Acute kidney injury is a term used to characterize an abrupt decline in renal activity, resulting in a loss of urea and creatinine excretion that raises the amount of serum creatinine above the standard reference range (Mugford et al. 2013). Renal dysfunction is among the main causes of canine deaths. It is life-threatening and often requires urgent diagnosis and treatment. (Athaley et al. 2018).
Acute kidney injury in the current study was induced using 30 mg/ kg of gentamicin sulphate 10% daily for ten days which is a potent broad-spectrum aminoglycoside that is commonly used especially in the treatment of life-threatening infections caused by Gram-negative and Gram-positive bacilli(Ali 2003). The renal toxicity of gentamicin was associated with its concentration in the renal proximal convoluted tubule, which induced a variety of morphological and biochemical changes in humans and laboratory animals. (Sepehri et al. 2011).
The dogs showed signs of depression, dullness, polyuria, polydipsia, vomiting, dehydration, and tremors due to the harmful effect of gentamicin on renal tissue, and accumulation of nitrogenous wastes, metabolic acidosis, and changes in the gastrointestinal tract (Kumar et al. 2011)and these findings were similar to Helal (2005)and Allaam et al. (2012).
Examination of urine sample revealed that the presence of proteinuria on the 5th day of induction and became more obvious on the 10th day which might be due to decrease glomerular filtration rate which follows the proximal tubular damage caused by a high dose of gentamicin, Glomerular damage increases the permeability of the filtration barrier which increased filtration of protein in urine lead to proteinuria(Cianciolo et al. 2016) and these findings were similar to Macanović et al. (2000) ad Helal (2005).
The most promising novel biomarker for early diagnosis of kidney failure that appeared in the last few years is SDMA. SDMA, with asymmetric dimethylarginine and mono methylarginine, is one of the methylated forms resulting from arginine metabolism (Savarese et al. 2018). The findings of 18 human case trials observed a high correlation between SDMA and both GFR and serum creatinine and concluded that SDMA has significant potential as a biomarker of renal function (Kielstein et al. 2006). SDMA has more advantages over serum creatinine in detecting decreased GFR. SDMA detects loss of renal function earlier and is less affected by extrarenal factors such as age, sex, breed, and lean body mass (Kopke et al. 2018).
This study revealed that there was a significant increase in SDMA on the 5th day of induction and 10th day of induction and this indicated that SDMA is a useful novel urinary biomarkers for the detection of acute kidney injury in dogs and these findings were similar to Hall et al. (2016); Relford et al. (2016)and Dahlem et al. (2017).
SDMA is more preferable than creatinine due to serum SDMA concentrations are not affected by lean body mass in dogs or cats, creatinine is an unreliable indicator during acute changes in kidney function due to creatinine concentrations can vary widely with age, gender, muscle mass, muscle metabolism, and its concentration may not change until a significant amount of kidney function has already been lost (Devarajan 2008)and these findings agreeable to Hall et al. (2016)and McKenna et al. (2020).
Concerning to serum level of urea and creatinine, there was a significant increase in serum urea and creatinine level in the present study due to the harmful impact of gentamicin on the kidneys, contributing to renal harm and the failure of the kidneys to eliminate waste products through reducing the rate of glomerular filtration (Sun et al. 2019), and these findings were agreeable with Helal (2005); Allaam et al. (2012)and Udupa and Prakash (2019).
There was a significant increase in serum potassium and phosphorus on the 5th day of induction and became highly significant on the 10th day of induction and this occurs due to acute renal insufficiency lead to reduced GFR with low urine flow lead to decrease renal excretion of potassium and subsequent hyperkalemia (Lehnhardt and Kemper 2011) and also significant hyperkalemia and hyperphosphatemia may occur due to leakage of potassium and phosphate from the intracellular fluids to the extracellular fluids (Haycock 2003; Ramesh and Reeves 2003) and these findings were coincided with Vaden et al. (1997)and Helal (2005).
Regarding to serum level of calcium, chloride, and sodium, the significant decrease in serum sodium, chloride, and calcium appeared on the 5th day of induction and became highly significant on the 10th day of induction might be attributed to the adverse effect of gentamicin on renal tubules, in particular proximal convoluted tubules, and kidney failure to maintain the balance of electrolytes (Stephen et al.,2017) and these findings were similar to Helal (2005)and Christo et al. (2011).
The kidney diseases diagnosed by ultrasonography can be classified into diffuse renal diseases, regional renal diseases, and focal or multifocal renal diseases. The diffuse renal diseases diagnosed were nephritis and end-stage kidney (Dehmiwal et al. 2016).
The results of the ultrasonographic examination in the present study revealed that increase renal cortical echogenicity of right and left kidney on the 5th day of induction of acute kidney injury and had the same echogenicity of adjacent liver and spleen, respectively, and became more echogenic than adjacent liver and spleen, respectively on 10th day of induction and this due to extensive accumulation of gentamicin in kidney and increase amount of gentamicin bound to the renal cortex (Wiland and Szechiński 2003) and these findings were similar to Rivers et al. (1996); Helal( 2005); Allaam et al. (2012)and Sonet et al. (2018).
Alterations in the RI have been observed in many conditions affecting the kidney, such as acute variations in renal vascular resistance and renal damage in multiple organ dysfunction syndromes (Agut et al. 2020). For the evaluation of renal hemodynamics, Doppler ultrasonography can be used and becomes very helpful in the diagnosis of the renal artery and vein diseases such as thrombosis (Donia et al. 2019). The renal resistive index is probably the most commonly used parameter to evaluate blood flow in kidney vessels (Samoni et al. 2016). The resistive index (RI) measures the arterial resistance in the peripheral vessels by calculating the ratio between the peak systolic velocity (PSV) and the end diastolic velocity (EDV) (RI = (PSV – EDV)/PSV), which is independent of the angle and the position of the transducer, allowing accurate and reproducible measurements (Tipisca et al. 2016).
The Renal RI was significantly increased in the present study on the 5th day of induction and became highly significant on the 10th day of induction due to vasoconstriction resulting from renin release in response to the decreased blood flow in the renal arteries secondary to renal injury(Chang et al. 2010). These results coincided with Morrow et al. (1996); Novellas et al. (2007) and Donia et al. (2019). Therefore, the RI is useful for the diagnosis of acute kidney injury when the only observable change is an increase in renal cortical echogenicity and also when there is no alteration in B-mode ultrasound examination(Rivers et al. 1997).