Outcomes for Medically Managed AKI in Dogs and Cats PDF

Gilad Segev DVM, Dip. ECVIM-CA Hemodialysis academy, 2024/5 Features of severe acute kidney injury (AKI) High morbidity and mortality Prolonged hospitalization May require renal replacement therapy High treatment costs Prognosis will influence owners’ decision to pursue treatment Different ori...

Gilad Segev DVM, Dip. ECVIM-CA Hemodialysis academy, 2024/5 Features of severe acute kidney injury (AKI) High morbidity and mortality Prolonged hospitalization May require renal replacement therapy High treatment costs Prognosis will influence owners’ decision to pursue treatment Different original conditions Normal Increased susceptibility CKD Different outcomes are possible Normally functioning kidney - normal baseline GFR and intact functional reserve Susceptible kidney: normal GFR but no reserve - previous history of AKI CKD of any stage Multiple factors determine prognosis of animals with AKI Etiology - Reversibility Severity of injury Organs involved Comorbidities 80 P = 0.04 Complications 60 % mortality 40 Availability and type of therapy 20  Medical, dialytic, surgical intervention 0 1,2 2,3,4 5> Number of organs involved Medical management Provides a narrow window of opportunity for recovery when the disease is severe Surgical intervention to eliminate the underlying cause Associated with favorable prognosis Dialytic Intervention Expand the window of opportunity for recovery Associated with a better outcome Survival rates are influenced Died by euthanasia 37 cats Survived 55 (28%) (42%) Studies report euthanized Euthanized 40 cats patients as non survivors (30%) Patients may be euthanized Poor outcome Died 48 dogs Financial constraints (26%) Survived 86 dogs (48%) Survival rates may be underestimated Aggressive treatment would have been applied in all patients Dialysis would have been readily available Major bias – we tend to euthanize when we perceive the prognosis is grave Retrospective studies might “falsely confirm” the clinical impression  Vicious cycle  Dogs, n=99 Risk factors EG intoxication Old dogs Sever azotemia (>10 mg/dL) Euthanized Proteinuria Survived 34 dogs Hypocalacemia (34.3%) 43 dogs Presence of DIC 43.4% Died sCr normalized in 19% 23 dogs (23.2%) Vaden SL et al JVIM 1997 Characteristics Cats, n=24 24 cats were managed medically Eighteen cats were oliguric Risk factors Hyperkalemia Died Survived  For each unit (mEq/L) increase in potassium, there was a 57% decrease in chance of survival 10 cats 14 cats Hypoalbuminemia 41.7% 58.3% Low HCO3- azotemia was not associated with survival sCr normalized in 25% Worwag S. and Langston, C JAVMA 2008  Plus one, 2018 Jan 25;13 Eighteen case series involving 1,201 animals Overall mortality Cats - 53% Dogs - 45% Survivors Survivors Non survivors Non survivors 249 dogs with AKI Etiologies Inflammation Toxicity Ischemia Outcome improving 20% of the non survivors were euthanized Non Survivors 34% Survivors 66% Reported survival rate ~50% Different etiologies Dialysis is readily available Not influenced by euthanasia Not influenced by financial constraints Older patients & higher prevalence of comorbid disorders  Plus one, 2018 Jan 25;13 Overall mortality based on etiology (dogs and cats) Infectious etiology (Lepto, pyelo, pyometra, sepsis) - 19.2% Non-infectious etiology - 59.9% Survival 56-85% (medical & hemodialysis, PD) Typically injury is reversible Patients may die from comorbid disorders The infecting serovar may influence the outcome Pulmonary hemorrhagic syndromes is associated with high mortality rate (43%) Pyelonephritis in cats n=4, 100% survival vs. 40% in other causes n=7, 58% survival vs. 52% in other causes 1Langston CE et al:. J Vet Intern Med 11:348-355, 1997. 2Pantaleo et al. ACVIM forum, 2004 Prognosis is highly dependent on the toxins Ischemic injuries are often reversible  ACE inhibitors, NSAID Ethylene Glycol – Often irreversible once kidney injury occurred  Survival rates 5-20% Gentamicin – potentially reversible – slow recovery Lily toxicity – severe and often not reversible  Survival rates 0-50% Grapes and raisins  Survival rates 50-75% Ischemia and nephrotoxicity were the most common causes Mortality rate – 54- 62% Risk factors for mortality have been identified Old patients  Both higher risk to develop renal failure and lower survival rates Concurrent cardiac disease Initial urine output Behrend EN et al.. J Am Vet Med Assoc 1996;208:537-541 Identifying the etiology is important for prognostic projections Etiologies vary among geographical areas There is a shift in etiologies over the years Leptospirosis - 6% vs 27% EG - 23% vs 31% Etiology is important for outcome assessment, BUT Etiology is often unknown at presentation and might remain unknown throughout the disease course Etiology does not incorporate factors as disease severity, age, comorbidities etc. Other parameters should be used for outcome prediction Based on limited studies, few risk factors for mortality have been identified in dogs and cats Anuria / Oliguria The most consistent risk factor for mortality Surrogate for the severity Other risk factors are not consistent May help in the overall assessment Presence of multiple risk factors is likely associated with decreased survival It is difficult to weigh each on these risk factors to provide an accurate prognosis Used to assess severity of a disease and its prognosis Grading system for AKI Disease severity is assessed using markers of kidney function (e.g., sCr, urine production)  IRIS Grading system  (RIFLE and AKIN human classification systems for AKI) Scoring Systems Values are assigned to clinical variables  APACHE – human ICU patients IRIS Grading criteria Evidence for the association of the IRIS grading system and the survival is still limited IRIS AKI Grade is associated with severity 50 P < 0.001 45 40 35 Mortality (%) 30 25 20 15 10 5 0 1 2 3 4 5 AKI Grade 2004 - RIFLE: Risk, Injury, Failure, Loss of kidney function, and End stage kidney disease 2007 – AKIN: Acute Kidney Injury Network  A veterinary AKI staging system was applied Stage 1: 150–199% or ≥0.3 mg/dL Stage 2: 200–299% Stage 3: ≥300% AKI Stage (and age) were associated with mortality 54% mortality for dogs in stages 1-3 Scoring systems to predict the outcome in dogs and cats with AKI were constructed only for animals managed with hemodialysis These were not validated for medically managed animals  1.0 Model A Probability of Survival 0.8 Model B Model C 0.6 0.4 0.2 0 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 Predictive Score  A B C 19% Correctly classified 17% 13% Misclassified 81% 83% 87% Model Optimal cutoff Sensitivity (%) Specificity (%) A 20.00 77 85 B 20.51 81 85 C 19.92 83 90  A B C D 25% 25% 24% 23% 75% 75% 76% 77% Correctly classified Misclassified Model Optimal cut-off score Sensitivity Specificity AUC A 10 74 75 0.81 B 10.4 74 75 0.81 C 10 62 88 0.85 D 12 66 83 0.86  ROC analysis- Model B 1.00 E Cutoff Sensitivity Specificity D C Score (%) (%) 0.75 B A 18.44 52 98 Sensitivity 0.50 A B 19.68 73 88 C 20.51 81 85 0.25 D 21.96 88 73 Area under curve 0.89 E 24.45 90 51 0.00 0.00 0.25 0.50 0.75 1.00 1-Specificity There are no scoring systems that have been developed for medically managed AKI Scoring system are accurate in large group of patients and less accurate for the individual patient Scoring systems should never be used as a single tool to predict the outcome Scoring systems should never replace proper clinical judgment Need to be prospectively validated Grading schemes and scoring systems can objectively assess the disease severity Facilitate communication  Objective assessment of the disease severity Can be used to compare different cohorts  Efficacy of intervention  Outcome Most important predictors for animals with AKI managed medically Etiology – reversibility Severity – AKI Grade Body systems involved Comorbidities Treatment quality Seventeen (53%) cats survived 8 cats - resolution of azotemia 9 cats - CKD  4/9 cats were euthanized due to renal disease 7-51 months after the insult Serum creatinine normalized in 75% of the dogs 55% at discharge (association with the stage) 20% during the follow-up period (up to 3 months)  Normalization occurred due to repair processes and compensatory hypertrophy Animals recovering from AKI have a good short-and long-term outcome 76% of the dogs were alive at last contact Estimated MST - 1322 days (95% CI, 1147-1626) Only 10 dogs died due to renal related causes Dogs in which sCr did not normalize during follow-up period had median sCr concentration of 1.9 mg/dL 23% of the dogs were classified as CKD stage 2 No statistically significant difference between dogs with sCr normalization and dogs with CKD Slow progression of CKD  No inciting cause compared to dogs with acquired CKD (the inciting cause likely exerts its negative effect on kidney function throughout the disease)  Due to almost complete recovery compensatory hypertrophy processes (contributing to further progression) did not occur Acute decompensation is common Short and long-term prognosis were not thoroughly studied  3 3 Unknown No associations between 8 Ureteral obstruction Ischemia 9 etiology and short term outcome Pyelonephritis Cardio-renal syndrome 11 Other 66 A relatively long hospitalization is to be expected  inflammatory ischemic No significant difference in pyelonephritis other renal 30% overall mortality among 45% unknown etiologies (P = 0.46) 7% 3% 15% A relatively long hospitalization is to be expected 47 65% survival to discharge in dogs Risk factors  Respiratory rate  Anemia, serum creatinine, urea, phosphate, CK, DGGR-lipase  Association in survival with IRIS AKI Grade at presentation 58% survival to discharge in cats Risk factors  Age  Temperature  Serum creatinine, urea, phosphate, venous pH ‫תשפ"ה‬/‫חשון‬/‫ט"ו‬ Follow up and long-term survival Median survival time (MST) – 105 days  Up to 6 months – 57% (35 dogs)  Up to 12 months – 13% (8 dogs)  24 months – 5% (3 dogs) Median Survival Time ACKD CKD OVERALL 105 174 Crea 1.4-2.8 130 220 Crea 2.9-5 89 180 Crea >5 32 80 Median survival time All cats - 66 days  Up to 6 months - 43 cats (81%) (P=0.001)  Up to 12 months - 4 cats (8%)  24 months - 6 cats (11%) Grades II-III Grades IV - V IRIS AKI Grade at presentation AKI Grade I-II – 233 days AKI Grade III-IV – 29 days