Nigel D. Toussaint

Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters

The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update of the prior CKD-MBD Guideline published in 2009. This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant. This review highlights key aspects of the 2017 CKD-MBD Guideline Update, with an emphasis on the rationale for the changes made to the original guideline document. Topic areas encompassing updated recommendations include diagnosis of bone abnormalities in CKD-mineral and bone disorder (MBD), treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of abnormalities in parathyroid hormone in CKD-MBD, treatment of bone abnormalities by antiresorptives and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease.

Bisphosphonates in Chronic Kidney Disease; Balancing Potential Benefits and Adverse Effects on Bone and Soft Tissue

Cardiovascular disease is highly prevalent in chronic kidney disease (CKD) and is often associated with increased vascular stiffness and calcification. Recent studies have suggested a complex interaction between vascular calcification and abnormalities of bone and mineral metabolism, with an inverse relationship between arterial calcification and bone mineral density (BMD). Although osteoporosis is recognized and treated in CKD 1 to 3, the interpretation of BMD levels in the osteoporotic range is controversial in CKD 4, 5, and 5D when renal osteodystrophy is generally present. In addition, there is a paucity of data for patients with CKD mineral and bone disorder (MBD), because studies using bisphosphonates in postmenopausal and glucocorticoid-induced osteoporosis have generally excluded patients with significant CKD. For these patients, treatment of low BMD using standard therapies for osteoporosis is not without potential for harm due to the possibility of worsening low bone turnover, osteomalacia, mixed uraemic osteodystrophy, and of exacerbated hyperparathyroidism; and bisphosphonates should only be used selectively and with caution. Some experimental and clinical studies have also suggested that bisphosphonates may reduce progression of extra-osseous calcification and inhibit the development of atherosclerosis. The authors review the potential benefits and risks associated with bisphosphonate use for bone protection in CKD, and assess their effect on vascular calcification and atherosclerosis.

KHA-CARI Guideline: Early chronic kidney disease: Detection, prevention and management

Early detection of CKD may therefore have value,although criteria for a screening programme to detect thedisease must be met to balance the aggregate benefits withthe risks and costs of the screening tests. General practition-ers, in particular, play a crucial role in CKD early detectionand management. All people attending their general practi-tioner should be assessed for CKD risk factors as part ofroutine primary health encounters.A number of studies

Serum fetuin-A concentration and fetuin-A-containing calciprotein particles in patients with chronic inflammatory disease and renal failure

Fetuin‐A (Fet‐A) is an important regulator of extracellular matrix mineralization. Fet‐A plays a critical role in the formation and stabilization of high molecular weight colloidal protein–mineral complexes known as calciprotein particles (CPP). The aim of this study was to examine the effects of inflammation, renal function and dialysis modality on serum Fet‐A and CPP.

Improving CKD-MBD management in haemodialysis patients: barrier analysis for implementing better practice

BACKGROUND Although clinical guidelines exist for optimal levels of serum markers of chronic kidney disease mineral and bone disorder (CKD-MBD), target parameters are not achieved in many haemodialysis (HD) patients. The reason for this evidence-practice gap is unclear and more information from patients and healthcare professionals is required to improve knowledge transfer. We aimed to determine potential barriers by surveying HD patients and staff about awareness and management of CKD-MBD. METHODS A total of 136 prevalent HD patients, 25 nephrologists and 58 dialysis nurses/technicians were surveyed. Three separate questionnaires included issues of knowledge and awareness of CKD-MBD and factors limiting management (including compliance, medications and general understanding). RESULTS Of patients surveyed, 84% had heard of phosphate, but 42% were unsure of high phosphate foods and 46% unaware of consequences of elevated phosphate. Twenty-seven percent and thirty-five percent of patients, respectively, had difficulty taking or forgetting to take phosphate binders. Seventy-four percent of patients wanted to know more about CKD-MBD (40% via written material). Of nephrologists surveyed, 76% thought non-compliance with phosphate binders was the main reason for poor control of phosphate (predominantly related to poor patient understanding); 84% thought patients wanted to know more but only 28% provided written material on CKD-MBD. Of dialysis staff surveyed, 63% thought non-compliance with binders explained poor control, the main reason being lack of patient understanding; 88% thought patients wanted to know more but only 17% provided written education. CONCLUSIONS Implementation of an intensive educational programme, with a multi-faceted approach, for HD patients may promote better control of CKD-MBD and improve achievement of target levels.

Phosphate in early chronic kidney disease: Associations with clinical outcomes and a target to reduce cardiovascular risk

There is an intimate association between mineral and bone disorders in chronic kidney disease (CKD) and the extensive burden of cardiovascular disease (CVD) in this population. High phosphate levels in CKD have been associated with increased all‐cause mortality and cardiovascular morbidity and mortality. Observational studies have also shown a consistent relationship between serum phosphate in the normal range and all‐cause and cardiovascular mortality, left ventricular hypertrophy (LVH) and decline in renal function. Furthermore, fibroblast growth factor‐23 (FGF‐23), a phosphaturic hormone, increases very early in the course of CKD and is strongly associated with death and CVD, including LVH and vascular calcification. Few studies have addressed outcomes using interventions to reduce serum phosphate in a randomized controlled fashion; however, strategies to address cardiovascular risk in early CKD are imperative and phosphate is a potential therapeutic target. This review outlines the epidemiological and experimental evidence highlighting the relationship between excess phosphate and adverse outcomes, and discusses clinical studies required to address this problem.

Determination and Validation of Aortic Calcification Measurement from Lateral Bone Densitometry in Dialysis Patients

BACKGROUND AND OBJECTIVES Vascular calcification (VC) contributes to increased cardiovascular (CV) disease in dialysis patients and is inversely correlated with bone mineral density (BMD). Screening for VC may determine patients at greater CV risk and bone densitometry may have dual role in assessing VC as well as BMD. The aim of this study was to determine measurement of VC using dual-energy x-ray absorptiometry (DXA) with correlation to gold standard computed tomography (CT). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Forty hemodialysis patients had abdominal aortic CT and lateral DXA of lumbar spine to determine aortic VC and BMD. Semiquantitative measurement of aortic VC from lateral DXA was determined using previously validated 24- and 8-point scales and correlated with aortic VC with CT. Anteroposterior (AP) and lateral DXA-reported BMD was compared with BMD from L2 through L4 with CT. RESULTS Patients, 70% men, 38% diabetic, had median age 58.5 yr. Aortic VC was present in 94% with CT and 68% on lateral DXA. For 24- and 8-point scores, intraclass correlation coefficients for intrarater agreement were 0.93 and 0.88, respectively. DXA-measured VC correlated with CT. Sensitivity and specificity for CT aortic VC > or = 500 HU was 50 and 86%, respectively, for DXA VC > or = 6 on a 24-point scale. Lateral DXA-reported BMD significantly correlated with BMD from CT, but AP DXA did not. CONCLUSIONS Lateral DXA may be useful because images may provide concurrent assessment of aortic calcification as well as more accurate lumbar spine BMD, avoiding some of the limitations of AP DXA.

Temporal distribution of arrhythmic events in chronic kidney disease: Highest incidence in the long interdialytic period.

BACKGROUND Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) have a high risk of sudden cardiac death (SCD). A unique risk factor may be a longer interval between HD sessions (interdialytic period). Inherent in conventional HD (thrice-weekly) are two 48-hour short breaks (SIDP) and one 72-hour long break (LIDP) between HD sessions. OBJECTIVE We used an implantable cardiac monitor (ICM) to define the incidence and timing of significant arrhythmias in an HD population. METHODS Fifty CKD patients undergoing HD with left ventricular ejection fraction >35% had an ICM inserted, with intensive follow-up to record SCD events and predefined bradyarrhythmias and tachyarrhythmias. RESULTS Mean age of the patients was 67 ± 11 years; 72% were male, and the mean follow-up was 18 ± 4 months. There were 8 unexpected SCDs (16%), all during the LIDP. The terminal event was severe bradycardia with asystole in each recorded case. No episodes of polymorphic ventricular tachycardia (VT) occurred. A total of 7686 arrhythmia events were recorded in 43 patients (86%), including bradycardia in 15 patients (30%), sinus arrest in 14 (28%), second-degree atrioventricular block in 4 (8%), nonsustained VT in 10 (20%), and new-onset paroxysmal atrial fibrillation in 14 (28%). The LIDP was the highest-risk period for all arrhythmias (P < .001). The arrhythmia event rate per hour was greatest during the first pre-HD period of the week compared with any other peri-HD period (P < .001). CONCLUSION Risk of SCD and significant arrhythmias is greatest during the LIDP. SCD was attributable to severe bradycardia and asystole. Interventions to prevent this type of SCD or shorten the LIDP deserve further evaluation. CLINICAL TRIAL REGISTRATION INFORMATION URL: https://www.anzctr.org.au (Unique identifier: ACTRN12613001326785).

Bradycardia and Asystole Is the Predominant Mechanism of Sudden Cardiac Death in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) undergoing hemodialysis experience a high annual mortality rate (7% per year) with 25% of all deaths due to sudden cardiac death (SCD) [(1)][1]. There has been conjecture as to the mechanism of SCD. This prospective study (Identification and

The importance of klotho in phosphate metabolism and kidney disease.

The discovery of fibroblast growth factor‐23 (FGF23) and its co‐receptor α‐klotho has broadened our understanding of mineral metabolism and led to a renewed research focus on phosphate homeostatic pathways in kidney disease. Expanding knowledge of these mechanisms, both in normal physiology and in pathology, identifies targets for potential interventions designed to reduce the complications of renal disease, particularly the cardiovascular sequelae. FGF23 has emerged as a major α‐klotho‐dependent endocrine regulator of mineral metabolism, functioning to activate vitamin D and as a phosphatonin. However, increasingly there is an appreciation that klotho may act independently as a phosphate regulator, as well as having significant activity in other key biological processes. This review outlines our current understanding of klotho, and its potential contribution to kidney disease and cardiovascular health.