Calcium balance in dialysis is best managed by adjusting dialysate calcium guided by kinetic modeling of the interrelationship between calcium intake, dose of vitamin D analogues and the dialysate calcium concentration.
Calcium mass balance (Ca(MB)) is determined by the difference between Ca absorbed between dialyses (Ca(Abs)) and the Ca removed during dialysis (J(d)Ca(2+)). A mathematical model to quantify (1) Ca(Abs) as a function of Ca intake (Ca(INT)) and the doses of vitamin D analogues, and (2) J(d)Ca(2+) as a function of Ca(2+) dialysance, the mean plasma Ca(2+) ((M)C(pi)Ca(2+)) minus dialysate Ca(2+) (C(di)Ca(2+)), ultrafiltration rate (Q(f)) and treatment time is developed in this paper. The model revealed a basic design flaw in clinical studies of Ca-based as opposed to non-Ca-based binders in that C(di)Ca(2+) must be reduced with the Ca-based binders in order to avoid a positive Ca(MB) relative to the non-Ca-based binders. The model was also used to analyze Ca(MB) in 320 Renal Research Institute hemodialysis patients and showed that all patients irrespective of type of binder were in positive Ca(MB) between dialyses (mean +/- SD 160 +/- 67 mg/day) with current doses of vitamin D analogues prescribed. Calculation of the optimal C(di)Ca(2+) for the 320 Renal Research Institute patients revealed that in virtually all instances, the C(di)Ca(2+) required for neutral Ca(MB), where Ca removal during dialysis was equal to Ca accumulation between dialyses, was less than 2.50 mEq/l and averaged about 2.00 mEq/l. This sharply contradicts the recent KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease - Mineral and Bone Disorder, that suggests a C(di)Ca(2+) of 2.5-3.0 mEq/l. Review of the KDIGO work group discussions shows that this discrepancy stems from the unwarranted work group assumption that intradialytic Ca(MB) is zero. We strongly believe that this guideline for dialysate Ca(2+) is inappropriate and should be modified to more realistically reflect the needs of dialysis patients.
Gotch
Frank
F
Renal Research Institute, New York, N.Y., USA. frank.gotch.md @ fmc-na.com
Levin
Nathan W
NW
Kotanko
Peter
P
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use; D000465:Algorithms; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002117:Calcitriol / Q000097:blood / Q000627:therapeutic use; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D017610:Calcium Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D002128:Calcium Metabolism Disorders / Q000209:etiology / Q000517:prevention & control*; D002136:Calcium, Dietary / Q000493:pharmacokinetics; D002614:Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology / Q000517:prevention & control; D015314:Dialysis Solutions / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004872:Ergocalciferols / Q000008:administration & dosage* / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D007408:Intestinal Absorption; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D008954:Models, Biological; D010758:Phosphorus / Q000378:metabolism; D017410:Practice Guidelines as Topic; D012016:Reference Values; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods; D012107:Research Design; D014462:Ultrafiltration
D000085:Acetates; D050071:Bone Density Conservation Agents; D017610:Calcium Compounds; D002136:Calcium, Dietary; D002614:Chelating Agents; D015314:Dialysis Solutions; D004872:Ergocalciferols; D010758:Phosphorus; C042533:1 alpha-hydroxyergocalciferol; C084656:paricalcitol; D002117:Calcitriol; D002118:Calcium; C120662:calcium acetate