Urinary Flashcards
Preliminary evaluation of hepatitis A virus cell receptor 1/kidney injury molecule 1 in healthy horses treated with phenylbutazone
• HAVCR1/KIM1 was detectable in horse urine using a human-specific ELISA kit, despite potential cross-species variability.
• Serum creatinine increases of >26.5 μmol/L were strongly associated with urinary HAVCR1/KIM1 detection.
• The findings suggest that HAVCR1/KIM1 could be a sensitive biomarker for early kidney injury, even when serum creatinine levels remain within the reference range and ultrasonographic abnormalities are undetectable.
• None of the 10 horses had detectable HAVCR1/KIM1 in urine at baseline.
• Serum creatinine concentrations in placebo group did not increase, and HAVCR1/KIM1 was undetectable in urine.
• At the end of treatment, 3 of 5 horses receiving PBZ developed increases in serum creatinine of >26.5 μmol/L (>0.3 mg/dL), only 1 of these horses had a serum creatinine above the reference interval and 1 developed isosthenuria
- HAVCR1/KIM1 was detectable in urine, despite normal findings on kidney ultrasonography in all horses.
• The association between HAVCR1/KIM1 detection and PBZ treatment was significant
• There was a strong correlation between HACVR1/KIM1 detection and the increase in serum creatinine concentration (log odds ratio, 16.12).
• An increase in serum creatinine concentration >26.5 μmol/L (>0.3 m g/dL) was associated with detectable HACVR1/KIM1 at ≥56 pg/mL
Retrospective evaluation of acute kidney injury in horses treated with nonnitrogenous bisphosphonates (2013–2020): 8 cases
• Acute kidney injury (AKI) in horses post-administration of nonnitrogenous bisphosphonates (clodronate, tiludronate).
• NSAID Combination: Concurrent NSAID use was frequent but not statistically linked to increased AKI incidence due to limited sample size.
Primary Signs:
• Decreased appetite (6/8 horses; 75%).
• Abnormal urination (2/8; 25%).
• Vital Parameters: Mostly normal, though mild tachypnea, tachycardia, and fever noted.
• Fever linked to acute phase reactions (e.g., cytokine release of IL-6, TNF-α).
Other Findings:
• Systemic inflammation (e.g., monocytosis, hyperfibrinogenemia) noted in some cases.
• Electrolyte imbalances common; hypophosphatemia in 66.7% of horses.
Risk Factors and Outcomes
• Breed Predisposition: Warmbloods overrepresented among AKI cases (62.5% of affected horses; OR: 11.5).
• 7 horses (7/8; 87.5%) survived the initial episode of AKI and 1 horse (1/8; 12.5%) was euthanized.
• 2 horses (28.5%) went on to develop chronic renal dysfunction. Of the 5 horses with follow-up creatinine data, 2 horses had serum or plasma creatinine concentration >159.12 μmol/L
Concurrent NSAID Use:
• Present in 75% of cases (6/8).
• Manufacturer warnings for bisphosphonates and NSAIDs advise a washout period (48 hours for tiludronate, 2–3 days for clodronate).
• There were no statistically significant findings between cases and the 29 control horses that also received tiludronate or clodronate without evidence of AKI for age (P = 0.08), concurrent NSAID use (P = 1.0), or type of bisphosphonate administered (P = 0.37).
• The prevalence of bisphosphonate-induced AKI in the hospital population during the study period was 0.57%
Estimation of glomerular filtration rate by plasma clearance of iohexol in healthy horses of various ages
GFR Variation:
• Young horses (Group A): Median GFR = 2.60 mL/min/kg.
• Aged horses with normal creatinine (<1.5 mg/dL, Group B): Median GFR = 2.10 mL/min/kg.
• Aged horses with elevated creatinine (≥1.5 mg/dL, Group C): Median GFR = 1.45 mL/min/kg.
• Significant reduction in GFR in Group C compared to Group A (P < 0.0003).
• No significant GFR difference between Group A and Group B.
• Urea and creatinine levels were significantly higher in Group C.
Symmetric Dimethylarginine and Renal Function Analysis in Horses with Dehydration
• Moderate correlation between serum SDMA and creatinine at T0 (r = 0.412, P < 0.001).
• SDMA did not consistently correlate with other renal function parameters, such as urea, urine-specific gravity (SG), fractional sodium excretion (FENa+), and gamma-glutamyl transferase (GGT)/creatinine ratio.
• SDMA concentrations significantly differed between mild and moderate dehydration groups but not among other dehydration categories.
• SDMA increases were seen in some cases prior to creatinine elevation, suggesting potential early detection of renal injury.
Dehydration Levels:
• SDMA concentrations at T0 were significantly higher in moderately dehydrated horses compared to mildly dehydrated ones (P = 0.03).
• SDMA concentrations overlapped considerably across dehydration categories, limiting clear distinctions.
Prognostic Implications:
• No statistically significant association between SDMA at T0 and survival outcomes (P = 0.1).
• Higher SDMA concentrations were observed in nonsurvivors compared to survivors, but with significant overlap.
Clinical Relevance
• Comparison with Creatinine:
- SDMA appeared less affected by hydration status than creatinine, potentially making it a more stable biomarker in dehydration contexts.
-Horses with increased SDMA but normal creatinine may have underlying renal impairment, particularly in older or low-body-mass individuals.
Potential for Early Detection:
• SDMA elevations were seen before creatinine increases in some cases, highlighting its utility for early kidney injury detection.
Current Limitations:
• SDMA inconsistently correlated with urine parameters, reducing its standalone reliability for assessing renal function.
• Extrarenal factors, such as muscle mass, liver function, and hydration status, may influence SDMA concentrations.
• No info on AKI in this study
SDMA and Creatinine in Healthy Draft Horses
Validation of SDMA Immunoassay (IA):
• Strong correlation between SDMA concentrations measured by immunoassay (IA) and liquid chromatography-mass spectroscopy (LC-MS) (R = 0.74, P < 0.001).
• Excellent linearity and accuracy in equine serum samples across the clinically relevant range (10–100 μg/dL).
• SDMA stability confirmed under different storage conditions (up to 7 days at -20°C, 4°C, and 25°C).
SDMA Concentrations in Draft Horses:
Median SDMA values:
• LC-MS: 10.0 μg/dL (95% CI: 9.4–10.2).
• IA: 9.7 μg/dL (95% CI: 9.5–10.0).
• SDMA was higher in Clydesdales compared to Percherons and Belgians, but differences were small and not clinically significant.
• No significant effects of sex, age, body condition score (BCS), or weight on SDMA concentrations.
Creatinine (Cr) and Urea Nitrogen (UN) Comparisons:
• Creatinine values correlated with SDMA (R = 0.66, P < 0.001 by IA).
• No correlation between UN and SDMA.
• Cr showed weak correlation with weight but was unaffected by age, sex, or BCS.
• SDMA appears to be a reliable indicator of renal function, with less influence from extrinsic factors like muscle mass and sex compared to creatinine.
• A cutoff of 14 μg/dL aligns with thresholds for dogs and cats, suggesting it may also be applicable for draft horses, though further validation in light breed horses is needed.
Equine idiopathic hemorrhagic cystitis: Clinical features and comparison with bladder neoplasia
Idiopathic Hemorrhagic Cystitis (IHC):
• A newly identified cause of hematuria and stranguria in horses.
• Characterized by hemorrhagic, thickened bladder mucosa with resolution in 3–8 weeks following treatment.
• All cases resolved without recurrence, indicating a favorable prognosis.
• Histopathology findings (e.g., neutrophilic infiltration, epithelial hyperplasia) occasionally suggested dysplasia or neoplasia but were not indicative of malignancy.
Bladder Neoplasia:
• Typically presented with hematuria, stranguria, and mass-like lesions on ultrasonography.
• Histopathology confirmed neoplasia (transitional cell carcinoma or squamous cell carcinoma) in all cases.
• Prognosis was poor, with most horses euthanized or succumbing to disease.
Comparison of IHC and Neoplasia:
• Horses with IHC were younger (median age: 16 years vs. 24 years for neoplasia).
• IHC cases were predominantly male, while neoplasia cases were exclusively female.
• Masses detected via ultrasonography were significantly more common in neoplasia cases.
• Horses with IHC had higher hematocrit levels than those with neoplasia.
Effects of phenylbutazone, firocoxib, and dipyrone on the diuretic response to furosemide in horses
NSAID Impact on Furosemide-Induced Diuresis:
• Pretreatment with phenylbutazone (PB), firocoxib (FX), and dipyrone (DP) reduced furosemide-induced diuresis by approximately 25%, compared to furosemide alone (FU).
• The magnitude of diuretic inhibition was similar across the three NSAIDs, indicating no significant difference in their effects on renal response to furosemide.
Electrolyte Excretion:
• All NSAID treatments attenuated furosemide-induced increases in fractional sodium (FClNa) and chloride (FClCl) clearances during the first hour post-administration.
• Potassium excretion (FClK) increased after furosemide administration but was not significantly affected by NSAID pretreatment.
Interindividual Variability:
• Considerable variability in the magnitude of diuresis was observed among individual mares, both with and without NSAID pretreatment.
• Differences in urine production were less pronounced in horses with lower diuretic response to furosemide.
• The similar inhibitory effects of all three NSAIDs suggest that even COX-2 selective (firocoxib) or atypical NSAIDs (dipyrone) may not provide “renoprotective” benefits compared to nonselective NSAIDs like phenylbutazone.
Mechanistic Insights:
• Furosemide-induced diuresis depends on prostaglandin E2 (PGE2) production, which enhances solute delivery to the distal nephron and reduces water reabsorption.
• NSAIDs inhibit cyclooxygenase (COX) enzymes, reducing PGE2 production and thereby attenuating the diuretic and natriuretic effects of furosemide.
Prevalence of acute kidney injury in a population of hospitalized horses
Prevalence:
• AKI prevalence: 14.8% in hospitalized horses using Veterinary Acute Kidney Injury (VAKI) criteria.
• Baseline azotemia prevalence: 4.3%.
Stages of AKI:
• Stage 1: 13.5% (mild AKI).
• Stage 2: 1.2% (moderate AKI).
• No cases of severe AKI (Stage 3).
Severity Comparison:
• Lower AKI severity in horses compared to humans and dogs.
• AKI in humans and dogs strongly correlates with disease severity and systemic illness, which was not observed here.
Risk Factors
No Significant Associations:
• No strong links between age, breed, sex, or systemic inflammatory response syndrome (SIRS) and AKI.
• Hypovolemia, number of diagnoses, and tetracycline administration showed weak trends but lacked statistical significance.
Survival and Outcomes
• Survival to Discharge: Overall survival: 87.7%.
• AKI group survival: 87.5% (Stages 1–2).
• Azotemic horses: 71.4% survival.
• No statistically significant difference between survival rates of horses with AKI/azotemia and those without renal dysfunction.
