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Glomerulus
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What do we know about phosphorus and its role in Chronic Renal Disease?
Phosphate in the diet is absorbed from the small intestine and the kidneys are the major organ responsible for regulating serum phosphate levels. Phosphorus is freely filtered through the glomerulus and normally 80-90% of the filtered phosphorus load is reabsorbed by the proximal tubules. Chronic renal disease leads to a progressive decline in glomerular filtration rate (GFR) due to loss of functional nephrons. As the GFR decreases in renal insufficiency, phosphorus is retained in the blood. Initially, remaining nephrons compensate by increasing excretion levels, mediated by parathyroid hormone (PTH). In response to increasing phosphorus levels, and decreased ionized calcium, the parathyroid gland is stimulated to synthesize and release PTH.
Initially this adaptive response is beneficial, reducing the reabsorption of phosphorus from the renal tubules, thereby increasing excretion. However, as chronic renal insufficiency progresses over time and glomerular filtration rate (GFR) decreases to less than 20% of normal, this compensatory mechanism fails and the continued elevation of PTH leads to the mobilisation of calcium and phosphorus from bones. Eventually this leads to the deposition of calcium and phosphorus in soft tissues, including mineralisation of renal tissue, which further compounds the renal injury and fibrosis already present. Additionally, it has been suggested that phosphorus itself, and perhaps parathyroid hormone, may have direct negative effects on the kidneys.
Retention of phosphorus occurs when dietary intake exceeds the excretory capacity of remaining nephrons and is associated with renal secondary hyperparathryroidism and further progressive decline in kidney dysfunction. On average, cats consume 6 times as much phosphorus in their diets as humans when eating typical commercial maintenance foods.
Phosphorus restriction has been shown to be renoprotective in both experimental models of renal failure and clinical patients, protecting surviving nephrons from progressive tissue damage associated with mineralisation and fibrosis, and prolonging survival. Phosphorus restriction early in the disease process may be desirable as elevations in PTH and secondary hyperparathyroidism are occurring before there is evidence of overt hyperphosphataemia. In fact, when there is a decrease in kidney function, one can assume that there is phosphorus retention, however serum phosphate levels may not increase out of the normal range until relatively late in the disease.
Extended survival of cats with phosphorus restriction
Cats fed a diet restricted in phosphate were shown to survive ~2.4 times longer than cats fed a diet without phosphate restriction.
Restriction of phosphate plays an essential role in curbing renal secondary hyperparathyroidism, soft tissue calcification and progression of renal failure1, 2.
When to restrit dietary phosphate?
Phosphate restriction early in the disease process may be desirable as elevations in PTH and secondary hyperparathyroidism are occurring before there is evidence of overt hyperphosphataemia.
In fact, when there is a decrease in kidney function, one can assume that there is phosphorus retention, however serum phosphate levels may not increase out of the normal range until relatively late in the disease when excretory failure is advanced.
- Phosphate levels in the normal range could still be abnormal in early renal disease
What is the target plasma phosphate concentration?
- The International Renal Interest Society (IRIS) has suggested targets for each IRIS stage (two months post-commencement of intervention):
- Targeting plasma phosphate concentration in the mid-lower end of the normal reference range may be desireable
Dietary intervention with renal diets may sometimes encounter problems with acceptance due to decreased palatability – phosphate binding agents provide another option to help address this issue.
Especially in later stages, a low phosphate diet alone may not be sufficient to control phosphate levels effectively. If renal diets are used and the plasma phosphate still falls above the IRIS target ranges above, an intestinal phosphate binding agent should be introduced in combination with the diet.
1. Rubin SI. Chronic renal failure and is management and nephrolithiais. Vet Clin Small Anim 1997, 27(6): 1331-1354.
2. Barber PJ. et al, Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat. J Small Anim Prac 1999, 40: 62-70
This is where Renalzin steps in...
Click on the picture below to view chapters 4-6 which shows the effect of 'elevated phosphorus'.
To view chapter 7 in the video series showing Renalzin Action and Phosphate Binding, click here.
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