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  • 1
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 36, No. Supplement_1 ( 2021-05-29)
    Abstract: 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:
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 2
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 37, No. Supplement_3 ( 2022-05-03)
    Abstract: Alterations of mineral metabolism in patients with chronic renal failure (MBD-CKD) are frequently found and appear in the earliest stages of the disease. If not accurately diagnosed and treated, they could lead to serious clinical complications. With the same safety and better tolerability compared with cinacalcet, etelcalcetide demonstrated greater efficacy in the control of parathyroid hormone (iPTH) with an improvement in patients' compliance. Several reports in the literature document the effect of elevated levels of iPTH on anaemia. In vitro experiments showed that elevated concentrations of PTH (comparable to those found in the blood of uraemic patients with secondary hyperparathyroidism) exert a significant inhibition on erythroid progenitors, decreasing the number of erythropoietin receptors on erythroid progenitors and making these cells insensitive to erythropoietin. High levels of iPTH could have, furthermore, a haemolytic effect on the peripheral RBCs causing disturbed calcium metabolism, increased cytosolic calcium and enhanced osmotic fragility of the cells. Aim of this study was to verify in a dialysis cohort if etelcalcetide could not only improve iPTH levels but also haemoglobin levels with a reduction in weekly doses of erythropoiesis-stimulating agents (ESA). METHOD We analysed data from 130 haemodialysis adult patients over 2 years from three different centres. A total of 24 patients treated with etelcalcetide (Image 1) were enrolled and followed at different time points (1–3–6–12–24 months). Patients were on stable doses of ferric carboxymaltose, active vitamin D analogues, phosphorus binders, supplement of oral calcium and calcium concentration in dialysate (1.25–1.50 mmol/L). RESULTS Data analysed after 24 months of treatment with etelcalcetide (Image 2) demonstrated not only a drastic improvement in iPTH values (772.53 ± 452.6 pg/mL versus 308.7 ± 207 pg/mL–60.05%) but also a statistically significant improvement of haemoglobin values ( 10.35 ± 1.45 g/dL versus 11.57 ± 0.97 g/dL;  P & lt; .05) in addition to a reduction in the weekly ESAs units required (193.39 ± 148 UI/kg/week versus 142.71 ± 118 UI/kg/week; P & lt; .05). This effect was achieved by maintaining constant ferritin and TSAT levels and without substantial changes in iron carboxymaltose therapy. No side effects were recorded for the entire duration of the treatment. CONCLUSIONS Considering the well-known direct and indirect inhibition of parathyroid hormone on erythropoiesis, reduction of iPTH levels achieved with etelcalcetide could improve haemoglobin levels and reduce required weekly ESA units, with obvious clinical and economic advantages. Further studies, on large populations and over longer periods of time, are required.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1465709-0
    Location Call Number Limitation Availability
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  • 3
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Worldwide, amatoxin-containing mushrooms account for & gt;95% of mushroom poisoning-related death. Recently, Amanita species not containing amatoxin, such as Amanita Proxima, have been implicated in poisonings resulting in acute kidney injury. Allenic norleucine has been isolated from these fungi and accounts for their nephrotoxicity. AKI is characterized by interstitial nephritis on renal biopsy and resolves over weeks. Here we report several case of AKI associated with cardiac involvement. We aimed to describe improvement of cardiac output and resolution of AKI after replacement dialysis treatment. Method From January 2013 to January 2020, eight consecutive patients with AKI from Amanita Proxima poisoning were enrolled in a large Italian community hospital. We collected clinical data including hepatic, cardiac and renal function parameters. In all the cases studied, in addition to renal failure, there were a worsening of cardiac function. Results We identified 8 patients suffering from Amanita Proxima intoxication, with a mean age of 57.8±24.5 years (62.5% were female). All patients presented preliminary gastrointestinal symptoms occurred within 24 hours from the mushroom intake and suddenly developed kidney injury and underwent replacement dialysis treatment using standard bicarbonate dialysis. At baseline, patients' mean eGFR was 7±2.3 mL/min/1.73m, with a mean BUN of 124±41 mg/dl, AST 52,6±42,5 IU/L, ALT 115,5±105,7 IU/L,. Cardiac involvement was also found in all cases, evidenced by ECG alteration (62,5%), an increase in myocardial necrosis enzymes (87,5%) and a reduction in the ejection fraction (50%) of about 15 percent. In 25% of cases, typical chest pain was also found. Mean troponin was 3,82±7,31 ng/ml, myoglobin 243,55±275,18 ng/ml CPK 187,6±42 IU/L and CK-MB of 13,72±14,96 IU/L. Kidney failure and cardiac impairment was successfully resolved in 87.5% of poisonings. At the end of treatment all renal and cardiac parameters significantly decreased (P & lt;0.001): mean eGFR was 57±24 mL/min/1.73m, mean BUN was 69±12.7 mg/dl, AST 23,57±9,77 IU/l, ALT 25±10,64 IU/L. Mean troponin was 0,04±0,03 ng/ml, myoglobin 111,8±93,39 ng/ml, CPK 68,33± IU/L and CK-MB 0,66± 0,61 IU/L. Only one patient died for intoxication-related complication. The mean number of dialysis treatments to achieve the resolution of renal failure was eight. Conclusions The cases reported suggest that Amanita proxima have a potential severe cardiac toxicity that request a precise cardiac evaluation. Early identification of intoxication and rapid start of dialysis therapy are crucial for the resolution of heart damage.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1465709-0
    Location Call Number Limitation Availability
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