Intermittent Bi-Daily Sub-cutaneous Teriparatide Administration in Children With Hypoparathyroidism: A Single-Center Experience

Introduction: The use of teriparatide has been reported in children with hypoparathyroidism as an investigational physiologic replacement therapy.Methods: We aimed to retrospectively report our pediatric experience of bi-daily sub-cutaneous teriparatide. Results are presented as median (25th−75th quartile). As part of the routine follow-up of these patients with hypoparathyroidism, total calcium at H0 (i.e., just before injection) and H4 (i.e., 4 h after teriparatide injection) and other biomarker parameters were regularly assessed.Results: At a median age of 10.7 (8.1–12.6) years, an estimated glomerular filtration rate (eGFR) of 110 (95–118) mL/min/1.73 m2, calcium levels of 1.87 (1.81–1.96) mmol/L and an age-standardized phosphate of 3.8 (2.5–4.9) SDS, teriparatide therapy was introduced in 10 patients at the dose of 1.1 (0.7–1.5) μg/kg/day (20 μg twice daily), with further adjustment depending on calcium levels. Six patients already displayed nephrocalcinosis. Severe side effects were reported in one child: two episodes of symptomatic hypocalcemia and one of iatrogenic hypercalcemia; one teenager displayed dysgueusia. Calcium levels at H0 did not significantly increase whilst calcium at H4 and phosphate levels significantly increased and decreased, respectively. After 12 months, eGFR, calcium and age-standardized phosphate levels were 108 (90–122) mL/min/1.73 m2, 2.36 (2.23–2.48) mmol/L, 0.5 (−0.1 to 1.5), and 68 (63–74) nmol/L, respectively, with a significant decrease in phosphate levels (p = 0.01). Urinary calcium and calcium/creatinine ratio remained stable; no nephrolithiasis was observed but two moderate nephrocalcinosis appeared.Conclusion: Intermittent teriparatide therapy significantly improves calcium and phosphate control, without increasing calciuria. It appears to be safe and well-tolerated in children.

Implementation and effectiveness of an intensive education program on phosphate control among hemodialysis patients: a non-randomized, single-arm, single-center trial

Background Hyperphosphatemia is a common complication in patients on maintenance hemodialysis. Patients’ adherence to phosphorus control can be improved by consistent education. However, few studies have focused on the model construction and effects of health education on phosphate control for hemodialysis patients. Objective To develop an intensive education program focusing on phosphate control among hemodialysis patients and to analyze the effectiveness of this program. Design A non-randomized, single-arm, single-center trial lasting for 6 months. Setting This program was conducted in a hemodialysis center in a teaching hospital in Zhuhai, China. Participants Patients on maintenance hemodialysis with hyperphosphatemia. Methods An intensive hyperphosphatemia control education program lasting for 6 months was conducted among 366 hemodialysis patients applying the First Principles of Instruction model, which focused on mastering four stages: (a) activation of prior experience, (b) demonstration of skills, (c) application of skills and (d) integration of these skills into real-world activities. The controlled percentage of serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders before and after the education program were assessed. Results The proportion of controlled serum phosphorus was significantly increased from 43.5 to 54.9% (P<0.001). The scores on the knowledge of phosphate control were improved significantly from 59.0 ± 18.9 to 80.6 ± 12.4 (P < 0.001). The proportion of high adherence to phosphate binders was increased dramatically from 21.9 to 44.5% (P < 0.001). Conclusion The intensive education program can effectively improve serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders among hemodialysis patients. Trial registration Chinese Clinical Trial Registry, ChiCTR2100042017. Retrospectively registered January 12th, 2021.

Phosphate Control: The Next Frontier in Dialysis Cardiovascular Mortality

<b><i>Background:</i></b> Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD) on dialysis. Mortality rates are still unacceptably high even though they have fallen in the past 2 decades. Hyperphosphatemia (elevated serum phosphate levels) is seen in almost all patients with advanced CKD and is by far the largest remaining modifiable contributor to CKD mortality. <b><i>Summary:</i></b> Phosphate retention drives multiple physiological mechanisms linked to increased risk of CVD. Fibroblast growth factor 23 and parathyroid hormone (PTH) levels, both of which have been suggested to have direct pathogenic CV effects, increase in response to phosphate retention. Phosphate, calcium, and PTH levels are linked in a progressively worsening cycle. Maladaptive upregulation of phosphate absorption is also likely to occur further exacerbating hyperphosphatemia. Even higher phosphate levels within the normal range may be a risk factor for vascular calcification and, thus, CV morbidity and mortality. A greater degree of phosphate control is important to reduce the risk of CV morbidity and mortality. Improved phosphate control and regular monitoring of phosphate levels are guideline-recommended, established clinical practices. There are several challenges with the current phosphate management approaches in patients with CKD on dialysis. Dietary restriction of phosphate and thrice-weekly dialysis alone are insufficient/unreliable to reduce phosphate to &#x3c;5.5 mg/dL. Even with the addition of phosphate binders, the only pharmacological treatment currently indicated for hyperphosphatemia, the majority of patients are unable to achieve and maintain phosphate levels &#x3c;5.5 mg/dL (or more normal levels) [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information), 2011, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information), 2020, RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Phosphate binders do not target the primary pathway of phosphate absorption (paracellular), have limited binding capacity, and bind nonspecifically [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information). 2013, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information) 2020]. <b><i>Key Messages:</i></b> Despite current phosphate management strategies, most patients on dialysis are unable to consistently achieve target phosphate levels, indicating a need for therapeutic innovations [RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Given a growing evidence base that the dominant mechanism of phosphate absorption is the intestinal paracellular pathway, new therapies are investigating ways to reduce phosphate levels by blocking absorption through the paracellular pathway.

The Importance of Phosphate Control in Chronic Kidney Disease

A series of problems including osteopathy, abnormal serum data, and vascular calcification associated with chronic kidney disease (CKD) are now collectively called CKD-mineral bone disease (CKD-MBD). The pathophysiology of CKD-MBD is becoming clear with the emerging of αKlotho, originally identified as a progeria-causing protein, and bone-derived phosphaturic fibroblast growth factor 23 (FGF23) as associated factors. Meanwhile, compared with calcium and parathyroid hormone, which have long been linked with CKD-MBD, phosphate is now attracting more attention because of its association with complications and outcomes. Incidentally, as the pivotal roles of FGF23 and αKlotho in phosphate metabolism have been unveiled, how phosphate metabolism and hyperphosphatemia are involved in CKD-MBD and how they can be clinically treated have become of great interest. Thus, the aim of this review is reconsider CKD-MBD from the viewpoint of phosphorus, its involvement in the pathophysiology, causing complications, therapeutic approach based on the clinical evidence, and clarifying the importance of phosphorus management.

Implementation and Effectiveness of an Intensive Education Program on Phosphate Control Among Hemodialysis Patients: A Non-Randomized, Single-Arm, Single-Center Trial

Background: Hyperphosphatemia is a common complication in patients on maintenance hemodialysis. Patients’ adherence to phosphorus control can be improved by consistent education. However, few studies have focused on the model construction and effects of health education on phosphate control for hemodialysis patients.Objective: To develop an intensive education program focusing on phosphate control among hemodialysis patients and to analyze the effectiveness of this program.Design: A non-randomized, single-arm, single-center trial lasting for 6 months.Setting: This program was conducted in a hemodialysis center in a teaching hospital in Zhuhai, China.Participants: Patients on maintenance hemodialysis with hyperphosphatemia.Methods: A intensive hyperphosphatemia control education program lasting for 6 months was conducted among 366 hemodialysis patients applying the First Principles of Instruction model, which focused on mastering four stages: (a) activation of prior experience, (b) demonstration of skills, (c) application of skills and (d) integration of these skills into real-world activities. The controlled rate of serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders before and after the education program were assessed. Results: The controlled rate of serum phosphorus was significantly increased from 43.5% to 54.9% (P＜0.001). The scores of the patients’ knowledge of phosphate control were improved significantly from 59.10±12.90 to 80.98±14.82 (P<0.001). The percentage of high adherence to phosphate binders was increased dramatically from 21.9% to 44.5% (P<0.001). Conclusion: The intensive education program can effectively improve the controlled rate of serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders among hemodialysis patients.Trial registration: Chinese Clinical Trial Registry, ChiCTR2100042017. Registered 12 January 2021 - Retrospectively registered, http://www.chictr.org.cn/login.aspx

Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients

BackgroundIn patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges.MethodsWe conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5–4.5 mg/dl in the strict group and 5.0–6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment.ResultsThe full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, −1.0–23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0–36.1; P=0.006). This effect was pronounced in older (aged 65–74 years) versus younger (aged 20–64 years) participants (P value for interaction =0.003). We observed a similar finding for the absolute change in CAC scores.ConclusionsFurther study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis.Clinical Trial registry name and registration number:Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048

Multidisciplinary Team Versus a 'Phosphate Counting' APP for Serum Phosphate Control: A Randomized Controlled Trial

Background: Hyperphosphatemia is almost universal in well-nourished patients with end stage kidney disease treated with dialysis due to an imbalance between dietary intake and phosphate removal via residual kidney function and dialysis. Although food phosphate content can vary dramatically between meals, the current standard is to prescribe a fixed dose of phosphate binder that may not match meal phosphate intake. The primary objective of our study was to determine if the use of an APP that matches phosphate binder dose with food phosphate content would be associated with an improvement in serum phosphate and a reduction in calcium carbonate intake compared to the multidisciplinary renal team. Methods: Eighty patients with end stage renal disease treated with peritoneal dialysis at a tertiary care hospital in Canada were randomized to the standard of care for serum phosphate management (multidisciplinary renal team) versus the OkKidney APP. Serum phosphate was measured at baseline and then monthly for 3 months with adjustments to phosphate management as deemed necessary by the multidisciplinary team (control) or the phosphate binder multiplier in the OkKidney APP (intervention) based on the laboratory values. The primary analysis was an un-paired t-test of the serum phosphate at study completion. Results: The participants were 56 (±14) years old, 54% were male; the most common cause of ESRD was diabetes mellitus. The serum phosphate was 1.96 (0.41) mmol/L and 1.85 (0.44) mmol/L in the control and intervention groups at the end of 3 months (p=0.30). The median elemental daily dose of calcium carbonate did not differ between the groups at study completion [587mg (309-928) versus 799mg (567-1183), p=0.29]. Conclusion: The OkKidney APP was associated with similar but not superior serum phosphate control to the standard of care which included renal dietician support.