fonseca, Jeffrey R Garber, W Timothy Garvey, George Grunberger, Yehuda Handelsman, Irl B Hirsch, Paul S Jellinger, Janet B McGill, Jeffrey I Mechanick, Paul D Rosenblit, Guillermo E Umpierrez
A1C = hemoglobin A1C; AACE = American Association of Clinical Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure; ACEI = angiotensin-converting enzyme inhibitor; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AGI = alpha-glucosidase inhibitor; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BAS = bile acid sequestrant; BCR-QR = bromocriptine quick release; BMI = body mass index; BP = blood pressure; CCB = calcium channel blocker; CHD = coronary heart disease; CKD = chronic kidney disease; CVD = cardiovascular disease; DASH = Dietary Approaches to Stop Hypertension; DPP4 = dipeptidyl peptidase 4; eGFR = estimated glomerular filtration rate; ER = extended release; FDA = Food and Drug Administration; GLP1 = glucagon-like peptide 1; HDL-C = high-density lipoprotein cholesterol; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C = low-density lipoprotein cholesterol; LDL-P = low-density lipoprotein particle; Look AHEAD = Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA = obstructive sleep apnea; RCT = randomized controlled trial; SU = sulfonylurea; SGLT2 = sodium glucose cotransporter-2; SMBG = self-monitoring of blood glucose; T2D = type 2 diabetes; TZD = thiazolidinedione; VADT = Veterans Affairs Diabetes Trial...
January 2018: Endocrine Practice
Katherine G Garlo, William B White, George L Bakris, Faiez Zannad, Craig A Wilson, Stuart Kupfer, Muthiah Vaduganathan, David A Morrow, Christopher P Cannon, David M Charytan
BACKGROUND AND OBJECTIVES: Biomarkers may improve identification of individuals at risk of eGFR decline who may benefit from intervention or dialysis planning. However, available biomarkers remain incompletely validated for risk stratification and prediction modeling. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined serum cystatin C, urinary kidney injury molecule-1 (uKIM-1), and urinary neutrophil gelatinase-associated lipocalin (UNGAL) in 5367 individuals with type 2 diabetes mellitus and recent acute coronary syndromes enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial...
March 7, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Ashok Kumar Yadav, Vivek Kumar, Debasish Banerjee, Krishan Lal Gupta, Vivekanand Jha
Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤ 20 ng/ml [CTRI/2013/05/003648]...
January 10, 2018: Journal of Steroid Biochemistry and Molecular Biology
Maxwell D Anderegg, Tyler H Gums, Liz Uribe, Eric J MacLaughlin, James Hoehns, Oralia V Bazaldua, Timothy J Ives, David L Hahn, Christopher S Coffey, Barry L Carter
OBJECTIVES: The objectives of this study were to 1) determine if hypertensive patients with comorbid diabetes mellitus (DM) and/or chronic kidney disease (CKD) receiving a pharmacist intervention had a greater reduction in mean blood pressure (BP) and improved BP control at 9 months compared to those receiving usual care and 2) compare Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) guideline and 2014 guideline (JNC-8) BP control rates in patients with DM and/or CKD...
January 13, 2018: Pharmacotherapy
Tetsu Okuda, Keisuke Okamura, Kazuyuki Shirai, Hidenori Urata
Background: Appropriate blood pressure control suppresses progression of chronic kidney disease (CKD). If an angiotensin-converting enzyme (ACE) inhibitor is ineffective, adding a calcium antagonist is recommended. We compared the long-term effect of two ACE inhibitor/calcium antagonist combinations on renal function in hypertensive patients with CKD. Methods: Patients who failed to achieve the target blood pressure (systolic/diastolic: < 130/80 mm Hg) with perindopril monotherapy were randomized to either combined therapy with perindopril and the L-type calcium antagonist amlodipine (group A) or perindopril and the T/L type calcium antagonist benidipine (group B)...
February 2018: Journal of Clinical Medicine Research
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