This toolkit provides practical guide for conducting high-quality, community-centered research on chronic kidney disease of unknown etiology (CKDu).
Objectives of the ISN i3C CKDu Toolkit
The ISN i3C (CKDu) Toolkit aims to equip investigators, clinicians’ community partners, and policymakers with harmonized sets of practical ethnically grounded methods to support high-quality CKDu research across diverse global contexts. Drawing on evidence synthesized and community engagement insights, the toolkit promotes consistent study design, standardized case definitions, and robust exposure and outcome measurements.
A central objective is to strengthen research capacity in CKDu-endemic regions. This involves providing guidance for developing laboratory and pathology infrastructure, adopting validated biomarkers where feasible, and implementing biorepository practices to support multidisciplinary and culturally sensitive community engagement, ensuring that CKDu-affected communities are partners in the research process.
The toolkit supports global data comparability by promoting the minimum dataset recommended by the i3C working group and offering practical templates for field procedures, sample collection, data management, and reporting. By enhancing methodological rigor and consistency, the toolkit seeks to accelerate scientific discovery, facilitate equitable collaboration, and generate actionable evidence for clinical practice, occupational health, and public policy.
The toolkit integrates research methods with real-world conditions, enabling field teams to conduct rigorous studies that respect and empower communities affected by CKDu.
How to use this toolkit?
This toolkit provides structured, step-by-step guidance for the design, implementation, analysis, and dissemination of chronic kidney disease of unknown etiology (CKDu) research globally. It consolidates advanced methodologies from the ISN i3C’s principal publications, including:
- Epidemiologic, molecular and genetic research methodologies.
- Guidance on population-level disease detection and minimum dataset specifications.
- Ethical considerations specific to CKDu research.
- Best practices for performing kidney biopsies in CKDu-endemic regions.
- Challenges and opportunities in the design and implementation of interventional studies.
- Frameworks for multicounty prospective cohort design.
Who is it for?
- Researchers and clinicians involved with studies on CKDu
- Field epidemiology teams and community health professionals
- Laboratory scientists, genetics specialists, and pathology collaborators
- Public health agencies and policymakers
- Non-governmental organizations and occupational or environmental health organizations
- Global and regional collaborators operating in CKDu endemic areas
Global equity & multi-regional applicability
CKDu affects multiples regions, each with distinct social, environmental, and health system challenges. The purpose of this toolkit is to:
- Promote equitable participation among researchers and communities from all regions affected by CKDu.
- Support harmonized yet contextually adaptable approaches to exposure assessment, laboratory methodologies, outcome definitions, and community engagement.
- Highlight challenges and knowledge gaps identified in i3C publications.
- Facilitate the identification of local challenges and resources, including climate, employment types, and health system capacity.
- Foster capacity building, equitable authorship practices, and data-sharing models that respect national sovereignty. Ensure methodological feasibility across low-, middle- and high-resource settings prioritizing researchers and communities most affected by CKDu.
- Embed ethical priorities, particularly in relation to informed consent, community trust, return of results and kidney biopsy decision-making within vulnerable populations.
Through the toolkit, sidebar notes will indicate:
- Equity considerations
- Region-specific adaptations
- Considerations for limited resource settings
- Ethical and cultural sensitivities
- Minimum dataset requirements
Study stages
- Anand, S., Caplin, B., Gonzalez-quiroz, M., Schensul, S. L., Bhalla, V., Nanayakkara, N., Fire, A., Levin, A., & Friedman, D. J. (2019). Epidemiology, molecular, and genetic methodologies to evaluate causes of CKDu around the world: report of the Working Group from the ISN International Consortium of Collaborators on CKDu. Kidney International, 6(96), 1254–1260. https://doi.org/10.1016/j.kint.2019.09.019
- Caplin, B., Yang, C., Anand, S., Levin, A., Madero, M., Saran, R., Jayasinghe, S., De Broe, M., Yeates, K., Tonelli, M., Jakobsson, K., Strani, L., Ruggiero, A., Glaser, J., Martin, E., Pearce, N., & Wijewickrama, E. (2019). The International Society of Nephrology’s International Consortium of Collaborators on Chronic Kidney Disease of Unknown Etiology: report of the working group on approaches to population-level detection strategies and recommendations for a minimum dataset. Kidney International, 1(95), 4–10. https://doi.org/10.1016/j.kint.2018.08.019.
- Smyth, B., Glaser, J., Butler-Dawson, J., Nanayakkara, N., Wegman, D. H., Anand, S., & Levin, A. (2023). Challenges and opportunities in interventions for chronic kidney disease of unknown origin ( CKDu ): Report from the International Society of Nephrology Consortium of Collaborators on CKDu. Kidney International, 103(1), 6–12. https://doi.org/10.1016/j.kint.2022.10.013.
- Wijewickrama, E., Behera, S., Garcia, P., Avila-Casado, C., Caplin, B., Paolo, V., Courville, K., Friedman, D., Madero, M., Jha, V., Kambham, N., Levin, A., & Anand, S. (2024). Kidney biopsies among persons living in hotspots of CKDu: a position statement from the International Society of Nephrology’s Consortium of Collaborators on CKDu. Kidney International, 3(105), 464–469. https://doi.org/10.1016/j.kint.2023.12.012.
- This toolkit reflects the collaborative work of the ISN International Consortium on CKDu (ISN i3C) and its regional partner, uniting expertise to advance community-engaged research.
- We recognize the diverse professional and community leaders who are shaping our understanding and response to CKDu across diverse global regions. As such, we acknowledge our regional scientific partners, field research collaborators, laboratory, pathology and genetics partners, ethics and community engagement advisors, as well as community stakeholders and patient representatives.
- We extend our gratitude to the affected communities, whose experiences and input guide our research priorities and actions.
- Ana Catalina Alvarez-Elías, MD, MSc, PhD.Sc (United States)
- Eranga Wijewikrama, MD, PhD (Sri Lanka)
- Ben Caplin, MD, PhD (United Kingdom)
The i3C Working Group members are listed here.
This toolkit is a dynamic resource and will be updated as new evidence becomes available.
Feedback, suggestions and examples from ongoing projects are welcome.
- Contact us at research@theisn.org