Calcitriol loading before total parathyroidectomy with autotransplant in patients with end-stage kidney disease: does it prevent postoperative hypocalcaemia?

BACKGROUND: Hungry bone syndrome (HBS) is one of the most serious complications following parathyroidectomy for severe hyperparathyroidism. There is a lack of literature informing the treatment and risk factors for this condition and the ideal pre-operative strategy for prevention. AIMS: The primary aims were to examine the incidence of HBS with pre-operative calcitriol loading for 10 days and to determine the risk factors for HBS. The secondary aims were to determine the rate of intravenous calcium replacement in those with HBS and to assess whether cinacalcet removal has increased rates of parathyroidectomy in the end-stage kidney disease population. METHODS: We performed a retrospective study from 2011 to 2018 on 45 patients with end-stage kidney disease undergoing total parathyroidectomy with autotransplantation for severe hyperparathyroidism. This was based at the John Hunter and Newcastle Private Hospitals in New South Wales. RESULTS: 28.3% of patients with calcitriol loading undergoing parathyroidectomy fulfilled criteria for HBS. Pre-operative variables that were associated with HBS were elevated parathyroid hormone (P = 0.028) and longer duration of renal replacement therapy (P = 0.033). Rates of total parathyroidectomy were higher after the removal of calcimimetics from the Pharmaceutical Benefits Scheme (P = 0.0024). CONCLUSIONS: HBS remains a common complication of parathyroidectomy, even with prolonged high-dose calcitriol loading. This emphasises the need for further trials investigating other targeted therapies, such as bisphosphonates, to prevent HBS. Those most at risk of HBS are patients with high bone turnover and prolonged renal replacement therapy.

Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study.

BACKGROUND AND OBJECTIVES: Elevated parathyroid hormone levels may be associated with adverse clinical outcomes in patients on dialysis. After the introduction of practice guidelines suggesting higher parathyroid hormone targets than those previously recommended, changes in parathyroid hormone levels and treatment regimens over time have not been well documented. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the international Dialysis Outcomes and Practice Patterns Study, trends in parathyroid hormone levels and secondary hyperparathyroidism therapies over the past 15 years and the associations between parathyroid hormone and clinical outcomes are reported; 35,655 participants from the Dialysis Outcomes and Practice Patterns Study phases 1-4 (1996-2011) were included. RESULTS: Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan, where it remained stable. Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time. Compared with 150-300 pg/ml, in adjusted models, all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio, 1.09; 95% confidence interval, 1.01 to 1.18) and >600 pg/ml (hazard ratio, 1.23; 95% confidence interval, 1.12 to 1.34). Parathyroid hormone >600 pg/ml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations. In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy, very low parathyroid hormone (<50 pg/ml) was associated with mortality (hazard ratio, 1.25; 95% confidence interval, 1.04 to 1.51). CONCLUSIONS: In a large international sample of patients on hemodialysis, parathyroid hormone levels increased in most countries, and secondary hyperparathyroidism treatments changed over time. Very low and very high parathyroid hormone levels were associated with adverse outcomes. In the absence of definitive evidence in support of a specific parathyroid hormone target, there is an urgent need for additional research to inform clinical practice.

[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.

Long-term outcome after total parathyroidectomy for the management of secondary hyperparathyroidism.

In patients with chronic renal failure, secondary hyperparathyroidism (sHPT) is a common problem requiring surgical parathyroidectomy (PTX) if medical treatment with active vitamin D and calcimimetics fails. To minimize the risk for recurrence, we perform total PTX (tPTX) without autotransplantation. From October 1997 to January 2004, 46 patients (31 men and 15 women) underwent tPTX without autotransplantation (median age 51 years; range 19-80 years; median dialysis time before PTX 5 years; range 0-25 years). Indications for PTX were hyperparathyroid bone disease in 41 cases and calciphylaxis in 5 cases. Postoperatively, all patients were supplemented with vitamin D analogues, both calcitriol and cholecalciferol. Patients were followed up for 4-107 months (median 63 months). Although tPTX was intended in all cases, we saw recurrent or persistent hyperparathyroidism in 26% and supernumerary glands in 15% of cases. In 7 patients (15%), five or more glands were documented and in another four suspected confirming the clinical relevance of intraoperative parathyroid hormone (PTH) measurement. In our study, the positive predictive value of a low intraoperative PTH (<20 pg/ml) for a successful tPTX was 92%. 15 patients received a renal transplant after tPTX without autotransplantation. Here, an uncomplicated hypocalcaemia was noted in 3 patients. Last available calcium levels were between 1.72 and 2.66 mmol/l (median 2.35 mmol/l). After follow-up, active vitamin D was given in a median daily dose of 0.5 microg calcitriol (range 0-2.5 microg/day). There was no evidence of clinical bone disease and no pathological fractures after tPTX after a median observation period of 63 months. tPTX still offers the highest percentage of cure for sHPT, it is safe and postoperatively easily manageable. It allows for adequate supplementation with active vitamin D, and it is the most cost-effective procedure. It should be reconsidered an option for the treatment of sHPT.