Drug Testing for Chronic Kidney Disease and Diabetes in Animals versus Humans: A Comparative Analysis of Study Designs and Reporting Qualities.

Introduction: Diabetes is a highly prevalent accelerator or even cause of chronic kidney disease imposing a large unmet medical need at the global scale. Massive research activities continue to be in search of a cure but the yield of the classical bench-to-bedside research approach has been low. We speculated that a significant mismatch in design and quality of animal and clinical studies in this domain is a hurdle for translation.

Methods: We performed a meta-analysis of matched pairs of animal and human studies that tested the efficacy of distinct drug interventions for diabetic kidney disease (DKD). We reviewed study designs and reporting quality of such studies over the last decade according to the standards listed in the CONSORT and ARRIVE recommendations, respectively.

Results: We noted a wide diversity in the study designs of animal studies in terms of diabetes induction. Major mismatches with the respective human studies referred to age and sex distribution, comorbidities, stage of the kidney disease, and selection of primary endpoints. Usually, treatment was initiated before onset of kidney disease without any standard of care as a background therapy. The reporting quality of animal studies was poor for randomization procedures, blinding, sample size calculation for a prespecified primary endpoint or the safety analysis. Reporting quality of clinical studies had deficits in trial design-, recruitment-, allocation-, and outcome-related aspects.

Conclusion: Bench-to-bedside translation in the domain of DKD suffers from major deficits in the design of experimental studies in view of the projected clinical trials as well as from significant deficits in the reporting quality in preclinical and clinical studies.