Personalized Prediction of Short- and Long-Term PTH Changes in Maintenance Hemodialysis Patients

Abstract

Background: Personalized management of secondary hyperparathyroidism is a critical part of hemodialysis patient care. We used a mathematical model of parathyroid gland (PTG) biology to predict (1) short-term peridialytic intact PTH (iPTH) changes in response to diffusive calcium (Ca) fluxes and (2) to predict long-term iPTH levels.Methods: We dialyzed 26 maintenance hemodialysis patients on a single occasion with a dialysate Ca concentration of 1.75 mmol/l to attain a positive dialysate-to-blood ionized Ca (iCa) gradient and thus diffusive Ca loading. Intradialytic iCa kinetics, peridialytic iPTH change, and dialysate-sided iCa mass balance (iCaMB) were assessed. Patient-specific PTG model parameters were estimated using clinical, medication, and laboratory data. We then used the personalized PTG model to predict peridialytic and long-term (6-months) iPTH levels.Results: At dialysis start, the median dialysate-to-blood iCa gradient was 0.3 mmol/l (IQR 0.11). The intradialytic iCa gain was 488 mg (IQR 268). Median iPTH decrease was 75% (IQR 15) from pre-dialysis 277 to post-dialysis 51 pg/ml. Neither iCa gradient nor iCaMB were significantly associated with peridialytic iPTH changes. The personalized PTG model accurately predicted both short-term, treatment-level peridialytic iPTH changes (r = 0.984, p < 0.001, n = 26) and patient-level 6-months iPTH levels (r = 0.848, p < 0.001, n = 13).Conclusions: This is the first report showing that both short-term and long-term iPTH dynamics can be predicted using a personalized mathematical model of PTG biology. Prospective studies are warranted to explore further model applications, such as patient-level prediction of iPTH response to PTH-lowering treatment.

Pre-Transplant Calcimimetic Use and Dose Information Improves the Accuracy of Prediction of Tertiary Hyperparathyroidism after Kidney Transplantation: A Retrospective Cohort Study

“…First, this was a single-center, retrospective study. Second, serum phosphorus data were lacking to evaluate its clinical relevance as a key factor influencing PTH levels [ 49 ]. Third, assessment of parathyroid gland size is another challenge as noted in a previous study [ 50 ].…”

Mathematical Models of Parathyroid Gland Biology: Complexity and Clinical Use

“…In ( 44 ), we could show that we can estimate the model parameters for individual patients based on physiological principles and readily available clinical data, i.e., dialysis vintage, six months routinely measured Ca 2+ concentration, and phosphate concentration, information of calcitriol therapy. We could predict short-term PTH kinetics and trends in long-term PTH concentrations with the personalized parameters.…”

“…The peridialytic change was calculated as post-HD iPTH minus pre-HD iPTH levels. Reproduced from ( 44 ); Creative Commons BY 4.0; published by Frontiers (2021).…”

Misdiagnosis of chronic kidney disease and parathyroid hormone testing during the past 16 years

“…The low blood calcium caused by these diseases induces over-secretion of PTH 7 . SHPT is a consequence and critical mediator of CKD–mineral bone disorder (CKD-MBD) 8 . The pathogenesis of SHPT is complex and driven by many factors, including deficiency of 1,25-dihydroxyvitamin D, hypocalcemia, and hyperphosphatemia 9 , 10 ; CKD is regarded as the primary etiology.…”

“…The exploration of CKD-MBD, which is associated with hyperphosphatemia, hypocalcemia, low serum levels of vitamin D, and increased PTH secretion, has gradually increased in recent years 15 . SHPT is one of the most important clinical manifestations of CKD-MBD, and PTH is also a crucial indicator of prognosis in CKD 8 , 11 , 12 . However, there are some indications that clinicians do not seem to pay as much attention to the diagnosis of CKD and the detection of PTH.…”