Uncontrolled Secondary Hyperparathyroidism Research Articles

Sagliker syndrome in a patient with end-stage renal disease and uncontrolled secondary hyperparathyroidism.

Sagliker syndrome in a patient with end-stage renal disease and uncontrolled secondary hyperparathyroidism.

Sagliker syndrome: a rare manifestation of uncontrolled secondary hyperparathyroidism in chronic renal failure – a comprehensive case report

We present a case of a 22-year-old female patient with a history of chronic kidney disease (CKD) and secondary hyperparathyroidism, complicated by pathological fractures of both femurs and subsequent joint replacements. The patient exhibited craniofacial deformities with lytic lesions in the maxilla and mandible, airway abnormalities and cardiovascular adaptations due to hypertensive heart disease. A subtotal parathyroidectomy was performed, a combination of medications and nerve blocks was used for anesthesia induction and intubation, with subsequent bronchospasm and desaturation necessitating intervention. The surgical procedure was successful, with no further intraoperative issues.

#4993 EFFECT OF ETELCALCETIDE TREATMENT ON ERYTHROPOIESIS-STIMULATING AGENTS (ESAS) REQUIREMENT IN HEMODIALYSIS PATIENTS: A SINGLE CENTER STUDY

Abstract Background and Aims Anemia is a common consequence of advanced chronic kidney disease (CKD). There are various causes of renal anemia like decreased production of and resistance to Erythropoietin, shortened survival of red blood cells and chronic blood loss. Secondary hyperparathyroidism is a potential cause of renal anemia in CKD patients due to direct effect on Erythropoietin synthesis, red cell survival and bone marrow fibrosis [1]. There are several reports of the beneficial effect of treatment of hyperparathyroidism on hemoglobin (Hb) levels. Etelcalcetide is a novel intravenous calcimimetic used for the treatment of secondary hyperparathyroidism in hemodialysis patients. However, there are very few reports of Etelcalcetide's effect on anemia management in hemodialysis patients. We aimed to study the effect of Etelcalcitide on ESAs requirement in our hemodialysis cohort. Method This is a retrospective study in Al Wakra Hospital hemodialysis unit conducted on patients with uncontrolled secondary hyperparathyroidism who needed to be started on Etelcalcetide. Mean Hb and mean ESAs dose were calculated for a period of 6 months before and 6 months after starting Etelcalcetide, while iPTH levels were measured at the beginning and 6 months after starting Etelcalcetide. Inclusion criteria: hemodialysis patients who are on Etelcalcetide for at least 6 months. Exclusion criteria: Patients’ age < 18 years, hemodialysis duration < 12 months and patients with acute blood loss. Results Out of 94 hemodialysis patients, 26 (27.6%) were on Etelcalcetide. 2 patients were excluded, one for acute hematuria and the other for erosive gastritis. 24 patients were included (13 females and 11 males). Mean age of the patients was 58.7 years. 15 patients were on Darbepoetin, 8 on Erythropoietin and 1 patient was switched from Darbepoetin to Erythropoietin due to poor response. There was no significant difference in mean Hb levels for all the patients before and after starting Etelcalcetide (10.6 g/dl and 10.8 g/dl, respectively). Out of 24 patients, 19 had reduction while 5 had increase in ESAs dose requirement. In total, the mean reduction of ESAs dose for all the patients was 17.3%. There was a mean of 33.4% reduction in ESAs requirement for the 19 patients while a mean of 44% increase in the requirement for the 5 patients. Mean iPTH for the cohort at the time of starting Etelcalcetide and 6 months after was 1036 pg/ml and 473 pg/ml respectively. The mean reduction of iPTH for those who had decreased ESAs requirement was 58% while it was 38.8% for those who had increased ESA requirement. Conclusion This study showed that control of severe secondary hyperparathyroidism with Etelcalcetide was associated with reduction in ESAs requirement in hemodialysis patients. The more the control of hyperparathyroidism, the more the reduction of ESAs requirement. These findings were observed also in a one case report [2]. We believe that our study has one of the largest number of patients to show such an observation, however larger controlled studies are needed to confirm these preliminary findings in the improvement of anemia after treatment of hyperparathyroidism by Etelcalcetide.

Selective vitamin D receptor activator Paricalcitol and its potential benefits in hemodialysis patients with secondary hyperparathyroidism

Currently, the incidence and prevalence of chronic kidney disease (CKD) are increasing annually worldwide, and clinical data show that CKD patients commonly experience relative vitamin D insufficiency or deficiency. Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients. SHPT is an adaptive and in many cases ultimately maladaptive process that develops in response to declining kidney function, impaired phosphate excretion, failure to bioactivate vitamin D and hypocalcemia. SHPT is characterized by persistently elevated levels of parathyroid hormone (PTH) and complicated by important disturbances in mineral metabolism. Maintaining the level of vitamin D and parathyroid hormone concentrations in the target range reduce its associated complications (e.g., fractures, chronic kidney disease and cardiovascular calcification). Effective therapeutic interventions are highly desirable if the morbidity and mortality associated with uncontrolled SHPT are to be reduced. Major renal guidelines recommend use of vitamin D for secondary hyperparathyroidism in chronic kidney disease. However, because of the difficulties associated with lowering PTH while simultaneously controlling serum levels of calcium and phosphorous, traditional therapies for managing SHPT have several limitations. Selective vitamin D receptor activator paricalcitol mainly targets vitamin D receptors (VDR) in the parathyroid glands, has less effect on VDR in the intestine and other tissues, inhibits PTH strongly, triggers less hypercalcemia, and has less effect on intestinal absorption of calcium, phosphorus and bone metabolism and significantly lowers renin levels, albuminuria and blood pressure, which is supported by the results of most studies conducted over these decades. The article is devoted to the problem of treatment of patients with SHPT inpatient with renal replacement therapy with program hemodialysis.

Abstract #1148697: Severe Facial Disfiguration due to Uremic Leontiasis Ossea from Underlying Secondary Hyperparathyroidism

Renal osteodystrophy is a common complication of end-stage renal disease (ESRD) patients. Rarely, it can be associated with uremic leontiasis ossea (ULO) that is characterized by progressive enlargement of the facial bones and is thought to be secondary to uncontrolled secondary hyperparathyroidism (sHPTH) in the setting of ESRD. Few case reports have been described in the literature with our case appearing to be the most severe. Due to the rarity of this disease, there is no current standard of treatment.

The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation.

BackgroundOptimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation.MethodsWe studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4–6 (2009–18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9–12 months on HD.ResultsThe 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9–12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150–300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9–12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation.ConclusionsIncreased PTH before HD start predicted a higher PTH level 9–12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients.

P0890EFFICACY AND SAFETY OF CINACALCET IN CHINESE MAINTENANCE HEMODIALYSIS PATIENTS WITH DIFFERENT STAGES OF SECONDARY HYPERPARATHYROIDISM: INTERIM ANALYSIS RESULTS OF ACTIVE STUDY

Abstract Background and Aims Chronic kidney disease (CKD) is a major public health issue worldwide including in China. One of the most common complication in advanced Chronic kidney disease (CKD) is secondary hyperparathyroidism (SHPT). Reports show higher risk of bone fracture, cardiovascular events and all-cause mortality is associated with uncontrolled SHPT in patients with CKD. Cinacalcet, a calcimimetic agent was reported to reduce iPTH levels without Ca increase in patients with SHPT previously. However there has been no large-cohort study and stratified analysis of cinacalcet based on the level of iPTH in China. Moreover, the optimal therapeutic doses of cinacalcet with mild-to-severe SHPT is remaining unknown. ACTIVE study is an IV, open-label, multicenter clinical trial aimed to: (1) evaluate the efficacy and safety of cinacalcet in maintenance hemodialysis patients with mild-to-severe SHPT; (2) explore optimal combinations therapy with cinacalcet and other agents for treating patients with CKD-mineral and bone disorder. (3) investigate the benefit of long-term, continuous medication with cinacalcet in the real-world setting. Method The study design was reported on 2019 ASN. Key inclusion criteria were a baseline iPTH ≥300 pg/mL with life expectancy of ≥2 years, and ≥12 weeks of maintenance dialysis (three dialysis sessions per week) prior to enrollment. The enrollments were grouped based on their iPTH level as having mild (300-600 pg/mL), moderate (600-900 pg/mL) or severe (≥900 pg/mL). Patients initiated treatment with cinacalcet orally at a starting dose of 25 mg once daily (qd). The primary efficacy endpoint is the proportion of patients achieving iPTH targets (iPTH between 150-300pg/mL) at 20 and 32 weeks after the initiation of cinacalcet treatment. Adverse events and serious adverse events were recorded. An interim analysis was scheduled as 375 patients completed 32 weeks visit. Results 911 patients were recruited and of 750 eligible patients, 275 were identified as mild, 224 were considered as moderate and left 251 were grouped as severe SHPT. The study flowchart of 375 patients including mild(127), moderate(106) and severe(142) SHPT for interim analysis was shown in Fig 1. The baseline results including demographic and biomarkers level were reported on 2019 ASN. After 4 weeks’ cinacalcet treatment, serum PTH decreased in all three group, while extremely remarkable in the severe SHPT group. Interim analysis results revealed that the proportion of patients achieving iPTH target (150-300 pg/mL) at 20 wk visit among mild, moderate and severe groups were 38.61% (39/101), 30.11% (28/93) and 10.91% (12/110) respectively. The proportion of patients achieving iPTH target at 32 wk visit in 3 groups increased to 44.68% (42/94), 27.27% (24/88) and 14.56% (15/103) respectively (Table.1). The trends of the proportion of patients achieving iPTH target increased in all 3 different groups (Fig.2). The safety analysis showed the most common treatment-related AE in top 3 including hypocalcemia, hyperlipidemia, and loss of appetite. In vital signs, electrocardiogram (ECG) and laboratory examination of descriptive analysis, found no obvious safety tips. This study is sponsored by Kyowa Hakko Kirin (China) Pharmaceutical Co., Ltd. The analysis is still ongoing and results will be released at EDTA meeting this year. Conclusion Oral cinacalcet HCl was effective and safe in reducing iPTH in patients receiving HD with mild-to-severe SHPT.

SAT-102 ECTOPIC MEDIASTINAL PARATHYROID CARCINOMA ACCOMPANYING BY PARATHYROID HYPERPLASIA IN A HEMODIALYTIC PATIENT

Parathyroid carcinoma is a rare cancer, and the development under secondary hyperparathyroidism is also clinically infrequent. The diagnosis of parathyroid carcinoma under secondary hyperparathyroidism may be difficult due to a radiological similarity between parathyroid carcinoma and adenoma. Moreover, if hemodiaytic patients only show parathyroid hyperplasia without parathyroid adenomatous change by uncontrolled hyperphosphatemia, maligant change of parathyroid gland may be rarely developed. We report an interesting case showing an ectopic mediastinal parathyroid carcinoma related with uncontrolled secondary hyperparathyroidism and parathyroid hyperplasia in patient with end-stage renal disease (ESRD) undergoing hemodialysis. N/A (This abstract is a case report) A 30-year-old man on maintenance hemodialysis due to chronic rejection of transplanted kidney showed a recurrently high level of serum intact parathyroid hormone (iPTH) without remarkable decreases despites of intensive medications including intravenous calcitriol and lanthanum carbonate. Parathyroid scan revealed parathyroid hyperplasia in the both upper portions of thyroid. Ultrasound did not show extrathyroidal nodular lesions. Firstly, simultaneous use of cinacalcet and calcitriol was implemented, and we performed a follow-up scan due to persistently uncontrolled hyperparathyroidism and hypercalcemia. When compared with prior parathyroid scan, it showed more increased parathyroid hyperplasia in the same area, and new hot lesions in left lower portion of thyroid and right upper paratracheal area in mediastinum were newly shown. Computed tomography (CT) of neck showed multiple nodular lesions in the mediastinal area, compatible with ectopic parathyroid adenoma, along with hyperplasia on both upper and left lower parathyroid glands. Firstly, we referred to thoracic surgery for the mediastinal mass. The preoperative laboratory results were as follows: serum calcium, 10.4 mg/dL; serum iPTH, 1150 pg/mL. The mediastinal masses with diameters of less than 2.2 cm were removed and histologically compatible with parathyroid carcinoma. Serum iPTH did not postoperatively decrease, but serum calcium decreased. We performed a 18F-fluorodeoxyglucose positron-emission tomography-CT scan for parathyroid gland and distant metastases of parathyroid carcinoma. It revealed no locoregional and distant metastases of parathyroid carcinoma except remained parathyroid hyperplasia. We recommended total thyroidectomy immediately due to uncontrolled secondary hyperparathyroidism. After one month, the patient was performed total thyroidectomy and serum iPTH level was normalized after the operation. The pathologic results after total thyroidectomy showed only parathyroid hyperplasia without adenomatous changes and it also revealed no locoregional metastatic lesion of parathyroid carcinoma. A diagnosis of parathyroid carcinoma without a confirmative surgery is difficult particularly in uncontrolled secondary hyperparathyroidism without parathyroid adenoma. Moreover, an ectopic mediastinal parathyroid carcinoma under same condition may be easily underdiagnosed. Thus, dialytic patients with refractory secondary hyperparathyroidism irregardless of existence of parathyroid adenoma should perform a radiologically close follow-up, even if the first scan show only parathyroid hyperplasia.

SUN-208 Cost Analysis of Parathyroidectomy for Patients with Severe Uncontrolled Secondary Hyperparathyroidism at a Large Integrated Health Care Service in United Arab Emirates

SUN-208 Cost Analysis of Parathyroidectomy for Patients with Severe Uncontrolled Secondary Hyperparathyroidism at a Large Integrated Health Care Service in United Arab Emirates

Evolution of secondary hyperparathyroidism in patients following return to hemodialysis after kidney transplant failure

IntroductionSevere uncontrolled secondary hyperparathyroidism and kidney transplantation history are both risk factors for fractures in hemodialyzed patients. Moreover, patients who return to dialysis after transplant failure have more severe infections/anemia and higher mortality risk than transplant-naive patients starting dialysis with native kidneys. In this context, our aim was to test the hypothesis that transplant failure patients have more secondary hyperparathyroidism than transplant-naive patients. MethodsWe retrospectively compared 29 transplant failure patients to 58 transplant-naive patients matched for age, sex, chronic kidney disease duration and diabetes condition (1 transplant failure/2 transplant-naive ratio), who started dialysis between 2010 and 2014. Clinical and biological data were collected at baseline, 6 and 12 months. FindingsAt baseline, neither serum parathyroid hormone (transplant-naive: 386±286pg/mL; transplant failure: 547±652pg/mL) nor serum 25-hydroxyvitamin D (transplant-naive: 27.8±17.0μg/L, transplant failure: 31.1±14.9μg/L) differed between groups. However, serum parathyroid hormone at 12 months and the proportion of patients with uncontrolled secondary hyperparathyroidism (parathyroid hormone>540pg/mL, KDIGO criteria) were significantly higher in transplant failure than in transplant-naive (parathyroid hormone: 286±205 vs. 462±449, P<0.01; uncontrolled secondary hyperparathyroidism: 30% vs. 13%, P<0.01, respectively). Within the transplant failure group, patients with uncontrolled secondary hyperparathyroidism at 12 months were younger than patients with normal or low parathyroid hormone. DiscussionThis retrospective and monocentric study suggests that transplant failure patients are more likely to develop secondary hyperparathyroidism. Thus, finding high serum parathyroid hormone in young transplant failure patients, who are expected to undergo further transplantations, should incite physicians to treat early and more aggressively this complication.

SUN-505 The Invincible Parathyroid Gland

Background: Uncontrolled secondary hyperparathyroidism sometimes requires parathyroidectomy for control of parathyroid levels. We present a case of secondary hyperparathyroidism with recurrence due to hyperplasia of her re-implanted parathyroid gland and atypical features concerning for parathyroid carcinoma. Case Presentation: A 56 year old woman with a history of ESRD on peritoneal dialysis and gastric bypass surgery developed secondary hyperparathyroidism that required a parathyroidectomy with transplantation of a portion of her parathyroid gland in the right forearm in 2015. Surgical pathology showed four-gland hyperplasia. Following surgery, labs revealed a calcium of 8.6mg/dl and a PTH of 206 pg/ml. Subsequently, she developed hypocalcemia with a calcium of 5.7mg/dL, which was treated with calcitriol 2.5mcg three times daily, phoslo three times daily, and sensipar 90mg daily. Her PTH continued to rise from years 2015-2018, ranging between 1200- 1900 pg/ml. Labs in May 2018 revealed a calcium of 10.1 mg/dL, phosphorus of 9.0 mg/dL, and of PTH 1811 pg/ml. Physical exam showed a 4 cm mass in her right forearm at the site of parathyroid re-implantation. Due to inability to control her PTH and phosphorus levels, the re-implanted parathyroid tissue was removed and a small piece was re-implanted in the brachioradialis muscle in June 2018. Pathology demonstrated a 5.5x3x2cm mass with atypical parathyroid proliferation with necrosis and focal vascular invasion suspicious for parathyroid carcinoma. After surgery, PTH was 184 pg/ml and calcium was 5.4 mg/dL. The patient was referred to oncology for evaluation. CT chest was negative and ultrasound of the forearm showed a 6x2x5mm hypoechoic structure in the subcutaneous fat. The patient is currently maintained on calcium 1500mg four times a day, lanthanum, and calcitriol 7mcg divided four times a day. Most recent calcium was 8.4mg/dL and phosphorus was 5.9mg/dL. She will continue ultrasound surveillance of her forearm due to the atypical pathology of her re-implanted parathyroid tissue. Conclusion: We present a case of secondary hyperparathyroidism requiring parathyroidectomy with subsequent hyperplasia of the re-implanted parathyroid gland. A recent meta-analysis suggests that total parathyroidectomy may be preferred due to the risk of recurrence with total parathyroidectomy with autotransplantation (1). To our knowledge, there are no reported cases of a parathyroid carcinoma occurring in a re-implanted parathyroid gland. While this patient’s pathology was not definitely a parathyroid carcinoma, the pathology was atypical and concerning for malignancy.

Managing hyperparathyroidism in hemodialysis: role of etelcalcetide.

Secondary hyperparathyroidism (SHPT) is common in patients receiving maintenance hemodialysis and is associated with adverse outcomes. Currently, SHPT is managed by reducing circulating levels of phosphate with oral binders and parathyroid hormone (PTH) with vitamin D analogs and/or the calcimimetic cinacalcet. Etelcalcetide, a novel calcimimetic administered intravenously (IV) at the end of a hemodialysis treatment session, effectively reduces PTH in clinical trials when given thrice weekly. Additional clinical effects include reductions in circulating levels of phosphate and FGF-23 and an improved profile of markers of bone turnover. However, despite being administered IV, etelcalcetide appears to be associated with rates of nausea and vomiting comparable to those of cinacalcet. Additionally, etelcalcetide, relative to placebo, causes hypocalcemia and prolonged electrocardiographic QT intervals, effects that must be considered when contemplating its use. Etelcalcetide likely has a role in treating hemodialysis patients with uncontrolled SHPT or with hypercalcemia or hyperphosphatemia receiving activated vitamin D compounds. However, its use should be at least partially constrained by consideration of the risk of hypocalcemia and resultant prolonged QT intervals in vulnerable patients. Because of its effectiveness as a PTH-reducing agent administered in the dialysis unit, etelcalcetide represents a potentially promising new therapeutic approach to the often vexing problem of SHPT in hemodialysis patients. However, whether its use is associated with changes in surrogate clinical end points, such as effects on rates of parathyroidectomy, fracture, vascular calcification, or mortality or on quality of life, remains to be studied.

Hyperplastic Autotransplanted Parathyroid Tissue Migrating into Fatty Tumor after Total Parathyroidectomy

Secondary hyperparathyroidism (SHPTH) occurs commonly in patients with end-stage renal disease (ESRD). Uncontrolled SHPTH is associated with...

Trajectories of CKD-MBD biochemical parameters over a 2-year period following diagnosis of secondary hyperparathyroidism: a pharmacoepidemiological study

ObjectivesTo define groups of patients according to the changes of biochemical parameters, that is, serum calcium, phosphate and parathyroid hormone (PTH), over a 2-year follow-up period using group-based multi-trajectory modeling...

A Swelling in the Mouth in a Chronic Hemodialysis Patient.

Oral manifestations of severe secondary hyperparathyroidism include maxillary and mandibular deformities, brown tumors, dental abnormalities, and metastatic calcification of soft tissues. We report on a chronic hemodialysis (HD) woman with severe, uncontrolled secondary hyperparathyroidism and a painful, nontender mass in the floor of her mouth. The most likely clinical diagnosis was a bone tumoral lesion of the oral cavity, secondary to renal osteodystrophy. Unexpectedly, pathological examination showed characteristic features of ossifying fibroma (OF) of the jaw, a rare, benign fibroosseous lesion characterized by the replacement of normal bone by collagen and fibroblasts containing varying amounts of mineralized substance. The occurrence of an OF in chronic HD patients is exceptional. Differential diagnosis must be made with bone tumoral lesions secondary to renal osteodystrophy. Surgical removal is the treatment of choice. The pathogenesis of OF in the setting of secondary hyperparathyroidism remains unknown. Parathyroidectomy may not be necessary to avoid OF recurrence after surgical removal.

The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial.

Uncontrolled secondary hyperparathyroidism (sHPT) in patients with ESRD is a risk factor for calcific uremic arteriolopathy (CUA; calciphylaxis). Adverse event reports collected during the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial were used to determine the frequency of CUA in patients receiving hemodialysis who had moderate to severe sHPT, as well as the effects of cinacalcet versus placebo. CUA events were collected while patients were receiving the study drug. Among the 3861 trial patients who received at least one dose of the study drug, 18 patients randomly assigned to placebo and six assigned to cinacalcet developed CUA (unadjusted relative hazard, 0.31; 95% confidence interval [95% CI], 0.13 to 0.79; P=0.014). Corresponding cumulative event rates (95% CI) at year 4 were 0.011% (0.006% to 0.018%) and 0.005% (0.002% to 0.010%). By multivariable analysis, other factors associated with CUA included female sex, higher body mass index, higher diastolic BP, and history of dyslipidemia or parathyroidectomy. Median (10%, 90% percentile) plasma parathyroid hormone concentrations proximal to the report of CUA were 796 (225, 2093) pg/ml and 410 (71, 4957) pg/ml in patients randomly assigned to placebo and cinacalcet, respectively. Active use of vitamin K antagonists was recorded in 11 of 24 patients with CUA, nine randomly assigned to placebo, and two to cinacalcet, in contrast to 5%-7% at any one time point in patients in whom CUA was not reported. Cinacalcet appeared to reduce the incidence of CUA in hemodialysis recipients who have moderate to severe sHPT.

Factors precipitating erythropoiesis-stimulating agent responsiveness in a European haemodialysis cohort: case-crossover study.

PurposeHyporesponsiveness to erythropoiesis‐stimulating agents (ESAs) is clinically and economically important in the treatment of anaemia in chronic kidney disease (CKD) patients. Previous studies focused on baseline predictors of ESA hyporesponsiveness, rather than factors associated with the transition to this state. Reversibility of ESA hyporesponsiveness has also not been studied previously.MethodsCase‐crossover methodology was applied to a cohort of 6645 European CKD patients undergoing haemodialysis and prescribed ESAs. Ninety‐day ESA exposure periods were defined, haemoglobin (Hb) response was calculated using the last 30 days of one period and the first 30 days of the next, and periods were classified based on a median ESA dose (80.8 IU/kg/week) and a 10 g/dL Hb threshold. Clinical, dialysis and laboratory data from patients' first hyporesponsive ‘case’ period was compared with the preceding responsive ‘control’ period using conditional logistic regression. A similar approach was applied to hyporesponsiveness reversal.ResultsOf the patients, 672 experienced hyporesponsiveness periods with preceding responsive periods; 711 reversed to normality from hyporesponsiveness periods. Transition to hyporesponsiveness was associated with hospitalization, vascular access changes or worsening inflammation, with these factors accounting for over two‐thirds of transitions. Findings were largely insensitive to alternative ESA doses and Hb thresholds. Continued hospitalization, catheter insertion and uncontrolled secondary hyperparathyroidism were associated with a lack of regain of responsiveness.ConclusionsTransition to hyporesponsiveness is linked to the development of conditions such as hospitalization events, vascular access issues or episodes of systemic inflammation. However, a third of hyporesponsive episodes remain unexplained. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Serum calcium and phosphorus levels in patients undergoing maintenance hemodialysis: A multicentre study in Korea

BackgroundIn many countries, nephrologists follow clinical practice guidelines for mineral bone disorders to control secondary hyperparathyroidism (SHPT) associated with abnormal serum calcium (Ca) and phosphorus (P) levels in patients undergoing maintenance hemodialysis (MHD). The Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines have long been used in Korea, and this study was undertaken to investigate the current status of serum Ca and P control in MHD patients. MethodsData were collected from a total of 1,018 patients undergoing MHD without intercurrent illness, in 17 hemodialysis centers throughout the country. Serum levels of Ca, P, and intact parathyroid hormone (iPTH) were measured over 1 year, and the average values were retrospectively analyzed. ResultsSerum levels of Ca, P, and the Ca×P product were 9.1±0.7mg/dL, 5.3±1.4mg/dL, and 48.0±13.6mg2/dL2, respectively. However, the percentages of patients with Ca, P, and Ca × P product levels within the KDOQI guideline ranges were 58.7%, 51.0%, and 70.7%, respectively. Of the 1,018 patients, 270 (26.5%) had iPTH >300pg/mL (uncontrolled SHPT), whereas 435 patients (42.7%) showed iPTH <150pg/mL. Patients with uncontrolled SHPT had significantly higher values of serum Ca, P, and Ca×P product than those with iPTH ≤300pg/mL. ConclusionDespite the current clinical practice guidelines, SHPT seems to be inadequately controlled in many MHD patients. Uncontrolled SHPT was associated with higher levels of serum Ca, P, and Ca × P product, suggestive of the importance of SHPT management.

Intermittent Dosing of Cinacalcet is also Effective in Treating Secondary Hyperparathyroidism in Hemodialysis Patients

Background: The calcimimetic, cinacalcet hydrochloride acting on the calcium-sensing receptors is being used quite often in the management of secondary hyperparathyroidism (SHPT). It is given in daily dose of 30-180 mg but there have not been enough comparative trials with intermittent dosing schedule. Aim: To evaluate effectiveness of daily cinacalcet hydrochloride dose and its 3 weekly doses in reducing serum intact PTH levels and relative concentrations of calcium and phosphorous in patients with end stage renal diseases (ESRD) with SHPT on maintenance hemodialysis (HD). Material and methods: Chronic kidney disease (CKD) patients (n=29) who were receiving daily dose (OD) of cinacalcet for SHPT for I year were shifted to an intermittent dosing regimen of cinacalcet at the end of each hemodialysis session (HD), 3 times per week (study patients). After taking baseline measurements of PTH, its monthly assessment along with serum calcium, phosphorous and alkaline phosphatase level estimations at 1, 3, 6, 9 and 12 months were then compared with the baseline levels. Results: Overall the mean intact PTH value was 174.2 + 16.8 pg/ml at the end of one year treatment prior to the study, while receiving a mean dose of 83.7 ± 11 mg cinacalcet OD. This controlled value of PTH did not show any statistically significant difference over the next 12 months when the study patients were given intermittent dosing (3/ week) at the end of each hemodialysis session. Similarly the calcium values did not change to a significant level in the study subjects, although the serum phosphorus showed a significant rise at the end of the study period (p=0.003). Conclusion: Cinacalcet effectively controls parathyroid hormone levels and uncontrolled secondary hyperparathyroidism both when given daily and intermittently (3/week). Frequent monitoring and adequate replacement with calcium and vitamin D sterols prevent hypocalcemia with cinacalcet therapy. Thus intermittent dosing of cinacalcet is an excellent cost-effective therapeutic option in HD patients with SHPT. In addition, it improves drug compliance.

Clinical Benefits of an Adherence Monitoring Program in the Management of Secondary Hyperparathyroidism with Cinacalcet: Results of a Prospective Randomized Controlled Study

Background/Aims. One of the causes of uncontrolled secondary hyperparathyroidism (sHPT) is patient's poor drug adherence. We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet. Methods. Prospective, randomized, controlled, multicenter, open-label study. Fifty hemodialysis patients on a stable dose of cinacalcet were randomized to an integrated care approach (IC) or usual care approach (UC). In the IC group, cinacalcet adherence was monitored using an electronic system. Results were discussed with the patients in motivational interviews, and drug prescription adapted accordingly. In the UC group, drug adherence was monitored, but results were not available. Results. At six months, 84% of patients in the IC group achieved recommended iPTH targets versus 55% in the UC group (P = 0.04). The mean cinacalcet taking adherence improved by 10.8% in the IC group and declined by 5.3% in the UC group (P = 0.02). Concomitantly, the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group (P = 0.03). Conclusions. The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet.