Table 4.

Recommendations for an action plan to improve the understanding of the genetic determinants of chronic kidney disease¹

Goals	Activities	Category				Partners	Special aspects in LMICs	Possible deliverables	Commentary
		Research	Clinical care	Education	Advocacy
1.Increase awareness about the value and importance of genetics for understanding and treating CKD
	Educate clinicians and researchers about the value and importance of clinical genomics and genetic research for CKD, including challenges (e.g., ethical aspects, limitations in variant interpretation), opportunities, and realistic timelines for mechanistic understanding and translation			x		Nephrology fellows, medical schools, geneticists, professional organizations, patient advocacy groups, pharmaceuticals, technology and biotechnology companies; pairing with other organizations	Information relevant to LMICs in order to facilitate the understanding and awareness of the importance of clinical genomics and genetic research alongside more basic health care needs	Inventory of existing training and educational programs; double the number of programs in 5 years; offer training programs in nephrogenetics at international nephrology meetings or as standalone meetings	LT deliverable: Improved understanding of the importance of genetics by all clinicians and patients (consent to participate in genetic research)
	Educate patients and the public about the value of clinical genomics and genetic research			x		Geneticists, professional organizations, patient advocacy groups, journals, mass media, pharmaceuticals; pairing with other organizations	Information relevant to LMICs in order to facilitate the understanding and awareness of the importance of clinical genomics and genetic research alongside more basic health care needs	Increase media coverage in the next 2–5 yr	LT deliverable: Improved understanding of the importance of genetics by all clinicians and patients (consent to participate in genetic research)
	Educate clinicians and researchers about findings from large-scale sequencing projects of nephrology patients and asymptomatic individuals that provide adjusted estimates of prevalence and penetrance of presumed pathogenic variants necessary for counseling and risk prediction	x	x	x		Medical schools, teaching hospitals, nephrology divisions, professional societies, patient advocacy groups, pharmaceuticals, nephrology journals	Has implications in LMICs for genetic variants that are region or ancestry specific or are specific to a CKDu hotspot	Research reports and review articles in the next 2 yr, including discussion of potential implications for counseling	LT deliverable: Improved understanding of the importance of genetics by all clinicians and patients (consent to participate in genetic research)
	Educate clinicians about diverse clinical presentations of genetic kidney disease and revise genetic testing accordingly		x	x		Medical schools, teaching hospitals, professional societies, patient advocacy groups, pharmaceuticals, journals, clinical sequencing laboratories	Has implications in LMICs for genetic variants that are region or ancestry specific or are specific to a CKDu hotspot; gene panels for certain presentations may vary for different parts of the world	Research reports and reviews on the spectrum of clinical presentations for kidney disease genes Published recommendations about which genes to sequence for which presentation Development of standard gene panels for different nephrologic diseases (tubular disease, FSGS, etc.) with region-specific content
2.Increase the diversity of genotyped populations
	Protect indigenous populations, rare disease groups, ethnic minorities, small communities, family-heritage beliefs in order to enable their inclusion in genetic analysis and increase the diversity of genotyped populations	x		x	x	Communities, governments, regulators, IRBs	Information relevant to LMICs in order to facilitate genotyping of ethnically diverse individuals	Inventory of genotyped populations and their diversity in CKD hotspots, review of existing protocol-policy recommendations, and publication of recommendations on where to focus genotyping efforts in the next 2 yr	LT deliverable: Improved understanding of the importance of genetics by all clinicians and patients (consent to participate in genetic research)
	Improve SNP diversity on commercially available chips; improve imputation reference panels for ethnically diverse populations	x				Genotyping companies (Affymetrix, Illumina), computational biologists (for enhanced and diverse imputation platforms)	Information relevant to LMICs to enable targeted genotyping of high-risk populations	Development of affordable genotyping for worldwide populations, provision of improved genotype imputation for non-European ancestry populations, and promote comprehensive SNP array genotyping for CKDu in CKD hotspots in order to identify a potential major gene effects and research reports
	Educate groups, patients, populations, and other stakeholders about the value of genetic research in diverse populations		x	x		In addition to the above, media	APOL1 and HIV infection can illustrate the concept	Increase media and journal coverage regarding the value of genetic research in diverse populations over the next 2–5 yr
3.Increase the accessibility of genetic data
	Increase the accessibility and usability of existing and future datasets by promoting standardized format, broad data sharing, and enhanced use	x			x	iNET CKD, journal editors, technology companies, CKDGen, biobanks and biorespositories, dbGaP, BD2K initiative, AMP portal, CHARGE consortium, NHGRI GWAS catalog (now EMBL)	Information relevant to LMICs as this can make existing data more accessible to resource-poor regions where primary data generation can be more challenging	Development and publication of position statement on standardized format for data sharing, tracking of the number of publications and the number of requests for data, review of cataloged resources, and reduction of redundancies
	Develop data mining tools and search functions to catalog existing datasets	x				Computational scientists, pharmaceuticals		Share tools (e.g., search functions) to investigate publicly available data; research publications based on existing datasets (secondary use)
	Promote common data elements/phenotypes/standards in existing and future datasets (e.g., age, sex, SCr, UACR, and ethnicity). Improve renal phenotype harmonization and laboratory assays used to measure renal function parameters. Develop search tools for renal patients’ electronic health records	x				Clinical chemists, epidemiologists, laboratory assay developers	Need a minimum set of affordable laboratory assays to allow for LMIC participation	Over the next 2 yr, establishment of a consensus on a set of core nephrologic parameters to enable kidney disease genetics research and consensus of how to identify CKD patients using electronic medical records	LT deliverable: More focused research in genetics within the renal space
	Create incentives for data sharing	x			x	Journals, pharmaceuticals		Development of journal guidelines that require data sharing for publication. Sponsor platforms/portals/infrastructure to share data	LT deliverable: More focused research in genetics within the renal space
	Catalog and aggregate existing data repositories and biobanks-biospecimens to enable more rapid and accessible research	x				Computational scientists, pharmaceuticals	Information relevant to LMICs as this can make existing data more accessible to resource-poor regions where primary data generation can be more challenging	Development of a concept for centralized platforms/portals/infrastructure to share data and identify funding mechanisms	LT deliverable: More focused research in genetics within the renal space
	Link biomarkers to genetic data to determine causality (Mendelian randomization)	x				Statisticians, pharmaceuticals		Over the next 2–5 yr, development of software that facilitates Mendelian randomization analyses and make it publicly available
4.Tool generation for functional genomics
	Develop tools for functionalization of genetic findings to identify the causal gene/variant and genetic mechanism of action to facilitate translational research. Tools should be shared broadly	x				Geneticists, bioinformaticians and computational biologists, technology companies, pharmaceuticals, funding agencies	No direct benefit to LMICs in the short term. However, these tools are critical to turn genetic findings into potential novel therapeutics	Inventory of available tools, cell types, cell lines in the next 2–5 yr and tracking of published articles with mechanism of action of genetic findings and collection in a centralized resource	LT deliverable: Faster time from discovery to phase 1 and 2 trials in nephrology with less failure of compounds
	Promote the creation of disease-relevant cellular assays, bioinformatics pipelines, and tools for use in the scientific community	x				Geneticists, bioinformaticians and computational biologists, technology companies, pharmaceuticals, funding agencies		Published research reports elucidating the mechanism of action of newly uncovered genetic loci; development of assays that are available on request	LT deliverable: Faster time from discovery to phase 1 and 2 trials in nephrology with less failure of compounds
	Generate tools to study genetic modifiers, including epigenetic effects, to understand mutations in their genomic context and identify potential therapeutic targets	x				Geneticists, bioinformaticians and computational biologists, technology companies, pharmaceuticals, funding agencies		Creation of tools as documented in published research reports of epigenetic catalogs of different kidney cell types	LT deliverable: Faster time from discovery to phase 1 and 2 trials in nephrology with less failure of compounds

AMP, accelerated medicine partnership; APOL1, apolipoprotein L1; BD2K, Big Data to Knowledge; CHARGE, Cohorts for Heart and Aging Research in Genomic Epidemiology; CKD, chronic kidney disease; CKDGen, CKDGen Consortium; CKDu, chronic kidney disease of unknown etiology; dbGaP, database of Genotypes and Phenotypes; EMBL, European Molecular Biology Laboratory; FSGS, focal segmental glomerulosclerosis; GWAS, genome-wide association study; iNET CKD, International Network of Chronic Kidney Disease cohort studies; IRBs, institutional review boards; LMICs, low- and middle-income countries; LT, long term; NHGRI, National Human Genome Research Institute; SCr, serum creatinine; SNP, single-nucleotide polymorphism; UACR, urinary albumin-to-creatinine ratio.