Intradialytic Calcium Kinetics and Cardiovascular Disease in Chronic Hemodialysis Patients

Abstract

Background/Objective: Calcium loading has been associated with cardiovascular risk in hemodialysis (HD) patients. However, it remains to be elucidated whether alterations of intradialytic calcium buffering add to the increased cardiovascular disease burden in this high-risk population. Methods: Intradialytic calcium kinetics was evaluated in a crosssectional observational study by measuring dialysate-sided ionized calcium mass balance (iCa MB), calcium buffer capacity, and change in serum calcium levels in 40 chronic HD patients during a routine HD session. A dialysate calcium of 3.5 mEq/L was used to adequately challenge calcium buffer mechanisms. Aortic pulse wave velocity and serum osteocalcin levels were measured prior to the HD session. Presence of cardiovascular disease and diabetes was assessed. Results: The mean dialysate-sided iCa MB , extracellular fluid ionized calcium mass gain, and buffered ionized calcium mass were 469 (±154), 111 (±49), and 358 (±145) mg/HD, respectively. The mean ionized serum calcium increase (∆iCa) was 0.42 (±0.14) mEq/L per HD. The mean intradialytic calcium buffer capacity was 73 (±18)%. Multivariate regression analysis revealed significant independent association of (1) iCa MB with the dialysate-to-blood calcium gradient at HD start and (2) intradialytic calcium buffer capacity with undercarboxylated osteocalcin. The presence of coronary heart disease was associated with higher ∆iCa but not iCa MB in the multivariate model. Conclusions: In line with our proof-of-concept study, we provide clinical evidence for a rapidly accessible and exchangeable calcium pool involved in intradialytic calcium regulation and for the role of osteocalcin as a potential biomarker. Our findings argue for evaluating the prognostic potential of intradialytic calcium kinetics in prospective clinical trials.

Mathematical Models of Parathyroid Gland Biology: Complexity and Clinical Use

“…They enable the generation of new working hypotheses and quantitative and qualitative predictions that can be compared with clinical or experimental data. An example would be the prediction of calcium buffer capacity during hemodialysis (46) which was confirmed by clinical data on the population level (47). In recent years, mathematical models have become an essential tool in personalized medicine.…”

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

“…While previous studies exclusively investigated associations of clinical parameters with population-level iPTH dynamics, we utilized computational and mathematical analysis and modeling of the PTG to make patient-specific predictions of short- and long-term iPTH dynamics. In this study we used the generic PTG model and applied it to real-world data from maintenance HD patients from a previous iCaMB study ( 13 ). We were able to validate the individualized model parameters by using short-term changes of iCa as well as long-term iCa and phosphate changes.…”

“…This research utilized biochemical measurements, intradialytic iCa kinetics, and iCa mass balance (iCaMB) data from 28 previously studied maintenance hemodialysis (HD) patients ( 13 ). In this study, patients received one dialysis treatment with a dialysate Ca concentration of 1.75 mmol/l to attain a positive dialysate-to-blood iCa gradient and diffusive Ca loading.…”

“…Two patients received cinacalcet before iCaMB assessment and were excluded from this study. Dialysate-sided iCaMB assessment is described in detail elsewhere ( 13 ). Long-term clinical and laboratory data (iCa, phosphate, and iPTH), as well as medication, was obtained from patients' electronic health records over a 6-months period before and after iCaMB assessment, respectively.…”

Dialysevorschrift

“…> 1,75 mmol/l) über eine exzessive intradialytische Kalziumbeladung zu überschießender PTH-Suppression, adynamer Knochenerkrankung und vaskulärer Kalzifizierung mit entsprechend erhöhtem kardiovaskulären Risiko [16,27]. Die aktuellen KDIGO(Kidney Disease: Improving Global Outcomes)-CKD-MBD(Chronic Kidney Disease -Mineral and Bone Disorder)-Leitlinien empfehlen daher, eine Dialysatkalziumkonzentration von 1, 25 [21] konnte mittlerweile mehrfach klinisch bestätigt werden [20], wobei mittels aufwendiger dialysatseitiger Kalziummassenbilanzbestimmung gezeigt werden konnte, dass bis zu 75 % der zugeführten Kalziummenge akut abgepuffert werden. Ob Veränderungen der Kalziumpuffermechanismen zusätzlich zur intradialytischen Kalziumbeladung zu einem erhöhten kardiovaskulären Risiko beitragen, ist derzeit Gegenstand laufender Studien.…”