Albuminuria or Transferrinuria? Reading the Glomerular Signal in Feline CKD

A cat can have chronic kidney disease (CKD) with only mild proteinuria. So, when urinary protein is increased, the next clinical question is not simply “How much protein is present?” but also “What type of protein is being lost?” 

Urinary albumin and transferrin can provide information about changes in the glomerular barrier. However, their interpretation in cats requires care because increased urinary protein is not necessarily specific to renal disease. 

Albumin: A Marker of Glomerular Barrier Leakage 

Albumin is a 65-kDa protein produced by hepatocytes. Under normal conditions, the intact glomerular barrier restricts its passage into tubular fluid. Small quantities that do cross the glomerulus are normally reabsorbed by proximal tubular cells. Consequently, healthy cats have less than 1 mg/dL of urinary albumin (uALB)^[1]. 

When glomerular permeability increases, urinary albumin can rise. 

Albuminuria may also occur with tubular dysfunction, however, so increased uALB should not automatically be interpreted as evidence of primary glomerular disease. This distinction is particularly relevant in feline CKD, where tubulointerstitial inflammation is the most common histopathological finding^[2]. 

Microalbuminuria is defined as a urinary albumin concentration of 1–30 mg/dL, whereas overt albuminuria is >30 mg/dL^[1]. 

How Useful is the Urinary Albumin-to-Creatinine Ratio? 

The urinary albumin-to-creatinine ratio (uALB/Cr) has shown associations with CKD and survival. 

Cats with CKD and higher uALB/Cr ratios had shorter survival times than cats with lower ratios. Urinary ALB/Cr was also approximately twofold higher in cats with stage 1 CKD than in healthy cats in one investigation^[3]. 

But there is an important limitation. 

Albuminuria can occur with several non-renal diseases in cats. Microalbuminuria has been detected in a variety of non-renal conditions, meaning that increased uALB/Cr does not reliably distinguish CKD from other diseases^[1]. 

This limits its specificity in everyday practice. 

Transferrin Adds a Different Glomerular Perspective 

Transferrin is another protein whose molecular weight is similar to albumin—approximately 77 kDa. Because of its size, transferrinuria is expected when glomerular damage increases permeability. 

Evidence in cats is more limited than for albumin. In cats with IRIS stage 1 CKD, urinary transferrin concentrations were higher than in healthy cats. Using a cutoff of 0.93 mg/dL, urinary transferrin concentration showed greater sensitivity and specificity for detecting early-stage CKD than plasma creatinine concentration^[3]. 

This finding suggests that transferrinuria may help identify early renal changes when conventional functional markers are less informative. 

However, the precise source of the increased transferrin remains uncertain. Because tubulointerstitial nephritis is the predominant lesion in feline CKD, it cannot yet be assumed that increased urinary transferrin specifically represents primary glomerular disease. 

Albuminuria Does Not Replace UPC^[1],[5] 

Urinary protein-to-creatinine ratio (UPC) remains a routine renal biomarker and traditional indicator of proteinuria. Proteinuria can reflect glomerular disease but may also increase with tubular dysfunction in cats. 

Importantly, uALB/Cr has not demonstrated a clear clinical advantage over UPC. The available evidence suggests that the clinical importance of uALB/Cr has not surpassed that of the routinely available UPC. 

This makes the role of albuminuria more complementary than substitutive. 

What Should the Clinician Take from an Increased Result?^[1] 

An increased urinary albumin or transferrin concentration can provide useful information about renal barrier abnormalities, but neither should be interpreted in isolation. 

Consider the broader context: 

• Albuminuria: Potentially associated with CKD and prognosis, but not specific to renal disease. 
• Transferrinuria: Potentially useful for early CKD detection, but evidence remains limited. 
• UPC: Remains an established and routinely available measure of proteinuria. 
• Non-Renal Disease: Can substantially influence urinary protein findings. 

Clinical Bottom Line 

Urinary albumin and transferrin can offer additional insight into protein loss in cats with suspected or established CKD. However, increased urinary protein does not automatically identify primary glomerular disease. The most useful interpretation comes from combining urinary biomarkers with the cat's overall renal assessment rather than treating albuminuria or transferrinuria as standalone diagnostic answers.

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. Chakrabarti S, Syme HM, Brown CA, Elliott J. Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction. Veterinary pathology. 2013 Jan;50(1):147-55. https://journals.sagepub.com/doi/pdf/10.1177/0300985812453176
3. Maeda H, Sogawa K, Sakaguchi K, Abe S, Sagizaka W, Mochizuki S, Horie W, Watanabe T, Shibata Y, Satoh M, Sanda A. Urinary albumin and transferrin as early diagnostic markers of chronic kidney disease. Journal of Veterinary Medical Science. 2015;77(8):937-43. https://www.jstage.jst.go.jp/article/jvms/77/8/77_14-0427/_pdf
4. Chakrabarti S, Syme HM, Brown CA, Elliott J. Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction. Veterinary pathology. 2013 Jan;50(1):147-55. https://journals.sagepub.com/doi/pdf/10.1177/0300985812453176
5. Grauer DG. Proteinuria: measurement and interpretation. Topics in companion animal medicine. 2011 Aug 1;26(3):121-7. https://elearning.up.pt/ppayo/MEDICINA%20INTERNA%2019-20/PROGRAMA/PROTEINURIA/Proteinuria%202011.pdf