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"Nivy, Ran"
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Continuous Renal Replacement Therapy: Application of Kidney Disease Improving Global Outcomes Guidelines for Treatment Prescription in Dogs With Acute Kidney Injury and Outcome Prediction
by
Raskansky, Hilli
,
Bruchim, Yaron
,
Nivy, Ran
in
acute kidney injury
,
Acute Kidney Injury - therapy
,
Acute Kidney Injury - veterinary
2025
Background Continuous renal replacement therapy (CRRT) is routinely used in human patients with acute kidney injury (AKI) but studies in dogs are scarce. Objective To describe CRRT in dogs and assess the utility of a previously validated scoring system for dogs with AKI undergoing hemodialysis, and the Acute Patient Physiological and Laboratory Evaluation (APPLEFull/APPLEFast) scores, for outcome prediction. Animals Thirty, client‐owned dogs. Methods Cases were retrospectively reviewed. Prognostic scores were calculated upon admission and before CRRT initiation. The CRRT effluent dose followed the KDIGO guidelines. Receiver operating characteristic curves (ROCC) were constructed to evaluate the prognostic utility of these scores. Results Median (IQR) serum creatinine (mg/dL) at CRRT initiation, at discharge, and 3 months after discharge were 9.4 (7.4), 3.4 (1), and 1.3 (0.3) respectively. Median (IQR) treatment duration and total number of treatments were 24 (18.5) h and 2 (2) treatments, respectively. The prescribed median (IQR) CRRT effluent dose was 29 (18.5) mL/kg/h. Median (IQR) overall time‐average concentration for urea and creatinine were 92 (60) mg/dL and 3.7 (1.7) mg/dL, respectively. The normalized weekly median (IQR) standardized Kt/V was 2.41 (2.29). Eleven dogs (37%) survived to discharge/3‐months after treatment. Areas under the ROCC for the APPLEFull/APPLEFast scores before CRRT initiation were 0.99 (95% CI, 0.99–1.00) and 0.91 (95% CI, 0.81–1.00), respectively. Optimal cutoff points were < 35 for the APPLEFull and < 23 for the APPLEFast, yielding sensitivities/specificities of 100% (95% CI, 74.12%–100.0%)/94.7% (95% CI, 75.36%–99.73%) and 90.9% (95% CI, 62.26%–99.53%)/78.95% (95% CI, 56.67%–91.49%), respectively. Conclusion The APPLE scores, unlike clinicopathological findings or the Segev score, proved to be a highly discriminatory prognostic tool. Additionally, the human‐derived, KDIGO guideline‐based CRRT protocol proved safe and efficacious in dogs undergoing CRRT.
Journal Article
Blood Carboxyhemoglobin Concentrations as a Diagnostic Biomarker of Hemolytic Anemias in Cats
by
Bruchim, Yaron
,
Sutton, Gila Abells
,
Nivy, Ran
in
absorption
,
Anemia
,
Anemia, Hemolytic - blood
2025
Background Endogenous carboxyhemoglobin (COHb) production is a byproduct of hemoglobin metabolism. Hypothesis Blood carboxyhemoglobin concentrations are higher in cats with hemolytic anemia (HA). Animals Twenty cats with HA, 29 cats with non‐HA, and 22 controls were prospectively followed. Methods Blood tests were performed upon admission. The Mann–Whitney and Kruskal–Wallis tests were used for comparisons. Receiver‐operating characteristic (ROC) analyses tested COHb as a marker of HA or survival. Results The HA group included 17 cats with immune‐mediated HA and 3 with Heinz body (HB) anemia. In the non‐HA group, leading diagnoses included kidney disease (n = 14), acute/chronic blood loss (n = 11) and pancytopenia (n = 3). Carboxyhemoglobin concentrations (median [IQR]) significantly differed between cats with HA (5.55% [1.9]) and cats with non‐HA (1.9% [0.7]) or controls (1.9% [0.67]; p < 0.001 for both), but not between the last two groups (p = 0.6). Among 13 nonanemic stray cats with significant HB formation, the median (IQR) COHb concentration was 6.1% (1.2). The area under the ROC curve for COHb as a predictor of HA among all anemic cats was 0.996 (95% CI, 0.985–1), with an optimal cut‐off point of 2.95% yielding a sensitivity/specificity of 95% (95% CI, 76%–99%) and 100% (95% CI, 88%–100%), respectively. Survival and COHb concentrations were not associated in either group. Conclusions and Clinical Importance COHb proved a useful ancillary test in cats with suspected HA. Nevertheless, endogenous COHb production occurs with the absorption of large hematomas, not studied herein, or during hemolysis irrespective of anemia. These caveats must be considered when applying the present findings to the clinical and research setting.
Journal Article
Carboxyhemoglobin as a diagnostic and prognostic biomarker of hemolytic anemias in dogs
by
Sutton, Gila
,
Bruchim, Yaron
,
Nivy, Ran
in
Anemia
,
Anemia, Hemolytic - metabolism
,
Anemia, Hemolytic - veterinary
2023
Background Endogenous production of carbon monoxide during hemoglobin metabolism leads to the formation of carboxyhemoglobin. Carboxyhemoglobin concentration is abnormally high in humans with hemolytic anemia (HA). Hypothesis Measurement of carboxyhemoglobin concentration can discriminate HA from other forms of anemia. Animals Twenty‐seven dogs with HA (immune‐mediated HA, n = 22; microangiopathic HA, n = 5), 27 dogs with non‐HA (kidney disease, n = 14; immune‐mediated thrombocytopenia, [n = 6]; miscellaneous, n = 7) and 24 nonanemic control dogs. Methods Prospective cohort study. Carboxyhemoglobin quantification, a CBC and biochemistry profile were performed upon admission, and survival to hospital discharge and at 30 days were the measured outcomes. Groups were compared by the Mann‐Whitney and Kruskal‐Wallis tests. Receiver‐operator characteristic (ROC) analyses were used to examine the predictive utility of carboxyhemoglobin for the diagnosis of HA in anemic dogs. Results Carboxyhemoglobin (median [interquartile range]) differed between dogs with HA (7.7% [2.5%]) and non‐HA (3.6% [1.05]; P < .001) and dogs with HA and nonanemic dogs (3.5% [0.65%]; P < .001). No difference was detected between nonHA and nonanemic dogs. The area under the ROC curve for carboxyhemoglobin as predictor of HA in anemic dogs was 0.997 (95% CI, 0.99‐1.00). Three optimal cut‐off points were identified, including 5.05%, 4.55% and 4.85%, with corresponding sensitivity/specificity of 92.6%/100%, 100%/92.6% and 96.3%/96.3%, respectively. Neither carboxyhemoglobin nor any of the CBC or chemistry analytes were associated with survival. Conclusions and Clinical Importance Carboxyhemoglobin proved an excellent predictor of HA in dogs and might constitute a useful, ancillary tool for diagnosing and monitoring hemolytic anemias.
Journal Article
Prospective evaluation of 5 urinary biomarkers as predictors of acute kidney injury in nonazotemic, hospitalized dogs
by
Hanael, Erez
,
Segev, Gilad
,
Aroch, Itamar
in
acute kidney injury
,
Acute Kidney Injury - diagnosis
,
Acute Kidney Injury - veterinary
2021
Background Early recognition of acute kidney injury (AKI) is hindered by current definitions and use of traditional, insensitive markers. Hypothesis/Objectives Urinary (u) activity of γ‐glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP), and concentrations of heat‐shock protein 70 (HSP70) and interleukins (ILs) ‐6 and ‐18, are predictive biomarkers for AKI and survival. Animals Nonazotemic, hospitalized dogs (n = 118) and healthy controls (n = 20). Methods A prospective observational study. Nonazotemic dogs at risk of AKI were recruited and their urinary biomarker concentrations were measured at presentation. Serum creatinine (sCr) and symmetric dimethylarginine (sSDMA) were measured daily until discharge/death. Results The overall case fatality rate was 18.6%. Fifteen dogs (12.7%) developed AKI, which was associated with death (relative risk, 3.2; 95% confidence interval [CI], 1.57‐6.55). All 5 urinary biomarkers were significantly higher in hospitalized dogs compared to controls, with minimal overlap. uHSP70/uCr, uGGT/uCr, and uIL‐6/uCr at presentation were higher in dogs which later developed AKI. Areas under the receiver operator characteristic curve (AUROC) (95% CI) for the 3 biomarkers as predictors of AKI were 0.67 (0.51‐0.83), 0.68 (0.55‐0.81), and 0.78 (0.65‐0.91), respectively. When they were categorically classified as elevated/normal, each additional elevated biomarker increased the odds for AKI (OR, 2.83; 95% CI, 1.23‐6.52, P = .01). Agreement between sCr and sSDMA was poor (Cohen's kappa = .071). The AUROC of SDMA at presentation for AKI prediction was 0.73 (0.51‐0.95). Conclusions and Clinical Importance Kidney injury was common, irrespective of subsequent worsening of azotemia or death. The predictive value of individual urinary biomarkers was reduced by moderate sensitivities and specificities. SDMA showed moderate discriminatory utility for AKI prediction, and often displayed discordant results with sCr.
Journal Article
Protease inhibitors, inflammatory markers, and their association with outcome in dogs with naturally occurring acute pancreatitis
2020
Background Acute pancreatitis (AP) presumably is associated with pancreatic protease activation, protease inhibitor (PI) depletion, and inflammatory mediator secretion. Objectives Examine PIs and inflammatory mediator concentrations in dogs with AP and their association with death. Animals Thirty‐one dogs diagnosed with AP based on clinical signs, ultrasonographic findings, and increased canine pancreatic lipase immunoreactivity (cPLI) and 51 healthy control dogs. Methods Antithrombin and α2‐antiplasmin activity (ATA and α2AP, respectively) and concentrations of α1‐proteinase inhibitor (α1PI), α2‐macroglobulin (α2MG), C‐reactive protein (CRP), interleukins (ILs)‐2,6,8 and tumor necrosis factor‐α (TNF‐α) were prospectively measured. Severity of AP was assessed by clinical severity scoring systems. Results Mortality rate was 19%. Antithrombin activity was lower (P = .004) and maximal CRP, IL‐6, and TNF‐α concentrations higher (P < .04) in the AP group compared to the controls, whereas IL‐2, IL‐8, α1PI, and α2AP concentrations did not differ between groups. Serum α2MG concentration was not reliably detected. Serum cPLI, CRP, and IL‐6 concentrations were significantly and positively correlated. The ATA was lower (P = .04), and canine acute pancreatitis severity (CAPS) scores higher (P = .009) in nonsurvivors compared to survivors. Higher CAPS scores were associated (P < .05) with decreased ATA and increased cPLI, CRP, and IL‐6 concentrations. Conclusions and Clinical Importance Systemic inflammation in dogs with AP is manifested by increased inflammatory mediator concentrations, correlating with cPLI and CRP concentrations. Hypoantithrombinemia is associated with death. Serum concentrations of α2AP and α1PI are less useful prognostic markers. The CAPS score is a useful prognostic marker in dogs with AP.
Journal Article
A prospective randomized study of efficacy of 2 treatment protocols in preventing recurrence of clinical signs in 51 male cats with obstructive idiopathic cystitis
by
Segev, Gilad
,
Aroch, Itamar
,
Bruchim, Yaron
in
Adrenergic alpha-Antagonists - therapeutic use
,
Alprazolam - therapeutic use
,
Animal euthanasia
2019
Background Urethral obstruction (UO) is a common complication of feline idiopathic cystitis (FIC). Robust treatment recommendations to prevent its recurrence are scarce. Objectives To evaluate meloxicam treatment for prevention of clinical recrudescence in male cats with obstructive FIC. Animals Fifty‐one client‐owned cats. Methods Prospective, randomized clinical trial. Every male cat with FIC‐associated UO was deemed eligible for the study and was recruited during hospitalization. After discharge, cats were treated with phenoxybenzamine and alprazolam for 2 weeks, with (24 cats) or without (27 cats) low‐dose meloxicam (0.025 mg/kg/day PO) and monitored for 6 months. Results Cumulative number (%) of cats with recurrent UO at 10 days, 1‐, 2‐, and 6‐months after discharge was 1 (2%), 2 (4%), 4 (8%), and 8 (16%), respectively. Overall, 12 (24%) cats experienced signs of recurrent FIC within 6 months, with (8 cats) or without (4 cats) concurrent UO. No difference in the cumulative incidence of UO within 6 months was detected with addition of meloxicam (odds ratio [95% confidence interval], 0.63 [0.13‐2.97]; P = .70). All cats were alive at 6 months. Conclusions and Clinical Importance No clinical benefit was detected with the addition of low‐dose meloxicam to phenoxybenzamine and alprazolam treatment for 2 weeks after discharge. Nevertheless, this study was underpowered to identify potential differences, and its findings must be corroborated in larger studies.
Journal Article
Treatment of a cat with presumed Bartonella henselae‐associated immune‐mediated hemolytic anemia, fever, and lymphadenitis
by
Nachum‐Biala, Yaarit
,
Golani, Yael
,
Harrus, Shimon
in
Anemia
,
Antibiotics
,
Bartonella henselae
2022
A 2.5‐year‐old castrated male cat presented with fever and marked generalized lymphadenopathy of 4‐months duration, despite treatment with amoxicillin‐clavulanate/marbofloxacin. Abnormalities were not detected on complete blood count, serum chemistry, and FIV/FeLV test apart from a borderline, non‐regenerative anemia. Peripheral lymph node fine needle aspirations revealed a marked increase in the percentage of intermediate‐ and lymphoblastic‐lymphocytes in addition to reactive macrophages. Three weeks after presentation, the cat developed a severe, regenerative, immune‐mediated hemolytic anemia (IMHA) which responded to immunosuppressive therapy. Fever and lymphadenopathy persisted. Peripheral lymph nodes tested positive for Bartonella henselae DNA in real‐time PCR assay and sequencing. Treatment with pradofloxacin and doxycycline resulted in resolution of clinical signs, and negative PCR tests. Despite its reported low pathogenicity, B. henselae infection should also be considered in cats with protracted unexplained fever, lymphadenitis, and IMHA. Furthermore, a combination of pradofloxacin and doxycycline might be considered in cats with bartonellosis given its apparent clinical efficacy.
Journal Article
The interpretive contribution of the baseline serum cortisol concentration of the ACTH stimulation test in the diagnosis of pituitary dependent hyperadrenocorticism in dogs
by
Refsal, Kent R.
,
Kuzi, Sharon
,
Yas‐Natan, Einat
in
added‐value
,
Adrenocortical Hyperfunction - blood
,
Adrenocortical Hyperfunction - diagnosis
2018
Background Current recommendation for performing the ACTH stimulation test (ACTHST) for diagnosis of hyperadrenocorticism (HAC) advocates the collection of baseline serum cortisol concentration (BC), but no references for interpretation of its results exist. Objective Evaluate the contribution of BC of the ACTHST to the diagnosis of HAC. Animals Fifty‐four dogs were evaluated for suspected HAC at a referral hospital. Methods Records of dogs that had been evaluated by ACTHST for suspected HAC were reviewed. Receiver operator characteristics (ROC) analyses were used to assess the performance of BC, post‐stimulation serum cortisol concentrations (PC), post‐to‐baseline cortisol concentration difference (DeltaC) and quotient (RatioC) for the diagnosis of HAC by comparing the area under the ROC curve (AUC) of PC to each of the other tests. Results The AUC of PC (95% confidence interval [CI]: 0.92; 95% CI, 0.81‐0.98) was significantly higher than AUCs of BC (0.70; 95% CI, 0.56‐0.82; P = .01) and RatioC (0.55; 95% CI, 0.41‐0.69; P < .001), and was not significantly different from AUC of DeltaC (0.86; 95% CI, 0.74‐0.94; P = .09). An optimal cutoff value of 683 nmol/L (24.8 μg/dL) for PC yielded a sensitivity of 86% and a specificity of 94%, respectively, and a cutoff value of 718 nmol/L (26.0 μg/dL) yielded a specificity of 100% with of 81% sensitivity for the diagnosis of pituitary‐dependent HAC. Conclusion and Clinical Importance The PC had good discriminatory ability for the diagnosis of HAC. It was comparable to DeltaC, whereas BC and RatioC were ineffective. Current recommendations to collect samples for BC appear redundant.
Journal Article
Time course of serum cobalamin, folate, and total iron binding capacity concentrations in pregnant bitches and association with hematological variables and survival
2019
Background Hypocobalaminemia, hypofolatemia and iron deficiency are associated with pregnancy‐related anemia (PRA) and neonatal survival (NS) in women. Similar associations have not been investigated in pregnant bitches. Objectives To investigate time course and associations of serum cobalamin, folate and iron status indicators with hematological variables and NS in pregnant bitches. Animals Forty‐eight pregnant bitches. Methods A prospective cohort study. Pregnancy was confirmed by abdominal ultrasonography twice during mid‐ and late pregnancy, concurrently with blood sampling. Associations among pregnancy stage, NS and laboratory variables were assessed by generalized estimating equations. Results Compared with midpregnancy, serum cobalamin (adjusted mean [95% confidence interval, CI]) decreased at late pregnancy (430 pg/mL [394‐466] versus 330 pg/mL [303‐357], respectively; P < .001), whereas serum folate did not. Every increment of 1 in parity number or litter size corresponded to 28.6 pg/mL (95% CI, 5.6‐51.6; P = .02) and 20.3 pg/mL (95% CI, 10.9‐29.7; P < .001) decrease in serum cobalamin concentration. Compared with midpregnancy, serum iron (P < .001) and transferrin saturation (P = .01) increased at late pregnancy. The decrease in red blood cell count (P < .001) at late pregnancy was significantly, albeit weakly, correlated with decreasing serum folate concentration (r = 0.33; P = .02). None of the measures was associated with NS. Conclusions and Clinical Significance Pregnancy‐related anemia was common at late pregnancy. Unlike in women, in pregnant bitches, serum iron and transferrin saturation were increased at late pregnancy. Future studies are warranted to investigate the clinical ramifications of hypocobalaminemia in pregnant bitches and the utility of prophylactic folate administration in mitigating PRA.
Journal Article
Short Term Safety, Immunogenicity, and Reproductive Effects of Combined Vaccination With Anti-GnRH (Gonacon) and Rabies Vaccines in Female Feral Cats
2021
Overpopulation of free-roaming cats is a major problem leading to negative impacts on animal health and welfare, public nuisance, transmission of zoonotic diseases, and well-documented harm to wildlife. Surgical sterilization had failed to provide a practical solution to free-roaming cats' overpopulation under field conditions; therefore, efficient and safe non-surgical immunocontraception methods are aspired. Rabies is a deadly virus that may infect people and animals. However, the safety and efficacy of combined vaccination with anti-GnRH and rabies vaccines in feral cats, which often suffer from disrupted health conditions and experienced high stress level, has never been studied. Therefore, our objective was to examine the short-term safety and efficacy of anti-GnRH vaccine (Gonacon), in combination with rabies vaccine in female feral cats. Mature feral female cats were captured and divided into the following groups: (I) GonaconX1-Rabies: queens vaccinated with both Gonacon and rabies ( n = 5); (II) GonaconX2-Rabies: queens vaccinated twice with Gonacon (3 weeks apart) and with Rabies ( n = 4); (III) OVx-Rabies: queens ovariohysterectomized and vaccinated with rabies ( n = 4); (IV) Intact-Rabies: queens vaccinated against rabies and remained intact ( n = 3). Comprehensive veterinary examinations and blood tests were performed every 2 weeks for 14 weeks. Data were analyzed by Repeated-Measures-ANOVA or Fisher-Exact-Test. There were neither systemic nor local adverse reactions at the vaccination sites. Blood count (PCV, TS, RBC, HGB, HCT, WBC) and chemistry (Total protein, Total globulin, Albumin, Urea, Creatinine, Creatine kinase, Bilirubin, GGT, ALT, AST) analyses revealed no differences among groups. There were no differences in serum rabies antibodies titers among groups, and queens kept a protective titer (>0.5 IU/mL) starting at 2–4 weeks after vaccination. Anti-GnRH antibodies were detected in all Gonacon-vaccinated queens, excluding one queen (GonaconX2-Rabies group). Anti-müllerian hormone serum concentrations reduced significantly after ovariohysterectomy, as well as gradually following vaccination with Gonacon, but it remained high in intact queens. Evaluation of vaginal cytology and ovarian histology suggested that reproductive cyclicity was suppressed in Gonacon-vaccinated queens. Our results support the conclusion that in the short term, the combined vaccination with Gonacon and rabies is safe and effective in female feral cats. However, further long-term studies are warranted to test this immunologic regimen in feral cats.
Journal Article