Vitamin D and its analogues: Do they protect against cardiovascular disease in patients with kidney disease?

Vitamin D and its analogs: Do they protect against cardiovascular disease in patients with kidney disease?BackgroundPatients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, and despite recent advances in hypertension control, anemia management, and dialysis adequacy, mortality remains high. Improved understanding of nontraditional risk factors, including those present at early phases in CKD, may lead to novel therapeutic strategies. CKD has been demonstrated to be an independent risk factor for cardiovascular disease in the general population, but data are lacking as to the associated potential abnormalities that occur in association with reduced glomerular filtration rate (GFR), which may contribute to this increased risk. Data are accumulating regarding the role of abnormalities of calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) in cardiovascular disease. Vitamin D deficiency is present even in the early stages of CKD. Vitamin D plays a central role in calcium-phosphorus homeostasis, regulation of PTH, and formation and maintenance of bone. However, until recently, vitamin D has not been considered to have a biologic role in CKD beyond mineral regulation, or has been considered as a negative factor contributing to soft tissue and cardiovascular calcification. In light of recent observational studies showing an association of vitamin D therapy and survival benefit in hemodialysis patients, the effects of vitamin D on cardiovascular system have become a heavily debated issue.MethodsA Medline search was performed to identify relevant literature describing the role of vitamin D in the pathogenesis of cardiovascular disease. Both the experimental and clinical literatures in English were reviewed.ResultsThe accumulating published data demonstrate both associative relationships and mechanisms for biologic plausibility. The following three potential mechanisms may be important for the protective effects of vitamin D against cardiovascular disease mortality: vitamin D can inhibit various aspects of inflammation, which have been established as a key pathogenic mechanism in atherosclerosis; vitamin D exerts an antiproliferative effect on myocardial cell hypertrophy and proliferation, which underlies the pathogenesis of congestive heart failure; and vitamin D acts as a negative endocrine regulator for the renin-angiotensin system, which itself plays an important independent role in hypertension and cardiovascular health.ConclusionVitamin D deficiency might be an underestimated nonclassical risk factor for cardiovascular disease in CKD. Based on a review of the evidence, from both basic science and clinical studies, this article supports the possible protective role of vitamin D beyond its effect on mineral metabolism, and suggests the need for ongoing evaluation of the role of vitamin D in cardiovascular health in the CKD population

Cohort profile: Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT)

Background: The Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT) is a large, prospective, pan-Canadian, cohort study designed to improve our understanding of determinants of renal and cardiovascular (CV) disease progression in patients with chronic kidney disease (CKD). The primary objective is to clarify the associations between traditional and newer biomarkers in the prediction of specific renal and CV events, and of death in patients with CKD managed by nephrologists. This information could then be used to better understand biological variation in outcomes, to develop clinical prediction models and to inform enrolment into interventional studies which may lead to novel treatments. Methods/Designs: Commenced in 2008, 2546 patients have been enrolled with eGFR between 15 and 45 ml/min 1.73m2 from a representative sample in 25 rural, urban, academic and non academic centres across Canada. Patients are to be followed for an initial 3 years at 6 monthly intervals, and subsequently annually. Traditional biomarkers include eGFR, urine albumin creatinine ratio (uACR), hemoglobin (Hgb), phosphate and albumin. Newer biomarkers of interest were selected on the basis of biological relevance to important processes, commercial availability and assay reproducibility. They include asymmetric dimethylarginine (ADMA), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), troponin I, cystatin C, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6) and transforming growth factor beta 1 (TGFβ1). Blood and urine samples are collected at baseline, and every 6 monthly, and stored at −80°C. Outcomes of interest include renal replacement therapy, CV events and death, the latter two of which are adjudicated by an independent panel. Discussion: The baseline distribution of newer biomarkers does not appear to track to markers of kidney function and therefore may offer some discriminatory value in predicting future outcomes. The granularity of the data presented at baseline may foster additional questions. The value of the cohort as a unique resource to understand outcomes of patients under the care of nephrologists in a single payer healthcare system cannot be overstated. Systematic collection of demographic, laboratory and event data should lead to new insights. The mean age of the cohort was 68 years, 90% were Caucasian, 62% were male, and 48% had diabetes. Forty percent of the cohort had eGFR between 30–45 mL/min/1.73m2, 22% had eGFR values below 20 mL/min/1.73m2; 61% had uACR < 30. Serum albumin, hemoglobin, calcium and 25-hydroxyvitamin D (25(OH)D) levels were progressively lower in the lower eGFR strata, while parathyroid hormone (PTH) levels increased. Cystatin C, ADMA, NT-proBNP, hsCRP, troponin I and IL-6 were significantly higher in the lower GFR strata, whereas 25(OH)D and TGFβ1 values were lower at lower GFR. These distributions of each of the newer biomarkers by eGFR and uACR categories were variable

Exploring the Relationships between Hemoglobin, the Endothelium and Vascular Health in Patients with Chronic Kidney Disease

Background/Aims: The ideal hemoglobin target in chronic kidney disease remains unknown. Ultimately, individualized targets may depend upon the properties of the patient’s endothelial and vascular milieu, and thus the complex relationships between these factors need to be further explored. Methods: Forty-six patients with a glomerular filtration rate (GFR) 2 or on renal replacement therapy underwent measurement of hemoglobin, endothelial microparticles (EMPs) and aortic pulse wave velocity (PWV) at 0, 3 and 6 months. In addition, a number of inflammatory, cardiac and vascular biomarkers were measured at baseline. Results: No correlation was observed between baseline values of PWV and EMPs, PWV and hemoglobin, or hemoglobin and EMPs in the overall cohort. When stratified by CKD status, a positive correlation was observed between PWV and EMP CD41–/CD144+ in patients with GFR 2 only (r = 0.54, p = 0.01). Asymmetric dimethylarginine correlated with baseline PWV (r = 0.27, p = 0.07), and remained significantly correlated with the 3- and 6-month PWV measurement. Conclusions: In this small heterogeneous cohort of dialysis and non-dialysis patients, we were unable to describe a physiologic link between anemia, endothelial dysfunction and arterial stiffness

Predicting kidney failure risk after acute kidney injury among people receiving nephrology clinic care

ACKNOWLEDGEMENTS We are grateful to Dr Nadia Zalunardo for her comments on this study. FUNDING Dr Sawhney received funding from a research training fellowship from the Wellcome Trust to conduct this study (102729/ Z/13/Z).Peer reviewedPublisher PD

Intermediate and Long-Term Outcomes of Survivors of Acute Kidney Injury Episodes

Background The long-term prognosis after acute kidney injury (AKI) is variable. It is unclear how the prognosis of AKI and its relationship to prognostic factors (baseline kidney function, AKI severity, prior AKI episodes, and recovery of kidney function) change as follow-up progresses. Study Design Observational cohort study. Setting & Participants The Grampian Laboratory Outcomes Morbidity and Mortality Study II (GLOMMS-II) is a large regional population cohort with complete serial biochemistry and outcome data capture through data linkage. From GLOMMS-II, we followed up 17,630 patients hospitalized in 2003 through to 2013. Predictors AKI identified using KDIGO (Kidney Disease: Improving Global Outcomes) serum creatinine criteria, characterized by baseline kidney function (estimated glomerular filtration rate [eGFR] ≥ 60, 45-59, 30-44, and <30 mL/min/1.73 m2), AKI severity (KDIGO stage), 90-day recovery of kidney function, and prior AKI episodes. Outcomes Intermediate- (30-364 days) and long-term (1-10 years) mortality and long-term renal replacement therapy. Measurements Poisson regression in time discrete intervals. Multivariable Cox regression for those at risk in the intermediate and long term, adjusted for age, sex, baseline comorbid conditions, and acute admission circumstances. Results Of 17,630 patients followed up for a median of 9.0 years, 9,251 died. Estimated incidences of hospital AKI were 8.4% and 17.6% for baseline eGFRs ≥ 60 and <60 mL/min/1.73 m2, respectively. Intermediate-term (30-364 days) adjusted mortality HRs for AKI versus no AKI were 2.48 (95% CI, 2.15-2.88), 2.50 (95% CI, 2.04-3.06), 1.90 (95% CI, 1.51-2.39), and 1.63 (95% CI, 1.20-2.22) for eGFRs ≥ 60, 45 to 59, 30 to 44, and <30 mL/min/1.73 m2, respectively. Among 1-year survivors, long-term HRs were attenuated: 1.44 (95% CI, 1.31-1.58), 1.25 (95% CI, 1.09-1.43), 1.21 (95% CI, 1.03-1.42), and 1.08 (95% CI, 0.85-1.36), respectively. The excess long-term hazards in AKI were lower for lower baseline eGFRs (P for interaction = 0.01). Limitations Nonprotocolized observational data. No adjustment for albuminuria. Conclusions The prognostic importance of a discrete AKI episode lessens over time. Baseline kidney function is of greater long-term importance

Salud renal y salud en la mujer: Una oportunidad para mejorar las condiciones de las generaciones actuales y futuras

y el impacto de la enfermedad en el paciente y sus familias puede ser devastador. En el 2018 el Día Mundial del Riñón y el Día Internacional de la Mujer coinciden, ofreciéndonos una oportunidad para demostrar el impacto que tiene la salud de la mujer, específicamente su salud renal, en la comunidad y en las generaciones futuras, es importante fomentar el conocimiento sobre aspectos específicos de la enfermedad renal en la mujer y poder aplicarlos de forma extensiva. Las mujeres y niñas representan aproximadamente el 50 % de la población mundial, siendo integrantes fundamentales de la sociedad y de sus familias. Las diferencias de género persisten alrededor del mundo, afectando su acceso a la educación, cuidados de salud y su inclusión en estudios clínicos. Actualmente, el embarazo en la mujer es una etapa única que ofrece la oportunidad de diagnosticar la enfermedad renal, donde las enfermedades renales agudas y crónicas pueden manifestarse, lo cual podría impactar en la salud renal de las generaciones futuras. Existen varias enfermedades autoinmunes y algunos otros factores que afectan más comúnmente a la mujer, con serias consecuencias durante el embarazo para la madre y para el feto. Las mujeres en diálisis en comparación con los hombres tienen complicaciones diferentes; además son más comúnmente donadoras que receptoras del trasplante renal. En esta editorial, nos enfocamos en qué hacemos y en qué no conocemos sobre la mujer, la salud y enfermedad renal, y qué podemos aprender para mejorar sus condiciones en todo el mund

Chronic kidney disease

Chronic kidney disease (CKD) is defined by persistent urine abnormalities, structural abnormalities or impaired excretory renal function suggestive of a loss of functional nephrons. The majority of patients with CKD are at risk of accelerated cardiovascular disease and death. For those who progress to end-stage renal disease, the limited accessibility to renal replacement therapy is a problem in many parts of the world. Risk factors for the development and progression of CKD include low nephron number at birth, nephron loss due to increasing age and acute or chronic kidney injuries caused by toxic exposures or diseases (for example, obesity and type 2 diabetes mellitus). The management of patients with CKD is focused on early detection or prevention, treatment of the underlying cause (if possible) to curb progression and attention to secondary processes that contribute to ongoing nephron loss. Blood pressure control, inhibition of the renin-angiotensin system and disease-specific interventions are the cornerstones of therapy. CKD complications such as anaemia, metabolic acidosis and secondary hyperparathyroidism affect cardiovascular health and quality of life, and require diagnosis and treatmen

The KRESCENT Program (2005-2015) : an evaluation of the state of Kidney Research Training in Canada

Background: The Kidney Research Scientist Core Education and National Training (KRESCENT) Program was launched in 2005 to enhance kidney research capacity in Canada and foster knowledge translation across the 4 themes of health research. Objective: To evaluate the impact of KRESCENT on its major objectives and on the careers of trainees after its first 10 years. Methods: An online survey of trainees (n = 53) who had completed or were enrolled in KRESCENT was conducted in 2015. Information was also obtained from curriculum vitae (CVs). A bibliometric analysis assessed scientific productivity, collaboration, and impact in comparison with unsuccessful applicants to KRESCENT over the same period. The analysis included a comparison of Canadian with international kidney research metrics from 2000 to 2014. Results: Thirty-nine KRESCENT trainees completed the survey (74%), and 44 trainees (83%) submitted CVs. KRESCENT trainees had a high success rate at obtaining grant funding from the Canadian Institutes of Health Research (CIHR; 79%), and 76% of Post-Doctoral Fellows received academic appointments at the Assistant Professor level within 8 months of completing training. The majority of trainees reported that KRESCENT had contributed significantly to their success in securing CIHR funding (90%), and to the creation of knowledge (93%) and development of new methodologies (50%). Bibliometric analysis revealed a small but steady decline in total international kidney research output from 2000 to 2014, as a percentage of all health research, although overall impact of kidney research in Canada increased from 2000-2005 to 2009- 2014 compared with other countries. KRESCENT trainees demonstrated increased productivity, multiauthored papers, impact, and international collaborations after their training, compared with nonfunded applicants. Conclusions: The KRESCENT Program has fostered kidney research career development and contributed to increased capacity, productivity, and collaboration. To further enhance knowledge creation and translation in kidney research in Canada, programs such as KRESCENT should be sustained via long-term funding partnerships.Mise en contexte: Le programme KRESCENT (Kidney Research Scientist Core Education and National Training) a été lancé en 2005 pour augmenter la capacité de la recherche sur les maladies du rein à travers le Canada, et pour encourager la transmission des connaissances au sein des quatre axes de recherche en santé. Objectifs de l’étude: Cette étude avait pour but d’évaluer les répercussions du programme KRESCENT sur ses principaux objectifs ainsi que des retombées sur la carrière des stagiaires participants, dix ans après sa création. Méthodologie: Un sondage en ligne a été mené en 2015 auprès des stagiaires (n = 53) ayant été admis ou ayant complété le programme KRESCENT. Des renseignements ont également été obtenus par la consultation de curriculum vitae (CV). Une analyse bibliométrique a évalué la productivité scientifique et la collaboration des participants ainsi que les répercussions de leur participation à KRESCENT sur leur carrière. Les données de cette analyse ont été comparées à celles des candidats n’ayant pas été retenus au cours de la même période. L’analyse comprenait également une comparaison des données canadiennes avec celles obtenues en recherche sur les maladies du rein ailleurs dans le monde

Implementing personalized medicine in diabetic kidney disease:Stakeholders' perspectives

The promise of personalized medicine to deliver "the right treatments at the right time to the right person" is the next frontier in healthcare. However, to implement personalized medicine in chronic diseases such as diabetes mellitus and diabetic kidney disease (DKD), a number of different aspects need to be taken into account. Better risk stratification and more precise options for treatment need to be developed and included in clinical practice guidelines. A patient's unique psychological, social and environmental situation also drive disease progression and outcomes. Appraising the cost effectiveness of precision medicines is necessary, not just as the cost of new therapies, but also the cost of diagnosis with novel methodologies and averted complications. As the prevalence of DKD grows worldwide to epidemic proportions, challenges such as global disparities in resources, access to healthcare and prevalence need to be addressed. This review considers these issues to achieve the short and longer-term goals of implementing personalized medicine in clinical practice