Vitamin D - Increase calcium and phosphorous in all categories

PTH - Same as Vitamin D, only decreases PO4 in renal reabsorption, and thus overall as well. 

Abnormal Bone - Renal Osteodystrophy --> compromised bone strength and risk of fractures

Abnormal Mineral Metabolism - Calcium, Phosphorous, PTH, Vitamin D, and alkaline Phosphotase

Extraskeletal Calcification - Extraosseious calcification, including arterial, valvular, and myocardial calcification

High - Predominant hyperPTH, Osteitis Fibrosa (bones turn soft and become deformed)

Low - Osteomalacia, aluminum-related bone disease, adynamic bone disease

Mixed - Mild to moderate hyperPTH disease, with defective bone mineralization

- Affects nearly half of dialysis patients

- Clinician induced

Etiology - Aggressive medical suppression of PTH secretion with Cinacalcet and/or Vitamin D analogues

- Increases risk of calcification, fractures, and CVD

- ALP is produced in the liver and bones

- Removes phosphate groups

- INCREASED ALP can lead to bone growth issues

- Two types, total ALP and bone ALP

- NL = 20-140IU/L

- Should be used in conjunction with PTH level

- Elevated ALP may indicate continued bone deterioration regardless of PTH

- Increase or decrease in normal Vitamin D levels can lead to increasing promoters of VSMC, or decreasing inhibitors of VSMC.

- VSMC = Vascular smooth muscle cells

- Cardiac perivascular fibrosis were significantly increased in remnant kidney groups, and further increased in paricalcitrol rats

- Disproportion in the promoting or inhibiting could yeild an osteoblast-like phenotype.

- In dialysis patients, this phenomenon occurs FREQUENTLY

- Calcific Uremic Arteriolopathy

- Referred to as Calciphylaxis

- S&S include painful nodules, ulcerating lesions that can become gangrenous, presents in fatty areas of body

Risk Factors:  Increase Calcium, DM, Obesity, Female, Elevated iPTH

- No randomized studies only case reports available

- Parathyroidectomy

- Cinacalcet

- Bisphosphonates

- Sodium thiosulfate

- Hyperbaric oxygen therapy

- Resolution from weeks to months

- Stage 3

- Moderate decrease in GFR at about 30-79ml/min

- Should evaluate and treat complications

- Associations with morbidity/mortality

- KDOQI in 2003 recommended levels <55mg2/dl2

- In 2009 they recommended against this

- Levels greater than 70 thought to increase soft tissue calcification, but contemporary cases argue against this, demonstrating levels <60 can do this as well

Stage 3:  Ca and P q6-12 months; PTH based on baseline level and progression, Vitamin D level

Stage 4:  Ca and P q3-6month; PTH q6-12months

Stage 5, including 5D:  Ca and P q1-3months, PTH q3-6 months

Stages 4-5D:  Alkaline phosphotase q12 months, or more frequently in the presence of elevated PTH

- Vitamin D drugs

- Control serum iP

- Target Ca2+ receptor on PTH gland: Calcimimetic

- Nutritional Supplements

- Active Vitamin D Analogst

- Restrict iP intake

- Phosphorous binders

- Hemodialysis

- Number 1 job, maintain Ca2+ levels

- When GFR <60, PTH increases

- SHPT is Secondary Hyperparathyroidism

Can be caused by:  Hypocalcemia, Low Vitamin D, elevated phosphorous, hypertrophy of the gland

Target Levels

3:  35-70

4:  70-110

5:  150-300

Skeletal:

- High-turnover bone lesions

- Osteitis Fibrosa

- Brown Tumors

- Bone pain

- Osteopenia

- Fractures

- Hypercalcemia

- Hyperphosphatemia

- Calciphylaxis

ExtraSkeletal:

- Nervous System

- Neuropathy

- Heart (HTN, LVH, interstitial fibrosis, Myocardial/valvular, calcification

- Glucose intolerance

- Hyperlipidemia

- Anemia

Vitamin D receptor:  Vitamin D rx

Phosphorous:  iP binders

Ca2+ receptor:  Calcimimetic

- Check levels at Stage 3 CKD

Insufficient:  <30ng/ml

Deficient:  <15ng/ml

Vitamin D3 (cholecalciferol), D3 from fish/meat, and Vitamin D2 (Ergocalciferol), all need to be hydroxylated by the liver first.  This creates 25-hydroxyvitamin D3.  This is filtered and then I assumed reasbsorbed by the kidneys in the form of 1,25-dihydroxyvitamin D3, which maintains calcium levels in the body. 

< 5 - Severe Deficiency --> D2 qw x 12 weeks, then monthly injection for 6 months

5-15 - Mild Deficiency --> D2 qw x 4 weeks, then monthly injection for 6 months

16-40 - Insufficiency --> D2 qmonth x 6 months

Target Calcium Ranges:  Stage 3&4:  Normal

Stage 5:  8.5-9.5mg/dL

Do NOT exceed 2g/day

Use correct Ca equation so as account for ionized calcium and calcium bound to albumin.

Total Ca(mg/dL) + 0.8x[4-serum albumin(g/dL)]

- Sensipar

- treatment of SHPT

- Increases sensitivity of calcium-sensing receptor in PT gland

- Common ADR is N/V

- CI in seizures and Ca levels < 8.4

- In studies of sensipar, showed long-term safety and efficacy, significantly reduced and sustained:  iPTH, Ca, P, Ca x P

- NR = 2.5-4.5mg/dL or 0.8-1.4 mmol/L

Distribution:  85% in bone and teeth, 14% in soft tissue, small amount in ECF

- Phosphorous is used in:  Cellular metabolism, acid-base balance, metabolic pathways

- If we consume 20mg of phosphorous through food, 7mg is excreted via feces, 13 is left then you have 3mg in limbo with digestive juices, 3mg of this is taken away for bone resorption, and then you have 13mg left to be excreted in urine. 

- Begins early in CKD (Stage 1)

- Levels in high end of normal range associated with LVH, CV mortality

- Major contribution to initiation of vascular calcification

- Serum levels may remain normal until GFR < 20-30ml/min (due to increased fraction excretion of iP per nephron)

 Treatment:  Restrict dietary phosphate to 800-1000mg/day, monitor monthly, Foods high in phosphorous (meat, cola, beans, cheese, milk products, wine)

- Binders do as you'd think and prevent absorption in GI (Aluminum-based, Calcium-based, Polymer-based, Element agent)

- Aluminum Carbonate has better PO4 binding capacity than Aluminum Hydroxide, take 1-4 tabs pc and 1hs, or 15-30ml pc and hs

- ADR's include AL toxicity, constipation, Na overload

- Rx intx include Digoxin, isoniazid, iron, phenytoin, warfarin, phenobarbital, tetracycline

- Should be avoided for chronic use

- Only recommended for short-term use

- use for < 4 weeks

- Serum iP should be > 7mg/dL

- All citrate products should be avoided during this time (increases abs. of AL)

Aluminum Toxicity:  Dialysis encephalopathy, hypoparathyroidism, hypochromic microcytic anemia, resistance to erythropoietin therapy, osteomalacia, adynamic bone disease, mixed disease

- AL is poorly removed via dialysis

- 90% bound to plasma proteins

- Desired AL levels < 20mcg/L

- Treatment:  Deferoxamine

- Calcium acetate better phosporous binding than calcium carbonate, take 1-2g Ca BID or TID with meals

ADR's:  N/V/C, hypercalcemia and extraskeletal calcifications

Intx:  Chelates abx, inhibits Levothyroxine absorption. 

- Sevelamer is a polymer-based agent, take 2-4 tabs TID with meals

ADR's:  N/V/D/C

Intx:  Mycophenolate, FQ's, Levothyroxine

- Lanthanum Carbonate is an elemental agent, take 500mg-1g TID with meals

ADR's - N/V, accumulation in bone, liver, brain (don't know effects yet)

Intx - FQ's, mycophenolic acid

- Attenuates Calcification progression

- No hypercalcemia

- Lowers LDL

- CV benefit

- Survival benefit is controversial

Fosrenol - Take with or immediately after food

Initial dose based on iP level

Renegal - with meals

Phoslo - with meals, initial dose 2 tablets with each meal

Dialysis:  Increase duration of dialysis treatment

Use larger pore filter

Parathyroidectomy - Patients with persisten iPH > 800 pg/ml + with associated hyperphosphotemia and hypercalcemia refractory to medial treatment

- Who failed medical/pharmacological therapy

- Additional consideration for cinalcacet use for  treatment of calciphylaxis and hypercalcemia