Urinary Biomarkers in Feline CKD: Interpreting Glomerular and Tubular Injury in Clinical Practice

Urinary biomarkers provide a unique diagnostic advantage in feline chronic kidney disease because they reflect structural and functional changes at the level of the nephron. Since tubulointerstitial nephritis is the most common histopathological finding in CKD cats¹, urinary biomarkers often offer earlier and more specific insights than serum-based markers. 

Proteinuria: A Classical but Non-Specific Indicator 

Proteinuria remains one of the most widely used renal biomarkers in clinical practice. Persistent protein loss in urine, measured using urinary protein to creatinine ratio (UPC), is associated with disease progression and survival outcomes in cats. However, interpretation is complex because UPC elevation is not exclusively renal in origin. Conditions such as hyperthyroidism, infections, and lower urinary tract disease can significantly alter UPC values^1,2. 

Thus, while UPC is valuable for prognosis, it lacks specificity for primary kidney disease. 

Albuminuria: Sensitive but Limited in Specificity 

Albuminuria reflects glomerular or tubular dysfunction depending on severity. In healthy cats, urinary albumin levels are typically very low. Microalbuminuria may indicate early renal or systemic disease but is not specific to CKD. Studies have shown that albuminuria can occur in a wide range of non-renal conditions, reducing its diagnostic precision^1,3. 

Although albuminuria correlates with survival and disease severity¹, it does not reliably distinguish CKD from systemic illness. 

Tubular Injury Biomarkers: A More Targeted Diagnostic Window 

Given that feline CKD is predominantly tubulointerstitial, tubular biomarkers provide more relevant diagnostic information. 

Neutrophil gelatinase-associated lipocalin (NGAL) is one such marker that increases in response to tubular injury. It is freely filtered and reabsorbed in healthy kidneys but accumulates in urine when tubular dysfunction occurs. In cats, NGAL is elevated in both AKI and CKD, but interpretation is complicated by confounding factors such as urinary tract infections and pyuria^1,4. 

Liver-type fatty acid-binding protein (L-FABP) has emerged as a particularly promising marker. It reflects oxidative stress and proximal tubular injury and is elevated in CKD and AKI conditions. Importantly, it may detect tubular stress before azotemia becomes evident^5,6,7. This makes it one of the most clinically relevant early injury biomarkers currently available. 

Kidney injury molecule-1 (KIM-1) is another tubular injury marker that is minimally expressed in healthy kidneys but increases significantly following injury. In cats, it is strongly associated with acute tubular injury but shows variable expression in CKD, particularly in advanced fibrosis where marker expression may decline¹. 

Clinical Interpretation Strategy 

For practical clinical use, urinary biomarkers should be interpreted as part of a layered diagnostic framework rather than in isolation: 

Albuminuria reflects general renal or systemic stress, NGAL reflects active tubular injury but is confounded by infection, L-FABP indicates oxidative tubular stress and early CKD changes, and KIM-1 is most useful for acute injury detection. 

This layered interpretation improves diagnostic accuracy and allows earlier identification of renal pathology.  

References 

1. Kongtasai T, Paepe D, Meyer E, Mortier F, Marynissen S, Stammeleer L, Defauw P, Daminet S. Renal biomarkers in cats: A review of the current status in chronic kidney disease. Journal of veterinary internal medicine. 2022 Mar;36(2):379-96. https://academic.oup.com/jvim/article-pdf/36/2/379/66666729/jvim16377.pdf 

2. Ghys LF, Paepe D, Taffin ER, Vandermeulen E, Duchateau L, Smets PM, Delanghe J, Daminet S. Serum and urinary cystatin C in cats with feline immunodeficiency virus infection and cats with hyperthyroidism. Journal of feline medicine and surgery. 2016 Aug;18(8):658-65. https://journals.sagepub.com/doi/pdf/10.1177/1098612X15592343 

3. Ferlizza E, Dondi F, Andreani G, Bucci D, Archer J, Isani G. Validation of an electrophoretic method to detect albuminuria in cats. Journal of feline medicine and surgery. 2017 Aug;19(8):860-8. https://journals.sagepub.com/doi/pdf/10.1177/1098612X16664112 

4. Wu PH, Hsu WL, Tsai PS, Wu VC, Tsai HJ, Lee YJ. Identification of urine neutrophil gelatinase-associated lipocalin molecular forms and their association with different urinary diseases in cats. BMC veterinary research. 2019 Aug 27;15(1):306.  https://link.springer.com/content/pdf/10.1186/s12917-019-2048-9.pdf 

5. Kongtasai T, Meyer E, Paepe D, Marynissen S, Smets P, Mortier F, Demeyere K, Vandermeulen E, Stock E, Buresova E, Defauw P. Liver-type fatty acid-binding protein and neutrophil gelatinase-associated lipocalin in cats with chronic kidney disease and hyperthyroidism. Journal of veterinary internal medicine. 2021 May;35(3):1376-88. https://academic.oup.com/jvim/article-pdf/35/3/1376/66652588/jvim16074.pdf 

6. Katayama M, Miyazaki T, Ohata K, Oikawa T, Kamiie J, Sugaya T, Miyazaki M. Temporal changes in urinary excretion of liver-type fatty acid binding protein (L-FABP) in acute kidney injury model of domestic cats: a preliminary study. Journal of Veterinary Medical Science. 2019;81(12):1868-72. https://www.jstage.jst.go.jp/article/jvms/81/12/81_19-0325/_pdf 
7. Katayama M, Ohata K, Miyazaki T, Katayama R, Wakamatsu N, Ohno M, Yamashita T, Oikawa T, Sugaya T, Miyazaki M. Renal expression and urinary excretion of liver-type fatty acid-binding protein in cats with renal disease. Journal of veterinary internal medicine. 2020 Mar;34(2):761-9. https://academic.oup.com/jvim/article-pdf/34/2/761/66660176/jvim15721.pdf