The Calcium Conundrum: When, What and How to Give Calcium in Pediatric CKD/ESRD

Transcription

1 The Calcium Conundrum: When, What and How to Give Calcium in Pediatric CKD/ESRD Jess Tower MS RD LD 3/18/19 Children s Mercy Hospital jdtower@cmh.edu Disclosures Nothing to disclose 1

2 How do bones work? How much calcium is optimal in children without CKD? Why? The Calcium Conundrum: How does CKD affect calcium homeostasis? Are the calcium needs of children with short stature lower? Why do children with CKD develop hypocalcemia? What does hypocalcemia look like and why is it bad? Should we supplement over the RDA in children with hypocalcemia? If so, how much more? How much calcium is optimal in children with CKD? Why do children with CKD develop hypercalcemia? The Calcium Conundrum: What does hypercalcemia look like and why is it bad? Should we supplement to RDA in children with hypercalcemia? When should we intervene? What is the best way to correct calcium? What affects calcium balance and lab interpretation? How do we increase calcium intake when dairy products are limited? Bone Anatomy of bone Functions of skeleton Modeling vs. remodeling Bone mineralization Bone strength 2

3 Bone Anatomy of bone Functions of skeleton Modeling vs. remodeling Bone mineralization Bone strength Longitudinal growth Radial growth Bone Anatomy of bone Functions of skeleton Modeling vs. remodeling Bone mineralization Bone strength Bone Anatomy of bone Functions of skeleton Modeling vs. remodeling Bone mineralization Bone strength 3

4 Bone Anatomy of bone Functions of skeleton Modeling vs. remodeling Bone mineralization Bone strength Bone Anatomy of bone Functions of skeleton Modeling vs. remodeling Bone mineralization Bone strength Calcium Biochemical functions Absorption & factors regulating calcium level Calcium balance & excretion Calcium regulation Effect of CKD on calcium homeostasis 4

5 Infants 0 6 months: AI Based on mean intake data from infants fed human milk as the principal fluid and on studies that have determined mean calcium content of breast milk Infants 7 12 months: AI Based on mean calcium intake from solid foods and human milk Infants 0 6 months: AI Based on mean intake data from infants fed human milk and on studies that have determined mean calcium content of breast milk Infants 7 12 months: Based on mean calcium intake from solid foods and human milk Infants 0 6 months: Based on mean intake data from infants fed human milk as the principal fluid and on the studies that have determined mean calcium content of breast milk Infants 7 12 months: AI Based on mean calcium intake from solid foods and human milk 5

6 6

7 HealthProfessional/ 7

8 Without dairy HealthProfessional/ Without high potassium foods (>300 mg per serving) HealthProfessional/ Without high sodium foods (>140 mg per serving) HealthProfessional/ 8

9 Calcium additives in food Calcium carbonate Calcium chloride Calcium disodium EDTA Calcium sulfate Monocalcium phosphate There are 86 Tap water Parameter Calcium KCMO Average 37.4 KCMO Range Units ppm (mg/l) SMCL NA Year Sampled content/uploads/2013/04/2018 Water Quality Report rev.pdf Biochemical functions Hi, we don t even contain 1% of the body s total calcium but it does all of this: muscle contraction, blood clotting, transmission of neural impulses, enzyme activation, intracellular messaging, and more! Hi, I contain 99% of the body s total calcium! Absorption & factors regulating calcium level Active transport + vitamin D Increases with low calcium intake Passive transport Most active at Ca intake >2 gm/d 9

10 Absorption & factors regulating calcium level Inhibits Ca absorption Gut contents that bind Ca Oxalate Phytate Phosphate Free fatty acids Less acidic gastric environment Steroids Magnesium deficiency Promotes Ca absorption Low calcium intake Hormones Vitamin D PTH Calcium balance & excretion Neutral & sweat & feces Total calcium intake = total body calcium losses Negative balance Positive balance Increased risk for osteoporosis and fracture Older adults, especially post menopausal women Increased risk for extraskeletal calcification and cardiovascular events Growing children Calcium balance & excretion Neutral & sweat & feces Total calcium intake < total body calcium losses Negative balance Positive balance Increased risk for osteoporosis and fracture Older adults, especially post menopausal women Increased risk for extraskeletal calcification and cardiovascular events Growing children 10

11 Calcium balance & excretion Neutral & sweat & feces Total calcium intake > total body calcium losses Negative balance Positive balance Increased risk for osteoporosis and fracture Older adults, especially post menopausal women Increased risk for extraskeletal calcification and cardiovascular events Growing children Calcium metabolism & regulation 7 calcium homeostasis interactions of the skeletal system and other organ systems/ Urinary elimination pathway is severely impaired or absent Effect of CKD on calcium homeostasis Calcium intake is limited as a result of phosphate restriction and decreased appetite Calcitriol production is reduced, leading to reduced calcium absorption Medical management of CKD MBD affects serum calcium levels 11

12 Recommended calcium intake in CKD KDOQI: 2008 KDIGO: 2017 What affects interpretation of serum calcium? Albumin Vitamin A Vitamin D Alkaline phosphatase Parathyroid hormone 12

13 Parathyroid hormone Why do kids w/ CKD develop hypocalcemia? Causes Signs/symptoms Long term consequences Intervention Phosphate restriction Hyperphosphatemia Hypovitaminosis D Hypomagnesemia Kayexalate administration Parathyroidectomy Cinacalcet overdose Poor absorption (PPI) Up To Date Low calcium, low ionized calcium Acute: neuromuscular irritability (tetany), cardiovascular symptoms, papilledema, psychiatric Chronic: ectopic calcification, extrapyramidal signs, Parkinsonism, dementia, cataracts, abnormal dentition, dry skin Kidney damage Growth failure Musculoskeletal deformity Soft tissue and vascular calcification Osteitis fibrosa cystica Increase calcium intake Decrease phosphorus intake or add binder Start or increase calcium supplement Start or increase vitamin D supplement or active vitamin D Treat magnesium deficiency Increase dialysate calcium What does hypocalcemia look like? Causes Signs/symptoms Long term consequences Intervention Phosphate restriction Hyperphosphatemia Hypovitaminosis D Hypomagnesemia Kayexalate administration Parathyroidectomy Cinacalcet overdose Poor absorption (PPI) Up To Date Low calcium, low ionized calcium Acute: neuromuscular irritability, cardiovascular symptoms, papilledema, psychiatric manifestations Chronic: ectopic calcification, extrapyramidal signs, dementia, cataracts, abnormal dentition, dry skin Kidney damage Growth failure Musculoskeletal deformity Soft tissue and vascular calcification Osteitis fibrosa cystica Trousseau s sign Increase calcium intake Decrease phosphorus intake or add binder Start or increase calcium supplement Start or increase vitamin D supplement or active vitamin Chvostek s D sign Treat magnesium deficiency Increase dialysate calcium 13

14 What happens if hypocalcemia is not treated? Causes Signs/symptoms Long term consequences Intervention Phosphate restriction Hyperphosphatemia Hypovitaminosis D Hypomagnesemia Kayexalate administration Parathyroidectomy Cinacalcet overdose Poor absorption (PPI) Up To Date Low calcium, low ionized calcium Acute: neuromuscular irritability, cardiovascular symptoms, papilledema, psychiatric manifestations Chronic: ectopic calcification, extrapyramidal signs, dementia, cataracts, abnormal dentition, dry skin Kidney damage Growth failure Musculoskeletal deformity Soft tissue and vascular calcification Osteitis fibrosa (high turnover bone disease) Increase calcium intake Decrease phosphorus intake or add binder Start or increase calcium supplement Start or increase vitamin D supplement or active vitamin D Treat magnesium deficiency Increase dialysate calcium How do you fix hypocalcemia? Causes Signs/symptoms Long term consequences Interventions Phosphate restriction Hyperphosphatemia Hypovitaminosis D Hypomagnesemia Kayexalate administration Parathyroidectomy Cinacalcet overdose Poor absorption (PPI) Up To Date Low calcium, low ionized calcium Acute: neuromuscular irritability, cardiovascular symptoms, papilledema, psychiatric manifestations Chronic: ectopic calcification, extrapyramidal signs, dementia, cataracts, abnormal dentition, dry skin Kidney damage Growth failure Musculoskeletal deformity Soft tissue and vascular calcification Osteitis fibrosa (high turnover bone disease) Increase calcium intake Decrease phosphorus intake or add binder Start or increase calcium supplement Start or increase vitamin D supplement or active vitamin D Treat magnesium deficiency Increase dialysate calcium Calcium supplements Consider: Type Cost Timing Availability Administration method Pill burden Vitamin D status 14

15 Vitamin D supplementation Serum 25(OH) D Supplementation with cholecalciferol OR ergocalciferol >30 ng/ml Maintenance dose between IU daily 16 to 30 ng/ml 2000 IU daily x 3 months 50,000 IU monthly x 3 months 5 to 15 ng/ml 4000 IU daily x 3 months 50,000 IU every other week x 3 months <5 ng/ml 8000 IU daily x 1 month, then 4000 IU daily x 2 months 50,000 IU weekly x 1 month, then 50,000 IU every other week for 2 months ESPN CKD MBD guidelines recommend a treatment schedule guided by age and vitamin D level which includes an intensive replacement phase followed by a maintenance phase for vitamin D supplementation in children with CKD stage 2 to 5D Monitor serum 25(OH) D 3 months after completion of therapy Up To Date/KDOQI Vitamin D analogues Calcitriol Paricalcitol Why do kids w/ CKD develop hypercalcemia? Causes Signs/symptoms Long term consequences Interventions Excessive calcium intake Loss of renal function Hypervitaminosis D Hypervitaminosis A Severe SHPT Metabolic acidosis High serum calcium, elevated urinary calcium/creatinine ratio Severity, chronicity Common: polyuria, polydipsia, dehydration, constipation, anorexia, nausea, muscle weakness, lethargy, confusion, coma Kidney stones Kidney damage Growth failure Musculoskeletal deformity Soft tissue and vascular calcification Adynamic bone disease Reduce calcium load Reduce Ca based binder or change to/add non Cabased binder Decrease or discontinue vitamin D supplement and/or vitamin D analogue Decrease dialysate calcium Supplement phosphorus? 15

16 What does hypercalcemia look like? Causes Signs/symptoms Long term consequences Interventions Excessive calcium intake Loss of renal function Hypervitaminosis D Hypervitaminosis A Severe SHPT Metabolic acidosis High serum calcium, elevated urinary calcium/creatinine ratio Severity, chronicity Common: polyuria, polydipsia, dehydration, constipation, anorexia, nausea, muscle weakness, lethargy, confusion, coma Kidney stones Kidney damage Growth failure Musculoskeletal deformity Soft tissue and vascular calcification Adynamic bone disease Reduce calcium load Reduce Ca based binder or change to/add non Cabased binder Decrease or discontinue vitamin D supplement and/or vitamin D analogue Decrease dialysate calcium Supplement phosphorus? What happens if hypercalcemia is not treated? Causes Signs/symptoms Long term consequences Interventions Excessive calcium intake Loss of renal function Hypervitaminosis D Hypervitaminosis A Severe SHPT Metabolic acidosis High serum calcium, elevated urinary calcium/creatinine ratio Severity, chronicity Common: polyuria, polydipsia, dehydration, constipation, anorexia, nausea, muscle weakness, lethargy, confusion, coma Kidney stones Kidney damage Growth failure Musculoskeletal deformity Soft tissue and vascular calcification Adynamic bone (lowturnover bone disease) Reduce calcium load Reduce Ca based binder or change to/add non Cabased binder Decrease or discontinue vitamin D supplement and/or vitamin D analogue Decrease dialysate calcium Supplement phosphorus? How do you fix hypercalcemia? Causes Signs/symptoms Long term consequences Interventions Excessive calcium intake Loss of renal function Hypervitaminosis D Hypervitaminosis A Severe SHPT Metabolic acidosis High serum calcium, elevated urinary calcium/creatinine ratio Severity, chronicity Common: polyuria, polydipsia, dehydration, constipation, anorexia, nausea, muscle weakness, lethargy, confusion, coma Kidney stones Kidney damage Growth failure Musculoskeletal deformity Soft tissue and vascular calcification Adynamic bone (lowturnover bone disease) Reduce calcium load Change to a non calciumbased binder Decrease or discontinue vitamin D supplement and/or vitamin D analogue Decrease dialysate calcium Supplement phosphorus? Up To Date 16

17 Age 6+ since 2016 Investigate cause of hypercalcemia Consider changing dialysate Ca concentration Corrected serum Ca (mg/dl) Review changes in dialysate Ca concentration Ca carbonate Ca free P binder Ac ve vitamin D Ca free P binder Ca carbonate Ac ve vitamin D Ca free P binder Ca carbonate between meals Ac ve vitamin D Cinacalcet ** Ca carbonate Switch to Ca free P binder Ac ve vitamin D Cinacalcet * Target Ca and P levels Ca carbonate Ca carbonate between meals Ac ve vitamin D Cinacalcet ** Ca carbonate Ca free P binder Ac ve vitamin D Cinacalcet * Ca free P binder Ca carbonate Ac ve vitamin D Cinacalcet * Ca carbonate Ca free P binder Cinacalcet ** Evaluation of food consumption and nutrition Serum P level (mg/dl) Ensure adequate dialysis dose Dietary guidance (restricted P) When do you start doing something? Stage 2 Stage 3b Stage 5 Kuro o M and Moe OW. FGF23 aklotho as a paradigm for a kidney bone network. Bone. 2017; 100:

18 Why do we care? Abnormal labs CKD MBD Vascular & soft tissue calcification Abnormal bone Why do we care? Evaluation of CKD MBD used to be limited to evaluation of rates of bone turnover Bone biopsy required to assess all 3 aspects in the TMV classification system Turnover: alteration in rate of bone resorption and formation Mineralization: alteration in volume of unmineralized bone and mineralization rate Volume: alteration in amount of bone mass (AKA osteoporosis, usually seen in adults) Disturbed mineralization and/or bone volume can occur in the setting of normal bone turnover Ca PTH Ca PTH Sources: Bakkaloglu 2010 Why do we care? Growth failure, bone deformity CKD Biochemical changes Bone changes Soft tissue calcification Heart disease 18

19 Amount and safety of calcium supplementation s/p parathyroidectomy The Calcium Conundrum Continues: The relationship between magnesium and calcium Calculating vitamin A intake for accurate assessment How much calcium does a 6 to 12 month old actually eat? Take Home Points Follow trends Interpret labs in context Consider all factors that contribute to calcium load Would follow KDIGO: keep in normal range Remember: A bone biopsy needed to diagnose osteodystrophy CKD MBD is linked to heart disease Positive calcium balance is not good if you are not growing nope 19

20 Thank you. Questions? Jess Tower References Dietary Reference Intakes for Calcium and Vitamin D. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors. Washington (DC): National Academies Press (US); Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol (suppl 3): S131 S /10/18. Case Study from ListServ Pt history: 7 month old male CGA 6 months on PD (adding another cycle) with formula providing 126 kcal/kg through GT, no PO Questions asked: GA: 34 6/7 weeks Underlying disease state? MCDK K+ trends? Hemolyzed samples, low to normal overall ( mmol/l) Growth trend? Poor, 5 gm/day (goal 12 gm/day) Vitamin D level? Lipid levels? 20

21 Case Study from ListServ Pt history: 7 month old male CGA 6 months on PD (adding another cycle) with formula providing 126 kcal/kg through GT, no PO Current diet: 24 kcal/oz Similac PM 60/ kcal/oz Liquigen to 32 kcal/oz 110 ml 5 times daily 120 ml 5 times daily Current labs: Calcium Ionized calcium 5.1 Phosphorus PTH Alkaline phosphatase (OH) vitamin D 48 a few months ago Current medications: Calcitriol increasing from 0.4 mcg to 0.6 mcg/day 550 ml Energy Protein Phosphorus K+ Ca Vitamin A Vitamin D Case Study from ListServ The team would like to switch to 100% Calcilo XD with Liquigen for the high calcium. 100% Similac 60/40 100% Calcilo XD RDA 6 months Phosphorus mg/day 180 mg/day 100 mg/day Calcium mg/day 17 mg/day 200 mg/day K mg/day mg/day 400 mg/day Would you do a combination of Similac PM 60/40 or Renastart to provide less phosphorus, a bit more calcium and some vitamin D? Case Study from ListServ Created a recipe with Calcilo XD + Renastart + Liquigen to 32 kcal/oz to reduce the amount of calcium and phosphorus in formula. Energy Protein Phosphorus K+ Ca Vitamin A Vitamin D Renastart Calcilo XD Liquigen 216 Totals: 647 kcal 8 gm 92 mg 204 mg 61 mg 228 mcg 106 IU Needs: 106% 89% 92% 51% 31% 57% 27% % reduction

22 Case Study from ListServ: Responses Increase phosphorus intake Pre treat formula with Kayexalate to address increased K+ provision Trial low calcium PD fluid Consider different formula compositions if family capable kcal Similac PM 60/40 + Calcilo XD with Liquigen PRN kcal Similac PM 60/40 + Renastart with Liquigen PRN kcal Caliclo XD + Liquigen short term, then switch Is calcitriol contributing to calcium absorption? Consider paricalcitol. Check vitamin A level Martin KJ Gonzalez EA Metabolic bone disease in CKD JASN (3) /10/18 Effect of CKD 1 5D on calcium homeostasis Stage 2 Stage 3b Stage 5 Reduced calcitriol production Poor calcium & phosphate filtration Reduced calcium & phosphate excretion Limited diet Kuro o M and Moe OW. FGF23 aklotho as a paradigm for a kidney bone network. Bone. 2017; 100:

23 Tolerable Upper Limits Toxicity Hypercalcemia Hypercalciuria (>0.3 mg calcium/mg creatinine) Calcinosis Nephrolithiasis Calcium or milk alkali syndrome (>3000 mg) Earlier: Result of early treatment for gastric or duodenal ulcers w/ hypercalcemia, severe alkalosis, and hyperphosphatemia Modern: Result of calcium carbonate supplementation w/ hypophosphatemia How do you achieve target serum calcium? Goal: increase serum calcium Increase oral intake of calcium Calcium supplementation Calcium containing binders Start vitamin D Reduce dialysate calcium Goal: decrease serum calcium Decrease oral intake of calcium Discontinue supplementation Select alternative binders Adjust vitamin D Increase dialysate calcium 23

24 How do you actually achieve target serum calcium? Accurate assessment of baseline calcium intake NIH short calcium FFQ (Sebring NG) Dialysis FFQ (Kalantar Zadeh K) Most successful education strategies Available teaching materials Nutrients are listed in their elemental form Roll out: 1/1/20 for >$10 million in sales 1/1/21 for <$10 million in sales Calcium balance & excretion in CKD Neutral Total calcium intake total body calcium losses = calcium balance Negative balance Loss of bone mineral Risk for mineralization defect Risk for bone fragility fractures Morbidity and mortality Positive balance Soft tissue calcification Cardiovascular events Morbidity and mortality 24