Lecture 12 Chronic Kidney Disease-Management of Complications Flashcards
(25 cards)
What is CKD-MBD?
systemic disorder of mineral and bone metabolism due to CKD manifested by one or more of: abnormal Ca2+, phosphorus, PTH, vit D metabolism, bone turnover, mineralization, volume, linear growth, strength, vascular or other soft-tissue calcification
occurs in almost all pt with CKD stage 5D and majority of pt with CKD stages 4-5
Role of active vitamin D3 (calcitriol)
these receptors are found in most body cells including intestine, parathyroid glands, bone
Intestine: increases serum Ca2+ and PO43- by increasing absorption from intestinal tract
Bone: increases serum Ca2+ and PO43- by promoting bone resorption
Parathyroid glands: directly inhibits PTH production and indirectly inhibits PTH secretion (via increased Ca2+ levels)
Role of PTH
produced by these glands in response to: decrease serum Ca2+ (main regulator), increased serum PO43-, decreased serum calcitriol
regulates total serum Ca and PO4 levels, active receptors found in kidneys and bone
Kidney: increases serum Ca by increasing reabsorption, decreases serum PO4 by decreasing reabsorption (increases excretion)
Bone: increases serum Ca and PO4 by promoting resorption
stimulates production of calcitriol within kidney - indirectly increases intestinal Ca and PO4 absorption
Role of FGF-23 (fibroblast growth factor-23)
bone-derived hormone produced in response to elevated calcitriol and PO4 levels, decreases serum PO4 by decreasing PO4 reabsorption by kidneys (increases PO4 excretion)
decreases serum levels of calcitriol (vitamin D) (decreases production, increases catabolism)
inhibition secretion of PTH
Secondary Hyperparathyroidism, steps in pathophysiology
decreased kidney fxn leads to reduced phosphate excretion and increased serum phosphate
elevated PO4 directly suppresses calcitriol production
elevated PO4 leads to increased FGF-23 leading to decreased calcitriol
reduced kidney mass leads to decreased calcitriol production
decreased calcitriol with reduced calcium absorption from GI tract leads to hypocalcemia
steps 1-5 lead to increased production of PTH and proliferation of parathyroid cells
Summary: hyperphosphatemia, decreased Vit D and hypocalcemia leads to increased PTH production
How are bone abnormalities classified?
by turnover (low to high), mineralization (normal to abnormal), volume (low to high)
What is hyperparathyroid related bone disease, and what is included in management?
mild this (HPT) and advanced HPT-related bone disease (osteitis fibrosa) represent range of abnormalities from medium to high turnover
high-turnover bone disease is caused by secondary hyperparathyroidism
Management: reducing hyperphosphatemia, normalizing Ca2+ levels, suppressing PTH
How does adynamic or low-bone turnover disease occur, and what is included in management?
results from over-suppression of PTH, may be caused by meds that lower PTH (ex. Ca, active Vit D therapy, calcimimetics)
Management: allowing PTH levels to rise to increase bone turnover, reducing/stopping vitamin D analogs and/or calcimimetics,, osteomalacia can result from Al deposition ⇒ stop Al-containing phosphate binders
What are tx targets (KDIGO 2017) for CKD-BDMs and non-pharmacological managements for it?
PO4: Stage 3-5D - lower toward normal range
Ca: Stage 3-5D - avoid hypercalcemia
PTH: Stage 3-5ND - optimal target unknown, Stage 5D - maintain in range of 2-9 x ULN
Non-Pharm: dietary phosphate restriction
Phosphate Binders as tx for CKD-BDM (indication, MOA, drugs, dosing instructions)
KDIGO: in pt with CKD Stage 3-5D with decision to take being based on progressively or persistently elevated PO4
MOA: most binders are cations, when taken with food they bind PO4 in gut and it cannot be absorbed and it is excreted in feces
Drugs: Ca-based binders - calcium carbonate (TUMS, Os-cal), calcium acetate, calcium citrate
Non-Ca based binders - sevelamer HCl (Renagel), sevelamer carbonate (Renvela), lanthanum carbonate (Fosrenol)
Mg salts
Al salts
Fe-based binders - sucroferric oxyhydroxide (Velphoro),, Instructions: must be taken with meals to maximize efficacy
Calcium salts as phosphate binders for CKD-BDM management (Drugs, dose, AE, interactions, coverage)
most commonly used phosphate binder
Drugs: citrate (21% elemental Fe) ⇒ acetate (25%) ⇒ carbonate (40%)
Dose: usual is 0.6-4.5 g of elemental per day, initial is carbonate 500 mg (TUMS regular, 200 mg elemental) PO TID with meals, titrate based on Ca and PO4 levels, give higher doses with bigger meals
AE: hypercalcemia, if > 2.60 mmol/L reduce dose or switch to non-Ca, GI AEs (nausea, constipation)
Interactions (separate admin): Fe, fluoroquinolone antibiotics
Coverage: not by most private or public programs, ABC partial coverage of renal OTC products (special auth)
Sevelamer as phosphate binder for CKD-BDM Management (Drugs, MOA, dose, AE)
second lne agent due to cost, consider using in pt with hypercalcemia requiring phosphate binder, doesn’t contain Ca, Al, or Mg so can be used in combo with other binders
Drugs: HCl (Renagel), carbonate (Renvela),, MOA: non-absorbable hydrogel that binds phosphate in GI tract
Dose: 800-2400 mg PO TID with meals
AE: may decrease LDL, mainly GI (constipation, diarrhea, N/V, ab pain), metabolic acidosis (HCl salt)
Lanthanum carbonate as phosphate binder for CKD-BDM management (MOA, dose, AE)
can be used in combo with other binders, relatively high-binding capacity, costly
MOA: non-absorbable element, dissociates in upper GI to these ions which then bind dietary PO4
Dose: initial 250-500 mg PO TID with meals, titrate up to 3000 mg/day in divided doses, available as chewable 250, 500, 750, 1000 mg
AE: GI (N/V, diarrhea)
Aluminum salts as phosphate binder for CKD-BDM management (Indication, dose)
no longer recommended as first line
reserved for acute tx of severe hyperphosphatemia, risk of this toxicity (CNS, worsening of anemia), short term tx limited to max 4 weeks
Dose: 300-600 mg PO TID with meals
Magnesium salts as phosphate binders for CKD-BDM management (Drugs, AE, indication)
used for short-term or adjuvant use after other agents fail, less effective than Ca salts
Drugs: hydroxide, gluconate
AE: diarrhea, hypermagnesemia
Sucroferric oxyhydroxide (Velphoro) as phosphate binder for CKD0BDM management (MOA, Dose, AE)
MOA: Fe-based binder, binds phosphate in GI via ligand exchange of hydroxyl groups reducing dietary PO4 absorption
Dose: initial 500 mg PO TID with meals, titrate up to 3000 mg/day in divided doses, available as 500 mg chewable (must be chewed/crushed)
AE: GI (diarrhea, nausea), black stools
costly
What is active vitamin D3 used for in tx for CKD (drugs, AE)?
used in pt with elevated PTH despite use of Ca-containing phosphate binders, used to treat hyperparathyroidism
decreases PTH synthesis - indirectly by stimulating absorption of serum Ca and PO4 by intestinal cells, direct activity on parathyroid gland,, ideal to have PO4 controlled prior to initiation - increases GI PO4 absorption, do not initiate if PO4 > 2 mmol/L or Ca > 2.6 mmol/L
Drugs: calcitriol (Rocaltrol) - active form ⇒ AE: hypercalcemia (33%), H/A, pruritis, hyperphosphatemia, hypermagnesemia, metallic taste, nausea, elevated liver enzymes, bone pain, soft tissue calcification
also synthetic analogues: alfacalcidol - same dosing as calcitriol, more affinity for kidney receptors may result in less GI absorption of Ca and phosphate compared to calcitriol
What are calcimimetics used for in CKD tx (drugs, dose, AE)
used in pt with persistently elevated PTH despite use of phosphate binders and vitamin D analogs, suppresses PTH by increasing severity of the Ca-sensing receptors of parathyroid glands
Drugs: cinacalcet (Sensipar)
Dose: initial 30 mg PO QD, titrate up to max 180 mg QD
AE: hypocalcemia, GI upset, QT prolongation leading to arrhythmias
costly
Which txs for CKD-MBD cause decreases in calcium?
calcimimetics and parathyroidectomy
Which txs for CKD-MBD cause decreases in phosphate?
calcimimetics and parathyroidectomy,, bigger decreases seen with both calcium and non-calcium based phosphate binders
Which txs for CKD-MBD cause decreases in PTH?
vitamin D analogs, calcimimetics and parathyroidectomy cause major decreases as well as Ca-based phosphate binders
non-calcium based phosphate binders don’t really cause a decrease or increase
Which txs for CKD-MBD cause increases in calcium?
vitamin D analogs
calcium based phosphate binders cause higher increases
non-calcium based phosphate binders don’t really decrease or increase
Which txs for CKD-MBD cause increases in phosphate?
vitamin D analogs
What are some extraskeletal manifestations of CKD-MBD?
soft tissue calcification - blood vessels, heart valves, skin
calciphylaxis - 1-4% of dialysis pt, extensive calcifications of skin, muscles and SC tissue, leads to painful non-healing ulcerations and gangrene
