Acute Kidney Injury In Cats Research Articles

Urinary Cystatin B as a marker of acute kidney injury in cats

Diagnosing acute kidney injury (AKI) might be challenging due to lack of sensitive early markers. The objective of this study was to evaluate the diagnostic and prognostic utility of the urinary biomarker Cystatin B (uCysB) in cats with AKI. Seventy-six client-owned cats were included. Urine samples of healthy cats and cats with various urinary tract disease including urethral obstruction (UO), chronic kidney disease (CKD) and AKI, were collected. uCysB concentration was measured using a research sandwich format ELISA at IDEXX Laboratories, Inc.uCysB was different among groups (P <0.001). uCysB was higher in the AKI (P <0.001) and CKD (P =0.006) groups compared with controls [1052ng/mL (range, 7-3858) and 112ng/mL (range, 14-1370) vs. 22ng/mL (range, 11-154), respectively]. Cats with AKI had higher uCysB compared with cats with CKD (P =0.001) or UO (P =0.004). Receiver operator characteristic curve (ROC) analysis of uCysB as an AKI predictor vs. controls had an area under the curve (AUC) of 0.92 (95%CI, 0.84-1.0). A 84ng/mL cutoff point corresponded to sensitivity and specificity of 90% and 92%, respectively. uCysB concentration was higher in AKI non-survivors compared with survivors (1572ng/mL, range, 140-3858 vs. 584ng/mL, range, 7-2803 respectively; P =0.004). ROC analysis of uCysB as an AKI outcome predictor had an AUC of 0.84 (95%CI, 0.56-1.0), with an optimal cut-off point of 469ng/mL, corresponding to sensitivity and specificity of 100% and 75% respectively. In conclusion, uCysB is a useful diagnostic and prognostic marker of AKI in cats.

Acute kidney injury in 18 cats after subcutaneous meloxicam and an update on non-steroidal anti-inflammatory drug usage in feline patients in Australia.

Acute kidney injury (AKI) is a well-known but poorly documented adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) in cats. We aimed to describe instances of NSAID-associated AKI in cats and survey Australian veterinarians on NSAID use in acute settings. Medical records of cats that developed an AKI subsequent to the administration of meloxicam were obtained by searching the databases of seven practices in Queensland, as well as by contemporaneously contacting select veterinary colleagues of the authors in both general and specialist small animal practice. An online questionnaire was created for the survey, and the URL distributed to Australian practitioners. A total of 18 cases were retrieved, all of which received injectable meloxicam. The indication(s) for its use and the dosage prescribed were within the manufacturer's recommendations for Australian veterinarians. The majority of cases (13/18 cats) received the label dose of 0.3 mg/kg subcutaneously (SC) on the day of the procedure. In 12/18 cats, the injection was given in association with general anaesthesia or sedation. Fourteen cats survived to hospital discharge. Of 187 survey respondees, 89% routinely administered NSAIDs for surgery-related analgesia, with 98% prescribing meloxicam and 84% of these giving it SC. Ninety percent of respondees routinely administered NSAIDs for non-surgical-related analgesia, with 99% prescribing meloxicam and 35% of those giving it SC. We strongly recommend that practitioners avoid prescribing meloxicam SC in cats. This recommendation is emphatic in situations where concurrent dehydration and/or hypotension are possible.

Evaluation of symmetric dimethylarginine in cats with acute kidney injury and chronic kidney disease.

BackgroundSerum symmetric dimethylarginine (SDMA) concentrations are considered a biomarker for renal dysfunction in dogs and humans with acute kidney injury (AKI). No studies have assessed SDMA in cats with AKI.Hypothesis/ObjectivesSDMA correctly identifies cats with azotemic AKI.AnimalsFifteen control cats, 22 with novel AKI, 13 with acute on chronic‐AKI (AoC) and 19 with chronic kidney disease (CKD).MethodsRetrospective study. Cats with azotemia (serum creatinine concentrations >1.7 mg/dL) were defined as having AKI or CKD based on history, clinical signs, clinicopathological findings and diagnostic imaging, and classified using the International Renal Interest Society (IRIS) grading/staging systems. Serum SDMA concentrations were compared between groups with nonparametric methods, and correlations assessed using Spearman's correlation coefficient. Data are presented as median [range].ResultsSDMA concentrations were 11 (8‐21) μg/dL, 36 (9‐170)μg/dL, 33 (22‐75) μg/dL and 25 (12‐69) μg/dL in control, novel AKI, AoC and CKD cats. SDMA concentrations were significantly higher in cats with novel AKI (P < .001), AoC (P < .001) and CKD (P < .01) compared to controls. SDMA concentrations were significantly higher in cats with more advanced AKI (IRIS grade IV‐V) compared to less severe AKI (IRIS grade II). Serum creatinine and SDMA concentrations had a significant correlation in cats with novel AKI (r s = 0.826, n = 22; P < .001) and a significant correlation when all cats across all 4 groups were considered together (r s = 0.837, n = 69; P < .001).Conclusions and Clinical ImportanceSerum SDMA concentrations are elevated in cats with established AKI (novel and AoC) and CKD, providing evidence for use of SDMA as a biomarker for AKI in cats.

Kidney injury molecule-1 and urinary gamma-glutamyl transferase as biomarkers of acute kidney injury in cats.

To evaluate the concentration of kidney injury molecule-1 and activity of urinary gamma-glutamyl transferase in cats with urethral obstruction and healthy cats. Blood and urine samples were collected from a group of 15 healthy cats (control group) and a group of 20 cats with urethral obstruction at presentation, and 24hours and 7 days after unblocking the obstruction. The serum creatinine, urinary creatinine and urinary gamma-glutamyl transferase were measured by spectrophotometry and kidney injury molecule-1 by the sandwich enzyme-linked immunosorbent assay. On presentation, cats with obstruction had serum creatinine concentration and urinary gamma-glutamyl transferase index higher than healthy cats (mean difference 544 μmol/L, 95% confidence intervals 222 to 865 μmol/L, and 0.0022 U/μmol-uCre, 0.00043 to 0.0039 U/μmol-uCre, respectively), urine creatinine concentration lower (mean difference 25,624 µmol/L, 17,329 to 33,919 µmol/L), and no significant difference in the kidney injury molecule-1/urinary creatinine ratio (mean difference 13 pg/μmol-uCre, -33 to 59 pg/μmol-uCre). In the group of cats with urinary obstruction, over time serum creatinine decreased, urine creatinine increased, urinary gamma-glutamyl transferase index did not change significantly, and kidney injury molecule-1/urinary creatinine ratio increased. Cats with post-renal obstruction and potential intrinsic renal damage had higher urinary gamma-glutamyl transferase index than healthy cats at the time of presentation and showed increase in kidney injury molecule-1/urinary creatinine ratio over time.

Fractional electrolyte excretion and osmolality in the early diagnosis of acute kidney injury in cats with urethral obstruction

Acute Kidney Injury (AKI) can be defined as a spectrum of diseases associated with a sudden onset of a renal failure status, the feline patient has azotemia, the disorder in fractional electrolyte excretion (FE), and shedding of epithelial cells from renal tubular segments observed in the urinary sediment. Thus, the objective of the present study was to evaluate the FE, plasma and urinary osmolality, and urinary specific gravity (USG) in cats that spontaneously developed AKI due to urethral obstruction (UO) and healthy cats. Blood and urine samples were collected from a group of 20 cats diagnosed with AKI secondary to urethral obstruction (GAKI; n=20) and clinically healthy cats (GC; n=15). The serum creatinine (sCre) and urinary creatinine (uCre), were measured by spectrophotometry, serum and urinary analyzes of sodium, potassium and chloride by ion selective electrode device and serum and urinary osmolarity by osmometer. The GAKI results were statistically compared with those of the CG using Student's t tests to assess normal data, while the Maan-Whitney test was used for non-normal data. A significant increase in the sCr, sK, FENa, FECl and RFI parameters of the GAKI cats when compared to the GC (p &lt; 0.05). The sCl, USG, uCr, uK and uOSM parameters decreased significantly when compared between the two groups. Thus, given the established methodology and the results found, it is possible to infer that an increase in EFNa, EFCl in addition to the RFI and a decrease in USG and uOSM were associated with cats with AKI and can serve as markers of kidney damage, as well as monitoring the prognosis.

Urinary heat shock protein-72: A novel marker of acute kidney injury and chronic kidney disease in cats

Acute kidney injury (AKI) in cats is associated with high mortality, partially attributed to late recognition of the disease when using currently available markers. Feline chronic kidney disease (CKD) has a variable progression rate. This study aimed to evaluate the sensitivity and specificity of urinary heat shock protein-72 to urinary creatinine ratio (uHSP72:uCr) as a diagnostic and prognostic marker in feline AKI, and as a prognostic indicator in feline CKD. The study included 63 cats, divided into five groups: healthy controls (n=10), urethral obstruction (UO; n=7), CKD (n=15), AKI (16 cats) and acute decompensating CKD (ACKD; n=15).Median uHSP72:uCr (ng/mg) of healthy, UO, CKD, AKI and ACKD cats were 0.44 (range, 0.13–1.1), 1.96 (range, 0.64–11.9), 4.2ng/mg (range, 0.57–22.16), 3.2 (range, 0.42–10.91) and 7.0 (range, 1.2–20.96), respectively, and differed (P<0.001) among groups. uHSP72:uCr was significantly lower in the controls vs. the CKD, AKI and ACKD groups. Receiver operator characteristic analysis of uHSP72:uCr, including the AKI and control groups, showed an area under the curve of 0.93 (95% confidence interval, 0.84–1.00), indicating an excellent predictive performance for diagnosing AKI. A 0.54ng/mg cutoff point corresponded to 94% sensitivity and 70% specificity for diagnosing AKI. The median survival time of cats with CKD with low uHSP72:uCr was longer (P=0.036) than in those with high uHSP72:uCr (561 vs. 112 days, respectively). uHSP72:uCr is a highly sensitive, moderately specific marker of AKI in cats, and is associated with the survival of cats with CKD.

Acute kidney injury in cats and dogs: A proportional meta-analysis of case series studies.

IntroductionRisk of mortality in the setting of acute kidney injury (AKI) in cats and dogs remains unclear.ObjectivesTo evaluate the incidence of mortality in cats and dogs with AKI based on etiology (i.e. infectious versus non-infectious; receiving dialysis versus conservative treatment).Materials and methodsOvid Medline, EMBASE, and LILACS were searched up to July 2016. Articles were deemed eligible if they were case series studies evaluating the incidence of all-cause mortality in cats and dogs with AKI, regardless of etiology or the nature of treatment.ResultsEighteen case series involving 1,201animalsproved eligible. The pooled proportions for overall mortality were: cats53.1% [95% CI 0.475, 0.586; I2 = 11,9%, p = 0.3352]; dogs 45.0% [95% CI 0.33, 0.58; I2 = 91.5%, P < 0.0001]. A non-significant increase in overall mortality risk was found among dialysed animals relative to those managed with conservative treatment, independent of animal type and the etiology of their AKI. The pooled proportions for overall mortality according to etiology, regardless of treatment type, were: AKI due infectious etiology for cats and dogs, 19.2% [95% CI 0.134, 0.258; I2 = 37.7%, P = 0.0982]; AKI due non-infectious etiology for cats and dogs, 59.9% [95% CI 0.532, 0.663; I2 = 51.0%, P = 0.0211].ConclusionOur findings suggest higher rates of overall mortality in cats and dogs with AKI due to non-infectious etiologies relative to infectious etiologies, and showed non-significant differences in terms of higher rates associated with dialysis compared to conservative management. Further investigations regarding optimal time to initiate dialysis and the development of clinical models to prognosticate the course of disease and guide optimal treatment initiation for less severe cases of AKI in cats and dogs is warranted.

Expression of Kidney Injury Molecule-1 in Healthy and Diseased Feline Kidney Tissue.

Sensitive markers to detect acute kidney injury (AKI) in cats are lacking. Kidney injury molecule-1 (KIM-1) is a promising marker of acute tubular injury in humans, and sequence and structure of feline KIM-1 have been determined. KIM-1 is shed into urine of cats with natural AKI. The objectives of this study were to characterize temporal and cellular expression of KIM-1 in kidneys from cats without and with experimental and natural AKI using histopathology and immunohistochemistry. Tissue sections from 8 cats without kidney disease, 3 to 4 cats with experimentally induced AKI on each day 1, 3, 6, and 12 after unilateral ischemia/reperfusion, and 9 cats with natural AKI were assessed. In sections from cats without kidney disease, patterns of periodic acid-Schiff and aquaporin-1 staining allowed identification of 3 distinct segments of the proximal tubule. KIM-1 staining was absent in segments 1 (S1) and S2, and faint in S3. Injury of S3 in cats with experimental and natural AKI was characterized by cell loss and necrosis, and remaining intact cells had cytoplasmic blebs and reduced brush borders. In experimental AKI, intensity of KIM-1 expression increased in proportion to the severity of injury and was consistently present in S3 but only transiently in other segments. Vimentin was absent in proximal tubules of healthy cats but expressed in injured S3. These findings indicate that S3 is the proximal tubular segment most susceptible to ischemic injury and that KIM-1 is a sensitive tissue indicator of AKI in cats.

Lily poisoning

Lilies, that is, species of Lilium (Liliaceae) (true lily) and Hemerocallis (Hemerocallidaceae) (day lily), cause acute kidney injury in cats. This does not occur in dogs, rats or rabbits. All parts of the plant are toxic to cats and a small amount of plant material can have serious consequences if ingested. The mechanism of toxicity remains unknown. Signs develop rapidly, with gastrointestinal irritation followed by polyuria, dehydration and then renal failure. Seizures can occur in severe cases. Treatment is aimed at reducing absorption using emesis and/or activated charcoal; preventing renal shutdown; and enhancing renal perfusion with intravenous fluid diuresis for at least 48 hours. Once renal failure has occurred treatment options are limited. Prognosis is good in cats treated promptly and before the onset of acute kidney injury. Cats with renal failure have a more guarded prognosis.

Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease.

A Retrospective Study of Acute Kidney Injury in Cats and Development of a Novel Clinical Scoring System for Predicting Outcome for Cats Managed by Hemodialysis

Information regarding acute kidney injury (AKI) in cats is limited, and there are no reliable tools to objectively assess disease severity and predict outcome. To assess clinical signs, clinicopathologic abnormalities, etiology, and outcome of cats with AKI, and to develop models using clinical metrics and empirically derived scores to predict outcome. One hundred and thirty-two client-owned cats. Retrospective study. Bivariate logistic regression analyses were performed to identify variables predictive of 30-day survival. Continuous variables outside the reference range were divided into quartiles to yield quartile-specific odds ratios (OR) for survival. Models were developed incorporating weighting factors assigned to each quartile based on the OR. A predictive score for each model was calculated for each cat by summing all weighting factors. A second, multivariable logistic regression model was created from actual values of the same variables. Receiver operating characteristic curve analyses were performed to determine the models' performance. Models were further tested using a subset of cases not used in initial assessment. Fifty five of 132 cats (42%) remained dialysis-independent for at least 30 days after discharge, and the remaining 77 cats either died (n = 37, 28%) or were euthanized (n = 40, 30%). The most common etiology was ureteral obstruction (n = 46, 35%). Higher scores were associated with decreased probability of survival (P < .001). Models correctly classified outcomes in 75-77% of the cases and 84-89% of the cases in the subsequent evaluation. Models can provide objective guidance in assessing AKI prognosis and severity, but should be validated in other cohorts of cats.

Feline acute kidney injury: 2. Approach to diagnosis, treatment and prognosis.

Feline acute kidney injury (AKI) is a commonly recognized problem in small animal practice that requires prompt diagnosis and directed therapy. There are many treatment methods with which practitioners should be familiar, including medical options, surgical interventions and renal replacement therapy (dialysis). It is important to know which option is most appropriate for each cause and stage of AKI to deliver the most effective therapy. AKI can cause vague clinical signs, but a vast array of life-threatening sequelae. Rapid recognition of potential complications and knowledge of treatment options is imperative for successful management. Feline patients also require an understanding of their unique physiology as it relates to the therapeutic plan. This two-part review article is directed at small animal practitioners as well as specialists. Part 2 discusses the diagnosis of AKI in cats using physical examination findings, clinicopathologic results and imaging modalities. The treatment of AKI and its sequelae is also reviewed, with information on recent advances in this area. While there is very limited data comparing the outcomes of various treatment options, there is literature addressing the use of several medications, as well as renal replacement therapy, in cats.

Bilateral renal ischemia as a model of acute kidney injury in cats

The objective of this study was to evaluate the effect of 1h, bilateral, warm ischemia–reperfusion kidney injury as a model of acute kidney injury in the cat. Four adult healthy cats underwent 60min of bilateral, in vivo renal warm ischemia; three cats were sham operated controls. Kidney function was evaluated with creatinine and BUN concentration, urine protein: creatinine, and glomerular filtration rate. Post-reperfusion endothelin and renin was measured by ELISA and RT-qPCR. Blood pressure (BP), platelet count, and platelet aggregation were monitored. Renal biopsy specimens were evaluated histopathologically. There was significant reduction in renal function characterized by severe azotemia and proximal tubular brush border loss. Changes in renin or endothelin gene expression or serum concentration were not detected. No changes were detected in BP. Platelet count and hematocrit decreased markedly after ischemia and reperfusion. Sixty minutes bilateral renal ischemia is an effective model for acute renal injury.

Peritoneal Dialysis in Cats with Acute Kidney Injury: 22 Cases (2001–2006)

Peritoneal dialysis (PD) has been described for use in animals with acute kidney injury refractory to fluid therapy. However, no study has examined the use of PD in a large group of cats. PD is an important adjunctive therapy to treat acute kidney injury in cats. The medical records of 22 cats with acute kidney injury that had received PD were examined. Animals were excluded if acute uremia was a result of postrenal causes such as uroabdomen or urethral obstruction. Medical records were reviewed for the following: indication for PD, outcome, number of cycles performed, survival time, and predialysis and postdialysis results for blood urea nitrogen (BUN), creatinine, potassium, chloride, sodium, phosphorus, total protein, and albumin concentrations, and urine output. Indications for PD include acute-on-chronic kidney injury, acute kidney injury caused by toxins, bilateral ureteroliths, bilateral ureteral ligation as a complication of ovariohysterectomy, and unknown causes. The median survival time for all cats on PD was 4 days, although the median survival time for the cats that were discharged was 774 days. The most common complications were dialysate retention and sequestration of dialysate SC. There was a significant (P < .05) decrease between predialysis and postdialysis results for BUN, creatinine, potassium, phosphorus, total protein, and albumin concentrations. There was a significant (P < .05) difference in survival times between sexes. PD is an effective option for treatment of cats with acute kidney injury refractory to fluid therapy.