Background: There are limited options to diagnose acute kidney injury (AKI) in horses. Symmetric dimethylarginine (SDMA) is routinely used in human and small animal medicine. The aim of this study was to assess serum SDMA concentrations in healthy horses and horses with AKI. The objective of this study was to evaluate the association of: 1) age, 2) sex, 3) body weight and 4) serum creatinine and urea levels on serum SDMA concentrations. Fifty-three healthy horses, including 17 foals (2–6 months of age) and 36 adult horses (3–29 years of age), and 23 horses with AKI were included in the study based on history, physical examination, blood analysis, urinalysis and an ultrasonographic examination of the urinary tract. Serum SDMA concentrations were measured using a non-species specific commercial ELISA test. Results: In healthy adult horses, the value of SDMA was 0.53 ± 0.14 μmol/L. The value was higher in foals (1.5 ± 0.4 μmol/L, P < 0.001). Horses with AKI had significantly higher concentrations of SDMA compared to healthy horses (1.76 ± 1.05 μmol/L, P < 0.001). In the healthy adult horses, there was no association of sex, age or body weight on SDMA. However, a significant positive relationship was found between serum creatinine and SDMA concentrations. Conclusions: Healthy adult horses had SDMA values similar to those of other species. Foals had higher SDMA values. Therefore, different reference values should be created for them. The study confirmed an increased SDMA in horses with AKI. This, as well as the low influence of extrarenal factors on the SDMA values, may confirm its usefulness in the diagnosis of kidney dysfunction. Higher SDMA values may also indicate a more advanced degree of kidney dysfunction. Further research is required to determine whether SDMA could be used to detect kidney dysfunction in the asymptomatic stage of AKI.

The aim of this consensus statement is to summarize and appraise scientific evidence and combine this with the clinical experience of a panel of experts to optimize recommendations on how to recognize and manage kidney disease in horses.

Creatinine only allows detection of kidney disease when 60 to 75% of the glomerular function is lost and is therefore not an ideal marker of disease. Additional biomarkers could be beneficial to assess kidney function and disease. The objectives are to describe new equine kidney biomarkers. This systematic review assesses the available literature, including the validation process and reference values, following which the authors suggest recommendations for clinical use. SDMA may have some potential as equine kidney biomarker, but there is currently a lack of evidence that SDMA offers any advantage compared to creatinine in detecting Acute Kidney Injury (AKI). Cystatin C and podocin show potential as biomarkers for kidney disease (including detecting AKI earlier than creatinine) and should be studied further. NGAL has potential as a biomarker of kidney disease (including detecting AKI earlier than creatinine), and potential as an inflammatory marker. Literature on MMP-9 does not allow for conclusive statements about its potential as a biomarker for kidney disease. The future may show that NAG has potential. For all biomarkers, at this stage, available scientific information is limited or too scarce to support clinical use, and only SDMA can be measured for clinical purposes. In conclusion, there are multiple new biomarkers with the potential to diagnose kidney problems. However, there are only a few studies available and more data is needed before these biomarkers can be applied and recommended in our daily practice.

The early asymptomatic stage of glomerular injury is a diagnostic challenge in the course of renal and extra-renal disease, e.g., heart insufficiency. It was found that podocin, a podocyte-specific protein present in the urine, may serve as a biomarker in the diagnosis of glomerular disease in humans and animals including glomerulonephritis, glomerulosclerosis, amyloidosis, or nephropathy. Therefore, there is a need of development of the sensitive and straightforward method of urinary podocin identification. In this work, we report our extended research under the glomerular injury investigation in dogs by application of clinical examination and LC-MS-MRM method in the identification of canine podocin in urine samples. The LC-MS-MRM method is based on the identification of podocin tryptic peptide with the ²¹⁸H-AAEILAATPAAVQLR-OH²³² sequence. The model peptide was characterized by the highest ionization efficiency of all the proposed model podocin tryptic peptides in a canine urine sediment according to the LC-MS/MS analysis. The obtained results revealed the presence of the model peptide in 40.9% of dogs with MMVD (active glomerular injury secondary to heart disease = cardiorenal syndrome-CRS) and 33.3% dogs with chronic kidney disease. The potential applicability of the developed methodology in the analysis of podocin in canine urine sediments was confirmed.

Background: Acute kidney injury (AKI) in horses may develop as a complication of a primary disease or following the administration of nephrotoxic drugs, and may pose a diagnostic challenge. Hence, the main objective of this study was to evaluate the concentrations and diagnostic significance of serum symmetric dimethylarginine (SDMA) and conventional renal dysfunction biomarkers in healthy horses, horses at risk of developing AKI, and horses with clinically evident AKI. A second aim was to assess how gastrointestinal disease and exposure to potentially nephrotoxic drugs affected SDMA levels. Thirty healthy horses, 30 horses with gastrointestinal disease and/or receiving phenylbutazone or gentamicin (risk group) and 11 horses with AKI were included in the study. Serum SDMA levels were measured using commercially available enzyme immunoassay tests.Results: SDMA levels in healthy horses, horses at risk of AKI and horses with AKI were 12 µg/dL (11–14), 12 µg/dL (11–13) and 20 µg/dL (20–37), respectively (all results presented as a median (quartile 1–quartile 3)). There was a significant difference in SDMA concentration between the healthy horses and those with AKI, whereas the SDMA levels in healthy horses and those at risk of AKI were comparable. A SDMA cut-off value of 19 µg/dL was established. Horses from the risk group had higher urine protein concentration and urine protein to creatinine ratio compared with healthy horses. Furthermore, horses with colic from the risk group presented with elevated urine γ-glutamyl transpeptidase to creatinine ratio.Conclusion: The SDMA cut-off value established in healthy horses was higher than previously reported. The SDMA level correlated with the azotaemia levels. Horses from the AKI risk group had normal SDMA levels but single urine parameters was abnormal indicating their higher sensitivity in assessing subclinical kidney dysfunction.

No sensitive method for diagnosing early kidney dysfunction in horses has been identified so far. Many studies carried out in humans and small animals show that podocin can be useful to diagnose various kidney diseases, mainly affecting the glomeruli. The aim of this study was to perform a qualitative and quantitative analysis of podocin in urine samples obtained from healthy horses, horses with clinical kidney dysfunction and horses at risk of acute kidney injury. The study objectives aimed to assess: (1) whether the selected podocin tryptic peptide for LC-MS-MRM allows for podocin detection in horse; and (2) whether the species-specific ELISA test makes this detection possible as well;, (3) whether the chosen methods are sensitive enough to detect kidney dysfunction and glomerular injury, (4) whether the results of the tests applying both methods correspond with one another, (5) whether the results correlate with the hematological and biochemical data. The signals that may indicate the presence of trypsin fragments of podocin were found in three healthy horses, all the horses diagnosed with kidney dysfunction and half of the animals at risk for acute kidney injury. The concentration of podocin, diagnosed with the ELISA test was as follows: from 0.19 to 1.2 ng/ml in healthy animals, from 0.19 to 20.0 ng/ml in AKI horses, from 0.29 to 5.71 ng/ml in horses at risk for acute kidney injury. The results of both methods corresponded significantly. Podocin may be a potential biomarker of clinical kidney disease in horses and may be used in the detection of glomerular injury. However, its use is limited by the possibility of physiological podocyturia. LC-MS-MRM seems to be a more sensitive method to evaluate the presence of podocin than the ELISA test, whilst selected tryptic peptides of podocin appear to apply to horses. The ELISA test showed greater effectiveness in excluding the disease than in confirming it.