HYPERPHOPSPHATEMIA: DIET AND PHOSPHATE BINDERS

pharmacrSerum and plasma phosphorus levels in blood mainly depends on intestinal uptake and urine excretion.

Kidneys have a key role in maintaining serum phosphorus levels, as they can either increase or reduce the quantity excreted with urines. In case of a dog or a cat fed with a high-phosphorus diet, kidneys promote its excretion and the opposite happens with a low-phosphate diet.

In cats and dogs affected by chronic kidney disease, also in the early stages, it’s difficult for the kidney to maintain the phosphate balance because as the kidney function declines, patients tend to phosphorus accumulation: this is called hyperphosphatemia.

In both dogs and cats with renal disease, hyperphosphatemia is mainly caused from a diminished phosphorus excretion (phosphates) and, to a lesser extent, it is consequence of a high acidity of blood (metabolic acidosis).

Hyperphosphatemia is often accompanied to hypocalcemia (low calcium levels in the blood serum), which leads to the increase of parathyroid hormon (PTH) as an attempt to correct calcium concentration in serum.

If hyperphosphatemia is not treated, PTH can be excessively secreted leading to renal secondary hyperparathyroidism, responsible for bone demineralization, renal interstitial and soft tissue mineralization.

Studies in dogs affected by chronic kidney disease have shown the efficacy of a low-phosphate diet (0.4% phosphorus on dry matter) in slowing the progression of renal damage and reducing calcium deposition in the kidney.

Patients in IRIS stage 2, 3 e 4 can show hyperphosphatemia that can be diagnosed testing phosphorus levels in blood and correlating results to the patient’s IRIS stage. In stage 2, dogs and cats are hyperphosphatemic with serum phosphorus above 4.6 mg/dL, in stage 3 with a phosporus level above 5 mg/dL and, finally, patients in stage 4 in case of phosphorus above 6,0 mg/dL.

First therapeutic approach in case of hyperphosphatemia of renal origin is administering a renal diet, with a low-phosphate level. It is recommended to check serum phosphorus after 2-4 weeks: diet is efficacious if serum phosphorus is below 4.6 mg/dL in IRIS stage 2, 5.0 mg/dL in stage 3 and below 6.0 mg/dL in stage 4. In case the diet alone is not working, it will be necessary to introduce phosphate binders.

IRIS stage Phosphorus(mg/dL) Therapy
1   No
  >4.6 Diet ± Binders
3 >5.0 Diet ± Binders
4 >6.0 Diet ± Binders

 

 

Phosphorus-binding agents should be given together with meals or within 2 hours of feeding to maximize their binding of dietary phosphorus. Commonly employed oral phosphorus binders include aluminum hydroxide, calcium carbonate, and calcium acetate. The starting dosage of these phosphorus binders is approximately 60-90 mg/kg/day, usually divided twice, and the dosage should be adjusted by periodic evaluation of the serum phosphorus concentration. Calcium salts may be superior to other intestinal phosphate binders if ionized calcium is moderately to severely decreased, which is common in the later stages of the chronic kidney disease. Animals should be monitored for development of hypercalcemia whenever phosphorus binders containing calcium are used, especially if calcitriol is being administered concurrently.

Pharmacross NormaPhos® PLUS contains calcium carbonate and chitosamine, with Vit.C and folic acid. As a phosphate binding agent, calcium carbonate is considered safe for long term use while chitosamine is a naturally occurring substance that enhances phosphate binding of calcium carbonate and binds uremic toxins, reducing their absorption in the bloodstream. Finally, Vit.C shows antioxidant properties and the adequate content of folic acid supports the red blood cell function.

 

Dietetic approach to Chronic Kidney Disease

kcmega3A correct dietetic approach is the key of the therapeutic management of either dogs and cats affected by CKD.

Renal diets have some characteristics:

  • controlled protein level, with proteins of high quality
  • low phosphorus & sodium
  • alkalizing agents to control metabolic acidosis often associated to CKD
  • high content of Vit.B complex
  • high content in fibers
  • polyunsatured Omega-3 fatty acids (PUFA) and antioxidants

It is wrong to consider a renal diet a “low protein diet” as there are still many diets with a lower content in proteins, addressed to other diseases, that are not good to be administered to patients affected by CKD.

Some renal diets underwent clinical trials in order to establish their efficacy in slowing the progression of renal damage or reducing the risk of mortality because of uremic crisis in patients affected from renal failure.

Protein content

There is no consensus about the ideal protein content of renal diets for dogs and cats, although it is accepted clinical signs of uremia improve after a renal diet is administered to patients in IRIS stage 3 & 4. For IRIS stage 1 patients there is no consensus about the utility of a renal diet, but it can be introduced to treat other conditions such as proteinuria. The theoretical utility of a low protein diet in slowing the progression of renal damage in IRIS 2 dogs has not been demonstrated yet and is, therefore, anecdotally applied based on studies carried out in other species.

Clinical trials of efficacy

The efficacy of a renal diet in reducing both uremic crisis and mortality of dogs in IRIS stage 3 has been demonstrated in a randomized controlled clinical trial (RCCT). Dogs feeding a renal diet reduced their risk to develop uremic crisis of 75% as well as of 66% for the risk of renal related mortality, compared to dogs fed with a maintenance diet. In the same study, dogs feeding a renal diet showed better quality of life too.

In another trial, cats with serum creatinine between  2.0 and 4.5 mg/dL were randomized into two groups, one feeding a renal diet and the other feeding a maintenance one; the renal diet reduced the risk of developing uremic crisis and death for renal causes.

Furthermore, a clinical trial studied the difference in survival times of cats feeding a renal diet compared to ones eating a maintenance one. Also in this case, there was a significant difference in survival time between the groups: a median of 633 days for cats fed with a renal diet and 264 for those eating a maintenance one.

Diet change

It takes its time to make a patient accept a new diet. Passing to a new diet too fast as well as a force-feeding are all reasons potentially leading a patient to food aversion. Changing a diet too fast can also cause diarrhea, subsequent dehydration and worsening of renal function. The new diet has to be introduced in growing percentage compared to the old one, subdividing the period in 4 phases. Cats, and dogs with selective appetite, will be changing their diet in 4 weeks, while easier patients will be doing it in 2 weeks.

1st period 25% renal diet + 75% current diet
2nd period 50% renal diet + 50% current diet
3rd period 75% renal diet + 25% current diet
4th period 100% renal diet

 

Therapeutic suggestions and evidence based medicine

Clinical trials demonstrated the efficacy of renal diet in both improving quality of life and survival time, other than reducing the risk of uremic crisis in dogs in IRIS stages 3&4 and cats in stages 2, 3&4. The real utility of a renal diet for dogs in IRIS stage 2 has not been demonstrated yet, although hyperphosphatemic patients may take advantage of a low phosphorus diet. Regardless the IRIS stage, the renal diet should be used in both proteinuric dogs and cats; its efficacy in reducing serum creatinine and urea is evaluated in 4 weeks.

Omega 3 fatty acids are widely used in both dogs and cats affected from chronic kidney disease (CKD). In dogs with proteinuric renal disease, clinical trials demonstrated the efficacy of Omega3 in reducing the protein loss and slowing the progression of renal disease and glomerular damage particularly if administered in association with antioxidants. In cats, no clinical trials evaluating the efficacy of Omega3 in slowing the progression of renal disease is available, although a retrospective study evaluating survival times of cats feeding different diets have showed a longer life-span in those cats eating the greater content of Omega3 fatty acids.

No data is available about the efficacy of Omega3 administered not in association to a renal diet. Both EPA and DHA are useful in course of CKD, even though diet should be supplemented with fish oils mainly represented from EPA and a fewer amount of DHA, at high concentration in EPA and low DHA.

On a side note, it has to be stressed Omega3 deriving from vegetal oils contain ALA, and are converted to a minimal part in EPA and DHA in canines, while cats are not able to convert ALA at all thus resulting in a lack of efficacy in case of CKD.

Content of EPA to be administered to renal patients is 80 mg/kg daily if associated to a renal diet. Pharmacross kcMEGA3, due to its high content of omega 3 fatty acids and the optimal EPA:DHA ratio meets the EPA content requirements for the health of the kidneys.

 

 

General remarks on Chronic Kidney Disease (CKD)

ph cross 1                  Treatment of CKD aims at:

  • Improving both clinical condition and quality of life
  • Prolonging survival time
  • Slowing the progression of renal disease

Once chronic kidney disease has been diagnosed, it is recommended:

  1. Stop any drugs with certain or potential nephrotoxicity;
  2. Identify and treat any concurrent disease influencing renal function and determining renal damage. In some patients, other pathologic conditions (such as endocrinopathies) can make difficult either staging renal disease and setting an adequate therapy;
  3. Investigate all causes leading to renal damage and, if possible, treat it. Sometimes, a renal biopsy can be useful to evaluate histologic lesions; in case of proteinuria, results of renal biopsy can provide a specific diagnosis and therapy;
  4. To apply a conservative approach of clinical conditions associated to kidney failure such as metabolic, acid-base and electrolytic imbalances. Therapy is addressed to correct hydration and mineral disorders, acid-base alterations and nutritional impairments. Patients benefit from symptomatic treatment improving their quality of life although azotemia is not significantly modified as this is undoubtedly just one of the factors contributing to the clinical picture of renal patients.

As general recommendations, clinically stable dogs and cats affected from CKD should undergo a clinical examination and laboratory evaluations based on their IRIS stage (www.iris-kidney.com)

  • every 12 months in IRIS stage 1
  • every 6 months in IRIS stage 2
  • every 4 months in IRIS stage 3
  • every 6-8 weeks in IRIS stage 4

Clinical Evaluation– Other than general and particular clinical examination, a special attention goes to the nutritional condition of the patient, determined by body weight, Body Condition and Muscle Condition Score (available both for dogs and cats at WSAVA). Nutritional status of patients affected by CKD is related to risk of developing uremic crisis and mortality: bad nutritional condition is associated to higher risk of uremic crisis and mortality for renal related causes. Blood pressure is determined too and hypertensive patients are put under treatment.

Laboratory exams– Once CKD has been diagnosed, Veterinarian proceeds to request the laboratory exams useful to identify concurrent pathologies known to determine renal damage or the progression of kidney disease. After the initial evaluation of a complete blood count, biochemistry and urinalysis (included UPC) the Veterinarian will be requesting further exams based on patient’s laboratory results and clinical history such as exams for infectious disease, endocrinopathies, ect.

Below are IRIS stages and most common disorders by stage (modified from Polzin, 2006 and 2019)

 

Clinical signs IRIS stage
Polyuria/Polydipsia 1-4
Proteinuria 1-4
Hypertension 1-4*
Urinary infection 1-4
Hyperphosphatemia 2-4
Hypopotassemia 3-4
Anemia 3-4
Metabolic Acidosis 3-4
Anorexia and weight loss 3-4
Vomit 3-4
Dehydration 3-4

*although it is possible to identify hypertensive patients in any stage of the disease, the prevalence of hypertension increases with increasing of IRIS staging