Author:
Pirklbauer Markus,Bushinsky David A.,Kotanko Peter,Schappacher-Tilp Gudrun
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.
Funder
Oesterreichische Nationalbank
Reference21 articles.
1. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD);Kidney Int Suppl,2009
2. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis;Palmer;JAMA,2011
3. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD);Kidney Int Suppl (2011),2017
4. Molecular mechanisms of secondary hyperparathyroidism;Silver;Nephrol Dial Transplant,2000
5. Secondary hyperparathyroidism: pathogenesis, disease progression, therapeutic options;Cunningham;Clin J Am Soc Nephrol,2011
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献