Neutrophil gelatinase-associated lipocalin and symmetric dimethylarginine concentrations in dogs with carcinoma and sarcoma

Abstract

Although neutrophil gelatinase-associated lipocalin (NGAL) and symmetric dimethylarginine (SDMA) are considered sensitive biomarkers of kidney injury and function, respectively, their specificity is affected by extra-renal factors. The extra-renal effect of tumours on biomarker concentrations is yet to be fully elucidated despite their association with tumourigenesis. Due to the lack of renal histopathology in previous studies, it remains unclear if tumours or concomitant kidney disease is responsible for the appreciable increases in serum and urinary NGAL and SDMA concentrations reported in various cancers in both humans and dogs. This study aimed to determine the extra-renal effect of tumours on serum and urine NGAL and SDMA concentrations in dogs with carcinoma or sarcoma without significant kidney disease. Additionally, this study aimed to evaluate the association between biomarker concentrations and tumour type, as well as metastasis. If biomarker concentrations were found to be increased in tumour-bearing dogs, the potential contribution of tumour-associated systemic inflammation on NGAL concentrations would also be investigated. Concentrations of serum NGAL (sNGAL), SDMA, urinary NGAL (uNGAL) and uNGAL-to-creatinine ratio (uNGAL/Cr) were measured on stored samples from a previous prospective study. Patient clinicopathological and histopathology records were reviewed and those with renal azotaemia or moderate-severe histopathological renal changes were classified as having significant kidney disease. Biomarker concentrations were compared between tumour-bearing dogs without significant kidney disease and healthy age-controlled dogs. Additionally, comparisons between dogs with carcinoma and sarcoma; and dogs with and without metastasis; as well as correlations between urinary and serum NGAL and acute phase protein (APP) concentrations were analyzed. Twenty-one dogs with carcinoma, 18 dogs with sarcoma and 20 healthy age-controlled dogs were included. Tumour-bearing dogs without significant kidney disease had significantly increased uNGAL/Cr (P < .001), but not sNGAL, compared to healthy controls. Although median SDMA concentrations did not significantly differ between groups, increased concentrations were found in 32% and 20% of dogs with carcinoma and sarcoma, respectively. Additionally, no differences between dogs with carcinoma or sarcoma or those with and without metastasis were found. Urinary NGAL concentrations were moderately correlated with sNGAL concentrations, with moderate to no correlations shown with APPs, respectively. In conclusion, this study found that tumour presence, but not metastasis, effects uNGAL/Cr and SDMA concentrations in dogs with carcinoma and sarcoma. uNGAL should therefore not be used, and SDMA used with caution, as renal biomarkers in dogs with carcinoma and sarcoma. Additionally, the disproportionate increase in urinary, as compared to serum, NGAL concentrations in this cohort of dogs with carcinoma and sarcoma is suggestive of a potential glomerulopathy and increased glomerular permselectivity secondary to tumour presence.