Annotations by J. Shivali Patel, MD and Rebekah Nash, MD, PhD
September, 2025
The finding:
This study utilized cross-sectional data from the National Health and Nutrition Examination Survey (NHANES, 2015–2018) and Mendelian randomization (MR) analysis to investigate whether chronic kidney disease (CKD) is associated with an increased risk of depression and whether this relationship varies across demographic subgroups. Among 3,738 NHANES participants, CKD was significantly associated with higher odds of depression (OR > 1, 95% CI, p < 0.05), even after adjusting for confounders including age, gender, race, education, tobacco and alcohol use, sleep disorders, diabetes, and physical activity. The multivariate model incorporating CKD demonstrated strong predictive accuracy for depression (AUC = 0.818; 95% CI: 0.796–0.841). Older age, male gender, higher education, non-smoking status, and regular physical activity were associated with decreased depression risk, while Hispanic or multiracial background, alcohol use, and sleep disorders were associated with increased depression risk. Finally, the MR analysis suggested a potential, albeit very small, causal contribution of CKD to depression.
Strength and weaknesses:
This study leveraged observational data from a large, nationally representative sample and incorporated MR to strengthen causal inference and reduce bias from reverse causality. Advanced statistical methods, including weighted multivariate and stratified logistic regression, were used to adjust for confounding and improve analytical rigor. Subgroup and stratified analyses further highlighted lifestyle-related risk factors, adding granularity and clinical relevance.
However, while the MR-derived effect size was statistically significant (OR = 1.002; 95% CI: 1.000–1.003; p < 0.05), it was very small, raising questions about clinical significance. The exclusion of individuals under 18 and those missing PHQ-9 or CKD data may limit generalizability. Additionally, residual confounding may persist due to unmeasured factors such as psychiatric comorbidities, CKD stage, medication burden, socioeconomic status, and social support.
Relevance:
This study underscores a strong association between CKD and depression, even after adjusting for multiple covariates, and provides modest evidence of a possible causal relationship. These findings support the need for proactive depression screening in patients with CKD. Ultimately, C-L psychiatrists are well-positioned to address modifiable risk factors, such as physical inactivity and tobacco use, and manage contributing issues like sleep disorders and alcohol use. Early engagement through motivational interviewing and collaborative care models may improve both psychiatric and medical outcomes in this population.
PUBLICATION #2 — Psychonephrology
Mental Health Symptoms and Receipt of Mental Health Care Among US Adults Diagnosed with Kidney Disease.
Maria A Villarroel, Xun Wang
Abstract: Prev Chronic Dis. 2025 Jul 3:22:E34. doi: 10.5888/pcd22.240509.
Introduction:
Nationally representative estimates of mental health symptoms and services in adults with kidney disease are limited. The objective of this study was to examine the mental health status and use of health care among adults with and without kidney disease.
Methods:
We used data from the 2021 National Health Interview Survey. Diagnosed kidney disease is based on adults who reported ever being told by a doctor or other health professional that they had weak or failing kidneys. The survey question captures data on adults who are aware of having kidney disease and most likely have advanced kidney disease. Mental health measures examined were serious psychological distress (SPD), current symptoms of anxiety and depression, diagnosed anxiety and depressive disorder, prescription medication use for these disorders, and receipt of counseling. We used logistic regression models, with predicted marginal proportions, to calculate unadjusted and adjusted prevalence ratios, controlling for sociodemographic and health characteristics.
Results:
About 2.9% of adults reported having a diagnosis of kidney disease; prevalence varied by sociodemographic and health characteristics. The prevalence of SPD; current symptoms of anxiety or depression or both; history of diagnosed anxiety or depression or both; and receiving counseling and prescription use for these disorders were higher among adults with kidney disease than among adults without kidney disease. In multivariable models adjusted for sociodemographic and health characteristics, adults with diagnosed kidney disease remained more likely than adults not diagnosed with kidney disease to experience mental health conditions and receive counseling.
Conclusion:
A survey of the US population found a higher prevalence of poor mental health and receipt of mental health care among people diagnosed with kidney disease than among people not diagnosed with kidney disease.
Annotation
The finding:
This study analyzed data from the 2021 National Health Interview Survey (NHIS) and found that U.S. adults with diagnosed kidney disease had significantly higher rates of serious psychological distress (measured by the Kessler-6), current symptoms of depression or anxiety (based on the PHQ-2 and GAD-2), and diagnosed depressive or anxiety disorders compared to those without kidney disease. Many of these associations remained significant after adjusting for sociodemographic characteristics and health-related variables, though some, such as current depressive symptoms, were attenuated and no longer significant in fully adjusted models. Individuals with kidney disease were also more likely to receive mental health care, particularly counseling, even after full adjustment. While individuals with kidney disease reported higher use of prescription medications for anxiety and depression, this difference was not statistically significant after adjusting for sociodemographic and health-related factors.
Strength and weaknesses:
This study utilized data from a nationally representative sample and applied multivariable analyses to adjust for sociodemographic and health-related characteristics, strengthening the validity of its findings. However, as a cross-sectional analysis, it cannot establish temporality or causality between kidney disease and mental health symptoms or care. Additionally, reliance on self-reported data from the NHIS introduces potential recall bias, and unmeasured confounders, such as substance use history, may influence the observed associations. The study also excluded individuals unaware of their renal dysfunction, a population that may have limited engagement with the healthcare system and, consequently, reduced likelihood of mental health diagnosis or treatment.
Relevance:
This study highlights the elevated burden of mental health symptoms among adults with diagnosed kidney disease. While many already receive counseling, the adequacy and effectiveness of these interventions remain unclear. The findings support the need for integrated behavioral health models within nephrology care settings to proactively address psychological distress.
PUBLICATION #3 — Psychonephrology
Association of anemia and cognitive impairment in patients undergoing maintenance hemodialysis: a cross-sectional study.
Lin Huang, Yan Zhang, Jinbao Wang, Hongjin Tang, Jiajun Zhou.
Abstract: BMC Nephrol. 2025 Jul 15;26(1):387. doi: 10.1186/s12882-025-04336-4.
Background:
Cognitive impairment (CI) is common among end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (MHD), yet its relationship with hemoglobin levels remains underexplored. This study aimed to investigate the association between hemoglobin levels and CI in MHD patients, as well as to identify other contributing factors.
Methods:
A cross-sectional study was conducted with 248 MHD patients (49.60% male, mean age 57.23 ± 13.16 years) from a single hemodialysis center. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) with CI defined as a score < 24. Hemoglobin levels were divided into quartiles (Q1: < 90 g/L; Q2: 90-110 g/L; Q3: 110-130 g/L; Q4: >130 g/L). Various independent variables, including age, sex, education level, dialysis duration, comorbidities, and laboratory parameters were analyzed using Spearman correlation test, and univariate and multivariate regression.
Results:
Of the 248 patients, 33.90% (84 patients) had CI. Higher hemoglobin quartiles (Q3/Q4) were associated with better cognitive function (higher MMSE scores, P < 0.001) and improved performance across cognitive domains. The Spearman and logistic regression analyses revealed the potential associations between cognitive function (MMSE scores) and several factors, including age, education level, dialysis duration, comorbidities, pre-dialysis blood pressure, interdialytic hypotension, albumin, creatinine, uric acid, and hemoglobin (P < 0.05). Age (OR = 1.454, P < 0.001), male sex (OR = 0.171, P = 0.013), pre-dialysis diastolic blood pressure (OR = 0.884, P = 0.024), and uric acid (OR = 0.992, P = 0.007) were significantly linked with the presence of CI in MHD patients. Multivariate regression further confirmed that adequate hemoglobin concentration was an independent related factor against CI in MHD patients (Model 4, Q1 vs. Q3: OR = 15.395, 95% CI = 3.184-74.443, P < 0.001).
Conclusions:
Anemia is significantly associated with CI in MHD patients, and can still serve as a clinical marker for early detection and intervention in CI. Maintaining adequate hemoglobin levels may be linked with a reduced CI occurrence in hemodialysis patients. These findings highlight the importance of anemia management and tailored interventions to preserve cognitive function health in ESRD patients.
Annotation
The finding:
In a cross-sectional cohort of 248 adults undergoing maintenance hemodialysis (median 5 years of treatment) and without a known diagnosis of dementia, the authors explored the prevalence of cognitive impairment and its association with anemia and other clinical covariates. Cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score < 24, was identified in 34% of participants. Using Spearman’s correlation, MMSE scores were correlated with younger age, greater educational attainment, absence of comorbid conditions (e.g., hypertension, diabetes, cardiovascular disease), longer duration of hemodialysis, higher pre-dialysis blood pressure, elevated hemoglobin levels, and higher creatinine concentrations. Multivariable logistic regression revealed that older age, female gender, lower pre-dialysis blood pressure, reduced uric acid levels, and lower hemoglobin concentrations were independently associated with cognitive impairment, after adjusting for relevant covariates. Furthermore, when hemoglobin levels were stratified into quartiles, the risk of cognitive impairment increased progressively with each lower quartile, even after controlling for confounders.
Strength and weaknesses:
The study is limited by its single-center, cross-sectional design: causation cannot be inferred, and the findings may not translate completely to other dialysis centers or outside of East China. Patients with a diagnosis of dementia were excluded, limiting applicability to that subgroup. Lab values, including hemoglobin, were obtained at one point in time, as opposed to being averaged over several time points, thus increasing the likelihood of including outliers for values that can vary significantly over time. The use of the MMSE, a relatively less sensitive cognitive screening tool, may have underestimated the true prevalence of cognitive impairment—especially in a population where 48% had six or fewer years of education, which can negatively influence test performance. Notably, erythropoiesis-stimulating agents were provided to those in the cohort, presumably improving anemia and lessening its negative impact, and likely mimicking typical clinical practice, and improving applicability of the study findings. The study was strengthened by a robust collection of covariates, for which the authors could control when exploring the impact of anemia on their outcome of interest.
Relevance:
When caring for individuals receiving maintenance hemodialysis, C-L psychiatrists should always keep in mind the significant prevalence of cognitive impairment in this population and how cognitive impairment may contribute to an individual’s presentation. This paper demonstrates an association between cognitive impairment and lower hemoglobin concentrations; if cognitive impairment is of clinical concern, management of the individual’s anemia could represent a modifiable risk factor of cognitive impairment for the patient.
