Bone health in chronic kidney disease-mineral and bone disorder: a clinical case seminar and update.

The metabolic abnormalities affecting bone in the setting of chronic kidney disease (CKD) are complex with overlapping and interacting aetiologies and have challenging diagnostic and management strategies. Disturbances in calcium, phosphate, fibroblast growth factor 23, parathyroid hormone concentrations and vitamin D deficiency are commonly encountered and contribute to the clinical syndromes of bone disorders in CKD, including hyperparathyroidism, osteomalacia, osteoporosis and adynamic bone disease. Mineral and bone abnormalities may also persist or arise de novo post-renal transplantation. The Kidney Disease Improving Global Outcomes organisation describes these mineral metabolism derangements and skeletal abnormalities as 'CKD Mineral and Bone Disorder'. Patients with this disorder have an increased risk of fracture, cardiovascular events and overall increased mortality. In light of the recently updated 2017 guidelines from the Kidney Disease Improving Global Outcomes, we present a clinical case-based discussion to highlight the complexities of investigating and managing the bone health of patients with CKD with a focus on these updates.

CKD-MBD management: what is the role of parathyroidectomy? Results from a nationwide survey in Italy.

We herein report on a nationwide survey conducted in Italy to investigate the use of parathyroidectomy (PTX). In spite of the availability of newer and more effective drugs to control chronic kidney disease mineral bone disorder (CKD-MBD) biochemical abnormalities, PTX still remains a resource for nephrologists to use. However, observational analyses suggest that in recent years there has been a constant decline in the number of patients undergoing PTX. The reasons are not clear, though the increasing age and number of comorbidities of dialysis patients may partly explain this trend. Poor adherence to guidelines and/or geographical as well as logistic factors may also contribute to the lower use of PTX. The working group on CKD-MBD of the Italian Society of Nephrology launched a nationwide survey to investigate clinical practice patterns for PTX in Italy and identify modifiable factors that may limit accessibility to surgery.

Clinical features of CKD-MBD in Japan: cohort studies and registry.

Randomized controlled trials (RCTs) are essential for evidence-based medicine; however, cohort studies and registries provide an important information about risk factors and, hence, shed light on the target of laboratory parameters. The uniqueness of the current Japanese CKD-MBD guidelines lies in the lower target range of intact parathyroid hormone levels than those used in other countries, which is based on analyses of the nationwide Japan Renal Data Registry. Cohort studies were also useful in exploring risk factors of renal outcome in predialysis patients. It was revealed that low vitamin D status (very prevalent in Japan) and high fibroblast growth factor 23 (FGF23) levels predict poor renal outcome. The reported association of FGF23 levels with left ventricular hypertrophy (LVH) and heart failure observed in cohort studies may support the idea of adding the 4th component of CKD-MBD, namely, "LVH" to the three original components. When it is not feasible to conduct RCTs regarding intervention, we have no choice but to rely on observational studies with sophisticated analysis methods, such as facility-level analysis and marginal structural model minimizing indication bias. Observational studies conducted in Japan revealed that the side effects of medications for CKD-MBD, resultant compliance, and effective doses in terms of hard outcome in Japanese patients were found to be different from those in other countries. For example, the MBD-5D study confirmed the benefit of cinacalcet in terms of mortality despite its median dose of only 25 mg/day. These data are very helpful for future guidelines specific to Japanese patients with CKD.

Brown tumor of secondary hyperparathyroidism: surgical approach and clinical outcome.

BACKGROUND: Secondary hyperparathyroidism is a frequent complication of chronic renal failure. The brown tumor is an unusual presentation of fibrous osteitis that represents a serious complication of renal osteodystrophy, affecting predominantly the hands, feet, skull, and facial bones. CASE REPORT: The aim of this paper is to describe the case of a 53-year-old female patient, with renal failure who has been on dialysis for 6 years and developed severe secondary hyperparathyroidism and brown tumor of the maxilla and mandible, confirmed by incisional biopsy. Parathyroidectomy was indicated as a result of rapid growth of the tumor and the maintenance of laboratory findings. Despite the normalization of serum parathyroid hormone and alkaline phosphatase, tumor regression was slow and patient's important functional and esthetic deficits persisted. Excision of the mandible tumor was conservative. Osteoplasty was recommended because during a 5-year follow-up there was regression of the lesion, decreased pain, bleeding, and tooth mobility.

Parathyroidectomy Increases Heart Rate Variability and Leptin Levels in Patients with Stage 5 Chronic Kidney Disease.

BACKGROUND: In chronic kidney disease (CKD) patients, decreased heart rate variability (HRV) reflects impaired cardiac automatic nervous function and high risk of cardiovascular disease (CVD). Lower HRV in patients with severe secondary hyperparathyroidism (SHPT), a clinical manifestation of CKD-mineral and bone disorder (CKD-MBD), could be reversed by parathyroidectomy (PTX). It has been proved that leptin interacts with the autonomic nervous function. However, the associations between leptin and HRV in CKD patients and their longitudinal changes in SHPT patients after PTX are still unknown. METHODS: This was a cross-sectional study including 141 stage 5 CKD patients, and a prospective study in 36 severe SHPT patients with PTX. HRV was measured by Holter and serum leptin was measured by ELISA. Serum leptin levels were adjusted for body mass index (BMI) and transformed using natural logarithm (lnleptin/BMI). RESULTS: With a gradient of lnleptin/BMI across quartiles from Q1 to Q4 in CKD patients, HRV indices showed no differences among quartiles. Patients in Q1 group had higher mean 24 h heart rates, and lower ln(very low frequency) (lnVLF) than other quartiles, although there were no statistically significant difference. In multivariate stepwise regression, serum leptin/BMI was an independent predictor for low frequency/high frequency. HRV indices and lnleptin/BMI levels were increased in severe SHPT patients after PTX. Compared to other quartiles, SHPT patients in Q1 group had larger improvement of lnVLF after PTX. CONCLUSION: Circulating leptin levels may be a novel treatment target to reduce CVD risk in advanced CKD-MBD patients.

Challenges of cervical reconstruction for destructive spondyloarthropathy in renal osteodystrophy.

Patients with end stage renal disease on hemodialysis may present with destructive spondyloarthropathy of the spine, most commonly in the subaxial cervical and lumbar spine, often with severe stenosis and instability. However, surgical management of these patients is challenging due to a high pseudarthrosis rate, poor bone quality, and medical frailty. We present a 49-year-old man on hemodialysis who presented with C4-C5 vertebral body destruction and a focal kyphotic deformity with myelopathy. The patient underwent a 360 degree decompression and reconstructive procedure that resulted in posterior instrumentation failure. Several salvage techniques were used in order to adequately stabilize the spine while preserving the patient's remaining cervical motion.

Severe maxillofacial renal osteodystrophy in two patients with chronic kidney disease.

Renal osteodystrophy (ROD) is the bone pathology that occurs as an uncommon complication related to the several alterations in mineral metabolism present in patients with chronic kidney disease (CKD). This paper describes two cases of severe ROD affecting the maxilla and mandible and causing facial disfigurement of a young and a middle-aged female patient with CKD. Both patients had a history of secondary hyperparathyroidism, previously treated by surgery. The pathogenesis of the disease, as well as its clinical, imaging, and histopathological features, and management of the patient are discussed.

Aneurysmal bone cyst does not hinder the success of kidney transplantation. A case report.

Uremic osteodystrophy is an expected complication in subjects with chronic renal insufficiency. It develops gradually and progressively already during the conservative treatment and then during the dialysis treatment. It can present a wide histopathological spectrum including typical alterations (from osteitis fibrosa to osteomalacia and/or mixed lesions) or, more rarely, isolated bone lesions indicative of a brown tumor of the bone. These conditions must be clearly identified in the pretransplant phase, especially if a bone lesion indicative of a pathological condition possibly evolving into a neoplasm is detected fortuitously. We report the case of a 19-yr-old boy with renal insufficiency and candidate for a pre-emptive renal transplantation from a living donor, in whom the diagnosis of ABC of the pubic symphysis - asymptomatic and fortuitously detected while performing instrumental investigations - was suspected through the imaging studies (CT scan, MRI) and was confirmed by the histological examination. This made it possible to perform the renal transplant. The immunosuppressive treatment, which was subsequently administered, was based on steroids, calcineurin inhibitors (tacrolimus), and mycophenolate and did not determine any modification in the radiological aspect of the bone lesion, even after more than one yr from the transplant.

Clinical status of Sagliker syndrome: a case report and literature review.

In a 53-year-old woman, Sagliker syndrome developed during 22 years of treatment with intermittent hemodialysis as a result of severe secondary hyperparathyroidism (SHPT) complicating end-stage renal disease. She failed medical managements and lost her renal graft just after the kidney transplantation due to acute rejection. Although surgical parathyroidectomy was effective, the parathyroid hormone level became extremely high again due to recurrent hyperparathyroidism. It is possible that such patient could survive long-term with dialysis, but prevention of severe SHPT is the most important.

[Surgical management of renal hyperparathyroidism]. / Chirurgisches Management des renalen Hyperparathyreoidismus.

Conservative management of renal hyperparathyroidism has changed recently. Innovative substances, especially the advent of calcimimetics, have influenced the therapeutic concept. Consequently, a decline in surgical frequency for renal hyperparathyroidism has been reported. In this context it is now mandatory to evaluate the role of surgery, the surgical strategy and procedures for renal hyperparathyroidism anew. Based on a review of the literature the current position of surgical indications and care for renal hyperparathyroidism as well as possible influences of innovative medical treatment are highlighted. In summary, the timing and indications for surgery have been influenced, however, surgery still remains the only permanently effective treatment option for renal hyperparathyroidism.

Current trends in surgery for renal hyperparathyroidism (RHPT)--an international survey.

PURPOSE: The indications and results of preoperative localization, surgical strategy, indication for thymectomy, the application of intraoperative parathyroid hormone (PTH) monitoring, cryopreservation, and replantation of cryopreserved parathyroid tissue are not well documented in renal hyperparathyroidism (RHPT). The current trends in surgery for RHPT are to be evaluated in an international online survey. METHODS: Thirty-three questions regarding preoperative localization, surgical management of RHPT, intraoperative PTH monitoring, immediate/delayed autotransplantation (AT), and parathyroid cryopreservation were sent to members of various societies of endocrine surgeons. RESULTS: The data from 86 responses were analyzed, 61.6 % reported more than 50 parathyroid surgeries per year, and 62.7 % operated on less than 16 patients with RHPT per year. Subtotal or total parathyroidectomy (with/without AT) was the standard procedure in 98.8 % of the cases. Immediate AT was performed in 40.7 % (72.7 % in the forearm). In most patients, the onset of graft function was documented later than 1 week after AT. Cryopreservation was routinely performed in 27.4 %. In 10.7 %, replantation was performed in more than five patients (hypo- or aparathyroidism: n = 41; fresh graft failure: n = 13; reoperations: n = 9). Intraoperative PTH monitoring (in RHPT) was routinely used in 46.2 %. Its influence on surgical strategy was confirmed in 40 %. CONCLUSIONS: The survey reflects the divergent strategies applied for AT, cryopreservation, and PTH monitoring in RHPT.

Localized mandibular enlargement in end-stage renal disease: two case reports and a review of the literature.

Enlargement of the jaws is an infrequently reported complication of chronic kidney disease mineral and bone disorder (CKD-MBD). Two cases of localized mandibular swellings in young patients with histories of end-stage renal disease are discussed with a review of the literature. Although 17 of the first 19 cases that were reported exhibited diffuse enlargement, these reports increase the number of localized swellings to 8 and support the contention that localized expansion of the jaws as a manifestation of CKD-MBD is more common than originally recognized.

Renal osteodystrophy: neurosurgical considerations and challenges.

BACKGROUND: Dialysis-associated destructive spondyloarthropathy (DSA) is the major bony complication of end-stage renal disease, most commonly found in the lower cervical region. The risk factors for developing dialysis-associated DSA include duration of hemodialysis and patient age. Patients with DSA have a higher incidence of osteoporosis and poor bone mineral density, which may place them at greater risk of atraumatic fractures, instrumentation failure, and neurologic compromise. METHODS: We describe a case of cervical radiculopathy due to dialysis-associated DSA atraumatic vertebral body fractures with a postoperative course that was complicated by instrumentation failure. We reviewed the literature regarding all 138 published cases, presenting the complications, surgical treatment options, and outcomes. RESULTS: A 44-year-old dialysis-dependent man presented with acute neck pain, radiculopathy, and weakness due to atraumatic fracture of C5 and C6 vertebral bodies. He underwent anterior C5 and C6 corpectomies, reconstruction with mesh cage and plate, and supplemental posterior instrumentation (C4-T1). Six weeks later, a computed tomography scan revealed anterior translation across the instrumented area with failure of the posterior instrumentation. He subsequently underwent traction, revision reinstrumentation from C2 to T5, and placement of external halo ring/jacket for 6 months. At 18 months later, he remains ambulatory without evidence of construct failure. CONCLUSIONS: Patients with renal osteodystrophy present a challenge for the spine surgeon due to compromised bone density. Hardware failure at the bone-construct interface is common in these patients, with revision surgery needed in 22% of published cases. Longer constructs with circumferential instrumentation and halo immobilization may minimize the risk of pseudoarthrosis and construct pull-out.

Combined technique for the correction of lower-limb deformities resulting from metabolic bone disease.

We present the results of the surgical correction of lower-limb deformities caused by metabolic bone disease. Our series consisted of 17 patients with a diagnosis of hypophosphataemic rickets and two with renal osteodystrophy; their mean age was 25.6 years (14 to 57). In all, 43 lower-limb segments (27 femora and 16 tibiae) were osteotomised and the deformity corrected using a monolateral external fixator. The segment was then stabilised with locked intramedullary nailing. In addition, six femora in three patients were subsequently lengthened by distraction osteogenesis. The mean follow-up was 60 months (18 to 120). The frontal alignment parameters (the mechanical axis deviation, the lateral distal femoral angle and the medial proximal tibial angle) and the sagittal alignment parameters (the posterior distal femoral angle and the posterior proximal tibial angle) improved post-operatively. The external fixator was removed either at the end of surgery or at the end of the lengthening period, allowing for early mobilisation and weight-bearing. We encountered five problems and four obstacles in the programme of treatment. The use of intramedullary nails prevented recurrence of deformity and refracture.

[Indications for parathyroidectomy in renal hyperparathyroidism: comments on the significance of new therapeutics]. / Indikation zur operativen Therapie des renalen Hyperparathyreoidismus: Stellungnahme zur Bedeutung neuer medikamentöser Therapieverfahren.

New therapeutics for the treatment of chronic kidney disease and secondary hyperparathyroidism, such as calcium and aluminium-free phosphate binders, calcimimetic agents and active vitamin D metabolites may decrease the need for parathyroidectomy. The calcimimetic cinacalcet does not induce a longer lasting regression of renal hyperparathyroidism and autonomous growing of parathyroids and the therapeutic effect is limited to the period of treatment. The classical indications for surgery, hypercalcemia, vascular calcification, severe osteopathy, drug-resistant hyperphosphatemia and calciphylaxis are still valid if patients do not respond to medical therapy under the condition that adynamic bone disease is excluded. Individual operative risk factors and improvement of quality of life are important supplementary factors for the indication for parathyroidectomy.

Regression of brown tumor of the maxilla in a patient with secondary hyperparathyroidism after a parathyroidectomy.

Brown tumors or osteoclastomas are erosive bony lesions arising as a complication of hyperparathyroidism. In patients with end-stage renal disease, brown tumors are uncommon skeletal manifestations that are usually seen in severe forms of secondary hyperparathyroidism. Initial treatment involves the correction of hyperparathyroidism, which usually leads to regression of the tumors. We report a case of brown tumors of the maxilla in a 24-year-old female referred to us by a local hospital, where she had been on regular hemodialysis for >10 years. After a complete biochemical and radiological workup, she underwent a total parathyroidectomy, which subsequently resulted in significant regression of her tumor.

Increased bone turnover markers after renal transplantation.

Bone remodeling is a process that occurs continuously in a seemingly inactive tissue like bone. Because of decreased vitamin D synthesis, phosphorus retention and decreased calcium blood concentration, patients with chronic renal failure (CRF) develop secondary hyperparathyroidism. Elevated PTH levels shifts balance between osteoblast and osteoclast activity in favor of osteoclast activity and, therefore, bone resorption. Bone metabolic disorder that affects patients with CRF is called renal osteodystrophy (ROD). We presume that renal transplantation reverses bone metabolism disorder and our goal was to establish whether osteoblast and osteoclast activity returns to the levels of healthy individuals.

Spinal cord compression secondary to brown tumour in a patient on long-term haemodialysis: a case report.

Brown tumours may occur secondary to hyperparathyroidism in patients with chronic renal failure (CRF). Diagnosing a spinal brown tumour causing cord compression requires a high index of suspicion. We report a 65-year-old woman, who had been on haemodialysis for CRF for over 10 years, who presented with leg weakness and back pain over the thoracolumbar junction. She had a brown tumour at T8 causing subacute spinal cord compression. Ambulation was regained after surgical decompression and stabilisation. Adherence to the National Kidney Foundation guidelines in the management of patients with CRF may prevent renal osteodystrophy. Treatment of spinal brown tumour depends on the severity of the neurological deficit. Remineralization is expected after correction of the parathyroid level, thus negating the need for total excision of the parathyroid glands.

Correction of lower limb deformities in children with renal osteodystrophy by the Ilizarov method.

BACKGROUND: Children with renal osteodystrophy (ROD) may develop severe angular deformities of the limbs. Various methods, both medical and surgical, have been described for correction of these deformities, but a literature search showed only 1 child previously treated by the Ilizarov method. The purpose of this study was to characterize the deformities found in our group of patients and to describe our experience in treating these patients with the Ilizarov method. METHODS: Correction of angular deformity by the Ilizarov method was performed on 8 limb segments in 5 patients with ROD. Mean age was 14.9 years. Two patients were on hemodialysis, and 3 had functioning kidney grafts. Surgery was deferred until stabilization of metabolic parameters. RESULTS: There was 1 varus and 7 valgus deformities. Preoperative coronal deformity averaged 29 degrees (18-38 degrees). The Ilizarov apparatus was used in all cases. Correction time averaged 23 days (20-28 days). The time from completion of correction to frame removal averaged 71 days (48-113 days). There were no changes in metabolic parameters or frequency of hemodialysis throughout the treatment. Restoration of a normal mechanical axis was achieved in 4 of the 5 patients. One case failed due to intraarticular instability. There were no major complications. Minor complications included pin tract infections, which responded to antibiotic treatment, and premature consolidation in 1 case. Follow-up averaged 6.5 years (1-10 years). The alignment obtained at surgery was maintained in all 4 patients, and they are functional and symptom-free. The patient for whom the surgery failed remains wheelchair-bound. CONCLUSIONS: The Ilizarov method was found to be safe and effective for correction of malalignment due to ROD. Optimization of metabolic parameters is essential before surgery and throughout correction. The procedure is contraindicated in patients with significant intraarticular knee pathology.