Methylprednisolone alone or combined with cyclosporine or mycophenolate mofetil for the treatment of immune-mediated hemolytic anemia in dogs, a prospective study.

BACKGROUND: Benefit of adding a second-line immunosuppressive drug to glucocorticoids for the treatment of non-associative immune-mediated hemolytic anemia (naIMHA) in dogs has not been defined prospectively. HYPOTHESIS/OBJECTIVES: Evaluate the effectiveness of different immunosuppressive protocols in naIMHA dogs. ANIMALS: Forty-three client-owned dogs. METHODS: Open label, randomized, clinical trial. Dogs were treated with methylprednisolone (M-group), methylprednisolone plus cyclosporine (MC-group) or methylprednisolone plus mycophenolate mofetil (MM-group). Dogs were defined as responders by disappearance of signs of immune-mediated destruction and hematocrit stabilization. Frequency of responders was compared between M-group and combined protocols (MC and MM-group evaluated together), and among the 3 different therapeutic groups at 14 (T14), 30 (T30), 60 (T60) days after admission. Frequency of complications, length of hospitalization and relapse were also compared. Death rate was evaluated at discharge, T60 and 365 (T365) days. RESULTS: Proportion of responders was not significantly different between M-group and combined protocols (MC and MM-groups), nor among the 3 therapeutic groups at T14, T30, and T60 (P > .17). Frequency of relapse, complications, and length of hospitalization were not significantly different between M-group and dogs treated with combined protocols, nor among the 3 treatment groups (P > .22). Death was significantly more common only for MM-group compared with MC-group at T60 (+42.8%; 95% CI: 11.5-67.4; P = .009), and at T365 (+50%; 95% CI: 17.5-73.2; P = .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Combined immunosuppressive therapy did not improve hematological response in naIMHA.

Association between echocardiographic indexes and urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in dogs with myxomatous mitral valve disease.

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of tubular damage, and its elevation has been described in human and canine cardiorenal syndrome. The aim was to evaluate the association between echocardiographic indexes and urine NGAL (uNGAL) and uNGAL normalized to urine creatinine (uNGALC) in dogs with MMVD. This is a multicentric prospective cross-sectional study. A total of 77 dogs with MMVD at different ACVIM stages were included. All dogs underwent echocardiography, serum chemistry, and urinalysis. Echocardiographic data analyzed were shortening fraction (SF), left ventricular diastolic (LVIDDn) and systolic (LVIDSn) diameters normalized for body weight, left atrium to aortic root ratio (LA/Ao), maximal (LAVMax) and minimal (LAVMin) left atrial volumes, LA stroke volume (LASV), early diastolic mitral peak velocity (EVmax), EVmax to tissue Doppler E' wave (E/E'), aortic (VTIAo) and mitralic (VTIMit) velocity time integrals and their ratio (VTIMit/VTIAo), and tricuspid regurgitation velocity (TRVmax). In the univariate analysis LASV, TRVmax, LAVMax, LVIDDn, and VTIMit/VTIAo were independent predictors of increased uNGAL and uNGALC; however, only LASV [(OR: 1.96, 95% CI: 1.16 to 3.31) P = 0.01 for NGAL, and (OR: 2.79, 95% CI: 1.50 to 5.17) P < 0.001 for NGALC] and TRVmax [(OR: 1.73, 95% CI: 1.20-2.51) P = 0.002 for NGAL, and (OR: 1.50, 95% CI: 10.07-2.10) P = 0.015 for NGALC] remained statistically significant in the multivariable analysis. Based on our results, LASV and TRVmax are associated with increased uNGAL and uNGALC. These parameters might detect dogs with MMVD at higher risk of developing kidney damage.

Urine neutrophil gelatinase-associated lipocalin to diagnose and characterize acute kidney injury in dogs.

BACKGROUND: Urine neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury (AKI) in dogs. OBJECTIVES: To evaluate the utility of urinary NGAL for characterizing AKI according to volume responsiveness, presence of inflammation and sepsis, and prognosis. ANIMALS: Dogs with AKI (n = 76) and healthy controls (n = 10). METHODS: Prospective study. Clinical and clinicopathologic data including absolute urine NGAL concentration (uNGAL) and NGAL normalized to urine creatinine concentration (uNGALC) were measured upon admission. Dogs were graded according to International Renal Interest Society (IRIS) AKI guidelines and compared based on AKI features: volume-responsive (VR-) AKI vs. intrinsic (I-) AKI based on IRIS criteria; VR-AKI and I-AKI based on urine chemistry; inflammatory versus noninflammatory; septic versus nonseptic; and survivors versus nonsurvivors. Nonparametric statistics were calculated, and significance set at P < .05. RESULTS: Urinary NGAL was significantly higher in dogs with AKI compared to controls, regardless of AKI grade. Urinary NGAL did not differ between dogs with VR-AKI and I-AKI based on IRIS criteria, whereas higher uNGALC was recorded in dogs with I-AKI based on urine chemistry. Urinary NGAL was significantly higher in dogs with inflammatory AKI, whereas no difference with respect to sepsis or outcome was identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary NGAL is a sensitive marker for AKI in dogs, but its specificity is affected by systemic inflammation. Increased urinary NGAL in both I-AKI and VR-AKI also suggests the presence of tubular damage in transient AKI. Combining urine chemistry data with IRIS criteria could facilitate AKI characterization in dogs.

Fractional excretion of electrolytes in volume-responsive and intrinsic acute kidney injury in dogs: Diagnostic and prognostic implications.

BACKGROUND: The value of fractional excretion (FE) of electrolytes to characterize and prognosticate acute kidney injury (AKI) is poorly documented in dogs. OBJECTIVES: To evaluate the diagnostic and prognostic roles of FE of electrolytes in dogs with AKI. ANIMALS: Dogs (n = 135) with AKI treated with standard care (February 2014-December 2016). METHODS: Prospective study. Clinical and laboratory variables including FE of electrolytes, were measured upon admission. Dogs were graded according to the AKI-IRIS guidelines and grouped according to AKI features (volume-responsive, VR-AKI; intrinsic, I-AKI) and outcome (survivors/non-survivors). Group comparison and regression analyses with hazard ratios (HR) evaluation for I-AKI and mortality were performed. P < .05 was considered significant. RESULTS: Fifty-two of 135 (39%) dogs had VR-AKI, 69/135 (51%) I-AKI and 14/135 (10%) were unclassified. I-AKI dogs had significantly higher FE of electrolytes, for example, FE of sodium (FENa, %) 2.39 (range 0.04-75.81) than VR-AKI ones 0.24 (range 0.01-2.21; P < .001). Overall, case fatality was 41% (55/135). Increased FE of electrolytes were detected in nonsurvivors, for example, FENa 1.60 (range 0.03-75.81) compared with survivors 0.60 (range 0.01-50.45; P = .004). Several risk factors for death were identified, including AKI-IRIS grade (HR = 1.39, P = .002), FE of electrolytes, for example, FENa (HR = 1.03, P < .001), and urinary output (HR = 5.06, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Fractional excretion of electrolytes performed well in the early differentiation between VR-AKI and I-AKI, were related to outcome, and could be useful tools to manage AKI dogs in clinical practice.