Differential diagnosis of hypercalcemia in a patient with CKD G5D

Patients with chronic kidney disease are characterized by the development of mineral disorders due to a decrease in the number of functioning nephrons. These changes manifest by the development of secondary hyperparathyroidism (the overproduction of intact parathyroid hormone (PTH) associated with the serum hypocalcemia, hyperphosphatemia), dysfunctional vitamin D metabolism, bone mineralization and also extraosseous calcifications. Decreased serum PTH levels associated with hypercalcemia are suspicious for adynamic bone disease, but at the same time requires an extended differential diagnostic search (e.g. metastatic processes). One of the rare causes of hypercalcemia is a defect in 24-hydroxylase (CYP24A1). We present a case of a patient on hemodialysis with atypical secondary hyperparathyroidism and an established CYP24A1 defect.

Bone Histomorphometry and 18F-Sodium Fluoride Positron Emission Tomography Imaging: Comparison Between only Bone Turnover-based and Unified TMV-based Classification of Renal Osteodystrophy

Bone biopsy is the gold standard for characterization of renal osteodystrophy (ROD). However, the classification of the subtypes of ROD based on histomorphometric parameters is not unambiguous and the range of normal values for turnover differ in different publications. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a dynamic imaging technique that measures turnover. 18F-NaF PET has previously been shown to correlate with histomorphometric parameters. In this cross-sectional study, 26 patients on dialysis underwent a 18F-NaF PET and a bone biopsy. Bone turnover-based classification was assessed using Malluche’s historical reference values for normal bone turnover. In unified turnover-mineralization-volume (TMV)-based classification, the whole histopathological picture was evaluated and the range for normal turnover was set accordingly. Fluoride activity was measured in the lumbar spine (L1–L4) and at the anterior iliac crest. On the basis of turnover-based classification of ROD, 12% had high turnover and 61% had low turnover bone disease. On the basis of unified TMV-based classification of ROD, 42% had high turnover/hyperparathyroid bone disease and 23% had low turnover/adynamic bone disease. When using unified TMV-based classification of ROD, 18F-NaF PET had an AUC of 0.86 to discriminate hyperparathyroid bone disease from other types of ROD and an AUC of 0.87, for discriminating adynamic bone disease. There was a disproportion between turnover-based classification and unified TMV-based classification. More research is needed to establish normal range of bone turnover in patients with CKD and to establish the role of PET imaging in ROD.

MO581ASSOCIATION OF ETELCALCETIDE WITH ADYNAMIC BONE DISEASE IN DIABETIC PATIENTS : A MULTI-CENTRIC STUDY

Background and Aims Several dialysis patients frequently suffer of different mineral and bone disorders (CKD-MBD) associated with secondary hyperparathyroidism (sHPT). Among CKD-MBD, adynamic bone disease (ABD) is an alteration characterized by reduced osteblasts and osteoclasts, no accumulation of osteoid and low bone turnover. The histologic pattern of ABD is generally associated to low levels of PTH. Etelcalcetide is a novel second-generation calcimimetic given intravenously after each hemodialysis session that has a longer elimination half-life than cinacalcet. Plasmatic concentration remains stable from 24 h to 48 h after injection. One potential risk of calcimimetics, such as etelcalcetide, is the dramatic and sustained PTH lowering, which could lead to the induction of adynamic bone disease (ABD). ABD and elevated serum levels of advanced glycation end products (AGEs) often are found in patients with renal failure caused by diabetic nephropathy since AGEs are involved in the pathogenesis of ABD by inhibiting osteoblastic activity and by parathyroid hormone secretion in response to hypocalcemia. So, diabetic patients treated with etelcalcetide could be considered at increased risk of developing ABD. Aim of our study was to verify the incidence of adynamic bone disease, (defined by low PTH levels) in prevalent diabetic and non-diabetic HD patient of three large community Hospital. Method Data were collected from 3 dialysis units with n = 130 patients on the charge for a period of 1 year from start of the calcimimetic. A total of 40 patients ( 23 male, 17 female) on etelcalcetide were enrolled (21 Diabetic, 19 non diabetic patients). Time points of assessment included 1-3-6-12 months. Patients were 18-years-old or older; they were on stable doses of active vitamin D analogs, phosphorus binders, a supplement of oral calcium, and calcium concentration in dialysate (1.25–1.50 mmol/L) Results Median age was 55,9 years and dialysis vintage was 4.6 year. 59,5% percent of patients switched from cinacalcet to etelcalcetide (90 days from last cinacalcet prescription); the remaining patients were calcimimetic naive. 40% of patients had a history of at least one cardiovascular event 61.5% had a starting etelcalcetide dose of 5 mg and the median weekly dose was 7.5 mg (range: 2.5-15 mg). On Diabetic Group: mean PTHi, Ca2+ and P before calcimimetic start was respectively 844±479,30 pg /mL , 9,95±0,97 mg/dl , 5,02±0,99 mg/dl. In non diabetic patients: mean PTHi, Ca2+ and P before calcimimetic start was: 793,36±534,41 150 pg /mL, 9,33±0,70 mg/dl, 5,9±1,17 mg/dl Conclusion Results of our study show that after 1 year of etelcalcetide treatment, levels of PTHi are lower more in non-diabetic patients, ( M12: 473±340,08 vs 253,13 + 98,87 p:0.042) despite scientific evidence currently supporting hypothesis that osteoblastic activity is reduced by AGES and ABD risk is increased in diabetic nephropathy. Therefore, etelcalcetide could be used safely in diabetic patients and could even protect from the risk of development ABD. However, further studies are required to validate this hypothesis. Results are shown in the following table:

Treatment of Severe Tumoral Calcinosis with Teriparatide in a Dialysis Patient after Total Parathyroidectomy

Tumoral calcinosis is a rare but debilitating condition that can affect dialysis patients. Optimal management is largely unknown. We report the clinical course, treatment, and outcome of a peritoneal dialysis (PD) patient who developed tumoral calcinosis refractory to conventional treatment but improved with teriparatide therapy. A 26-year-old lady on PD for 2 years presented to us with tumoral calcinosis involving bilateral hands. Response to surgical excision, parathyroidectomy, and conversion to hemodialysis failed to result in sustained remission, and tumoral calcinosis progressed. After total parathyroidectomy, the patient had transient but partial remission in which her calcinosis deposits remained but were asymptomatic without pain or clinical signs of inflammation. However, she later experienced a relapse with involvement of the left elbow, right shoulder, right hip, and right thigh. Tumoral calcinosis remained uncontrolled resulting in debilitation, likely attributable to poor calcium and phosphate control because of adynamic bone disease after parathyroidectomy despite treatment of superimposed tuberculosis and therapy with sodium thiosulphate and pamidronic acid. Clinical improvement was however evident after the use of teriparatide. Asymptomatic hypocalcemia occurred after teriparatide therapy but resolved after 2 months. In conclusion, teriparatide appears to be useful for treating tumoral calcinosis in the presence of adynamic bone disease. Hypocalcemia can occur in the initial months of therapy.

Treatment of mineral-bone disorders in chronic kidney disease

Mineral-bone disorders (MBD) in chronic kidney disease (CKD) manifest by hyperphosphatemia, vitamin D deficiency, overproduction of fibroblast growth factor-23, and secondary hyperparathyroidism. CKD-MBD also results in bone resorp-tion and ectopic calcification that is associated with an increased risk of cardiovascular events and mortality. Diet is the initial and obligatory approach to treatment for CKD-MBD. Sevelamer is frequently used for correction of hyperphosphatemia in patients with renal failure who present with calcification of arteries, adynamic bone disease and/or stably low serum parathyroid hormone levels. Calcimimetics, that is, cinacalcet and evocalcet, are widely used in hemodialysis patients who do not respond to treatment with vitamin D.

SO07118F-SODIUM FLUORIDE POSITRON EMISSION TOMOGRAPHY AND BONE HISTOMORPHOMETRY - COMPARISON BETWEEN ONLY BONE TURNOVER -BASED AND EXPERT EVALUATION -BASED CLASSIFICATION OF RENAL OSTEODYSTROPHY

Background and Aims The diagnosis and the differentiation of renal osteodystrophy (ROD) are challenging. Bone biopsy is the golden standard, but it is invasive and not available in every center. Bone turnover rate is defined by bone formation rate and/or activation frequency. Adynamic bone disease is defined as low turnover bone with reduced osteoblast- and osteoclast activities. Hyperparahyreoid bone disease or osteitis fibrosa is defined as high turnover bone with osteoclast- and osteoblast activities and fibrosis. 18F- Sodium Fluoride positron emission tomography (18F-NaF PET) is a noninvasive imaging technique that allows assessment of regional bone turnover. The aim was to assess how well bone turnover –based classification of ROD correlates with the classification determined by an expert histomorphometrist (HK), and how these correlate with 18F-NaF PET analysis Method A total of 24 dialysis patients underwent a 18F-NaF PET scan. Fluoride activity was measured at the anterior iliac crest and in the lumbar region. An iliac crest bone biopsy was obtained within 4 weeks from the PET-scan. The diagnosis of bone histomorphometry was determined based on turnover-mineralization-volume (TMV) classification. Firstly, bone turnover was assessed using bone formation rate and activation frequency. Secondly, also other histomorphometric parameters (eg. osteoid volume, osteoid surface, resorption surface, mineralized surface, osteoblast and osteoclast surfaces and peritrabecular fibrosis) were also taking into account for classification of ROD by a histomorphometrist. Results Based on bone turnover parameters only, 12% of the patients had high turnover and 64% low turnover. When the diagnosis of renal osteodystrophy was made by a histomorphometrist, 40% had hyperparathyreoid bone/osteitis fibrosa and 24% adynamic bone disease or ostemalasia. 18F-NaF PET´s sensitivity to recognize hyperparathyreoid bone disease was 80% end specificity 100% (cut-of value 0.055).18F-NaF PET´s sensitivity to recognize adynamic bone disease was 100% and specificity 61% (cut-of value of fluoride-activity 0.038) Conclusion 18F-NaF PET works well as a diagnostic tool, when the diagnosis of ROD is based on the histopathological evaluation. It remains unknown how variations in normal bone turnover rate can be detected in CKD patients by 18F-NaF PET and if treatment decisions of ROD can be made only based on bone turnover.