Grahame J Elder

Westmead Hospital | SWAHS · Department of Renal Medicine

Introduction Calciphylaxis is a rare disorder associated with significant morbidity and mortality. Data registries are an invaluable source of information for rare diseases. We reviewed cases of calciphylaxis recorded in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and evaluated associations and outcomes of this conditio...

Background The mortality of dialysis patients greatly exceeds that of the general population and identifying predictive factors for mortality may provide opportunities for earlier intervention. This study assessed the influence of sarcopenia on mortality in patients on haemodialysis. Methods This prospective, observational study enrolled 77 haemod...

Most patients with end-stage kidney disease undergoing kidney transplantation are affected by the chronic kidney disease-mineral and bone disorder. This entity encompasses laboratory abnormalities, calcification of soft tissues, and the bone abnormalities of renal osteodystrophy that together result in an increased risk of fracture, cardiovascular...

Objective: Patients with end-stage kidney disease (ESKD) from type 1 diabetes mellitus (T1DM) have a heightened fracture risk. BMD may predict fracture less accurately in ESKD than in patients with chronic kidney disease (CKD) stages 1-3b or the general population. Alternate, readily available imaging modalities are needed to improve ESKD fracture...

Fracture risk evaluation of postmenopausal women is suboptimal, but most women undergo screening mammography. Digital X‐Radiogrammetry (DXR) determines bone mineral density (BMD) at the metacarpal shaft and can be performed on mammography equipment. This study examined correlations between DXR and dual‐energy X‐ray absorptiometry (DXA) in women und...

Background Calciprotein particles (CPP) are colloidal aggregates of calcium phosphate and the mineral-binding protein fetuin-A, and are potential mediators of cardiovascular disease in chronic kidney disease (CKD). Emerging evidence suggests non-calcium containing phosphate binders may reduce serum CPP in patients with kidney failure who require di...

Background: Benefits of phosphate-lowering interventions on clinical outcomes in patients with chronic kidney disease (CKD) are unclear; systematic reviews have predominantly involved dialysis patients. This study aimed to summarize evidence from randomized controlled trials (RCTs) concerning benefits and risks of non-calcium-based phosphate-loweri...

Patients with chronic kidney disease–mineral and bone disorder (CKD-MBD) frequently have low bone formation rates. A recent review suggested that adynamic bone disease is not always associated with negative outcomes and therefore antiresorptive medications could be used more often. However, there is currently no evidence to support an improvement i...

Objective Higher serum phosphate is associated with increased adverse outcomes including cardiovascular disease. Abnormalities of bone and mineral metabolism in chronic kidney disease (CKD), including higher serum phosphate, are important risk factors for increased cardiovascular disease. Associations between dietary phosphate intake and biochemica...

This article aims to review the methods used for the assessment of fracture risk and the use of osteoporosis medications for fracture prevention in the population with CKD, and highlights the difficulties faced by clinicians in the management of these patients and the latest recommendations and guidelines. Chronic kidney disease (CKD) and osteoporo...

Although frequently silent, mineral and bone disease (MBD) is one of the most precocious complication of chronic kidney disease (CKD) and is omnipresent in patients with CKD stage 5. Its pathophysiology is complex, but basically, disturbances in vitamin D, phosphate, and calcium metabolism lead to a diverse range of clinical manifestations with sec...

Chronic kidney disease (CKD) is associated with high rates of fracture, cardiovascular events, and mortality. The pathophysiology is complex, including reduced levels of Klotho and active vitamin D, and markedly elevated levels of fibroblastic growth factor 23 and parathyroid hormone. Abnormal Wnt and activin signaling pathways influence the matura...

Background Estimated glomerular filtration (eGFR) results based on serum creatinine are frequently inaccurate with differences against measured GFR (mGFR) often attributed to unmeasured non-functional factors, such as muscle mass. Methods The influence of muscle mass (measured by dual-energy x-ray absorptiometry, DEXA) on eGFR error (eGFR-mGFR) wa...

Background Reduction in bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) occurs in secondary hyperparathyroidism associated with chronic kidney disease. BMD generally increases following parathyroidectomy, however longitudinal changes to other DXA-derived parameters, the trabecular bone score (TBS) and hip structural an...

Patients on dialysis are highly prone to fracture, and radiographic absorptiometry can be used to measure their bone mineral density and assess fracture risk. However, to determine its place in management, radiographic absorptiometry should be compared with dual-energy X-ray absorptiometry, and with fracture risk assessment tools such as FRAX, test...

Background: Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain. Methods: To assess the effects of non-calcium-based phosphate binders on intermedi...

Objective Dietary phosphate modification is a common therapy to treat hyperphosphatemia in individuals with chronic kidney disease (CKD). However, current dietary intake and common food sources of phosphate typically consumed by individuals with CKD are not well characterized. This study examined a cohort of CKD patients to determine total dietary...

Chronic kidney disease (CKD) is associated with excess cardiovascular morbidity and mortality compared to the general population. Hyperphosphataemia, associated with vascular calcification and arterial stiffness, may play a key role in the pathogenesis of cardiovascular disease (CVD) associated with CKD, although phosphate reduction strategies have...

Background: Calciphylaxis is a rare disease, predominantly affecting patients with chronic kidney disease (CKD) and associated with significant morbidity and mortality due to progressive cutaneous calcification, necrotic ulceration and infection. Clinical registries have been established to better understand the risk factors, optimal treatments an...

Background: Patients with end-stage kidney disease (ESKD) have higher fracture rates and post-fracture mortality than the general population, but bone mineral density by dual-energy X-ray absorptiometry (DXA) is less predictive of fracture in this patient group. Bone biopsy and high-resolution imaging indicate that cortical thickness (CT) is reduc...

Background: Cardiovascular (CV) disease is the leading cause of death in kidney and simultaneous pancreas-kidney (SPK) transplant recipients. Assessing abdominal aortic calcification (AAC), using lateral spine x-rays and the Kaupilla 24-point AAC (0-24) score, may identify transplant recipients at higher CV risk. Methods: Between the years 2000...

We report on the case of a partial nephrectomy for a Juxtaglomerular apparatus (JGA) tumour in a 28 year old female who presented with fatigue and symptomatic hypertension, and a normal serum renin level on pre-operative work-up.

Introduction Patients with chronic kidney disease (CKD) are at heightened cardiovascular risk, which has been associated with abnormalities of bone and mineral metabolism. A deeper understanding of these abnormalities should facilitate improved treatment strategies and patient-level outcomes, but at present there are few large, randomised controlle...

Introduction Kidney and simultaneous pancreas kidney (SPK) transplant recipients are younger and fitter than most other dialysis patients, but are also more vulnerable in areas of social, emotional and physical interaction. Few studies have tracked their post‐transplant health related quality of life (HRQoL). Aim To assess HRQoL following kidney a...

Background: Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011. Objectives: The aim of this review w...

Background Secondary hyperparathyroidism (SHPT) in chronic kidney disease is associated with cardiovascular and bone pathology. Measures to achieve parathyroid hormone (PTH) target values and control biochemical abnormalities associated with SHPT require complex therapies, and severe SHPT often requires parathyroidectomy or the calcimimetic cinacal...

Background: Cortical bone is a significant determinant of bone strength and its deterioration contributes to bone fragility. Thin cortices and increased cortical porosity have been noted in patients with chronic kidney disease (CKD), but the "Turnover Mineralization Volume" classification of renal osteodystrophy does not emphasize cortical bone as...

Introduction: Progressive chronic kidney disease (CKD) confers a marked increase in risk for vascular calcification, cardiovascular disease, fracture and mortality, with likely contributing factors including dysregulated bone metabolism and mineral homeostasis. In general population studies, increased vascular calcification is directly related to...

Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in t...

Background: Chronic kidney disease (CKD) adversely affects bone microarchitecture and increases fracture risk. Historically, bone biopsy has been the 'gold standard' for evaluating renal bone disease but is invasive and infrequently performed. High-resolution magnetic resonance imaging (MRI) quantifies bone microarchitecture noninvasively. In pati...

Introduction: Declining renal function carries increased fracture risks, but BMD is less predictive of fracture for dialysis patients than the general population. The TBS, obtained from lumbar spine dual-energy X-ray absorptiometry (DXA) images, provides information on microarchitectural integrity not captured by BMD. The aim of this study was to...

Background: Osteoporosis is highly prevalent in the heart and lung transplant population. Given high rates of concurrent renal impairment, there is increasing use of denosumab in this population. However, denosumab may be associated hypocalcaemia, particularly in patients with chronic kidney disease (CKD). Aim: This study sought to explore the r...

Teriparatide, used for treatment of osteoporosis in patients at high risk of fracture risk, sometimes results in mild and transient hypercalcemia. There have been two recent reports of worsening dystrophic calcification in patients with autoimmune disorders following teriparatide treatment. We report a patient with severe osteoporosis and without a...

Background and objectives: Patients with progressive chronic kidney disease (CKD) develop positive phosphate balance that is associated with increased cardiovascular risk and mortality. Modification of dietary phosphate is a commonly used strategy to improve outcomes but is complicated by the need for adequate dietary protein. Surprisingly, the ev...

Background Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble...

Bone biopsy is currently the only means to accurately assess renal osteodystrophy and responses to therapeutic interventions. With sedation, the technique is relatively painless, and complications are uncommon. Bone biopsy should be considered when the aetiology of symptoms or biochemical abnormalities is in question, and results may lead to change...

Rising levels of serum phosphate occur late in the course of chronic kidney disease (CKD) and have been easy targets for nephrologists to treat using phosphate binding drugs, as well as fertile ground for the pharmaceutical industry, for meta-analysis and for the earnest pontifications of guideline writers. Unfortunately, the evidence does little t...

Background and objectives: People with CKD stages 3-5 and on dialysis (5D) have dramatically increased mortality, which has been associated with hyperphosphatemia in many studies. Oral phosphate binders are commonly prescribed to lower serum phosphate. We conducted an updated meta-analysis of the noncalcium-based binder (non-CBB) sevelamer versus...

A new definition and classification of chronic kidney disease-mineral and bone disorder (CKD-MBD) was proposed in 2005 and it was later followed by a guideline publication on this topic from Kidney Disease: Improving Global Outcomes (KDIGO) in 2009. This work recognized that CKD-MBD is a syndrome of bone abnormalities, laboratory abnormalities, and...

Background Chronic kidney disease (CKD) is a major public health issue and early detection may prevent morbidity and mortality. Screening for CKD is simply assessed using the Kidney Health Check (KHC), a compilation of blood pressure (BP), estimated glomerular filtration rate (eGFR) and urinalysis (UA). KHC screening of high risk hospital inpatient...

Vascular calcification (VC) is common in patients with chronic kidney disease (CKD) on dialysis, and an inverse relationship of VC to bone mineral density (BMD) has been reported. Because elderly patients are prone to atherosclerosis and BMD artefact, we examined the prevalence and epidemiology of VC in younger patients undergoing transplantation,...

To compare quality of life (QOL) of patients about to undergo kidney or simultaneous pancreas kidney (SPK) transplants with Australian dialysis outcomes and practice patterns (DOPPS) data and multiple co-morbidity and age-adjusted general population data. Patients undergoing kidney and SPK transplants are younger and fitter than the general dialysi...

A 77-year-old man, who received a renal transplant 13 years before for IgA glomerulonephritis, was referred after he developed bilateral mid-tibial aching pain that did not improve with simple analgesia. He had recently been changed from low-dose cyclosporine to tacrolimus, but the pain did not improve when this was reversed. He had a history of fo...

Since the kidney is essential for regulation of mineral metabolism, bone disease is an inevitable consequence of renal damage. Treatment is challenging due to the complex physiology and the dearth of clinical data, and is complicated by concern about vascular calcifications. A newly defined term CKD-MBD (chronic kidney disease mineral and bone diso...

Background and objectives: Observational studies suggest that calciferol supplementation may improve laboratory and patient-level outcomes of hemodialysis patients with reduced 25-hydroxyvitamin D [25(OH)D] levels. This randomized controlled trial examined effects of cholecalciferol supplementation in patients on hemodialysis. Design, setting, pa...

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 cons...

To maintain calcium and phosphate balance despite declining kidney function, adaptations must begin in the earliest stages of chronic kidney disease (CKD). These are generally successful in maintaining calcium and phosphate levels within the normal range through CKD stages 1–4. Although routine biochemistry is not informative about net gain of thes...

Concern that calcium use may increase cardiovascular risk was previously the domain of nephrologists. By contrast, calcium supplementation has been promoted within the general community as beneficial to the maintenance of bone mineral density, as an adjunct to osteoporosis therapies and as potentially useful for cardiovascular health. Studies of pa...

Following renal transplantation, hypercalcaemia is frequently caused by persisting hyperparathyroidism. Unregulated extrarenal 1,25-dihydroxyvitamin D (1,25(OH)2D) synthesis, which is well recognized as a cause of hypercalcaemia in granulomatous diseases, may also occur after kidney transplantation. This mechanism is also likely to be responsible f...

Clinical practice guidelines on the management of mineral and bone disorders due to chronic kidney disease recommend specific treatment target levels for serum phosphorus, parathyroid hormone, and calcium. To assess the quality of evidence for the association between levels of serum phosphorus, parathyroid hormone, and calcium and risks of death, c...

Phosphate binders are widely used to lower serum phosphorus levels in people with chronic kidney disease (CKD) but their impact in CKD remains controversial. To review the effects of various phosphate binders on biochemical and patient-level end-points in CKD stages 3 to 5D. In March 2010 we searched MEDLINE, EMBASE, the Cochrane Renal Group's Spec...

Suboptimal levels of 25-hydroxyvitamin D (25OHD) are common in haemodialysis patients (Chronic Kidney disease-5D: CKD-5D) and may be associated with reduced muscle strength and increased falls risk. We tested the hypothesis that 25OHD levels may be independently associated with falls risk in CKD-5D. Supplementation with calcium and cholecalciferol...

Extrapolation of evidence-based management of disorders in the general population to patients with chronic kidney disease (CKD) is not always appropriate, and the prevention of bone fracture and reduction of fracture risk in CKD stages 3-5 is one example. Compared to the general population, fracture risk is greater in CKD patients, especially those...

Most patients who undergo kidney or kidney-pancreas transplantation have renal osteodystrophy, and immediately after transplantation bone mineral density (BMD) commonly falls. Together, these abnormalities predispose to an increased fracture incidence. Bisphosphonate or calcitriol therapy can preserve BMD after transplantation, but although bisphos...

Clinical guidelines recommend vitamin D compounds to suppress serum parathyroid hormone (PTH) in chronic kidney disease (CKD), however treatment may be associated with increased serum phosphorus and calcium, which are associated with increased mortality in observational studies. Observational data also indicate vitamin D therapy may be independentl...

Vitamin D compounds are used to suppress elevated serum parathyroid hormone (PTH) in people with chronic kidney disease (CKD). To assess the efficacy of vitamin D therapy on biochemical, bone, cardiovascular, and mortality outcomes in people with CKD and not requiring dialysis. We searched The Cochrane Renal Group's specialised register, Cochrane's...

Phosphate binders are widely used to control serum phosphorus levels in patients with chronic kidney disease (CKD). We analyzed the effects of phosphate binders on biochemical and patient-level end points in patients with CKD. Systematic review and meta-analysis by searching MEDLINE (1966 to April 2009), EMBASE (1980 to April 2009), and the Cochran...

Chronic kidney disease mineral and bone disorder (CKD-MBD) describes the laboratory, bone and vascular abnormalities that exist in patients with CKD stages 3-5D and that may persist after transplantation. Persisting abnormalities of bone turnover and abnormal mineralization, together with bone mineral density (BMD) loss from glucocorticoids, may al...

Treatment of chronic kidney disease (CKD) may be life-saving, but can disrupt every aspect of a patient's life and the lives of family members. Many patients with CKD are elderly with significant comorbidities and sometimes therapies to improve survival may be less important than those that improve or maintain quality of life. In this setting, pati...

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 b...

Vitamin D compounds are widely used to prevent and treat secondary hyperparathyroidism. To determine whether vitamin D therapy improves biochemical markers of mineral metabolism and cardiovascular and mortality outcomes in chronic kidney disease. MEDLINE (January 1966 to July 2007), EMBASE (January 1980 to July 2007), and Cochrane databases were se...

Many patients with chronic kidney disease (CKD) have reduced levels of 25-hydroxyvitamin D (25(OH)D). Although renal conversion of 25(OH)D to calcitriol is reduced or absent in CKD stage 5 (GFR < 15 mL/min per 1.73 m(2) or on dialysis), 25(OH)D may have direct skeletal and non-skeletal paracrine actions. The aim of this study was to assess seasonal...

Osteonecrosis, the calcineurin-inhibitor-induced pain syndrome and transient marrow oedema may occur after renal transplantation, are generally painful and can be diagnosed by X-ray, radionuclide scan or magnetic resonance imaging. They share features of increased intraosseous pressure, compromised vascular supply, marrow oedema and the development...

In this study of 242 patients with renal failure, women, patients with diabetes, and patients on peritoneal dialysis had the highest risk of 25-hydroxyvitamin D deficiency. Levels correlated positively to BMD Z scores, and hip BMD was inversely related to prevalent fracture. Increasing 25-hydroxyvitamin D levels may benefit these patients. 25-Hydro...

Many randomized trials have now evaluated the effects of calcimimetics in patients with chronic kidney disease and secondary hyperparathyroidism (SHPT) on standard therapy with vitamin D and/or phosphate binders. We conducted a meta-analysis to evaluate outcomes of therapy with these novel agents. MEDLINE, EMBASE, the Cochrane Controlled Trials Reg...

Date written: May 2005 Final submission: January 2006

Date written: June 2005 Final submission: January 2006

Abnormalities of calcium and phosphorus metabolism are present in all individuals with chronic kidney disease (CKD). These biochemical changes lead to a condition known as secondary hyperparathyroidism (SPTH), resulting in an excessive production of parathyroid hormone which in turn causes bone and metabolic disorders. These disorders are associate...

With the introduction of the calcimimetic cinacalcet HCl, some patients who would previously have undergone parathyroidectomy are likely to remain on medical therapy. Data is available on complication rates and some important outcome measures of parathyroidectomy, but the efficacy of calcimimetics to influence patient-based endpoints such as cardio...

Pheochromocytomas and abdominal paragangliomas are catecholamine-producing tumors of the sympathetic nervous system, while head and neck paragangliomas are non-secreting tumors of parasympathetic origin. Recent developments in clinical and molecular research on these tumor forms have significantly clarified their genetic backgrounds and challenged...