Urinary interleukin-6 is a potentially useful diagnostic and prognostic marker of acute kidney injury in dogs.

BACKGROUND: Interleukin-6 (IL6) is a pro-inflammatory cytokine implicated in the pathophysiology of urinary tract diseases. The objective of this study was to evaluate the diagnostic and prognostic utilities of urinary IL6 (uIL6) in dogs with acute kidney injury (AKI) and other urinary tract diseases. METHODS: Eighty client-owned dogs were included and divided into four groups: AKI, chronic kidney disease (CKD), urinary tract infection and healthy controls. Urine samples were analysed for uIL6 and normalised to urinary creatinine (uIL6/uCr). RESULTS: Dogs in the AKI group had higher uIL6/uCr compared with the control and CKD groups (p < 0.001 and 0.012, respectively). Receiver operator characteristic (ROC) curve analysis of uIL6/uCr as a diagnostic marker for AKI had an area under the curve (AUC) of 0.91 (95% confidence interval [CI], 0.81-1.0) with 82% sensitivity and 90% specificity (cutoff point 4.5 pg/mg) when including the AKI and control groups. ROC analysis including AKI compared with all other groups had an AUC of 0.77 (95% CI, 0.67-0.87) for the diagnosis of AKI with sensitivity and specificity of 71% and 78%, respectively (cutoff point 10.4 pg/mg). The 30-day mortality of the AKI group was 34%, and there was no difference in uIL6/uCr between survivors and non-survivors of AKI. CONCLUSIONS: uIL6/uCr is a potentially sensitive and specific diagnostic marker for AKI in dogs.

Perioperative urinary heat shock protein 72 as an early marker of acute kidney injury in dogs.

OBJECTIVE: Acute kidney injury (AKI) may be a complication in dogs undergoing surgery. Urinary heat shock protein 72 (uHSP72) is a sensitive biomarker of canine AKI. To assess the occurrence of perioperative AKI, based on uHSP72 compared with serum creatinine (sCr), and whether its occurrence is associated with the American Society of Anesthesiology physical status (ASA status). STUDY DESIGN: Clinical prospective study. ANIMALS: A total of 80 client-owned and shelter dogs. METHODS: Dogs scheduled for elective or emergency surgery were assigned ASA status (ASA I-IV). Preoperative and 24 hour postoperative serum and urine samples were collected. sCr, uHSP72 and urinary creatinine (uCr) were measured. RESULTS: Postoperative uHSP72/uCr concentration [median (range)] of all dogs undergoing surgery [2.40 (0.14-252) ng mg-1] was significantly increased compared with preoperative uHSP72/uCr [1.30 (0.11-142) ng mg-1] concentration (p < 0.001). Conversely, postoperative sCr concentration of all dogs [0.88 (0.3-1.6) mg dL-1] significantly decreased compared with preoperative sCr concentration [0.8 (0.2-5.0) mg dL-1; p = 0.001]. Median uHSP72/uCr concentration differed both preoperatively (p = 0.007) and postoperatively (p = 0.019) among the ASA status groups. Increased uHSP/uCr was measured in 20 dogs preoperatively and 33 dogs postoperatively, whereas only five dogs fulfilled the criteria of AKI based on sCr. CONCLUSIONS: The occurrence of increased uHSP72/uCr perioperatively suggests that the proportion of dogs with AKI is considerably higher than perceived. CLINICAL RELEVANCE: Dogs undergoing surgery should be closely monitored for AKI before and after anesthesia, using currently available markers (e.g., sCr) and more sensitive markers.

Urinary heat shock protein 72 as a biomarker of acute kidney injury in dogs.

Early recognition of acute kidney injury (AKI) is important, as therapy is potentially more efficacious if instituted early in the course of disease. Urinary heat shock protein-72 to urinary creatinine ratio (uHSP72/uCr) was assessed as a diagnostic and prognostic marker in AKI in dogs. Fifty-three dogs were enrolled in five groups: healthy controls (n=11), urinary tract infection (n=10), chronic kidney disease (CKD; n=11), AKI (n=13), and acute decompensating CKD (n=8). Urinary heat shock protein-72 to urinary creatinine ratio was highest in the AKI group (P<0.001 when compared to the control and urinary tract infection groups, individually; P>0.05 compared to each of the other two groups). The area under the curve (AUC) for the receiver operator characteristic (ROC) analysis of uHSP72/uCr to predict AKI, compared to the control group, was 0.97. A cutoff value of 0.20ng/mg corresponded to sensitivity and specificity of 100% and 82%, respectively. Urinary heat shock protein-72 to urinary creatinine ratio was significantly lower in dogs categorized as survivors vs. non-survivors of AKI; ROC AUC, 0.91 (95% confidence intervals, 0.74-1.0). Urinary heat shock protein-72 to urinary creatinine ratio is a potentially useful diagnostic and prognostic biomarker of AKI in dogs.

Serum histones as biomarkers of the severity of heatstroke in dogs.

Heatstroke is associated with systemic inflammatory response syndrome, leading to multiple organ dysfunction and death. Currently, there is no specific treatment decreasing hyperthermia-induced inflammatory/hemostatic derangements. Emerging studies indicate that histones leaking from damaged cells into the extracellular space are toxic, pro-inflammatory, and pro-thrombotic. We therefore hypothesize that serum histones (sHs) are elevated during heatstroke and are associated with the severity of the disease. Sixteen dogs with heatstroke and seven healthy controls were included in the study. Median serum histones (sHs) upon admission in dogs with heatstroke were significantly higher (P = 0.043) compared to that in seven controls (13.2 vs. 7.3 ng/mL, respectively). sHs level was significantly higher among non-survivors and among dogs with severe hemostatic derangement (P = 0.049, median 21.4 ng/mL vs. median 8.16 ng/mL and P = 0.038, 19.0 vs. 7.0 ng/mL, respectively). There were significant positive correlation between sHs and urea (r = 0.8, P = 0.02); total CO2 (r = 0.661, P = 0.05); CK (r = 0.678, P = 0.04); and prothrombin time (PT) 12 h post presentation (r = 0.888, P = 0.04). The significant positive correlation between sHs and other heatstroke severity biomarkers, and significant increase among severely affected dogs, implies its role in inflammation/oxidation/coagulation during heatstroke. sHs, unlike other prognostic and severity biomarkers in heatstroke, can be pharmacologically manipulated, offering a potential therapeutic target.

Experimental investigation of the structural behavior of equine urethra.

BACKGROUND AND OBJECTIVE: An integrated experimental and computational investigation was developed aiming to provide a methodology for characterizing the structural response of the urethral duct. The investigation provides information that are suitable for the actual comprehension of lower urinary tract mechanical functionality and the optimal design of prosthetic devices. METHODS: Experimental activity entailed the execution of inflation tests performed on segments of horse penile urethras from both proximal and distal regions. Inflation tests were developed imposing different volumes. Each test was performed according to a two-step procedure. The tubular segment was inflated almost instantaneously during the first step, while volume was held constant for about 300s to allow the development of relaxation processes during the second step. Tests performed on the same specimen were interspersed by 600s of rest to allow the recovery of the specimen mechanical condition. Results from experimental activities were statistically analyzed and processed by means of a specific mechanical model. Such computational model was developed with the purpose of interpreting the general pressure-volume-time response of biologic tubular structures. The model includes parameters that interpret the elastic and viscous behavior of hollow structures, directly correlated with the results from the experimental activities. RESULTS: Post-processing of experimental data provided information about the non-linear elastic and time-dependent behavior of the urethral duct. In detail, statistically representative pressure-volume and pressure relaxation curves were identified, and summarized by structural parameters. Considering elastic properties, initial stiffness ranged between 0.677 ± 0.026kPa and 0.262 ± 0.006kPa moving from proximal to distal region of penile urethra. Viscous parameters showed typical values of soft biological tissues, as τ1=0.153±0.018s, τ2=17.458 ± 1.644s and τ1=0.201 ± 0.085, τ2= 8.514 ± 1.379s for proximal and distal regions respectively. DISCUSSION: A general procedure for the mechanical characterization of the urethral duct has been provided. The proposed methodology allows identifying mechanical parameters that properly express the mechanical behavior of the biological tube. The approach is especially suitable for evaluating the influence of degenerative phenomena on the lower urinary tract mechanical functionality. The information are mandatory for the optimal design of potential surgical procedures and devices.

Utility of urinary alkaline phosphatase and γ-glutamyl transpeptidase in diagnosing acute kidney injury in dogs.

The diagnostic utility of urinary alkaline phosphatase (uALP) and γ-glutamyl transpeptidase (uGGT) activities in naturally occurring acute kidney injury (AKI) was investigated in a heterogeneous group of dogs. The study included client-owned dogs with AKI (n = 32), chronic kidney disease (CKD, n = 13), lower urinary tract infection (LUTI, n = 15) and healthy controls (n = 24). uGGT and uALP activities were normalised to urinary creatinine (uCr) concentrations (uGGT/uCr and uALP/uCr, respectively). uALP/uCr and uGGT/uCr were positively and significantly correlated (r = 0.619, P <0.001), and differed significantly (P ≤ 0.001) among groups, as well as between AKI and LUTI or CKD groups (P < 0.05), but not between the AKI and control groups. Areas under the receiver operator characteristics (ROC) curve for uALP/uCr and uGGT/uCr as predictors of AKI were 0.75 and 0.65, respectively, with optimal cut-off points showing poor to moderate sensitivity (59% for uALP/uCr and 79% for uGGT/uCr) and specificity (59% for uALP/uCr and 75% for uGGT/uCr). Higher cut-off points, with 90% specificity, showed low sensitivity (41% for both uALP/uCr and uGGT/uCr). In conclusion, uALP/uCr is superior to uGGT/uCr as a marker of AKI, but both uGGT/uCr and uALP/uCr have unsatisfactory discriminatory power for diagnosing naturally occurring AKI in dogs and therefore cannot be recommended as sole screening tests for canine AKI. However, both may serve as ancillary, confirmatory, biomarkers for detecting AKI in dogs if appropriate cut-off points with high specificities are used.

Experimental investigation of the biomechanics of urethral tissues and structures.

NEW FINDINGS: What is the central question of this study? Prostheses for treatment of urinary incontinence elicit complications associated with an inadequate mechanical action. This investigation aimed to define a procedure addressed to urethral mechanical characterization. Experimental tests are the basis for constitutive formulation, with a view to numerical modelling for investigation of the interaction between the tissues and a prosthesis. What is the main finding and its importance? Horse urethra, selected for its histomorphometric similarity to human urethra, was characterized by integrated histological analysis and mechanical tests on the biological tissue and structure, leading to constitutive formulation. A non-linear, anisotropic and time-dependent response was found, representing a valid basis for development of a numerical model to interpret the functional behaviour of the urethra. Urinary dysfunction can lead to incontinence, with an impact on the quality of life. Severe dysfunction can be overcome surgically by the use of an artificial urinary sphincter. Nonetheless, several complications may result from inappropriate functioning of the prosthesis, in many instances resulting from an unsuitable mechanical action of the device on the urethral tissues. Computational models allow investigation of the mechanical interaction between biological tissues and biomedical devices, representing a potential support for surgical practice and prosthesis design. The development of such computational tools requires experimental data on the mechanics of biological tissues and structures, which are rarely reported in the literature. The aim of this study was to provide a procedure for the mechanical characterization of urethral tissues and structures. The experimental protocol included the morphometric and histological analysis of urethral tissues, the mechanical characterization of the response of tissues to tensile and stress-relaxation tests and evaluation of the behaviour of urethral structures by inflation tests. Results from the preliminary experiments were processed, adopting specific model formulations, and also providing the definition of parameters that characterize the elastic and viscous behaviour of the tissues. Different experimental protocols, leading to a comprehensive set of experimental data, allow for a reciprocal assessment of reliability of the investigation approach.