#5615 VALIDITY AND ADEQUACY OF ANIMAL MODELS IN HAEMODIALYSIS RESEARCH: A SYSTEMATIC REVIEW
Authors: de Vries Joost , Wever Kim , Verhaar Marianne , Gerritsen Karin , Krebber Merle 
Published: June 2023

Abstract

Background and Aims
with the worldwide dialysis population growing rapidly, improving haemodialysis (HD) outcomes is crucial and HD innovations are urgently needed. Prior to clinical application, novel HD technologies must undergo extensive preclinical testing. However, to date there is no consensus on the induction method of kidney failure in animal models nor which animal species is most suitable for research on HD innovations. Moreover, there is no consensus on which parameters should be used to validate adequate induction of kidney failure and functioning of novel HD devices. Using a systematic review approach, we summarized available literature of HD in kidney failure animal models.

Method
we performed a systematic search on PubMed and Embase for relevant studies up to February 4th 2022. After removal of duplicates, 5723 abstracts were screened for eligibility by three independent reviewers (JdV, KW and MK). Inclusion was based on publication of a HD intervention in an animal model with adequate (acute or chronic) kidney failure (independent of induction method). Detailed in- and exclusion criteria were registered in PROSPERO 2022 CRD42022307144. Data from individual reports, including animal species and sex, kidney injury parameters and HD details, were extracted in a pre-set data extraction form. Future efforts will focus on risk of bias and key quality indicators.

Results
of the 5723 abstracts screened, 195 records were included as full text and 41 full text articles were included for data-extraction (Figure 1). Current data extraction is completed for 31 articles (75%). Publication years range from 1973 to 2021 with over half (16/31) published after 2000. HD experiments were most frequently performed on dogs (45%), followed by rats (29%), goats (13%), pigs (10%), and sheep (3%) respectively. Parameters such as weight (81% reported), sex (58%) and age (29%) were not systematically reported. Most studies (67% of records reporting sex) used male animals only. Dog models were found in older studies, with no records after 2009. Other large animal studies were almost exclusively (88%) performed from the year 2007 onwards. Independent of animal species, studies mainly used acute kidney injury (AKI) models (84%), induced by bilateral nephrectomy (48%) or bilateral ureteral ligation (29%). The majority confirmed kidney failure by an increase in BUN and/or plasma creatinine. In AKI models, dialysis was on average initiated on AKI day 2 ± 0.8, and generally either HD (61%) or veno-venous hemofiltration as a single session (35%) was applied. Except for one clearance study, dialysis efficiency was reported as reduction ratios of BUN and/or plasma creatinine.

Conclusion
both large and small animal models have been used in HD research and preclinical validation of dialysis innovations. The use of dogs to test HD innovations has seen a sharp decline over the past decades, possibly resulting from a shift in public ethical perception. However, large animal models such as goat, sheep and pigs remain popular. A pressing issue appears the overall lack of adequate ARRIVE guideline adherence for reporting of animal parameters. We found no apparent improvement in reporting over time, emphasizing the need for clear guidelines to drive innovative HD research. Further (quantitative) analysis and meta-analysis are ongoing.