Bone and Mineral Disorders and Anemia of CKD Flashcards
how does the kidney play a role in phosphate balance?
- control of excretion of its filterable fraction in the urine
- production of the active form of vitamin D
describe renal excretion of phosphate
the amount of phosphate excreted by the kidneys depends on
- GFR: any decrease in GFR can increase blood phosphate
- tubular reabsorption, primarily in proximal tubular through sodium-phosphate transporters
-PTH and fibroblast growth factor-23 reduce phosphate reabsorption by decreasing the abundance of these co-transporters, so increases in plasma FGF-23 and/or PTH can lead to increase excretion of phosphate by the kidneys
describe calcium and phosphate homeostasis; describe in CKD
see chart
phosphate excretion and production of calcitriol are impaired in animals with chronic kidney disease, promoting changes in mineral homeostasis
describe regulation of phosphate
- FGF-23 is released from osteocytes in response to increased phosphate
- with its co-receptor alpha-klotho, FGF-23 decreases phosphate and calcitriol concentrations
- FGF-23 also downregulates 1-alpha hydroxylase in kidneys, so we don’t make as much calcitriol, decreasing phosphate absorption in intestines, further decreasing serum phosphate
describe CKD mineral and bone disorders
- changes in bone mineral metabolism and alterations in calcium and phosphate homeostasis
- reduced phosphate excretion in CKD causes CKD mineral and bone disorders
-renal secondary hyperparathyroidism
-accelerated progression of CKD
-increased mortality rate
-renal osteodystrophy
-extraskeletal calcification
-hypo or hyper calcemia or magnesemia
-hyperphosphatemia: one of the most important risk factors for progression of disease and survival - in early CKD, have a drop in GFR and phosphate retention/decreased phosphate clearance, then an increase in FGF-23 that increases fractional excretion of phosphate and decreases calcitriol activation, resulting in plasma phosphorous returning to normal limits (yay kidneys!)
- in late CKD, the kidneys are no longer able to compensate for the drop in GFR and decreased phosphate clearance so there is a net increase in plasma phosphate, which results in decreased plasma calcium and increased PTH, which inhibits the increase in fractional excretion of phosphate that FGF-23 is trying to accomplish, resulting in renal secondary hyperparathyroidism, which causes decreased survival, soft tissue mineralization, and demineralization of bone
however this varies widely between individuals and in some, calcium can actually increase (increased PTH) so kidney disease is a rule out for hypercalcemia too
what happens to calcium, phosphate, and their regulatory hormones in CKD?
- on average as CKD progresses, GFR declines
- blood creatinine/SDMA increase
- blood phosphate increases
- blood FGF 23 increases (before phosphate)
- blood PTH increases
- blood calcitriol decreases
- blood ionized calcium decreases
calcium concentrations can vary widely in CKD and can be increased in come animals, kidney disease is a rule out for hypercalcemia!
what happens to caclium and phosphorous in CKD?
calcium-phosphorous product tends to increase as CKD progresses
when this product increases over 60-70, can increase risk for soft tissue mineralization
hyperphosphatemia is associated with increased morbidity and mortality in CKD< and restricting dietary phosphate (and protein) in cats and dogs with CKD improves outcomes
describe phosphate restriction
indicated for:
1. dogs and cats with azotemic CKD (mid-late stage 2 through 4)
- dogs and cats with evidence of phosphate retention
-those with hyperphosphatemia
-those with blood phosphate concentration above target defined by IRIS
-those with elevated FGF-23
how do you restrict dietary phosphate?
- phosphate-restricted diets: feature of therapeutic renal diets
-challenges: acceptability and compliance
-solutions: slow transition, good timings, client communication, nutrition consult
-added challenge: protein rich ingredients are a source of phosphate
–cats and dogs have protein requirements that will limit how phosphate-restricted we can formulate a diet to be
–marked phosphate restriction may increase blood calcium absorption
–by itself, dietary phosphate restriction will not always control hyperphosphatemia
solution: drugs
describe enteric phosphate binder drugs
- used when phosphate-restricted diets alone fail to maintain target serum phosphate concentrations
- reduce intestinal absorption of phosphate binders so MUST be given with meals
-challenges: acceptability, compliance, efficacy
-solutions: start at lower dosage
describe aluminum based phosphate binders
- most frequently used
- effective and inexpensive
- possible adverse:
-Al tox
-decreased palatability of food with some formulations - avoid using with citrate based drugs bc they increase Al absorption
describe calcium based enteric phosphate binders
- freq use
- mod effective and inexpensive
- good choice for hypocalcemic animals
4 possible adverse: hypercalcemia, dystrophic mineralization, constipation
- contraindicated: hypercalcemic
how do you choose a phosphate binder?
- hypocalcemic: calcium based great choice
- normocalcemic: either, but keep an eye on calcium
- hypercalcemic: NO CALCIUM BASED!! choose something else
describe using calcitriol for CKD bone and mineral disorder
- inhibits PTH so would treat renal secondary hyperparathyroidism
- limited evidence, may prolong survival in dogs
- indication: treat CKD mineral and bone disorder in dogs with azotemic CKD and proven renal secondary hyperparathyroidism
- adverse:
-hypercalcemia and hyperphosphatemia
-dystrophic mineralization - important: control hyperphosphatemia before initiating therapy
-do NOT use if hypercalcemia present - monitoring: serum phosphate, ionized calcium, pTH, and creatinine concentrations regularly
- NOT admin with meals, as increases intestinal calcium and phosphate absorption
hella controversial, Dr. Lourenco no like
describe anemia of CKD
- non-regenerative, normocytic, normochromic anemia
- develops in advanced CKD stages: moderately to severely azotemic animals
- reduced RBC production due to:
-reduced erythropoietin production!!
-changes in iron metabolism
-nutritional deficiencies (iron and B12) - increased RBC destruction:
-uremic toxins decrease lifespan of circulating RBCs
-GI ulcers may lead to blood loss - affects quality of life: weakness, lethargy, inappetence
- triggers detrimental adaptations
-sympathetic NS and RAAS activation, resulting in cardiac remodeling/dysfunction and systemic arterial hypertension - can exacerbate the progression of CKD
-potentiates renal hypoxia and promotes tubulointerstitial fibrosis
