Genetic, Experimental, Mechanistic, and Methods Research
Although the main focus of the workshop was epidemiologic research, other disciplines also were discussed.
Genetic and Epigenetic Studies
Genetic and epigenetic studies may provide important information with respect to the genetic susceptibility of Mesoamericans to different environmental factors.Agenome-wide non–hypothesis-driven research model may be most successful in identifying such a gene or gene complex. Should a genetic susceptibility be identified in Mesoamericans, this genotype could be introduced into an animal model to assess the impact of different environmental risk factors on the pathogenesis of CKD.
Studies in Animal Models
Animal models can provide important information concerning specific agents and the synergistic interactions of different environmental risk factors. Such interactions might include, for example, water and solute loss in combination with arsenic, fructose, NSAIDs, or hard water. In this manner, we could better isolate environmental effects that would inform clinical practice and epidemiologic studies.
Kidney Biopsy Analysis
To date there have been an extremely limited number of CKD kidney biopsy specimens analyzed in MeN. Biopsy results show interesting preliminary findings. Given the potential clues to pathophysiology/etiology, carefully planned biopsies should be performed, but only when safety is guaranteed and patients, especially in early stages, can be followed up with good clinical practice to improve quality of life.
A Common Registry and Repository
A multilateral biobank that could store urine samples, serum samples, and DNA would be extremely beneficial. This would enable sample storage for future analysis with advanced techniques and understanding. However, specimen collection needs to be considered carefully and followed uniformly. Also, ethical consideration of participant consent to prospective sample testing has to be adhered to. This would be an expensive undertaking, requiring a large amount of funding. Similarly, a common database or registry would promote collaboration and advancement in the field of CKD. This is much less expensive and should be a priority action.
Other Areas of Potential CKD Experimental Research
Opportunities should be considered to explore kidney injury further in populations without hypertension or diabetes. For example, in elite athletes who consume high volumes of fluid and sugar and repeatedly are exposed to high heat load.
A Common Registry and Repository
A multilateral biobank that could store urine samples, serum samples, and DNA would be extremely beneficial. This would enable sample storage for future analysis with advanced techniques and understanding. However, specimen collection needs to be considered carefully and followed uniformly. Also, ethical consideration of participant consent to prospective sample testing has to be adhered to. This would be an expensive undertaking, requiring a large amount of funding. Similarly, a common database or registry would promote collaboration and advancement in the field of CKD. This is much less expensive and should be a priority action.
Advances in Biomarkers
Studies to identify subclinical kidney injury and biomarkers might be useful in defining the pathophysiology, natural history, and early clinical detection of CKD; possible treatment; and as surrogate end points in intervention studies. Early urinary markers of acute and chronic tubular injury should be sought to improve on albumin as a marker, that is, β2-microglobulin, clusterin, cystatin C, kidney injury molecule-1 (Kim-1), trefoil factor 3, neutrophil gelatinase-associated lipocalin (NGAL), and others. A number of emerging technologies have enabled researchers to measure several proteins in a single urine sample rapidly and reliably so that large numbers of samples can be run and analyzed in a high-throughput manner. Cystatin C in serum also may provide a more accurate measure for estimating GFR. There also is a need to develop biomarkers for better detection of exposures, such as pertinent agrichemicals and infections. Biomarkers of susceptibility should be considered based on genetic approaches.