Evaluation of urinary chemistry and urinary neutrophil gelatinase-associated lipocalin to detect renal tubular damage in dogs with myxomatous mitral valve disease

Cardiorenal syndrome (CRS) describes a reciprocal relationship between the heart and kidneys, where impaired function of one organ—whether acute or chronic—can trigger a similar decline in the other. In dogs with myxomatous mitral valve disease (MMVD), early detection of renal involvement allows for treatment adjustments that benefit both organs. Serum creatinine concentration remains the most common marker for assessing kidney function in these dogs, though it is unfortunately a poor indicator of early kidney damage and cannot differentiate between functional and structural lesions. This thesis reports the results of a multicenter study conducted at the University of Parma, and the University of Bologna exploring the occurrence and nature of renal damage in dogs with stable MMVD (first study phase) or in congestive heart failure (CHF) (second study phase). In the first phase, three descriptive studies addressing different aspects of Type 2 CRS were conducted. The objectives were to evaluate in dogs with stable MMVD: 1) the impact of the time frame between oral furosemide administration and sample collection on urinary electrolyte concentration and any potential fluctuations in urinary electrolytes between morning and evening in a group of healthy dogs; 2) the value of urine neutrophil gelatinase-associated lipocalin (uNGAL), a marker of tubular damage, across different American College of Veterinary Internal Medicine (ACVIM) stages and a comparison with healthy dogs; 3) the relationship between uNGAL levels and echocardiographic variables used for staging cardiac disease. The findings from this phase were as follows: 1) urinary electrolyte excretion significantly increases within 6 hours of furosemide administration in MMVD dogs at ACVIM stage C, whereas healthy, untreated dogs showed no significant circadian variations in urinary electrolyte excretion; 2) uNGAL levels were significantly higher in MMVD dogs and increased with higher ACVIM stages, indicating the presence of renal tubular damage even in stable MMVD dogs; 3) two echocardiographic indices left atrium stroke volume (LASV) and tricuspid regurgitation velocity (TRVmax) were associated with elevated uNGALC levels, suggesting these parameters might help identify MMVD dogs at greater risk of kidney damage. In the second phase of the study, renal responses in Type 1 CRS were evaluated, including dogs with MMVD presented to the intensive care unit in CHF. The aim of the study was to assess the prevalence and characteristics of acute kidney disease (AKI) during a short hospitalization period and evaluate the predictive role of urinary uNGAL for AKI. It was found out that 63% of dogs with CHF developed AKI within the first 48 hours of admission. However, uNGAL levels were not associated with renal function decline as indicated by creatinine changes. These studies can contribute to the understanding of cardiorenal syndromes, but future researches should explore reno-protective strategies for managing MMVD in dogs, as these approaches could potentially slow disease progression and mitigate related complications.