International renal interest society best practice consensus guidelines for intermittent hemodialysis in dogs and cats.

Intermittent hemodialysis (IHD) is an advanced adjunctive standard of care for severe acute kidney injury (AKI) and other indications. Most animals with AKI are managed medically, however, when the disease is severe, medical management may not control the consequences of the disease, and animals with a potential for renal recovery may die from the consequences of uremia before recovery has occurred. Extracorporeal therapies aid the management of AKI by expanding the window of opportunity for recovery of sufficient kidney function to become dialysis independent. Intermittent hemodialysis (IHD) was introduced into veterinary medicine over 50 years ago, however, updated guidelines for the delivery of IHD have not been published for several decades. To that end, the International Renal Interest Society (IRIS) constituted a Working Group to establish best practice guidelines for the safe and effective delivery of IHD to animals with indications for dialytic intervention. The IRIS Working Group generated 60 consensus statements and supporting rational for a spectrum of prescription and management categories required for delivery of IHD on designated intermittent dialysis platforms (i.e., AKI, chronic hemodialysis and intoxications). A formal consensus method was used to validate the recommendations by a blinded jury of 12 veterinarians considered experts in extracorporeal therapies and actively performing IHD. Each vote provided a level of agreement for each recommendation proposed by the Working Group. To achieve a consensus, a minimum of 75% of the voting participants had to "strongly agree" or "agree" with the recommendation.

Urinary cystatin B differentiates progressive versus stable IRIS Stage 1 chronic kidney disease in dogs.

BACKGROUND: Early identification of dogs with progressive vs stable chronic kidney disease (CKD) might afford opportunity for interventions that would slow progression. However, currently no surrogate biomarker reliably predicts CKD progression. HYPOTHESIS/OBJECTIVES: Urinary cystatin B (uCysB), a novel kidney injury biomarker, predicts progressive disease in International Renal Interest Society (IRIS) CKD Stage 1. ANIMALS: Seventy-two dogs, including 20 dogs from 4 university centers with IRIS CKD Stage 1, with IDEXX symmetric dimethylarginine (SDMA) concentration up to 17 µg/dL and no systemic comorbidities, and 52 clinically healthy staff-owned dogs from a fifth university center. METHODS: A multicenter prospective longitudinal study was conducted between 2016 and 2021 to assess uCysB concentration in IRIS CKD Stage 1 and control dogs. Dogs were followed to a maximum of 3 years (control) or 25 months (CKD). Stage 1 IRIS CKD was classified as stable or progressive using the slope of 1/SDMA, calculated from 3 timepoints during the initial 90-day period. Dogs with slope above or below -0.0007 week × dL/µg were classified as stable or progressive, respectively. Mixed effects modeling was used to assess the association between uCysB and progression rate. RESULTS: Estimates of first visit uCysB results predictive of active ongoing kidney injury based on the mixed effects models were 17 ng/mL for control, 24 ng/mL for stable CKD, and 212 ng/mL for progressive CKD (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary cystatin B differentiated stable vs progressive IRIS CKD Stage 1. Identification of dogs with progressive CKD may provide an opportunity for clinicians to intervene early and slow progression rate.

Differentiation of stable kidney function versus progressive dysfunction in dogs.

BACKGROUND: Circulating creatinine and symmetric dimethylarginine (SDMA) are biomarkers of kidney function that have been used variously to define stable vs progressive chronic kidney disease (CKD). Slope monitoring of inverse biomarker values (creatinine-1 or SDMA-1 ) has shown promise, but quantitative criteria to distinguish stable vs progressive CKD using this approach are lacking. OBJECTIVE: Assessment of creatinine-1 and SDMA-1 slope cutoffs to distinguish stable vs progressive CKD. ANIMALS: One hundred ten clinically healthy university staff-owned dogs and 29 male colony dogs with progressive X-linked hereditary nephropathy (XLHN). METHODS: Retrospective analysis combining 2 prospective observational studies, 1 tracking kidney function biomarkers in healthy dogs (HDs) to a maximum of 3 years, and 1 tracking kidney function biomarkers in male colony dogs with progressive XLHN to a maximum of 1 year. The minimum slope of creatinine-1 or SDMA-1 as measured using the IDEXX SDMA test from HD was assigned as the slope cutoff for stable kidney function. RESULTS: The stable vs progressive slope cutoff was -0.0119 week × dL/mg for creatinine-1 and -0.0007 week × dL/µg for SDMA-1 . CONCLUSIONS AND CLINICAL IMPORTANCE: In the studied CKD population, progressive dysfunction can be distinguished from stable kidney function by using the slope of creatinine-1 or SDMA-1 . These criteria may serve to characterize CKD in other cohorts of dogs and to establish guidelines for degrees of progression rate in dogs with naturally occurring CKD.

Updated ACVIM consensus statement on leptospirosis in dogs.

Since publication of the last consensus statement on leptospirosis in dogs, there has been revision of leptospiral taxonomy and advancements in typing methods, widespread use of new diagnostic tests and vaccines, and improved understanding of the epidemiology and pathophysiology of the disease. Leptospirosis continues to be prevalent in dogs, including in small breed dogs from urban areas, puppies as young as 11 weeks of age, geriatric dogs, dogs in rural areas, and dogs that have been inadequately vaccinated for leptospirosis (including dogs vaccinated with 2-serovar Leptospira vaccines in some regions). In 2021, the American College of Veterinary Internal Medicine (ACVIM) Board of Regents voted to approve the topic for a revised Consensus Statement. After identification of core panelists, a multidisciplinary group of 6 experts from the fields of veterinary medicine, human medicine, and public health was assembled to vote on the recommendations using the Delphi method. A draft was presented at the 2023 ACVIM Forum, and a written draft posted on the ACVIM website for comment by the membership before submission to the editors of the Journal of Veterinary Internal Medicine. This revised document provides guidance for veterinary practitioners on disease in dogs as well as cats. The level of agreement among the 12 voting members (including core panelists) is provided in association with each recommendation. A denominator lower than 12 reflects abstention of ≥1 panelists either because they considered the recommendation to be outside their scope of expertise or because there was a perceived conflict of interest.

5-Hydroxytryptophan toxicity successfully treated by haemodialysis in a dog.

OBJECTIVE: To describe a case of 5-hydroxytryptophan (5-HTP) toxicity successfully treated with haemodialysis in a dog. CASE SUMMARY: A 3-year-old, male neutered Labrador Retriever, weighing 28.2 kg, presented to the emergency department approximately 4-5 h after ingesting a human supplement containing 200 mg of 5-HTP. The amount of 5-HTP ingested was estimated between 980 and 1988 mg (35-71 mg/kg). At presentation, the dog demonstrated progressive neurologic abnormalities consistent with serotonin syndrome, including altered mentation and ataxia. Due to the magnitude of the ingested dose and progression of clinical signs, extracorporeal blood purification with intermittent haemodialysis was chosen to expedite clearance of 5-HTP. High-efficiency haemodialysis was initiated, and the dog showed continued clinical improvement throughout the 5-h treatment. Clinical signs resolved completely within 12 h. Sequential blood and urine samples were obtained to document levels of both 5-HTP and serotonin. The dog was discharged 24 h after presentation with complete resolution of clinical signs. NEW OR UNIQUE INFORMATION: This is the first report documenting the serial changes in 5-HTP concentrations during treatment with haemodialysis.

Ultrafiltration during intermittent hemodialysis in dogs with acute kidney injury.

BACKGROUND: Ultrafiltration is performed to alleviate fluid overload in dogs with acute kidney injury (AKI) undergoing intermittent hemodialysis (IHD). OBJECTIVES: To describe prescription patterns for ultrafiltration in dogs receiving IHD for AKI and risk factors for ultrafiltration-related complications. ANIMALS: Seventy-seven dogs undergoing 144 IHD treatments between 2009 and 2019. METHODS: Medical records of dogs receiving IHD for AKI were reviewed. The initial 3 IHD treatments in which ultrafiltration was prescribed were included. Ultrafiltration-related complications were defined as those requiring an intervention such as transient or permanent discontinuation of ultrafiltration. RESULTS: Mean fluid removal rate per treatment was 8.1 ± 4.5 mL/kg/h. Ultrafiltration-related complications occurred in 37/144 (25.7%) of treatments. Hypotension was rare (6/144, 4.2% of treatments). No ultrafiltration-related complications resulted in deaths. The mean prescribed fluid removal rate per treatment was higher in dogs with ultrafiltration-related complications than without (10.8 ± 4.9 mL/kg/h vs 8.8 ± 5.1 mL/kg/h, respectively; P = .03). The mean delivered fluid removal rate per treatment was significantly lower in dogs with UF-related complications compared to those without complications (6.8 ± 4.0 mL/kg/h vs 8.6 ± 4.6 mL/kg/h, respectively; P = .04). Variables associated with ultrafiltration-related complications (P < .05) included central venous oxygen saturation, body temperature before IHD treatment, total extracorporeal circuit volume and BUN at the end of IHD treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Ultrafiltration during IHD in dogs with AKI is overall safe. Higher prescribed ultrafiltration rates were associated with increased risk of complications. Decrease in central venous oxygen saturation is associated with ultrafiltration-related complications, emphasizing the utility of in-line blood monitoring.

Successful treatment of 5-fluorouracil toxicosis with hemodialysis.

OBJECTIVE: To describe the successful treatment of lethal dose 5-fluorouracil (5-FU) toxicosis using hemodialysis. CASE SUMMARY: A 4-month-old intact female Golden Retriever was presented to the emergency department after ingesting 20 g of 5% 5-FU cream. The puppy developed refractory seizures and became comatose with uncontrolled tonic-clonic convulsions. Because of the low molecular weight and minimal protein binding of 5-FU, a single hemodialysis treatment was employed for detoxification. The puppy improved clinically posttreatment and was successfully discharged 3 days after admission. Postingestion leukopenia and neutropenia occurred but were responsive to treatment with filgrastim. The puppy is neurologically normal and has no lasting effects 1 year postingestion. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first reported case in veterinary medicine of a potentially fatal 5-FU ingestion that has been treated with intermittent hemodialysis.

Association of ultrasonographic features with histologic findings in 71 dogs with protein-losing nephropathy (2008-2018).

OBJECTIVE: To determine whether ultrasonographic features in dogs with protein-losing nephropathy (PLN) were associated with renal biopsy findings and compare corticomedullary ratios between dogs with PLN versus non-renal disease. ANIMALS: 71 dogs with PLN and 33 dogs without renal disease. PROCEDURES: Medical records and archived ultrasonographic images for dogs with PLN that underwent renal biopsy between 2008 and 2018 were reviewed. Corticomedullary ratios were measured. RESULTS: In dogs with PLN, median serum creatinine and BUN concentrations and urine-protein-to-creatinine-ratio prior to renal biopsy were 3.4 mg/dL (interquartile range [IQR], 1.2 to 5.3 mg/dL), 80 mg/dL (IQR, 28 to 105 mg/dL), and 11.4 (IQR, 6.4 to 18.3), respectively. Histologic abnormalities within the tubulointerstitial space were associated with cortical echogenicity. Gastric wall thickness > 5 mm was associated with a histologic diagnosis of acute glomerular disease. Dogs with immune complex-mediated glomerular disease were more likely to have abnormal gastric mural architecture. Other ultrasonographic features of the kidneys, liver, and stomach and the presence of ascites did not help to differentiate immune complex-mediated from non-immune complex-mediated glomerular disease, acute from chronic disease, or amyloid from non-amyloid disease or distinguish whether tubulointerstitial disease was present or absent. Median left corticomedullary ratio for 66 dogs with PLN (1.2) was significantly higher than that for the 33 dogs without renal disease (1.0). CLINICAL RELEVANCE: Ultrasonographic features were poorly associated with specific pathological disorders in dogs with PLN. In this study, the corticomedullary ratio was higher in dogs with PLN, indicating the presence of cortical thickening, but the clinical relevance is unknown.

Comparison of IDEXX SediVue Dx® urine sediment analyzer to manual microscopy for detection of casts in canine urine.

BACKGROUND: Detection of urinary casts is difficult due to their intermittent presence and deterioration in urine samples. OBJECTIVE: To compare the performance of the IDEXX SediVue Dx® Urine Sediment Analyzer (SediVue) with manual microscopy for the detection of urinary casts. We hypothesized that the SediVue analyzer would perform similarly to manual microscopy in cast detection. ANIMALS: Four hundred forty-three samples from 420 dogs from a hospital population. METHODS: This is a prospective, cross-sectional study. For SediVue analysis (software version [SW] 1.0.1.3), uncentrifuged urine was pipetted into a disposable cartridge. Seventy images were captured and processed by an onboard algorithm. For manual microscopy, urine was centrifuged to obtain sediment. Any cast identified by either method was considered a positive result (>0/low-power field [LPF]). SediVue images were evaluated if casts were detected by either methodology. A revised sensitivity and specificity were calculated after image review and when using a threshold of >1 cast/LPF. RESULTS: The sensitivity of the SediVue analysis for the detection of urinary casts was 53.7% (43.85%-63.35%), and specificity was 86.0% (81.78%-89.51%). After image review, the revised sensitivity/specificity was 52.0% (42.89%-61.02%) and 90.6% (86.81%-93.54%), respectively. When using a more clinically relevant threshold of >1/LPF, the sensitivity was 52.6% (35.82%-69.02%) and specificity was 99.3% (97.85%-99.85%). CONCLUSIONS AND CLINICAL IMPORTANCE: The SediVue provides moderate agreement to manual methodology for detection of casts in urine.

Application of therapeutic plasma exchange in dogs with immune-mediated thrombocytopenia.

Therapeutic plasma exchange (TPE) is an emerging treatment for dogs with immune-mediated diseases, but reports for treatment of immune-mediated thrombocytopenia (IMT) are lacking. These case reports illustrate the application of centrifugal TPE in 4 dogs with IMT. All dogs presented with severe hemorrhage requiring ≥1 blood transfusions, were unresponsive to conventional treatment or both. Dogs were treated with 3 sequential centrifugal TPE sessions, totaling 4.0 to 4.9 total plasma volumes exchanged per dog. In 3 dogs, TPE was associated with improvement in clinical manifestations of bleeding and platelet count in combination with immunosuppressive drugs. One dog was euthanized after 3 treatments because of persistent severe thrombocytopenia and hemorrhage. Preliminary observations indicate that TPE is safe and may be a useful adjunct in the management of IMT that is severe or refractory to traditional treatment.

Sequential changes in urine production, glomerular filtration rate, and electrolyte excretion after mannitol administration.

INTRODUCTION: Acute kidney injury (AKI) leading to severe uremia is associated with high morbidity and mortality. Mannitol is an osmotic diuretic, widely used in the management of AKI, both as a bolus injection and as a constant rate infusion (CRI). OBJECTIVES: To determine the plasma concentration of mannitol after a bolus injection and CRI at the recommended dosages, and to assess the effect of mannitol on renal function variables including urine production, glomerular filtration rate (GFR), and solute excretion. METHODS: Prospective cross-over design study, using 6 healthy dogs. Each dog underwent 3 protocols with at least a 7-day washout period between protocols. The first protocol included bolus injection of mannitol, the second protocol included bolus injection followed by CRI of mannitol and the third protocol (control) included injection of 5% dextrose in water (D5W). Urine production, GFR, and fractional excretion (FE) of solutes were measured for 10 hours. RESULTS: For all protocols, urine production significantly (P < .001) increased after bolus injection, but no significant difference in urine production or GFR was observed among the treatment groups. Mannitol injection increased the FE of sodium and urea nitrogen, but these effects were short-lived. CONCLUSIONS: Mannitol has minimal effect on urine production and GFR but does increase FE of urea nitrogen and sodium, immediately after bolus injection. Constant rate infusion at a conventional dosage of 1 mg/kg/min cannot maintain these effects in dogs with normal renal function, because mannitol concentration decreases rapidly.

Associations between dialysate sodium concentration and plasma sodium concentration of dogs receiving intermittent hemodialysis treatments.

OBJECTIVE To compare dialysate sodium concentration and patient plasma sodium concentration of dogs during intermittent hemodialysis treatments. SAMPLE 211 intermittent hemodialysis treatments performed on 40 client-owned dogs for the management of dialysis-dependent uremia. PROCEDURES Medical records were reviewed to determine the plasma sodium concentration of each dog before and after routine hemodialysis treatments. Associations between detected changes in plasma sodium concentration and dialysate sodium concentration were evaluated by use of Spearman rank correlations and linear regression analysis. RESULTS Significant linear correlations were found between the dialysate sodium concentration and patient sodium concentration. The starting dialysate-to-patient sodium gradient was associated with the strongest correlation to the change in patient sodium concentration at the end of the dialysis session. Modest correlations existed between the dialysate sodium concentration and postdialysis patient sodium concentration as well as between the predialysis dialysate-to-patient sodium gradient and postdialysis dialysate-to-patient sodium gradient. CONCLUSIONS AND CLINICAL RELEVANCE The dialysate sodium concentration was correlated with the patient sodium concentration in dogs, and the dialysate-to-patient sodium gradient could be used to further refine this association to predict the postdialysis patient sodium concentration and potentially manage dysnatremia during hemodialysis. Prospective studies should be performed to determine how these associations can be used to correct aberrations as well as to avoid unwanted alterations in patient sodium concentrations.

Treatment of acute kidney injury associated with cyclosporine overdose in a dog using hemodialysis and charcoal hemoperfusion.

OBJECTIVE: To describe the management of cyclosporine overdose using hemodialysis and hemoperfusion in a dog. CASE SUMMARY: A 6-year-old, spayed female Australian Shepherd was presented for treatment of cyclosporine overdose and acute kidney injury. Five days prior to presentation, the dog had been diagnosed by its referring veterinarian with immune-mediated thrombocytopenia. Treatment was initiated with prednisone, but since no response was noted, azathioprine (50 mg PO q 24 h) and cyclosporine (6 mg/kg IV q 24 h) were added. On day 4, an overdose of cyclosporine (33 mg/kg IV) was administered accidentally. Upon presentation, serum biochemistry panel revealed azotemia [creatinine, 521.6 µmol/L (5.9 mg/dL); BUN, 59.3 mmol/L (166 mg/dL)], increased activities of liver enzymes, and hyperbilirubinemia. Due to the presumed diagnosis cyclosporine overdose and acute kidney injury, a combined hemodialysis and charcoal hemoperfusion treatment was planned. Hemosorba CH-350 charcoal hemoperfusion cartridge was placed in series upstream in the extracorporeal circuit from the hemodialyzer. A 3-hour treatment was performed and a total of 0.74 L/kg of blood was processed. Pretreatment blood cyclosporine concentration was 960 nmol/L (1154 ng/mL) and decreased to 440 nmol/L (529 ng/mL) posttreatment (54% fractional reduction, 18% per hour). Thirty-one hours following treatment, blood cyclosporine concentration was 220 nmol/L (265 ng/mL; 1.5% decrease per hour). Twelve days following presentation to our hospital, the dog was euthanized due to lack of response to medical management. NEW OR UNIQUE INFORMATION PROVIDED: Combined hemodialysis and charcoal hemoperfusion treatment can significantly reduce blood cyclosporine concentrations following acute intoxication or overdosage, and should be considered as an option for decontamination in such cases.

Cardiorenal Syndrome: Diagnosis and Management.

Cardiorenal syndrome (CRS) has not been well characterized in veterinary medicine, yet an accurate appreciation of the kidney and the cardiovascular system and their interactions may have practical clinical implications. A consensus for cardiovascular-renal axis disorders of dogs and cats was recently attempted. The outcome of patients with CRS is likely to improve with the increasing awareness and ability to identify and understand the pathophysiologic characteristics of CRS. The utilization of existing and emerging organ-specific biomarkers with greater sensitivities than conventional diagnostics forecast new opportunities to diagnose and manage cardiac disease.

Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats.

Resolution of anuric acute kidney injury in a dog with multiple organ dysfunction syndrome.

OBJECTIVE: To describe the management and resolution of anuric acute kidney injury (AKI) in a dog with multiple organ dysfunction syndrome (MODS) associated with gallbladder wall necrosis. CASE SUMMARY: An 11-year-old neutered female spayed dog was referred for evaluation of anuria following cholecystectomy. Following surgery, the patient became anuric with no response to appropriate medical therapy. During the course of hospitalization, the patient developed MODS as evidenced by alteration in renal function, but also cardiovascular dysfunction, coagulation disorders, and hypoglycemia. Several hemodialysis treatments were performed and, along with intensive care, led to resolution of clinical signs and return of urine production. NEW OR UNIQUE INFORMATION: This report describes resolution of anuria in a dog with AKI and MODS. In this clinical setting, despite a poor prognosis, survival and recovery of adequate renal function were possible with medical management that included hemodialysis.

Extracorporeal renal replacement therapy and blood purification in critical care.

OBJECTIVE: To review indications methods of renal replacement therapies (RRT) and practical considerations for the creation of a RRT program. DATA SOURCES: Current human and veterinary literature review with a focus on advanced renal physiology and clinical experience in RRT and acute/chronic kidney diseases. DATA SYNTHESIS: Renal replacement therapies encompass intermittent hemodialysis, continuous renal replacement therapy as well as some "hybrid" techniques. Each method of RRT has practical and theoretical advantages but currently there is no evidence that one technique is superior to the other. CONCLUSIONS: RRT is a valuable therapeutic tool for treatment of acute kidney injury and chronic kidney disease. The implementation of an RRT program needs to take into consideration multiple parameters beyond the choice of an RRT platform.