Nutritional Management of CKD and Urinary Disease Flashcards
What is fibroblast growth factor 23?
FGF‐23 is a factor synthesized and secreted by bone cells (fibroblasts)
What is FGF-23’s role in P regulation and how does it interact with Klotho?
FGF-23 reduces P in the serum by increasing renal secretion and decreasing intestinal absorption
• FGF-23: The N- terminal peptide binds to tissue receptors, and the C-terminal binds to Klotho.
What is Klotho?
Klotho is a transmembrane protein that acts as a coreceptor for FGF-23 in the kidney
What are signs of Klotho deficiency?
Animals with Klotho deficiency show signs of FGF‐23 deficiency with high serum phosphate and calcitriol concentration.
What is Klotho’s role in longevity?
More klotho-> longer life
What mechanisms are there to help reduce phosphorus in the blood?
When phosphorous is high, there are several mechanisms including PTH to help reduce it
• Hyperphosphatemia upregulates a factor called fibroblast-growth factor-23 (FGF-23) from the bone
• This factor reduces activation of vitamin D to calcitriol in the kidney
• Reduces P absorption form the GI tract
• Primary action- joins with a factor called Klotho to increase P excretion in the kidney
When we have kidney disease what is occuring in terms of phosphorus?
- decrease 1,25 vitamin D
- increase phosphate
- Decrease in calcium
This increases PTH levels
FGF-2 is link between phosphate load and decreased 1,25 vitamin D levels
This decreased calcium levels cause increased PTH secretion, increased PTH synthesis, and increased cell proliferation
What are the risk factors for CKD?
Risk factors for CKD:
• Age (estimated that up to 33% of cats above 13 years have
CKD)
• Body condition
• Hyperlipidemia
• Acute kidney injury
• Vaccination?
• Dietary??
What are the outcomes of CKD?
Dehydration (secondary to polyuria)
• Renal Secondary Hyperparathyroidism
• Hyperphosphatemia
• Azotemia/uremia
• Electrolyte & acid/base imbalances
• Hypertension
• Renal hypoxia and/or renal oxidative injury
• Loss of body condition and muscle…
How common is CKD in cats?
1/3 of cats above the age of 15 suffer from chronic renal disease
What is the link between obesity and CKD in humans? In dogs?
• In people = significant risk factor for development of glomerulosclerosis & failure
• Degree of obesity also correlates with degree of proteinuria in people
In Dogs?
• Associated with mild hypertension in dogs
• Increased HR & increased Na+ resorption from renal tubules
• Glomerular hyperfiltration & renal hypertension, damage to parenchyma
What was the outcome of the study of experimentally induced obesity in dogs
Experimentally induced obesity in dogs
• increased mean arterial pressure, increased plasma renin -> altered function & architecture
• Bowman capsule expansion, glomerular cell proliferation, thickening of glomerular & tubular basement membranes, increased mesangial matrix
• Changes in Bowman’s capsule -> pathologic proteinuria?
What are comorbidities that have growing evidence in regards to CKD?
- Evidence accumulates for proteinuria and hyperlipidemia being comorbidities
- Unknown whether treating one disorders impacts the other
Can food cause CKD?
- May be related to form of phosphorous, and Ca:P ratio
• A need to establish a safety limit for phosphorous
• Acidifying diets, limited in potassium, can also lead to CKD
(Dow et al. 1987)
Is high dietary phosphorus safe in adult animals?
While calcium is tightly regulated, phosphorus regulation is not as tight
• Meaning, calcium is usually kept in a tight range in the blood/plasma, whereas phosphorus has a wider range
• Phosphorous in foods can be organic (from fruit, vegetables, grains, meat) or inorganic (phosphoric salts)
• Highly bioavailable phosphorous have been found to damage the kidneys in rats
• In current guidelines, there is no maximum P in cats
Based on all the studies in this lecture what is the overall consensus?
Concentrations of P and Ca in many commercially available cat foods are highly variable
• Very low and very high both exist as well as inverted Ca:P ratio (under 1)
- Future limits on P, its forms used and Ca:P should be considered.
What IRIS stage has seen improvement with diet?
Benefits for kidney diets have been shown from IRIS CKD 2 and above; therefore, many would not change the diet in stage 1
Is there a correlation between PTH and Creatinine?
yes there is.
Much higher PTH at high creatinine levels.
What is important about hydration in terms of kidney disease? How can you maintain hydration?
Address/prevent dehydration
• Maintain renal perfusion
- How?
- Increase water consumption -> water fountains, canned food, etc
- Subcutaneous fluids -> also contains Na/K (may not be desired) patient tolerance…
- Feeding tube
- More physiologic than subcutaneous fluids…
What are essential nutritional factors for CKD?
- Maintain hydration & body condition
- Phosphorus reduction/restriction
- Protein –reduction?
- Address electrolyte abnormalities
- Address acid/base disturbances
- Sodium content
- Antioxidants
- Omega-3 PUFAs (marine sourced)!
Should you restrict phosphorus if patient is not hyperphosphatemic?
yes. Compensatory mechanism. Negative indications for having high PTH, so though it is not problematic, likely will cause other issues over time.
When should we start restricting phosphorus?
Stage 2 (early) • Stage 1? (no clear evidence, still makes sense to avoid a higher phosphorus diet when possible…)
What is the goal with reducing phosphorus in stage 3/4 kidney disease? What should we decrease phosphorus to?
Phosphorus restriction
• More severe restriction to deal with hyperphosphatemia -> decreased below NRC RA
• Stage 2 (late)
• Stage 3/4
What are the diagnostic signs of protein losing nephropathy? How is it treated?
Diagnostic signs:
• Elevated UPC
• Rule out non renal causes
• May lead to hypoalbuminemia, loss of ATIII (prevents hypercoagulation, so these patients may be hypercoaguable)
• A negative prognostic indicator; regardless of azotemia
Treatment:
• Dietary protein restriction = decrease renal blood pressure, GFR
• Omega-3 supplementation
What is important about protein reduction in patients with CKD?
Reduce bioavailable phosphorus…
• Reduce azotemia/uremia
• BUN is only a marker (other uremic toxins too)
• Proteinuria
• Independent of CKD/IRIS stage
• Reduction based on
• UPC/diet history!
• Response…
• Must provide enough digestible protein
What is important about protein quality of patients with CKD?
Highly digestible
• Protein quality (AA profile)
• Less oxidation of AA -> less uremic toxins
• Less undigested protein reaching the lower GI tract
What are the concerns associated with protein reduction?
Concerns with palatability or decreased intake
• Decreased E intake -> loss of BCS
• Decreased protein intake below MR -> muscle loss, hypoalbuminemia
• Less aggressive if only reducing phosphorus…
• Generally more aggressive/restrictive with
• Stage 3/4 (azotemia/uremia)
- Proteinuria
What is important about potassium in dogs with renal disease?
Dogs with renal disease -> Can be
• Normokalemic, hypokalemic, hyperkalemic
• ACE-inhibitors may predispose to K+ retention…
• Canine renal diets
• Typically normal to decreased in K+ content
• Look at product guides for K+ concentration
• Important to choose best option for individual patient
• May need custom home-cooked formulation for severe hyperkalemia or refusal to eat appropriate diet
What is important about potassium in cats with renal disease?
Cats -> more prone to hypokalemia
- Signs: plantigrade ( neuro signs appear in cats)
• Whole body potassium depletion
• Feline renal diets typically supplemented with K+
• May also need to supplement even more
• Cats can develop hyperkalemia (rare)
• Home-cooked renal diet only good option
What is important about sodium in patients with CKD?
- Hypertension contributes to CKD progression
- Avoid high salt diets
- May want sodium reduction with hypertension
- May want lower end if active hypertension
- Over-reduction activates RAAS… not good either don’t go <0.3 g/1000 kcal…
How are B vitamins utilized / indicated in patients with kidney disease?
- Water-soluble
- Important in energy metabolism!
- Loss may be increased with polyuria
- Most don’t have large body stores -> depletion?
- Most renal diets empirically supplemented
- Safe!
- oral over-supplementation difficult
What acid base issue can occur with CKD? Why? What is the potential treatments for this condition?
Metabolic acidosis can result from CKD
• Increases muscle catabolism
• Disrupts intracellular metabolism
• Bone mineral dissolution?
Treatment :
• Provide alkalinizing agents in diet OR supplement
• Bicarbonate, carbonate, citrate
• Beware potassium…
How do antioxidants benefit CKD patients?
- Renal oxidative stress (ROS)
- Possible contributor to progression
- May trigger fibrosis or glomerulosclerosis
- Scarce data on antioxidant use in cats & dogs
- Vit E, carotenoids, lutein may slow GFR decline in dogs…
Is there a benefit to Omega -3 PUFAs in CKD? How can it help?
- Marine sourced (fish oil, krill, algae) bioavailability
- EPA (eicosapentaenoic acid)
- DHA (docosahexaenoic acid)
- Incorporated into cell membranes -> compete with Omega-6
- Produce less inflammatory eicosanoids
- May reduce renal interstitial fibrosis, slow GFR decline
- Improve survival
- Lower glomerular capillary pressure, decreased inflammation
What are diet options for patients with CKD? What resource should not be recommended?
Commercial
• Custom formulated home-cooked diet
• Consult veterinary nutritionist
• Do NOT used recipes on-line or in books…
What are the pro’s and cons of a kidney friendly commercial therapeutic diet?
• Many options
- Look at product guides
• Differences between diets may make some better fit than others
• Different stages, differences in electrolytes, fat content, etc.
• Multiple options for palatability/variety. Be aware that many are high(er) in fat
• May be contraindicated for pancreatitis, hyperlipidemia, etc
- Some multi-function diets now available
• Hydrolyzed/renal diet (adverse food reactions/renal
disease)
What do you do if patient refuses appropriate CKD diet?
- Address underlying issues
- Diet rotation may be appropriate
- Ensure all diets offered are ok for patient
- Olfactory changes may affect appetite day to day
- Assisted feeding (feeding tubes)
- provide appropriate diet, can still accept treats, etc
- provided additional water & medications! (improve QOL)
What are potential causes of Dysorexia Anorexia relating to CKD?
- Primary disease/ concurrent disease
- gastritis/ enteritis.
- Uremic toxins
- Hormonal changes
- Anemia
- Dehydration, electrolyte disorders, metabolic acidosis.
- Stomatitis/ oral ulcerations, altered smell
- Unpalatable diet, Food aversion, Medications, Hospitalization.
What are the potential causes of an AKI in a patient?
Acute kidney failure can be secondary to CKD but can also occur as a result of another primary cause:
- Toxicity
- Infectious disease
- Neoplasia
- Trauma
- Heat stroke/ dehydration etc.
What are important points to remember/ tips for nutritional management of an AKI?
- The optimal nutritional management of acute kidney injury patients that do not have an underlying CKD is not determined
- Emphasis should be given to them receiving adequate caloric intake, and if there are electrolyte shift, these should be corrected
- Long-term management may depend on regeneration of kidney function
- It may not always be needed or advised to start with a renal diet while hospitalized
- This may cause food aversion (stress, noise, nausea) for the food
What are causes of hypercalcemia, what is the prognosis? When are clinical signs typically seen?
Hypercalcemia can be the result of dietary, metabolic, neoplastic, renal, and idiopathic causes in dogs and cats
• In cats, idiopathic hypercalcemia is most common
• The degree of hypercalcemia and its chronicity impacts prognosis
• clinical signs of hypercalcemia are usually most severe when the increase in calcium is rapid
• Most often, clinical signs are noted when usually serum total calcium is higher than 14.0 mg/dL and ionized calcium is greater than 6.5 mg/dL (1.6 mmol/L)
• If serum total calcium increases to 16.0 mg/dL or if ionized calcium increases above 7.5 mg/dL (1.9 mmol/L) -> require hospitalization and immediate care
Can diet cause hypercalcemia?
- Some anecdotally recommend feeding a diet with moderately reduced calcium and vitamin D in addition to added insoluble fiber for all-cause hypercalcemia
- High dietary calcium on its own does not appear to be a cause of hypercalcemia
- Some cats with CKD may develop hypercalcemia due to excessive phosphorus restriction
