A New Marker for Chronic Kidney Disease in Dogs?

Chronic kidney disease (CKD) has an estimated prevalence of up to 25% in dogs presenting to referral hospitals. Several parameters have been evaluated for potential usefulness in assessing CKD severity. For example, plasma fibroblast growth factor-23 (FGF-23), which is involved in phosphorus and vitamin D metabolism, is a reliable predictor of mortality in cats and humans.

Researchers at the Ohio State University (OSU) College of Veterinary Medicine recently sought to determine whether several markers, including FGF-23, could predict survival in CKD-affected dogs.

Methods

The 19-month study assessed client-owned dogs that were diagnosed with CKD at OSU’s Veterinary Teaching Hospital. CKD diagnosis was indicated by 2 or more episodes of minimally concentrated urine with stable azotemia, the presence of renal proteinuria, and/or consistent ultrasonographic findings. Dogs were all at least 1 year old, free of concurrent diseases, and not receiving any medications known to affect parathyroid hormone (PTH) concentrations. Those with acute kidney injury or exacerbation of CKD were ineligible.

Based on serum creatinine levels, only those dogs with International Renal Interest Society (IRIS) stage 2, 3, or 4 CKD completed the study. Cases were further characterized by the presence of proteinuria, indicated by a urine protein:creatinine (UPC) ratio of higher than 0.5, and hypertension, indicated by a systolic blood pressure value over 150 mm Hg. Hyperphosphatemia was noted as values exceeding 4.5, 5.0, and 6.0 mg/dL for dogs with IRIS stage 2, 3, and 4 CKD, respectively.

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Investigators performed a physical examination, hematology, serum biochemistry, urinalysis, urine culture, and UPC ratio on all participating dogs. FGF-23, parathyroid hormone, and vitamin D metabolites were also measured. The investigators then analyzed which of these variables were significantly related to survival time after CKD diagnosis.

Results

The study included 13 spayed dogs, 13 neutered dogs, and 1 intact male dog. Several breeds were represented, and median age at the time of CKD diagnosis was 9.5 years. Median survival time after diagnosis, which varied significantly depending on IRIS stage, was 14.8, 11.1, and 2.0 months for dogs with IRIS stage 2, 3, and 4 CKD, respectively.

The authors determined that increased plasma FGF-23 was indeed significantly associated with reduced survival, suggesting that this parameter may be a useful marker of CKD severity in dogs, as it is in cats and humans. However, additional research is needed to validate this association, especially given the small sample size in this study.

The following variables were also significantly associated with reduced survival:

• Total hypocalcemia
• Hypoalbuminemia
• Hyperphosphatemia
• Increased calcium phosphorus product
• Proteinuria
• Low body and muscle condition scores

Increased serum creatinine levels also increased the risk of death. However, several parameters, including hematocrit, ionized calcium, vitamin D metabolites, and PTH, showed no correlation with survival time after diagnosis.

Conclusions

Although additional research is needed, this study’s findings suggest that FGF-23 may serve as a useful marker for assessing the severity of canine CKD and subsequent patient survival.

Dr. Stilwell received her DVM from Auburn University, followed by a MS in fisheries and aquatic sciences and a PhD in veterinary medical sciences from the University of Florida. She provides freelance medical writing and aquatic veterinary consulting services through her business, Seastar Communications and Consulting.