Clinical Outcomes Among High-Risk Primary Care Patients With Diabetic Kidney Disease: Methodological Challenges and Results From the STOP-DKD Study.

BACKGROUND/OBJECTIVE: Slowing the progression of diabetic kidney disease (DKD) is critical. We conducted a randomized controlled trial to target risk factors for DKD progression. METHODS: We evaluated the effect of a pharmacist-led intervention focused on supporting healthy behaviors, medication management, and self-monitoring on decline in estimated glomerular filtration rate (eGFR) for 36 months compared with an educational control. RESULTS: We randomized 138 individuals to the intervention group and 143 to control. At baseline, mean (SD) eGFR was 80.7 (21.7) mL/min/1.73m2, 56% of participants had chronic kidney disease and a history of uncontrolled hypertension with a baseline SBP of 134.3 mm Hg. The mean (SD) decline in eGFR by cystatin C from baseline to 36 months was 5.0 (19.6) and 5.9 (18.6) mL/min/1.73m2 for the control and intervention groups, respectively, with no significant between-group difference (P=0.75). CONCLUSIONS: We did not observe a significant difference in clinical outcomes by study arm. However, we showed that individuals with DKD will engage in a pharmacist-led intervention. The potential explanations for a lack of change in DKD risk factors can be attributed to 5 broad issues, challenges: (1) associated with enrolling patients with low eGFR and poor BP control; (2) implementing the intervention; (3) limited duration during which to observe any clinical benefit from the intervention; (4) potential co-intervention or contamination; and (5) low statistical power.

Depressive Symptoms, Antidepressants, and Clinical Outcomes in Chronic Kidney Disease: Findings from the CRIC Study.

Rationale & Objective: The extent to which depression affects the progression of chronic kidney disease (CKD) and leads to adverse clinical outcomes remains inadequately understood. We examined the association of depressive symptoms (DS) and antidepressant medication use on clinical outcomes in 4,839 adults with nondialysis CKD. Study Design: Observational cohort study. Setting and Participants: Adults with mild to moderate CKD who participated in the multicenter Chronic Renal Insufficiency Cohort Study (CRIC). Exposure: The Beck Depression Inventory (BDI) was used to quantify DS. Antidepressant use was identified from medication bottles and prescription lists. Individual effects of DS and antidepressants were examined along with categorization as follows: (1) BDI <11 and no antidepressant use, (2) BDI <11 with antidepressant use, (3) BDI ≥11 and no antidepressant use, and (4) BDI ≥11 with antidepressant use. Outcomes: CKD progression, incident cardiovascular disease composite, all-cause hospitalizations, and mortality. Analytic Approach: Cox regression models were fitted for outcomes of CKD progression, incident cardiovascular disease, and all-cause mortality, whereas hospitalizations used Poisson regression. Results: At baseline, 27.3% of participants had elevated DS, and 19.7% used antidepressants. Elevated DS at baseline were associated with significantly greater risk for an incident cardiovascular disease event, hospitalization, and all-cause mortality, but not CKD progression, adjusted for antidepressants. Antidepressant use was associated with higher risk for all-cause mortality and hospitalizations, after adjusting for DS. Compared to participants without elevated DS and not using antidepressants, the remaining groups (BDI <11 with antidepressants; BDI ≥11 and no antidepressants; BDI ≥11 with antidepressants) showed higher risks of hospitalization and all-cause mortality. Limitations: Inability to infer causality among depressive symptoms, antidepressants, and outcomes. Additionally, the absence of nonpharmacological data, and required exploration of generalizability and alternative analytical approaches. Conclusions: Elevated DS increased adverse outcome risk in nondialysis CKD, unattenuated by antidepressants. Additionally, investigation into the utilization and counterproductivity of antidepressants in this population is warranted.

We analyzed data from 4,839 nondialysis chronic kidney disease (CKD) patients in the Chronic Renal Insufficiency Cohort Study to explore how depression and antidepressants affect CKD-related outcomes. Using the Beck Depression Inventory (BDI), we assessed depressive symptoms (DS) and identified antidepressant use through medication records. Outcomes included CKD progression, cardiovascular events, hospitalizations, and mortality. Elevated DS at baseline raised the risk of cardiovascular events, hospitalizations, and mortality, regardless of antidepressant use. Antidepressant use alone was associated with higher mortality and hospitalization risks. In comparison to those without elevated DS and no antidepressant use, all other groups faced increased hospitalization and mortality risks. Elevated DS posed a significant risk to nondialysis CKD patients, and antidepressants did not mitigate this risk.

A methylation risk score for chronic kidney disease: a HyperGEN study.

Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

Residential Structural Racism and Prevalence of Chronic Health Conditions.

Importance: Studies elucidating determinants of residential neighborhood-level health inequities are needed. Objective: To quantify associations of structural racism indicators with neighborhood prevalence of chronic kidney disease (CKD), diabetes, and hypertension. Design, Setting, and Participants: This cross-sectional study used public data (2012-2018) and deidentified electronic health records (2017-2018) to describe the burden of structural racism and the prevalence of CKD, diabetes, and hypertension in 150 residential neighborhoods in Durham County, North Carolina, from US census block groups and quantified their associations using bayesian models accounting for spatial correlations and residents' age. Data were analyzed from January 2021 to May 2023. Exposures: Global (neighborhood percentage of White residents, economic-racial segregation, and area deprivation) and discrete (neighborhood child care centers, bus stops, tree cover, reported violent crime, impervious areas, evictions, election participation, income, poverty, education, unemployment, health insurance coverage, and police shootings) indicators of structural racism. Main Outcomes and Measures: Outcomes of interest were neighborhood prevalence of CKD, diabetes, and hypertension. Results: A total of 150 neighborhoods with a median (IQR) of 1708 (1109-2489) residents; median (IQR) of 2% (0%-6%) Asian residents, 30% (16%-56%) Black residents, 10% (4%-20%) Hispanic or Latino residents, 0% (0%-1%) Indigenous residents, and 44% (18%-70%) White residents; and median (IQR) residential income of $54 531 ($37 729.25-$78 895.25) were included in analyses. In models evaluating global indicators, greater burden of structural racism was associated with greater prevalence of CKD, diabetes, and hypertension (eg, per 1-SD decrease in neighborhood White population percentage: CKD prevalence ratio [PR], 1.27; 95% highest density interval [HDI], 1.18-1.35; diabetes PR, 1.43; 95% HDI, 1.37-1.52; hypertension PR, 1.19; 95% HDI, 1.14-1.25). Similarly in models evaluating discrete indicators, greater burden of structural racism was associated with greater neighborhood prevalence of CKD, diabetes, and hypertension (eg, per 1-SD increase in reported violent crime: CKD PR, 1.15; 95% HDI, 1.07-1.23; diabetes PR, 1.20; 95% HDI, 1.13-1.28; hypertension PR, 1.08; 95% HDI, 1.02-1.14). Conclusions and Relevance: This cross-sectional study found several global and discrete structural racism indicators associated with increased prevalence of health conditions in residential neighborhoods. Although inferences from this cross-sectional and ecological study warrant caution, they may help guide the development of future community health interventions.