COMPASS: Protocol of a Study of Kidney Function and Diabetes in Rural New Mexico

Due to socioeconomic factors and limited access to primary and specialist care, the distribution of chronic kidney disease (CKD) in the United States is disproportionate in rural areas. Early CKD diagnosis and care, which are both difficult in rural areas, can slow the progression of the CKD to end-stage renal disease (ESRD). When patients do develop ESRD, those residing in rural areas have to travel long distances to receive dialysis services. Routine screening for CKD is not generally recommended among patients without diabetes and cardiovascular disease. However, according to Antonin Jaros, MD, and colleagues, such routine screening may be “particularly relevant in rural populations.”

New Mexico, where only 41% of the population identify as non-Hispanic white, has one of the highest prevalences of diabetes-related ESRD in the United States. A high proportion of the residents of New Mexico are Native Americans or Hispanic Americans, many of whom live below the federal poverty level. There have been relatively few residents of New Mexico included in clinical epidemiological studies of CKD and there is little opportunity for those patients to participate in translational studies evaluating novel biomarkers of renal function and renal damage, making New Mexico, along with Hawaii, “ground zero for the epidemic of diabetic CKD in the United States,” the researchers said.

Dr. Jaros et al. recently designed COMPASS (Community Based Study of the Epidemiology of Chronic Kidney Disease in Cuba, New Mexico, and Surrounding Areas), a prospective, longitudinal cohort study. The researchers described the design and implementation of the dual use, community-based CKD screening and translational research program and provided preliminary data on the baseline characteristics of the screened cohort during the first 18 months of the study in BMC Nephrology [10.1186/s12882-018-0842-4].

The primary end point of the study is the prevalence of participants with CKD stage G3 to 5, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 based on the CKD-Epidemiology Collaboration equation, and CKD stage A2 to 3, (defined as persistent albuminuria) at each visit. Secondary and biomarker-oriented end points include examining the relationship of emerging markers of renal filtration, such as beta 2 microglobulin or cystatin C (CysC) to levels of inflammation, indices of insulin resistance, and other laboratory measures of renal function. A secondary, non-biomarker end point is analysis of qualitative research methodologies used to understand participants’ perceptions and attitudes toward research activities regarding CKD.

The single major exploratory outcome is the description of relationships between clinical laboratory parameters of renal function and damage (e.g., albuminuria) to circulating plasma or urinary microRNAs. MicroRNAs are an emerging class of rational, biologically plausible biomarkers of organ damage in kidney disease. The researchers added this objective to the study protocol based on feedback from the first 50 participants indicating that this study provided value to the community.

In addition to medical history and physical examination, participants undergo a laboratory evaluation of blood and urine. A positive CKD screen is determined based on impaired eGFR or albuminuria in the initial testing. Patients with positive CKD screen are given the option to be followed up longitudinally with health questionnaires and extended laboratory examination after 1 year (visit 2, month 12). Patients who do not screen positive for CKD are not rescreened unless they are at high risk for CKD on the basis of clinical risk factors for the development of CKD.

At visit 1, month 0, all participants complete a medical questionnaire and undergo a targeted physical examination. The questionnaire includes elements from previous community screening programs for CKD as well as national health surveys. Demographic data are also collected.

The researchers then measure markers of renal function, insulin resistance, and epigenetics (microRNAs) on patients. Various indices of insulin sensitivity are assessed: (1) the C-peptide, an index of insulin release; (2) the non-fasting C-peptide to insulin ratio; (3) the Homeostatic Model Assessment of Insulin Resistance; and (4) the Quantitative Insulin Sensitivity Check Index. MicroRNAs are assessed in three different fractions: (1) total biofluid (plasma or urine); (2) Extracellular Vesicles (exosomes); and (3) concentrated Extracellular Vesicles-depleted fractions.

Qualitative interviews and focus groups will be conducted until saturation, defined as when no new concepts or themes emerge, is reached. The researchers planned a minimum of four focus groups, and up to 10, with five to eight community participants per group. Due to the enrollment size for this study, a total of 50 interviews is planned to serve as an adequate sample size. The interviews and focus groups will allow participants to characterize their attitudes toward research as barriers or facilitators to participation in future research trials about kidney disease.

In summary, the researchers said, “The COMPASS study combines a community based kidney health screening with a translational biomarker discovery program. The study will provide much needed data for the local epidemiology of CKD in an area with a high prevalence of diabetes, while generating a wealth of novel epigenetic, microRNA biomarker data and the techniques to analyze them. The results of COMPASS may form the basis for subsequent health and research disparities, while informing research on microRNA biomarkers in the general population.”

Takeaway Points

  1. There are limited data on risk factors of diabetic chronic kidney disease in many rural areas in the United States, including Cuba, New Mexico.
  2. Researchers in New Mexico are conducting the COMPASS study (Community Based Study of the Epidemiology of Chronic Kidney Disease in Cuba, New Mexico and Surrounding Areas).
  3. They describe study design and objectives in BMC Nephrology.