Chronic Kidney Disease-mineral Bone Disorder Research Articles

Potential effect of pharmaceutical care to improve outcomes in patients with chronic kidney disease-mineral bone disorder in Sulaimani dialysis centers

Objective: the present study was aimed to evaluate the role of pharmaceutical services in improving the outcome of mineral bone disorder in patients with advanced chronic kidney disease. Methodology: One hundred and twenty patients with chronic kidney disease-mineral bone disorder (CKD-MBD) screened for eligibility, seventy-six patients enrolled in the study and randomly allocated into two groups: pharmaceutical care and usual care, both groups interviewed by the pharmacist using specific questionnaire for assessing the quality of life (QoL). All the drug related problems (DRPs) including drug-drug interactions (DDIs) were recorded by the pharmacist. Blood samples were collected and utilized for analyzing the levels of vitamin D, phosphorous, calcium, albumin and parathyroid hormone at baseline and three months after. The pharmaceutical care group received all the educations about their medications and how to minimize DRPs; improve the QoL. Additionally, the pharmaceutical intervention included correcting the biochemical parameters. Results: Pharmaceutical care significantly improved patients QoL and minimized DRPs and DDIs. It was also effective in improving the biochemical parameters. Conclusion: Pharmaceutical care has a positive impact on improving the outcome of patients with CKD-MBD through attenuating DRPs, improving the biochemical parameters and the QoL.

Chronic Kidney Disease –Mineral Bone Disorder (CKD- MBD) – Further Insight at the Indian patients.

The kidneys play an important role in maintaining normal serum calcium (Ca) and phosphorous (P) concentrations. Chronic kidney disease (CKD) is associated with significant disturbances in bone and mineral metabolism, leading to altered serum concentrations of Ca, P, vitamin D and parathyroid hormone (PTH)1,2,3. These changes are initially detected when the glomerular filtration rate (GFR) falls to ≤60 mL/min and are nearly uniform as GFR drops to <30ml/min2,3. This leads to a number of bone abnormalities previously called “renal osteodystrophy”, renamed as CKD-Mineral Bone Disorder (CKD-MBD) by National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) consensus group4 . CKD-MBD is a systemic disorder manifested by either one or a combination of a) abnormalities of Ca, P, PTH or vitamin D metabolism, b) abnormalities in bone turnover, mineralization, volume, linear growth or strength c) vascular or soft tissue calcification. This has over time been expanded to include left ventricular hypertrophy, hypertension, immune dysfunction and inflammation5,6.

Evaluation of minerals, urea, and creatinine in chronic renal failure

Evaluation of minerals, urea, and creatinine in chronic renal failure - IJCBR- Print ISSN No: - 2394-6369 Online ISSN No:- 2394-6377 Article DOI No:- 10.18231/j.ijcbr.2019.094, International Journal of Clinical Biochemistry and Research-Int J Clin Biochem Res

Spectrum of mineral bone disorder in patients with CKD stage 3-5 from eastern India

Introduction:
 Chronic kidney disease mineral bone disorder (CKD-MBD) is a major determinant of CKD associated morbidity and morbidity. We sought to find the spectrum of CKD-MBD in Eastern India.
 Methodology:
 This cross-sectional study was conducted at the Department of Nephrology Institute of Postgraduate Medical Sciences and Research Seth Sukhlal Karnani Memorial hospital Kolkata India from June 2013 and July 2014. The patients with newly diagnosed stage 3-5 CKD were evaluated for bone mineral abnormalities. Patients already on some form of phosphate binders or vitamin D analogs were excluded.
 Results:
 Total of 242 patients was included. Male to female ratio was 2.1:1. 52.1% had Diabetic nephropathy. Mean eGFR was 26.51±12.33 ml/min/1.73m2. 36.8% had CKD stage 3, 46.7% CKD stage 4 and 16.5 % had CKD stage 5. 56% had hyperphosphatemia (Phosphate>4.0mg/dl). 30% had hypocalcaemia (corrected calcium <8.5mg/dl). 53.4% had Vit D deficiency (25-OH Vit D < 20ng/ml) and 64.9% had hyperparathyroidism (iPTH>65pg/ml). There was a significant negative correlation of eGFR with Phosphate, iPTH and ALP. The distribution of phosphate, ALP and iPTH across CKD stage 3-5 was significantly different; p-<0.001. 21.3% of patients with iPTH more than twice the upper limit of normal had normal ALP. There was no significant difference in serum calcium and 25-OH Vit D levels across CKD stage 3-5.
 Conclusions:
 CKD-MBD has a high prevalence. Secondary hyperparathyroidism is the most common type of CKD-MBD. 25-OH Vit D and serum calcium are determined predominantly by diet and exposure to sunlight. ALP can’t serve as a surrogate marker for iPTH.

Cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients below age 5 years .

Management of chronic kidney disease mineral bone disorder (CKD-MBD) in pediatric patients with end-stage renal disease (ESRD) is challenging. While the use of calcimimetics is well-studied in adults on dialysis, few studies have been performed in pediatrics. Little is known about the use of cinacalcet in young children with ESRD. The aim of this study was to report the efficacy and safety of cinacalcet for treatment of secondary hyperparathyroidism in chronic dialysis patients younger than 5 years. We included children aged < 5 years on chronic dialysis, either hemodialysis (HD) or peritoneal dialysis (PD), who were prescribed cinacalcet for more than 1 month. Retrospective chart review was performed to gather demographics, dialysis prescription, relevant mineral imbalance laboratory parameters, and medications. Data was collected for 6 consecutive months. 18 patients (9 male), mean age at initiation of cinacalcet was 2.3 years; 13 PD and 5 HD. Average starting dose of cinacalcet: 6.2 mg daily, 0.55 mg/kg/day. Average time on dialysis was 14.4 months. Parathyroid hormone significantly decreased over the 1st month following initiation of cinacalcet from 929 (IQR 572 - 1,056) to 427 (IQR 256 - 778) pg/mL, p = 0.009. Three patients developed asymptomatic hypocalcemia (Ca < 9.4 mg/dL). Serum phosphorous decreased after initiation, and this was persistent at 6 months. Significant improvement in linear growth was observed while on cinacalcet and growth hormone (GH). Cinacalcet can be effectively used in young children on dialysis with minimal side effects. Good linear growth was seen in patients on cinacalcet and GH therapy. Long-term large scale data is necessary to confirm. Institution-based management algorithm incorporating cinacalcet would be helpful to maintain uniformity in role of cinacalcet for management of CKD-MBD.

Effect of Advanced Glycation End-Products (AGE) Lowering Drug ALT-711 on Biochemical, Vascular, and Bone Parameters in a Rat Model of CKD-MBD.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic disorder that affects blood measures of bone and mineral homeostasis, vascular calcification, and bone. We hypothesized that the accumulation of advanced glycation end-products (AGEs) in CKD may be responsible for the vascular and bone pathologies via alteration of collagen. We treated a naturally occurring model of CKD-MBD, the Cy/+ rat, with a normal and high dose of the AGE crosslink breaker alagebrium (ALT-711), or with calcium in the drinking water to mimic calcium phosphate binders for 10 weeks. These animals were compared to normal (NL) untreated animals. The results showed that CKD animals, compared to normal animals, had elevated blood urea nitrogen (BUN), PTH, FGF23 and phosphorus. Treatment with ALT-711 had no effect on kidney function or PTH, but 3 mg/kg lowered FGF23 whereas calcium lowered PTH. Vascular calcification of the aorta assessed biochemically was increased in CKD animals compared to NL, and decreased by the normal, but not high dose of ALT-711, with parallel decreases in left ventricular hypertrophy. ALT-711 (3 mg/kg) did not alter aorta AGE content, but reduced aorta expression of receptor for advanced glycation end products (RAGE) and NADPH oxidase 2 (NOX2), suggesting effects related to decreased oxidative stress at the cellular level. The elevated total bone AGE was decreased by 3 mg/kg ALT-711 and both bone AGE and cortical porosity were decreased by calcium treatment, but only calcium improved bone properties. In summary, treatment of CKD-MBD with an AGE breaker ALT-711, decreased FGF23, reduced aorta calcification, and reduced total bone AGE without improvement of bone mechanics. These results suggest little effect of ALT-711 on collagen, but potential cellular effects. The data also highlights the need to better measure specific types of AGE proteins at the tissue level in order to fully elucidate the impact of AGEs on CKD-MBD. © 2019 American Society for Bone and Mineral Research.

Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats.

Osteoporosis patients with chronic kidney disease (CKD) are becoming common in our superaging society. Renal dysfunction causes phosphorus accumulation in the circulating plasma and leads to the development of CKD-mineral bone disorder (MBD). We have previously reported that type III Pi transporter-overexpressing transgenic (Pit-1 TG) rats manifest phosphate (Pi)-dependent podocyte injury. In the present study, we explored the effect of risedronate on Pi-induced podocyte injury in vivo. Pit-1 TG rats and wild-type rats at 5 weeks old were divided into a risedronate-treated group and an untreated group. We subcutaneously administered 5 μg/kg body weight of risedronate or saline twice a week during the experimental period. Risedronate did not alter serum creatinine levels at 5, 8, and 12 weeks of age. However, electron microscopy images showed that thickening of the glomerular basement membrane was improved in the risedronate treatment group. Furthermore, immunostaining for podocyte injury markers revealed that both desmin- and connexin43-positive areas were smaller in the risedronate-treated group than in the untreated group, suggesting that bisphosphonates could rescue Pi-induced podocyte injury. In conclusion, our findings suggest that risedronate could maintain glomerular barrier function by rescuing Pi-induced podocyte injury.

The Bone in Renal Transplant Recipients-A Nephrological and Orthopedic Review

The definition of Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) has suffered significant changes over the last decade as our knowledge on the matter grows. The complexity of this subject is even bigger if you consider renal transplant recipients (RTRs) - they already have a legacy of CKD-MBD previous to transplant, their bones will be under the direct and indirect effects of immunosuppression and they will develop CKD-MBD secondary to their graft (dis) function.

Unraveling the osteocyte in CKD-MBD post–renal transplantation

Changes in indices of mineral metabolism, bone protein expression, and bone turnover were assessed between pre- and post-renal transplant bone biopsies obtained 12 months apart. Circulating sclerostin and fibroblast growth factor 23 (FGF-23) levels decreased, and a low bone turnover state was highly prevalent on follow-up. In contrast, bone sclerostin expression increased, whereas FGF-23 bone expression was unchanged/decreased. These findings underscore the limitations of circulating biomarkers and the critical role of bone biopsy to understand osteocyte biology in chronic kidney disease-mineral bone disorder.

Kidney Disease Progression Does Not Decrease Intestinal Phosphorus Absorption in a Rat Model of Chronic Kidney Disease-Mineral Bone Disorder.

The Cy/+ rat has been characterized as a progressive model of chronic kidney disease-mineral bone disorder (CKD-MBD). We aimed to determine the effect of kidney disease progression on intestinal phosphorus absorption and whole-body phosphorus balance in this model. A total of 48 Cy/+ (CKD) and 48 normal littermates (NL) rats were studied at two ages: 20 weeks and 30 weeks, to model progressive kidney function decline at approximately 50% and 20% of normal kidney function. Sodium-dependent and sodium-independent intestinal phosphorus absorption efficiency were measured by the in situ jejunal ligated loop method using 33 P radioisotope. Our results show that CKD rats had slightly higher sodium-dependent phosphorus absorption compared to NL rats, and absorption decreased from 20 to 30 weeks. These results are in contrast to plasma 1,25OH2 D, which was lower in CKD rats. Gene expression of the major intestinal phosphorus transporter, NaPi-2b, was not different between CKD and NL rats in the jejunum but was lower in CKD rats versus NL rats in the duodenum. Jejunal ligated loop phosphorus absorption results are consistent with percent net phosphorus absorption results obtained from metabolic balance: higher net percent phosphorus absorption values in CKD rats compared with NL, and lower values in 30-week-olds compared with 20-week-olds. Phosphorus balance was negative (below zero) in CKD rats, significantly lower in 30-week-old rats compared with 20-week-old rats, and lower in CKD rats compared with NL rats at both ages. These results demonstrate no reduction in intestinal phosphorus absorption with progression of CKD despite lower 1,25OH2 D status when assessed by an in situ ligated loop test, which is in contrast to the majority of in vitro studies, and if confirmed in further studies, could challenge the physiological relevance of in vitro findings. © 2019 American Society for Bone and Mineral Research.

Sclerostin: a new biomarker of CKD-MBD.

The causes of the increased cardiovascular risk associated with kidney diseases partly reside in the chronic kidney disease-mineral bone disorder (CKD-MBD) syndrome. Three cardiovascular risk factors [hyperphosphatemia, vascular calcification, and elevated fibroblast growth factor 23 (FGF23)] levels have been discovered within the CKD-MBD over the last decades. In addition, sclerostin is recently presented as a new bone and vascular disease biomarker. This 22-kDa glycoprotein, secreted mainly by osteocytes, is a soluble inhibitor of the canonical Wnt pathway that has a pivotal role in bone biology and turnover. CKD patients are reported with higher levels of sclerostin, and levels decrease during dialysis. Sclerostin is associated with vascular calcification and CV risk in CKD, although data are still controversial. The question whether serum sclerostin has protective or deleterious role in CKD-MBD pathophysiology, and therefore in cardiovascular risk and overall mortality, is still open and needs to be answered. The standardization of assays and the establishment of a clear cut-off values when sclerostin starts to switch from physiological to pathophysiological role have to be another important step. Further research is needed also to define its relationship with other CKD-MBD biomarkers for future diagnostic and therapeutic strategies.

The Effects of Restricted Protein Diet Supplemented With Ketoanalogue on Renal Function, Blood Pressure, Nutritional Status, and Chronic Kidney Disease-Mineral and Bone Disorder in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

To systemically review the meta-analysis exploring the effectiveness and safety of restricted protein diet supplemented with ketoanalogues (KAs) when compared with regular diet or low protein diet (LPD) without KAs in chronic kidney disease (CKD) patients. We conducted electronic searches in PubMed, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from January 1960 to May 2018 to identify randomized controlled clinical trials that explored the effects of restricted protein diet including vegetarian and mixed type of protein with KAs on kidney endpoints including the changes in estimated glomerular filtration rate (eGFR) and proteinuria, nutritional status, and CKD-mineral bone disorder. Seventeen RCTs with 1,459 participants were included in our meta-analysis. Restricted protein diet with KAs significantly preserved eGFR and reduced proteinuria, serum phosphate, parathyroid hormone (PTH) level, systolic blood pressure, diastolic blood pressure, and serum cholesterol. By subgroup analysis, very low protein diet (VLPD) with KAs was plausibly superior to LPD with KAs in slowing the decline in eGFR. Only VLPD with KAs significantly improved serum PTH, systolic blood pressure, and diastolic blood pressure while both regimens significantly decreased serum phosphate. Only LPD with KAs significantly raised serum albumin and serum calcium. Restricted protein diet supplemented with KAs could effectively improve kidney endpoints including preserving eGFR and diminishing proteinuria, blood pressure levels, and CKD-mineral bone disorder parameters without causing malnutrition. VLPD with KAs appears to provide more effectiveness in slowing the decline in eGFR, lowering blood pressure, reducing serum PTH, and less increasing serum calcium level.

Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD).

Reduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality. We tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy/+ IU) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2-3 of CKD. We then measured the effects of wheel running on serum biochemistry, tissue weight, voluntary grip strength, maximal aerobic capacity (VO2max), body composition and bone micro-CT and mechanics. Wheel running improved serum biochemistry with decreased creatinine, phosphorous, and parathyroid hormone in the rats with CKD. It improved muscle strength, increased time-to-fatigue (for VO2max), reduced cortical porosity and improved bone microarchitecture. The CKD rats with voluntary wheel access also had reduced kidney cystic weight and reduced left ventricular mass index. Voluntary wheel running resulted in multiple beneficial systemic effects in rats with CKD and improved their physical function. Studies examining exercise interventions in patients with CKD are warranted.

A Multi-Compartment Model Capturing the Pharmacokinetics of the Calcimimetic Cinacalcet.

Chronic kidney disease-mineral bone disorder is a major complication affecting the vast majority of chronic kidney disease patients. A hallmark of the disorder is an altered parathyroid gland biology resulting in secondary hyperparathyroidism. This condition is widely treated by calcimimetics like cinacalcet which act by allosteric activation of the calcium sensing receptor. Here, we present a linear multi-compartment model based on physiological principles such as first-pass metabolism and protein binding, which captures all relevant pharmacokinetic parameters of cinacalcet. Due to the linear structure of the model, simulations are numerically stable and allow fast and accurate short or long-term predictions of cinacalcet concentrations in the body. The model compartments are physiological meaningful and can be easily adjusted to various conditions like impaired hepatic clearance or different drug administration regimens. Moreover, the model can be easily adapted to specific patient groups.

Native Hypovitaminosis D in CKD Patients: From Experimental Evidence to Clinical Practice.

Native hypovitaminosis D (n-hVITD) is frequently found from the early stages of chronic kidney disease (CKD) and its prevalence increases with CKD progression. Even if the implications of n-hVITD in chronic kidney disease-mineral bone disorder (CKD-MBD) have been extensively characterized in the literature, there is a lot of debate nowadays about the so called “unconventional effects” of native vitamin D (25(OH)VitD) supplementation in CKD patients. In this review, highlights of the dimension of the problem of n-hVITD in CKD stages 2–5 ND patients will be presented. In addition, it will focus on the “unconventional effects” of 25(OH)VitD supplementation, the clinical impact of n-hVITD and the most significant interventional studies regarding 25(OH)VitD supplementation in CKD stages 2–5 ND.

MON-150 STUDY OF SECONDARY HYPERPARATHYROIDISM IN DIALYSIS PATIENTS IN A SINGLE TERTIARY CARE CENTRE IN SOUTH INDIA

Chronic Kidney Disease- Mineral Bone Disorder (CKD-MBD) is a common accompaniment in CKD. Of the various markers of CKD-MBD, Parathyroid Hormone (PTH) is an important one. PTH is also considered as a uremic toxin contributing profoundly to cardiovascular morbidity and mortality. There has always been a controversy regarding the cut-off value, frequency of monitoring and the importance to be given for a single value. KDIGO having come out with guidelines for management of CKD-MBD, the evaluation has become more clear and structured. The same has been tried to be implemented at our centre. This is a retrospective descriptive study done at a single tertiary care centre in South India. The dialysis record and the laboratory data of all dialysis patients were searched and all the patients who had undergone PTH test in last 1 year were included for the study. Paediatric patients (<18yrs) and known tertiary hyperparathyroidism patients were excluded from the study. Data regarding Calcium, phosphorus and Vitamin D level was also noted when it was done within a month of PTH test. Data was analysed using Microsoft excel and SPSS software. The patients having PTH values beyond the lower and upper limit of normal recommended value were analysed. A total of 190 patients have undergone PTH test in last 1 year (approximate number of patients on maintenance haemodialysis at any given time is 250). The age group varied between 22 to 80 years, the median being 56 years. The PTH value varied from 37pg/mL to >2500 pg/mL, mean being 593.6 pg/mL and median was 440 pg/mL. 71 patients (37%) had PTH values above 600 pg/mL and 22 patients (11.5%) had PTH value of <130 pg/mL (which corresponds to the 2 to 9 times the upper limit of normal value for PTH). Only 105 patients had reports of calcium and phosphorus within one month of PTH test. Of these 45 (42.8%) patients had hyperphosphatemia (>4.5mg/dL) and 47 (44.7%) had hypocalcemia (<8.5mg/dL). If the higher cut-off value for PTH is taken as 300pg/mL, then the prevalence of hyperparathyroidism increases to 65.8%. Similarly if the cut-off for hyperphosphatemia is taken as 5.5mg/dL as in some studies, the prevalence decreases to 20.9%. This study shows a very high prevalence of hyperparathyroidism in spite of relatively low incidence of hyperphosphatemia and hypocalcemia in this dialysis cohort as compared with many other previous studies. This might warrant a different approach than just to mainly control the phosphorus level in these patients. Serial monitoring and long term follow-up of the outcomes might throw more clarity in dealing with this subset of patients. The high prevalence of secondary hyperparathyroidism might be apparent only by regular and structured monitoring of parameters as per KDIGO guidelines. A very high prevalence of hyperparathyroidism is seen in hemodialysis patients from south India. Regular evaluation for the same as per KDIGO guidelines will help in identifying these patients and for institution of targeted treatment.

Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats

Male Cy/+ rats have shown a relatively consistent pattern of progressive kidney disease development that displays multiple key features of late stage chronic kidney disease-mineral bone disorder (CKD-MBD), specifically the development of cortical bone porosity. However, progression of disease in female Cy/+ rats, assessed in limited studies, is more heterogeneous and to date has failed to show development of the CKD-MBD phenotype, thus limiting their use as a practical model of progressive CKD-MBD. Animal and human studies suggest that estrogen may be protective against kidney disease in addition to its established protective effect on bone. Therefore, in this study, we aimed to determine the effect of ovariectomy (OVX) on the biochemical and skeletal manifestations of CKD-MBD in Cy/+ female rats. We hypothesized that OVX would accelerate development of the biochemical and skeletal features of CKD-MBD in female Cy/+ rats, similar to those seen in male Cy/+ rats. Female Cy/+ rats underwent OVX (n = 8) or Sham (n = 8) surgery at 15 weeks of age. Blood was collected every 5 weeks post-surgery until 35 weeks of age, when the rats underwent a 4-day metabolic balance, and the tibia and final blood were collected at the time of sacrifice. OVX produced the expected changes in trabecular and cortical parameters consistent with post-menopausal disease, and negative phosphorus balance compared with Sham. However, indicators of CKD-MBD were similar between OVX and Sham (similar kidney weight, plasma blood urea nitrogen, creatinine, creatinine clearance, phosphorus, calcium, parathyroid hormone, and no cortical porosity). Contrary to our hypothesis, OVX did not produce evidence of development of the CKD-MBD phenotype in female Cy/+ rats.

Spectrum of Chronic Kidney Disease-Mineral Bone Disorders in Newly Detected Advanced Renal Failure Elderly Patients (CKD Stage 4 and 5)

Spectrum of Chronic Kidney Disease-Mineral Bone Disorders in Newly Detected Advanced Renal Failure Elderly Patients (CKD Stage 4 and 5)

Exercise Alleviates Osteoporosis in Rats with Mild Chronic Kidney Disease by Decreasing Sclerostin Production

Chronic kidney disease–mineral bone disorder (CKD–MBD), comprising mineral, hormonal, and bone metabolic imbalance, is a major CKD-related issue; it causes osteoporosis prevalence in CKD patients. Osteocyte-derived sclerostin inhibits the osteogenic Wnt/β-catenin signaling pathway; its levels rise when kidney function declines. Exercise modulates the physiological functions of osteocytes, potentially altering sclerostin production. It may aid bone and mineral electrolyte homeostasis in CKD. Mild CKD was induced in rats by partial nephrectomy. They were divided into: sham (no CKD), CKD, and CKD + exercise (8 weeks of treadmill running) groups. Micro-CT scanning demonstrated that the CKD + exercise-group rats had a higher bone mineral density (BMD) of the spine and femoral metaphysis and higher femoral trabecular bone volume than the CKD-group rats. Bone formation rates were not significantly different. The CKD + exercise-group rats had lower serum sclerostin (157.1 ± 21.1 vs 309 ± 38.1 pg/mL, p < 0.05) and CTX-1 (bone resorption marker) levels. Immunohistochemistry revealed higher tibial β-catenin concentrations in the CKD + exercise-group rats. Serum FGF-23, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, and phosphate levels showed no significant differences between these groups. Thus, exercise improves BMD and bone microstructure in mild CKD by inhibiting sclerostin production, but does not alter serum minerals.

A mathematical model of parathyroid gland biology.

Altered parathyroid gland biology in patients with chronic kidney disease (CKD) is a major contributor to chronic kidney disease‐mineral bone disorder (CKD‐MBD). This disorder is associated with an increased risk of bone disorders, vascular calcification, and cardiovascular events. Parathyroid hormone (PTH) secretion is primarily regulated by the ionized calcium concentration as well as the phosphate concentration in the extracellular fluid and vitamin D. The metabolic disturbances in patients with CKD lead to alterations in the parathyroid gland biology. A hallmark of CKD is secondary hyperparathyroidism, characterized by an increased production and release of PTH, reduced expression of calcium‐sensing and vitamin D receptors on the surface of parathyroid cells, and hyperplasia and hypertrophy of these cells. These alterations happen on different timescales and influence each other, thereby triggering a cascade of negative and positive feedback loops in a highly complex manner. Due to this complexity, mathematical models are a useful tool to break down the patterns of the multidimensional cascade of processes enabling the detailed study of subsystems. Here, we introduce a comprehensive mathematical model that includes the major adaptive mechanisms governing the production, secretion, and degradation of PTH in patients with CKD on hemodialysis. Combined with models for medications targeting the parathyroid gland, it provides a ready‐to‐use tool to explore treatment strategies. While the model is of particular interest for use in hemodialysis patients with secondary hyperparathyroidism, it has the potential to be applicable to other clinical scenarios such as primary hyperparathyroidism or hypo‐ and hypercalcemia.