Short-term intra-individual variation of urinary biomarkers in dogs with stable chronic kidney disease

Background: Active-ongoing kidney damage is present in animals with stable chronic kidney disease (CKD), as reflected by biomarkers in urine. Interpretation of serial messurements of biomarkers requires knowledge of its intra-individual variation. Aims: To evaluate the short-term intra-individual variation of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 (uNGAL, uKIM-1, respectively) in dogs with stable CKD, and to determine whether normalization to urinary creatinine (uCr) decreases variation. Animals: Twenty-five dogs with naturally-occurring stable CKD. Methods: Prospective, observational study. Dogs were diagnosed with CKD based on the International Renal Interest Society guidelines. Dogs were included only if the variation in serum creatinine concentration was <25% on at least 2 measurements during the 3 months preceding inclusion, and only if serum creatinine variation was <20% during the 14-day study period. Urine samples were collected on days 0, 4, 10 and 14. uNGAL and uKIM-1 were measured using ELISA. Results: The median coefficients of variation (CV) of uNGAL and uNGAL/uCr were 42% (range, 7%-127%), and 44% (range, 8%-100%), respectively, and the CV 90th percentiles were 97% and 83%, respectively. The median CV of uKIM-1 and uKIM-1/uCr were 29% (range, 16%-91%), and 23% (range, 6%-76%), respectively, and the CV 90th percentiles were 56% and 52%, respectively. Conclusions and Clinical Importance: Changes of >100% and >60% for uNGAL and uKIM-1, respectively, in serial measurements are higher than the normal expected variation and therefore might indicate need for further investigation for underlying causes of kidney damage.