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Canine Kidney Disease Emerging Themes

In addition to the Education Topics articles, the IRIS Board has opted to commission periodic articles and issue statements on topics currently under discussion in veterinary medicine, whose future significance is still being explored. The most recent statement addresses active kidney injury biomarkers and their application in the diagnosis and monitoring of kidney disease.

NEW: Active Kidney Injury Biomarkers in the Diagnosis of Kidney Diseases

Early detection of kidney diseases is crucial for timely intervention. However, it is challenging due to the limited sensitivity of traditional markers of kidney function. Commonly used markers such as serum creatinine, urea nitrogen, SDMA concentrations, and urine specific gravity indicate changes in kidney function but cannot detect active or ongoing subclinical injury or disease without concurrent changes in kidney function, regardless of severity. Functional filtration markers are also poor predictors of early decline in kidney function due to their nonlinear relationship with the glomerular filtration rate. Consequently, both acute kidney injury (AKI) and stable or progressive chronic kidney disease (CKD) diagnoses may be delayed. The diagnostic potential of novel active kidney injury biomarkers is increasingly recognized due to the limitations of functional markers. These biomarkers could identify active and persistent renal parenchymal damage, inflammation, oxidative stress, or fibrosis, facilitating early diagnosis and characterization of kidney diseases.

Recent research has focused on active injury biomarkers, which are released from stressed, damaged, or ruptured kidney cells and can predict acute or sustained renal tubular cell injury when present in urine. Epithelial damage has been observed in animals with AKI before any increase in functional markers, as well as in animals with apparently stable CKD based on functional markers. The degree of epithelial damage is also linked to disease progression and survival. However, rigorous evaluation of these markers in longitudinal studies of clinical patients is needed to determine their true predictive potential. IRIS encourages further research to be initiated and published in peer-reviewed journals to establish the evidence for their clinical use.

IRIS anticipates that real-time biomarkers with the potential to identify active or ongoing kidney injury in animals with kidney disease will revolutionize how practitioners diagnose, monitor, and treat these conditions. These novel biomarkers are not meant to replace traditional markers but to complement them diagnostically, revealing occult or subclinical kidney disease that is otherwise undetectable. Nephrologists are eager for this new era of early disease detection and management.

The IRIS Board, June 2023

FGF-23: a new player in the regulation of phosphate

FGF-23 is a 30 kD protein secreted by osteocytes and osteoblasts. It was discovered in 2000
as a circulating factor found in excess in hypophosphataemic patients with tumour-induced
osteomalacia.

FGF-23

Symmetric dimethylarginine (SDMA): a new biomarker of renal function in cats and dogs

Filtration, particularly the glomerular filtration rate (GFR), is the primary indicator of renal function adequacy. The severity of most renal diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), is assessed based on their impact on GFR. Although direct GFR measurement is widely regarded as the gold standard for renal function assessment, clinicians often rely on surrogate markers like blood urea nitrogen concentration or blood (plasma or serum) creatinine to estimate GFR. However, these common diagnostic tests struggle to detect mild to moderate decreases in GFR effectively. While repeated blood creatinine concentration assessments in the same animal can improve test sensitivity, the lack of baseline measurements is a common limitation. Please see IRIS PDF for more in-depth information.

SDMA

Renal Fibrosis in Cats

Chronic kidney disease (CKD) is prevalent among cats. Most affected cats show renal lesions primarily localized to the tubulointerstitial compartment. While primary glomerular diseases have been reported in cats, in the majority of cases, glomerular involvement is mild and likely secondary. Renal lesions associated with feline CKD are typically characterized by interstitial fibrosis, interstitial inflammation, and tubular degeneration. See IRIS PDF For more information

Renal Fibrosis In Cats

Stem Cell Therapy for CKD: What do we know? (2018)

Regenerative medicine represents a pioneering field of study with promising clinical implications for various diseases in veterinary medicine. Stem cells possess regenerative abilities and seem capable of modifying the environment in damaged and diseased tissues. While this therapy shows potential for chronic kidney disease (CKD), research into its application in this area is still in its early phases, highlighting the need for further investigation. See IRIS PDF For in-depth information.

Stem Cell Therapy For CKD