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Does using synthetic colloids cause acute kidney injury in cats?

Sigrist NE, Kälin N, Dreyfus A. Effects of Hydroxyethyl Starch 130/04 on Serum Creatinine Concentration and Development of Acute Kidney Injury in Nonazotemic Cats. J Vet Intern Med. 2017 Nov;31(6):1749-1756.

On this blog we have previously discussed the controversy in modern medicine surrounding the use of hydroxyethyl starch (HES) products. These “synthetic colloids” are a type of intravenous fluid product intended to rapidly and effectively replace circulating volume in situations of blood loss, sepsis, or other causes of low blood pressure. Traditionally, synthetic colloids have played an invaluable role in fluid resuscitation in both human and veterinary medicine. They are more effective than crystalloids (the more commonly used electrolyte solutions) at increasing blood volume and pressure, and are less expensive and more stable than blood products and do not carry the risk of transfusion reactions.

In recent years, HES products have come under severe scrutiny in human medicine due to their potential to cause kidney damage and potentially worsen outcomes compared to patients who do not receive synthetic colloids. This has led to a drastic drop in the use of HES in human medicine, including a partial restriction on their use in the European Union.

Significant data has been collected on the use of HES solutions in veterinary patients since the start of this controversy. Unfortunately, much of the data has been retrospective or in small patient populations, and results have been mixed. Some data has suggested a small negative effect on survival and increase in kidney injury with HES use, while others have seen no effect.

The current paper attempts to investigate the effects of HES use on kidney function in a population of cats. The study was designed as a retrospective cohort study using medical records from the University of Zurich Veterinary Hospital. Cats were included if they were admitted to the ICU, and had a creatinine concentration measured before and at least 48 hours after HES administration. Cats were excluded if they had an admission creatinine concentration >163mmol/L, received less than 5mL/kg HES, or received synthetic colloids other than HES-130/0.4. The control group was recruited from the same population of cats with the same exclusions, however included only cats who did not receive HES-130/0.4.

62 cats met all criteria and were included in the study. 26 of these cats received HES; 12 female and 4 male with a median age of 38 months. Mean total volume of HES received was 98.5mL/kg over 4 days. The exposed and control groups were similar in sex, breed, weight, days of fluid therapy, and number of hospital days. The HES receiving group received more RBC and plasma transfusions than the control group, and had a lower albumin on presentation. No difference was found in rate of discharge.

Unexposed cats had a significantly higher baseline creatinine than exposed cats and also had a higher creatinine post- therapy. The % change in creatinine from baseline to 2-10 days post therapy and 11-90 days post-therapy was not significantly different between groups.

Acute kidney injury was defined as an increase in creatinine of >150% of baseline or >26mol/L. Based on this definition, 19% of treated and 31% of control cats developed AKI within 2-10 days post therapy. Univariate analysis did not show an association between HES therapy and development of AKI. Long term analysis of creatinine (11-90 day post therapy) likewise did not show an increase associated with administration of HES.

Multivariate analysis with several linear regression models was performed to determine if an association existed between administration of HES, HES volume, days of HES exposure, mL/kg/day HES, and creatinine level. This was adjusted for confounding variables of blood product transfusion, age, sex, and duration of hospitalization. No significant change in creatinine was seen in this model (and indeed, the trend was to a decrease in creatinine with HES administration).

This study suffered from the usual deficits of retrospective data collection. Variations in individual treatment protocols, presenting complaints, and signalment contribute to variations in the data collected. Doses of colloid were not standardized between patients. Finally, creatinine is a relatively insensitive indicator of minor kidney damage, and decreases in GFR of up to 70% of normal may not be recognized. Finally, sample sizes (while large for a feline study) may not have been large enough to detect small variations in creatinine concentration.

The authors of this study concluded that administration of HES to non-azotemic cats did not significantly change creatinine values at 10 and 90 days follow up.

While this study does not end the controversy surrounding HES administration, it lends further credence to the emerging theory that synthetic colloids do not carry the same risks of acute kidney injury in cats as they do in humans. While their judicious use is still warranted and further work is needed, in a species where the availability of blood products is limited the use of synthetic colloids appears to still be a viable option. (MRK)

See also:

Adamik KN, Yozova ID, Regenscheit N. Controversies in the use of hydroxyethyl starch solutions in small animal emergency and critical care. J Vet Emerg Crit Care 2015;25:20–47.

Yozova ID, Howard J, Adamik KN. Effect of tetrastarch (hydroxyethyl starch 130/0.4) on plasma creatinine concentration in cats: a retrospective analysis (2010-2015). J Fel Med Surg. 2017 Oct;19(10):1073-1079.