FGF-23: Another Tool for Managing Chronic Kidney Disease in Cats
An important function of the kidneys is phosphate homeostasis. When a cat has CKD, their glomerular filtration rate (GFR) declines, causing phosphorus concentrations to increase and leading to a phosphate-calcium homeostasis imbalance.5 This syndrome is classified as chronic kidney disease-metabolic bone disease (CKD-MBD) and involves fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), 1,25 dihydroxy D3 (1,25 vitamin D3 calcitriol), calcium, and phosphorus.6 CKD-MBD typically leads to chronically elevated FGF-23 levels.
Clinical evidence in studies on FGF-23 in humans and FGF-23 in cats demonstrates that this hormone often identifies mineral disruption and phosphorus overload in CKD-MBD earlier than measuring total serum phosphorus, making it a valuable tool to help manage cats' CKD.7-10
What Is FGF-23?
Osteocytes and osteoblasts primarily produce FGF-23, which is likely the most important element controlling phosphate metabolism. Directed by the kidneys' alpha-klotho expression, this element progressively rises as GFR declines before changes in serum or plasma phosphorus levels occur.23 When phosphorus levels rise in response to decreased GFR, FGF-23 increases and works with its coreceptor alpha-klotho to maintain the phosphorus balance by:
Down-regulating sodium-phosphorus cotransporters.
Inhibiting renal 1 alpha-hydroxylase activity.
Increasing 24-hydroxylase activity.24-26
In humans, FGF-23 promotes a PTH reduction in early stage CKD, but as the disease advances, the biomarker appears to contribute to renal secondary hyperparathyroidism, increasing PTH.27,28 Studies of the hormone in cats with CKD demonstrate this same pattern.7,9 CKD-MBD is likely related to factors such as CKD etiology, comorbidities, and current therapies.
Why Is FGF-23 Testing Helpful?
As CKD worsens, FGF-23 increases.9-11 FGF-23 is a valuable tool for guiding decisions about therapeutic intervention and may help determine a cat's prognosis.10,12,13 Research suggests that a higher initial FGF-23 level may be a negative prognostic indicator for cats who have CKD.8,16
Phosphate metabolism in cats is important regardless of CKD stage. An increase in FGF-23 supports phosphate reduction therapy such as dietary phosphate restriction.8,16 The International Renal Interest Society (IRIS) recently updated the Treatment Recommendations for cats with CKD to include FGF-23 as a means to help identify cats that would benefit from dietary phosphate restriction. FGF-23 provides some clarity by identifying CKD-MBD and potential phosphate overload in early CKD. This helps guide appropriate use of a veterinarian-prescribed renal diet suited to a cat's CKD stage, and can improve longevity as well as quality of life.3,4,14
How Is FGF-23 Different From SDMA?
SDMA is a sensitive tool that can allow for earlier CKD diagnosis when tested along with traditional kidney biomarkers. SDMA values are included in the International Renal Interest Society (IRIS) staging guidelines. When a cat's SDMA values and other diagnostics, such as creatine and urine specific gravity, indicate they're in IRIS CKD stage 1 or 2, an increased FGF-23 concentration suggests the cat may have CKD-MBD.22
Having this information is valuable to guide and validate evidence-based decisions for feline patients. Knowing a cat's FGF-23 level provides tangible evidence to the client to support instituting and maintaining a therapeutic renal diet. This test is the only globally available renal management marker that can identify phosphate overload and CKD-MBD earlier than total serum phosphorus in cats who have early stage CKD.
When Should FGF-23 Testing Occur?
FGF-23 testing is recommended for cats that have been diagnosed with early CKD (IRIS stage 1 or 2).20 In fact, monitoring FGF-23 now included in the IRIS guidelines to stage and treat CKD. The test is most helpful to identify which IRIS CKD stage 1 and 2 cats will potentially benefit from phosphate-reduction therapy.15 In later stage CKD (IRIS stage 3 or 4) FGF-23 concentration is likely to exceed 400 pg/mL as many of these cats may already have elevated phosphate concentrations. As a result, FGF-23 testing is more useful in cats diagnosed with IRIS stage 1 or 2 CKD.9
In addition, research suggests that some comorbidities may impact FGF-23 levels, including uncontrolled hyperthyroidism, cardiac disease, moderate to severe systemic inflammation, neoplasia, lytic bone lesions, and profound anemia.3,30-32 Testing these cats isn not recommended, and testing is redundant in cats who have a total serum phosphorus higher than 4.6 mg/dl.
How Are FGF-23 Results Interpreted?
FGF-23 is likely the most important element controlling phosphate metabolism. As CKD worsens, the biomarker increases, and it's important to know how to interpret the findings accurately.
< 299 pg/ml. Normal. No evidence of CKD-MBD. This result does not indicate that CKD isn't present but rather that there is no current indication of phosphorus overload or CKD-MBD. Therapy to address phosphorus levels is likely unnecessary at this time. If other indications, such as increased biomarkers, proteinuria, or acid-base disturbances are present, intervention support should still be initiated.
300 to 399 pg/ml. Borderline. Levels are higher than expected but not high enough to indicate a clear need for phosphate-reduction therapy. In these cases, rechecking renal values including SDMA, FGF-23 and a complete urinalysis are recommended every three to six months to monitor for CKD-MBD development and understand when phosphate overload has reached clinical significance.
> 400 pg/ml. Increased. Targeted therapy to reduce phosphorus overload, such as dietary restriction, is warranted in conjunction with other recommended CKD therapies.
In addition to SDMA and other traditional diagnostics, FGF-23 is a valuable tool to help guide treatment plans for cats with CKD. If the results are abnormal, they can help us understand the patient's prognosis as well as how to manage treatment going forward.