Visual Abstract
Keywords: depression, kidney transplantation
Abstract
Key Points
Depressive symptoms increased modestly during the first 4 years after kidney transplant but remained below the threshold for clinical depression.
Post-kidney transplant Center for Epidemiologic Studies Depression scores improved in recipients with high pre-kidney transplant depressive symptoms.
Clinicians should counsel patients on the potential mental health implications of kidney transplant and individualize care decisions accordingly.
Background
Depressive symptoms are common in patients with ESKD and may persist after stopping dialysis because of challenges post-kidney transplant (KT) despite clinical benefits. We sought to assess changes in depressive symptoms pre- and post-KT.
Methods
We leveraged a multicenter prospective cohort of 4661 adult (aged ≥18) potential KT candidates and 1215 recipients (2008–2025). Participants reported depressive symptoms via the Center for Epidemiologic Studies Depression (CES-D) scale (range 0–60, high depressive symptoms ≥16) at evaluation, KT, and post-KT. We used linear mixed-effect models to estimate post-KT trajectories of CES-D scores overall and by characteristics at KT admission.
Results
Nineteen percentage of potential candidates at evaluation and 15% of recipients at admission had depressive symptoms; 46% and 38%, respectively, were non-Hispanic Black. Over the first 4 years post-KT, depressive symptoms slightly worsened (slope=0.4 points/yr, 95% confidence interval [CI], 0.3 to 0.6) but remained below the threshold for clinical depression. Post-KT, CES-D score change differed by pre-KT high depressive symptoms score (difference=−1.2 points/yr, 95% CI, −1.8 to −0.6). Specifically, post-KT depressive symptoms were 0.7 points/yr lower (95% CI, −1.2 to −0.1) among recipients with pre-KT high depressive symptoms and 0.5 points/yr higher (95% CI, 0.3 to 0.7) among those without. CES-D score change also differed by preemptive KT status (difference=−0.6 points/yr, 95% CI, −1.0 to −0.1, non-preemptive versus preemptive).
Conclusions
Depressive symptoms worsened slightly over the first 4 years post-KT but remained below the threshold for clinical depression. Notably, post-KT CES-D scores decreased in recipients with high pre-KT depressive symptoms. Clinicians should discuss the mental health impact of KT with patients and tailor care decisions to individual needs.
Introduction
The prevalence of depressive symptoms in patients with ESKD is approximately 40%.1 Patients with depressive symptoms face a higher likelihood of adverse outcomes such as cardiovascular events and mortality,2,3 even after a kidney transplant (KT). KT provides a better quality of life and survival benefits compared with dialysis4,5; however, fear of kidney rejection, medication side effects, and preexisting illness contribute substantially to post-KT psychological stress.6 Owing to limited longitudinal research on depression before and after KT, the long-term trajectory of depressive symptoms throughout the KT course remains insufficiently characterized.
Risk factors for elevated depressive symptoms in potential KT candidates and recipients include younger age, female sex, lack of spousal support, and lower socioeconomic status.7,8 As kidney disease professional organizations, including the Kidney Disease Improving Global Outcomes Clinical Practice Guideline, encourage routine depression screening and psychosocial support across the kidney disease spectrum,9,10 identifying high-risk groups is important for targeting interventions and guiding treatment strategies. However, there is a lack of standardized tools or established cutoff points tailored to detect depression among patients with ESKD.11 Therefore, little is known about how patient characteristics are associated with the temporal change of depressive symptoms following transplantation.
To better characterize the trajectories of depressive symptoms before and after KT, we leveraged a multicenter prospective cohort study of potential KT candidates and recipients. The goals of the study were to (1) quantify the change of depressive symptoms before and after KT and (2) test whether post-KT trajectories of depressive symptoms differ by patient characteristics.
Methods
Study Design
We leveraged a prospective multi-center study composed of a cohort of 4661 adult (age ≥18 years), English-speaking patients with ESKD being evaluated for KT (2009–2025; potential KT candidates hereafter) and a cohort of 1215 adult (age ≥18 years), English-speaking KT recipients (2008–2025). Potential KT candidates and KT recipients were enrolled at Johns Hopkins Hospital, University of Michigan University Hospital, and New York University (NYU)-affiliated hospitals.
In both cohorts, participant characteristics were ascertained from self-report, electronic medical records, or direct measurement, including age, sex, race/ethnicity, education, partnership status, employment status, smoking status, family income, cause of ESKD, donor type, dialysis type, body mass index, dialysis time, frailty (physical frailty phenotype),12,13 lower extremity impairment (short physical performance battery score),14,15 activities of daily living dependence,16 and instrumental activities of daily living dependence.17 Neighborhood deprivation (neighborhood deprivation index18) and social cohesion (social connectedness and supports, obtained from the Social Capital Atlas estimates19) were further ascertained based on residential Zone Improvement Plan codes. We evaluated cognitive function using the global cognitive composite score, calculated as the average of the Z-standardized modified Mini–Mental State examination and Z-standardized Montreal Cognitive Assessment scores.20,21 We obtained comorbidities according to the Charlson Comorbidity Index (CCI) adapted for patients with ESKD via self-report and supplemented with electronic medical records.22,23
We obtained race and ethnicity via self-report and supplemented with electronic medical records when self-report was unavailable. Race was categorized as White, Black, Asian, Native Hawaiian or Pacific Islander, other or multiracial, or unknown, and ethnicity as Hispanic or non-Hispanic. Individuals were then classified as non-Hispanic White, non-Hispanic Black, Hispanic, or non-Hispanic other (American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, other or multiracial).
All clinical and research activities reported adhere to the Declaration of Helsinki and the Declaration of Istanbul. The Johns Hopkins, University of Michigan, and NYU Institutional Review Boards (IRBs) approved the study. All participants provided written (including electronic e-consent) or verbal informed consent, with documentation waived for some minimal-risk phone-based procedures per IRB approval.
Depressive Symptoms
We evaluated participants' depressive symptoms using the Center for Epidemiologic Studies Depression (CES-D) scale, a 20-item, patient-reported measurement that is sensitive to subclinical and mild symptom elevation and often used to track changes in depressive symptoms.24 The CES-D scale measures the frequency of 20 symptoms over the past week.25 Each question has four possible response options (none, 1–2, 3–4, 5–7 days) scored as zero, one, two, or three, and the total score is then calculated from the responses. The CES-D score ranges from 0 to 60, with higher scores indicating greater severity of depressive symptoms. A score of ≥16 indicates clinically elevated depressive symptoms (high depressive symptoms hereafter), which is often considered a clinical cutoff for depression.25 The CES-D instrument identifies symptoms in areas of depressed mood, guilt/worthlessness, helplessness/hopelessness, psychomotor retardation, loss of appetite, and sleep disturbance25 and has been validated in the ESKD population.26,27 The full questionnaire is publicly available through: https://eprovide.mapi-trust.org/instruments/center-for-epidemiologic-studies-depression-scale. CES-D was administered at the evaluation for potential candidates. Recipients were assessed at KT admission and at follow-up during routine clinical visits at approximately 1, 3, and 6 months, 1 year, and annually thereafter.
Statistical Analysis
Descriptive Analysis
We reported the distribution of characteristics, overall and by presence of high depressive symptoms, using percentages for categorical variables, means with SD for normally distributed continuous variables, and medians with interquartile ranges (IQRs) for nonnormally distributed continuous variables.
Pre-KT Risk Factors for Depressive Symptoms
We estimated the odds ratios of depressive symptoms at the time of evaluation and the time of KT admission using logistic regression models. Models were adjusted for age, sex, race/ethnicity, smoking, education, cause of ESKD, dialysis type, dialysis time, and CCI. Models at admission are additionally adjusted for donor type.
Post-KT Trajectories of Depressive Symptoms
We estimated score points and adjusted trajectories of CES-D between KT admission and 4 years post-KT among KT recipients using mixed-effects models with random effects for person (intercept) and time (slope) with unconstructed covariance. The model did not include spline terms based on exploratory analysis. Models were adjusted for age, race/ethnicity, sex, partnership status, smoking, education, cause of ESKD, donor type, CCI, and dialysis time. We tested whether the CES-D score trajectories differed by the following factors using the Wald test: presence of high depressive symptoms at KT admission, age (>60 versus ≤60 years), sex, race/ethnicity (all other racial and ethnic groups versus non-Hispanic Black), education status (<high school versus ≥high school), partnership status, smoking status (previous/current smoking versus nonsmoking), preemptive KT status, and donor type (living versus deceased). We additionally tested whether CES-D score trajectories differed by neighborhood-level psychosocial support (social connectedness and social supports) using the Wald test.
Missing Data Approach
For logistic regressions analyses, missing data were handled using multiple imputation with 20 iterations for partnership (1% at evaluation and 2% at admission, respectively), smoking (0.3% and 0.6%), education (1% and 2%), dialysis type (14% and 14%), comorbidity (12% and 0.9%), dialysis year (17% and 18%), and cause of ESKD (45% and 4%). For mixed-effect models, we performed a complete case analysis, excluding patients with missing at-admission covariates.
Sensitivity Analysis
To test the robustness of our results and account for population differences, we redefined high depressive symptoms at KT admission using internal cutoffs based on our KT recipient population. Specifically, we stratified the trajectory using cohort-based CES-D score thresholds of nine (highest tertile) and 11 (highest quartile). We also applied a generalized estimation equation (GEE) model with robust standard errors to relax the correlation structure assumed in the main model. We additionally adjusted our models with individual-level employment, family income, and neighborhood-level deprivation to account for potential socioeconomic confounding. Finally, to address potential effects of loss to follow-up because of withdrawal or having competing events (graft failure or death), under the assumption of missing at random, we compared results from two approaches: (1) multiple imputations by chained equations with auxiliary variables and (2) inverse probability weighting, both implemented with GEEs.28
All analyses were performed using Stata version 18 (StataCorp, College Station, TX). The study determined statistical significance with two-sided P values < 0.05.
Results
Potential KT Candidate Characteristics
Among the 4661 potential KT candidates, the mean age at evaluation was 55.2 (SD: 13.5) years, 40% were female, 46% were non-Hispanic Black, 94% had ≥high school degree, 58% were partnered, 34% were currently or previously smoking, median time on dialysis was 0.9 years (IQR, 0.0–3.0), and median CCI was 2.0 (IQR, 0.0–3.0; Figure 1A and Table 1).
Figure 1.
Study cohort selection identified three-center KT candidate and recipient cohorts with available CES-D data for analysis. (A) Flow chart of derivation for KT evaluation cohort. (B) Flow chart of derivation for KT recipient cohort. CCI, Charlson Comorbidity Index; CES-D, Center for Epidemiologic Studies Depression; KT, kidney transplant.
Table 1.
Characteristics of kidney transplant candidates at time of evaluation by depressive symptoms status (Center for Epidemiologic Studies Depression scale ≥16; N=4661)
| Characteristic | Total (N=4661) | No High Depressive Symptoms (CES-D <16) (n=3764) |
High Depressive Symptoms (CES-D ≥16) (n=897) |
|---|---|---|---|
| Age in years, mean year (SD) | 55.2 (13.5) | 55.9 (13.6) | 52.4 (12.9) |
| Female, No. (%) | 1884 (40) | 1454 (39) | 430 (48) |
| Race/ethnicity, No. (%) | |||
| Hispanic | 337 (7) | 259 (7) | 78 (9) |
| Non-Hispanic Black | 2122 (46) | 1717 (46) | 405 (45) |
| Non-Hispanic Othera | 71 (2) | 58 (2) | 13 (1) |
| Non-Hispanic White | 2131 (46) | 1730 (46) | 401 (45) |
| BMI, median (IQR) | 28.2 (24.0–33.1) | 28.2 (24.1–33.0) | 28.2 (23.9–33.8) |
| Education, No. (%) | |||
| Below high school degree | 284 (6) | 218 (6) | 66 (8) |
| High school degree | 1705 (37) | 1357 (37) | 348 (39) |
| Above high school degree (technical school, college, graduate school) | 2612 (57) | 2143 (58) | 469 (53) |
| Partnered, No. (%) | 2647 (58) | 2245 (60) | 402 (45) |
| Employed, No. (%) | 1677 (37) | 1403 (38) | 274 (31) |
| Ever smoking, No. (%) | 1576 (34) | 1181 (31) | 395 (44) |
| Family income, No. (%) | |||
| <$50,000 | 860 (39) | 597 (40) | 263 (50) |
| $50,000–99,999 | 649 (30) | 509 (31) | 140 (27) |
| ≥$100,000 | 682 (31) | 558 (34) | 124 (24) |
| NDI, mean (SD) | −0.4 (0.9) | −0.4 (0.9) | −0.3 (0.9) |
| Social connectednessb, median (IQR) | 0.1 (0.1–0.1) | 0.1 (0.1–0.1) | 0.1 (0.1–0.1) |
| Social supportsc, median (IQR) | 0.9 (0.8–0.9) | 0.9 (0.8–0.9) | 0.9 (0.8–0.9) |
| Cause of ESKD, No. (%) | |||
| GN | 562 (12) | 467 (12) | 95 (11) |
| Diabetes mellitus | 554 (12) | 471 (13) | 83 (9) |
| Hypertension | 761 (16) | 642 (17) | 119 (13) |
| Others | 697 (15) | 582 (16) | 115 (13) |
| Not collected | 2087 (45) | 1602 (43) | 485 (54) |
| Dialysis type, No. (%) | |||
| Preemptive KT | 1004 (25) | 766 (24) | 238 (30) |
| Hemodialysis | 2445 (61) | 1988 (62) | 457 (57) |
| Peritoneal dialysis | 546 (14) | 434 (14) | 112 (14) |
| Year on dialysis, median (IQR) | 0.9 (0.0–3.0) | 1.0 (0.0–3.1) | 0.6 (0.0–2.4) |
| Frailtyd, No. (%) | 896 (21) | 628 (18) | 268 (35) |
| Lower extremely impairment, No. (%) | 2021 (55) | 1563 (53) | 458 (65) |
| ADL, No. (%) | 357 (9) | 261 (8) | 96 (13) |
| IADL, No. (%) | 835 (21) | 581 (18) | 254 (34) |
| Cognitive functione, median (IQR) | 0.2 (−0.5 to 0.7) | 0.2 (−0.5 to 0.7) | 0.3 (−0.4 to 0.7) |
| CCI, median (IQR) | 2.0 (0.0–3.0) | 2.0 (0.0–3.0) | 2.0 (0.0–3.0) |
| Myocardial infarction, No. (%) | 396 (10) | 309 (9) | 87 (11) |
| Peripheral vascular disease, No. (%) | 256 (6) | 193 (6) | 63 (8) |
| Cerebral vascular disease, No. (%) | 259 (6) | 188 (6) | 71 (9) |
| Dementia, No. (%) | 14 (0.3) | 7 (0.2) | 7 (0.9) |
| Chronic lung disease, No. (%) | 231 (6) | 188 (6) | 43 (5) |
| Rheumatological disease, No. (%) | 303 (7) | 235 (7) | 68 (8) |
| Peptic ulcer disease, No. (%) | 133 (3) | 99 (3) | 34 (4) |
| Diabetes, No. (%) | 1762 (43) | 1388 (42) | 374 (45) |
| Diabetes with complications, No. (%) | 1099 (32) | 861 (33) | 238 (31) |
| Moderate or severe liver disease, No. (%) | 144 (4) | 98 (3) | 46 (6) |
| Metastatic cancer, No. (%) | 46 (1) | 39 (1) | 7 (0.9) |
| Leukemia, No. (%) | 11 (0.3) | 10 (0.3) | 1 (0.1) |
| Lymphoma, No. (%) | 31 (0.8) | 26 (0.8) | 5 (0.6) |
| HIV, No. (%) | 129 (3) | 96 (3) | 33 (4) |
| Congestive heart failure, No. (%) | 455 (14) | 352 (13) | 103 (19) |
ADL, activities of daily living; BMI, body mass index; CCI, Charlson Comorbidity Index; CES-D, Center for Epidemiologic Studies Depression; IADL, instrumental activities of daily living; IQR, interquartile range; KT, kidney transplant; NDI, neighborhood deprivation index.
Non-Hispanic Other includes American Indian/Alaska Native, Asian, Native Hawaiian or Pacific Islander, other or multiracial.
Social connectedness, obtained from the Social Capital Atlas estimates (2022) at the Zone Improvement Plan (ZIP) code level, is defined as the average fraction of an individual's friend pairs who are also friends with each other, including people outside the ZIP code.
Social supports, obtained from the Social Capital Atlas estimates (2022) at the ZIP code level, is defined as the proportion of within-ZIP code friendships where the pair of friends share a third mutual friend within the same ZIP code.
Frailty is defined as ≥3 of the five components from the physical frailty phenotype.
Composite score of standardized Modified Mini–Mental State Examination score and standardized Montreal Cognitive Assessment score.
Potential KT Candidate Characteristics and Depressive Symptoms at Evaluation
At evaluation, the median CES-D score was 6.0 (IQR, 2.0–13.0), and 19% had high depressive symptoms (Figure 2A). The median CES-D score for potential candidates with high depressive symptoms (>16) was 22.0 (IQR, 18.0–29.0), and 4.0 (IQR, 1.0–8.0) for those without.
Figure 2.
Prevalence of high depressive symptoms (defined as CES-D score ≥16). (A) Prevalence of high depressive symptoms among KT candidates at evaluation and over time among transplant recipients. (B) Prevalence over time by high depressive symptoms at admission. The respective counts of available depressive symptoms information for each period were 4661 (Eval), 1215, 813, 379, 323, 242, 203, 182, and 223. If an individual was followed up several times during the period, the answers closest to 6-, 12-, 18-, 24-, 30-, 36-, and 48-month post-KT were used.
After adjustment, potential candidates aged ≤60 years (adjusted odds ratio [aOR], 1.75; 95% confidence interval [CI], 1.48 to 2.07), who were female (aOR, 1.40; 95% CI, 1.20 to 1.64), all other racial and ethnic groups (aOR, 1.18; 95% CI, 1.00 to 1.39), nonpartnered (aOR, 1.70; 95% CI, 1.46 to 1.99), current or previous smoking (aOR, 1.73; 95% CI, 1.48 to 2.02), frail (aOR, 1.55; 95% CI, 1.22 to 1.97), or with higher CCI (aOR, 1.04; 95% CI, 1.01 to 1.08) were more likely to have high depressive symptoms at evaluation (Table 2).
Table 2.
Depressive symptoms among kidney transplant candidates at kidney transplant evaluation (N=4661) and recipients at kidney transplant admission (N=1215)
| Covariates | Transplant Evaluation (N=4661) | Transplant Admission (N=1215) | ||
|---|---|---|---|---|
| cOR (95% CI) | aOR (95% CI) | cOR (95% CI) | aOR (95% CI) | |
| Age, yr | ||||
| ≥60 | Reference | Reference | Reference | Reference |
| <60 | 1.64 (1.40 to 1.91)a | 1.75 (1.48 to 2.07)a | 2.61 (1.74 to 3.90)a | 2.66 (1.68 to 4.21)a |
| Sex | ||||
| Male | Reference | Reference | Reference | Reference |
| Female | 1.46 (1.26 to 1.69)a | 1.40 (1.20 to 1.64)a | 1.33 (0.97 to 1.84) | 1.35 (0.96 to 1.91) |
| Race/ethnicity | ||||
| All other racial/ethnic groupsb | 1.02 (0.88 to 1.18) | 1.18 (1.00 to 1.39)a | 1.07 (0.77 to 1.48) | 1.03 (0.69 to 1.54) |
| Non-Hispanic Black | Reference | Reference | Reference | Reference |
| Partnership status | ||||
| Partnered | Reference | Reference | Reference | Reference |
| Nonpartnered | 1.83 (1.58 to 2.12)a | 1.70 (1.46 to 1.99)a | 1.52 (1.10 to 2.10)a | 1.41 (0.99 to 2.01) |
| Smoking status | ||||
| Never | Reference | Reference | Reference | Reference |
| Current/ever | 1.73 (1.49 to 2.01)a | 1.73 (1.48 to 2.02)a | 1.60 (1.15 to 2.23)a | 1.62 (1.12 to 2.34)a |
| Education | ||||
| Above high school | Reference | Reference | Reference | Reference |
| High school | 1.17 (1.00 to 1.37)a | 1.09 (0.93 to 1.29) | 1.16 (0.83 to 1.63) | 1.11 (0.77 to 1.61) |
| Below high school | 1.39 (1.04 to 1.86)a | 1.26 (0.93 to 1.72) | 1.03 (0.49 to 2.16) | 1.15 (0.52 to 2.52) |
| Social connectedness | ||||
| Highest tertile | Reference | Reference | Reference | Reference |
| Medium tertile | 0.88 (0.72 to 1.09) | 0.93 (0.75 to 1.15) | 0.62 (0.40 to 0.96)a | 0.67 (0.42 to 1.06) |
| Lowest tertile | 1.14 (0.93 to 1.39) | 1.08 (0.87 to 1.35) | 1.32 (0.90 to 1.94) | 1.33 (0.86 to 2.06) |
| Social supports | ||||
| Highest tertile | Reference | Reference | Reference | Reference |
| Medium tertile | 1.09 (0.89 to 1.34) | 1.11 (0.90 to 1.37) | 1.69 (1.12 to 2.57)a | 1.81 (1.17 to 2.79)a |
| Lowest tertile | 1.13 (0.92 to 1.38) | 1.14 (0.92 to 1.42) | 1.39 (0.90 to 2.12) | 1.49 (0.94 to 2.36) |
| Cause of ESKD | ||||
| GN | Reference | Reference | Reference | Reference |
| Diabetes mellitus | 0.99 (0.76 to 1.30) | 1.03 (0.75 to 1.42) | 0.64 (0.37 to 1.10) | 0.75 (0.41 to 1.39) |
| Hypertension | 0.93 (0.73 to 1.19) | 1.03 (0.79 to 1.34) | 0.59 (0.38 to 0.93)a | 0.70 (0.43 to 1.14) |
| Others | 0.99 (0.76 to 1.28) | 0.96 (0.73 to 1.26) | 0.89 (0.58 to 1.37) | 0.97 (0.62 to 1.51) |
| Dialysis type | ||||
| Preemptive KT | Reference | Reference | Reference | Reference |
| Hemodialysis | 0.78 (0.65 to 0.92)a | 0.76 (0.62 to 0.93)a | 0.71 (0.44 to 1.14) | 0.59 (0.34 to 1.02) |
| Peritoneal dialysis | 0.84 (0.65 to 1.09) | 0.86 (0.65 to 1.13) | 0.83 (0.47 to 1.46) | 0.66 (0.35 to 1.25) |
| Dialysis years | 0.98 (0.96 to 0.99)a | 0.99 (0.97 to 1.01) | 1.00 (0.97 to 1.03) | 1.00 (0.97 to 1.03) |
| Donor type | ||||
| Living | — | — | Reference | Reference |
| Deceased | 1.00 (0.72 to 1.39) | 1.21 (0.82 to 1.78) | ||
| CCI (per one-point increase) | 1.04 (1.01 to 1.07)a | 1.04 (1.01 to 1.08)a | 0.98 (0.90 to 1.07) | 1.05 (0.95 to 1.17) |
| Frailtyc | ||||
| No | Reference | Reference | Reference | Reference |
| Yes | 1.34 (1.07 to 1.68)a | 1.55 (1.22 to 1.97)a | 1.97 (1.25 to 3.12)a | 2.75 (1.67 to 4.54)a |
| Cognitive functiond | 1.07 (0.98 to 1.17) | 1.00 (0.91 to 1.10) | 0.97 (0.79 to 1.20) | 0.91 (0.72 to 1.15) |
Logistic regression was used to estimate the crude and adjusted odds ratios. Models are adjusted for age, sex, race/ethnicity, smoking status, education, cause of ESKD, dialysis type, years on dialysis, and comorbidity. Models at transplant admission are additionally adjusted for donor type. aOR, adjusted odds ratio; CCI, Charlson Comorbidity Index; CI, confidence interval; cOR, crude odds ratio; KT, kidney transplant.
Statistically significant (P value < 0.05).
All other racial/ethnic groups include non-Hispanic White, Hispanic, American Indian/Alaska Native, Asian, Native Hawaiian, or Pacific Islander, other or multiracial.
Frailty, the presence of ≥3 components of the modified four-item physical frailty phenotype, including unintentional weight loss, gait speed, grip strength, and physical activity.
Composite score of standardized Modified Mini–Mental State Examination score and standardized Montreal Cognitive Assessment score.
KT Recipient Characteristics
Among the 1215 KT recipients, the mean age at transplant admission was 52.5 (SD: 13.9) years, 40% were female, 38% were non-Hispanic Black, 95% had ≥high school degree, 63% were partnered, 29% were current or previous smoking, 60% had a deceased donor, median time on dialysis was 2.4 years (IQR, 0.7–5.4), and median CCI was 1.0 (IQR, 0.0–3.0; Figure 1B and Table 3). The average postsurgical stay was 10.0 (SD: 8.3) days and hospitalization within 5 years was 1.6 (SD: 1.0) times (Table 3). During follow-up, 97% of recipients had functioning transplants with minimal complications (33% rejection, 0% infection).
Table 3.
Characteristics of kidney transplant recipients at time of admission by depressive symptoms status (Center for Epidemiologic Studies Depression scale ≥16; N=1215)
| Characteristic | Total (N=1215) | No High Depressive Symptoms (CES-D <16) (n=1037) |
High Depressive Symptoms (CES-D ≥16) (n=178) |
|---|---|---|---|
| Age in years, mean year (SD) | 52.5 (13.9) | 53.2 (13.9) | 48.2 (13.4) |
| Female, No. (%) | 487 (40) | 405 (39) | 82 (46) |
| Black, No. (%) | 459 (38) | 394 (38) | 65 (37) |
| Race/ethnicity, No. (%) | |||
| Hispanic | 28 (2) | 24 (2) | 4 (2) |
| Non-Hispanic Black | 459 (38) | 394 (38) | 65 (37) |
| Non-Hispanic othera | 71 (6) | 63 (6) | 8 (5) |
| Non-Hispanic White | 657 (54) | 556 (54) | 101 (57) |
| BMI, median (IQR) | 27.3 (23.4–31.6) | 27.4 (23.6–31.7) | 26.4 (22.3–30.4) |
| Education, No. (%) | |||
| Below high school degree | 60 (5) | 51 (5) | 9 (5) |
| High school degree | 403 (34) | 338 (33) | 65 (37) |
| Above high school degree (technical school, college, graduate school) | 726 (61) | 623 (62) | 103 (58) |
| Partnered, No. (%) | 752 (63) | 656 (65) | 96 (55) |
| Employed, No. (%) | 552 (46) | 475 (46) | 77 (43) |
| Ever smoking, No. (%) | 349 (29) | 282 (27) | 67 (38) |
| Family income, No. (%) | |||
| <$50,000 | 153 (29) | 115 (27) | 38 (38) |
| $50,000–99,999 | 170 (32) | 139 (32) | 31 (31) |
| ≥$100,000 | 210 (39) | 179 (41) | 31 (31) |
| NDI, mean (SD) | −0.4 (0.9) | −0.4 (0.9) | −0.3 (0.9) |
| Social connectednessb, median (IQR) | 0.1 (0.1–0.1) | 0.1 (0.1–0.1) | 0.1 (0.1–0.1) |
| Social supportsc, median (IQR) | 0.9 (0.8–0.9) | 0.9 (0.8–0.9) | 0.9 (0.8–0.9) |
| Cause of ESKD, No. (%) | |||
| GN | 296 (24) | 245 (24) | 51 (29) |
| Diabetes mellitus | 187 (15) | 165 (16) | 22 (12) |
| Hypertension | 355 (29) | 316 (31) | 39 (22) |
| Others | 325 (27) | 274 (26) | 51 (29) |
| Not collected | 52 (4) | 37 (4) | 15 (8) |
| Dialysis type, No. (%) | |||
| Preemptive KT | 136 (13) | 107 (12) | 29 (18) |
| Hemodialysis | 721 (70) | 619 (70) | 102 (63) |
| Peritoneal dialysis | 190 (18) | 159 (18) | 31 (19) |
| Year on dialysis, median (IQR) | 2.4 (0.7–5.4) | 2.4 (0.7–5.1) | 2.7 (0.5–5.7) |
| Deceased donor, No. (%) | 723 (60) | 617 (60) | 106 (60) |
| Hospital length of stay, mean (SD) | 10.0 (8.3) | 10.1 (8.4) | 9.8 (7.1) |
| Hospitalization counts in 5 yr, mean (SD) | 1.6 (1.0) | 1.7 (1.1) | 1.6 (0.8) |
| Frailtyd, N (%) | 209 (17) | 147 (14) | 62 (35) |
| Lower extremely impairment, No. (%) | 482 (53) | 395 (51) | 87 (61) |
| ADL, No. (%) | 58 (6) | 42 (5) | 16 (12) |
| IADL, No. (%) | 130 (13) | 103 (12) | 27 (19) |
| Cognitive functione, median (IQR) | 0.3 (−0.1 to 0.5) | 0.3 (−0.1 to 0.5) | 0.3 (−0.1 to 0.5) |
| CCI, median (IQR) | 1.0 (0.0–3.0) | 1.0 (0.0–3.0) | 0.0 (0.0–3.0) |
| Myocardial infarction, No. (%) | 66 (6) | 60 (6) | 6 (3) |
| Peripheral vascular disease, No. (%) | 70 (6) | 62 (6) | 8 (5) |
| Cerebral vascular disease, No. (%) | 47 (4) | 39 (4) | 8 (5) |
| Dementia, No. (%) | 1 (0.1) | 1 (0.1) | 0 (0) |
| Chronic lung disease, No. (%) | 54 (5) | 42 (4) | 12 (7) |
| Rheumatological disease, No. (%) | 161 (13) | 137 (13) | 24 (14) |
| Peptic ulcer disease, No. (%) | 43 (4) | 37 (4) | 6 (3) |
| Diabetes, No. (%) | 361 (30) | 316 (31) | 45 (25) |
| Diabetes with complications, No. (%) | 202 (26) | 174 (27) | 28 (20) |
| Moderate or severe liver disease, No. (%) | 31 (3) | 24 (2) | 7 (4) |
| Metastatic cancer, No. (%) | 6 (0.5) | 5 (0.5) | 1 (0.6) |
| Leukemia, No. (%) | 3 (0.2) | 1 (0.1) | 2 (1) |
| Lymphoma, No. (%) | 3 (0.2) | 3 (0.3) | 0 (0) |
| HIV, No. (%) | 28 (2) | 23 (2) | 5 (3) |
| Congestive heart failure, No. (%) | 66 (6) | 53 (6) | 13 (9) |
ADL, activities of daily living; BMI, body mass index; CCI, Charlson Comorbidity Index; CES-D, Center for Epidemiologic Studies Depression; IADL, instrumental activities of daily living; IQR, interquartile range; KT, kidney transplant; NDI, neighborhood deprivation index.
Non-Hispanic other includes American Indian/Alaska Native, Asian, Native Hawaiian or Pacific Islander, other or multiracial.
Social connectedness, obtained from the Social Capital Atlas estimates (2022) at the Zone Improvement Plan (ZIP) code level, is defined as the average fraction of an individual's friend pairs who are also friends with each other, including people outside the ZIP code.
Social supports, obtained from the Social Capital Atlas estimates (2022) at the ZIP code level, is defined as the proportion of within-ZIP code friendships where the pair of friends share a third mutual friend within the same ZIP code.
Frailty is defined as ≥3 of the five components from the physical frailty phenotype.
Composite score of standardized Modified Mini–Mental State Examination score and standardized Montreal Cognitive Assessment score.
KT Recipient Characteristics and Depressive Symptoms at Admission
At admission, the median CES-D score was 6.0 (IQR, 2.0–11.0), and 15% of recipients had high depressive symptoms (Figure 2A). The median CES-D score for recipients with high depressive symptoms was 20.0 (IQR, 18.0–25.0) and 4.0 (IQR, 2.0–8.0) for those without. Among recipients with high depressive symptoms at admission, 48% and 58% resolved by one and 2 years post-KT, respectively (Figure 2B).
After adjustment, recipients aged ≤60 years (aOR, 2.66; 95% CI, 1.68 to 4.21), who were current or previous smoking (aOR, 1.62; 95% CI, 1.12 to 2.34), or frail (aOR, 2.75; 95% CI, 1.67 to 4.54) were more likely to have high depressive symptoms at admission (Table 2).
Trajectories of Depressive Symptoms among KT Recipients
The average follow-up time for the 1215 recipients enrolled at admission was 2 years. Follow-up assessments were not conducted at fixed time points; rather, we defined prespecified time windows around each nominal time point, with available assessments from 813, 379, 323, 242, 203, 182, and 223 patients at 6, 12, 18, 24, 30, 36, and 48 months post-KT, respectively (Figure 2A). When multiple assessments fell within a given window, we retained the observation closest to the target time point.
Among the reference population (>60 years, all other racial and ethnic groups, male, partnered, previous/current smoking, <high school, GN-caused ESKD, living donor, CCI score of 1.0 [median at KT admission], and dialysis vintage of 2.4 years [median at KT admission]), the estimated CES-D score was 7.95 (95% CI, 5.78 to 10.11) at KT admission, which differed by age (difference=1.04 points, 95% CI, 0.21 to 1.88), sex (difference=1.14 points, 95% CI, 0.33 to 1.96), partnership status (difference=0.83 points, 95% CI, 0.07 to 1.58), and smoking status (difference=−1.54 points, 95% CI, −2.24 to −0.83; Table 4).
Table 4.
Adjusted estimates of Center for Epidemiologic Studies Depression score at kidney transplant admission and post-transplantation among recipients (N=969)
| Recipient Characteristics at Admission | Estimated CES-D Score, Points (95% CI) | Estimated Annual Change (95% CI) | ||||||
|---|---|---|---|---|---|---|---|---|
| Pre-KT | 6 mo | 1 yr | 2 yr | 3 yr | 4 yr | Per Year Post-KT | P Value | |
| Overall | 7.95 (5.78 to 10.11) | 8.16 (6.00 to 10.32) | 8.37 (6.21 to 10.53) | 8.79 (6.63 to 10.95) | 9.21 (7.03 to 11.39) | 9.63 (7.42 to 11.84) | 0.42 (0.25 to 0.60)a | <0.001a |
| High depressive symptoms at admission | ||||||||
| No (CES-D <16) | 6.55 (4.85 to 8.26) | 6.82 (5.12 to 8.52) | 7.08 (5.39 to 8.78) | 7.61 (5.90 to 9.32) | 8.14 (6.39 to 9.88) | 8.66 (6.87 to 10.46) | 0.53 (0.34 to 0.71)a | <0.001a |
| Yes (CES-D ≥16) | 18.72 (16.82 to 20.61) | 18.39 (16.50 to 20.28) | 18.06 (16.13 to 19.99) | 17.40 (15.28 to 19.52) | 16.74 (14.31 to 19.18) | 16.09 (13.25 to 18.92) | −0.66 (−1.23 to −0.08)a | 0.03a |
| Difference | 12.16 (11.25 to 13.07)a | 11.57 (10.66 to 12.48)a | 10.98 (9.98 to 11.97) | 9.79 (8.42 to 11.16)a | 8.61 (6.74 to 10.47)a | 7.42 (5.01 to 9.83)a | −1.18 (−1.79 to −0.58)a | <0.001a |
| Age, yr | ||||||||
| >60 | 7.93 (5.77 to 10.10) | 8.15 (6.00 to 10.30) | 8.37 (6.22 to 10.51) | 8.80 (6.64 to 10.95) | 9.23 (7.04 to 11.42) | 9.66 (7.40 to 11.92) | 0.43 (0.18 to 0.69)a | 0.001a |
| ≤60 | 8.98 (6.90 to 11.05) | 9.18 (7.11 to 11.26) | 9.39 (7.32 to 11.46) | 9.80 (7.71 to 11.90) | 10.22 (8.08 to 12.35) | 10.63 (8.43 to 12.83) | 0.41 (0.20 to 0.63)a | <0.001a |
| Difference | 1.04 (0.21 to 1.88)a | 1.03 (0.24 to 1.82)a | 1.02 (0.25 to 1.80)a | 1.01 (0.16 to 1.85)a | 0.99 (−0.02 to 2.00) | 0.97 (−0.26 to 2.20) | −0.02 (−0.33 to 0.30) | 0.91 |
| Sex | ||||||||
| Male | 7.97 (5.82 to 10.13) | 8.16 (6.02 to 10.31) | 8.35 (6.21 to 10.50) | 8.73 (6.57 to 10.88) | 9.10 (6.91 to 11.30) | 9.48 (7.23 to 11.73) | 0.38 (0.15 to 0.60)a | 0.001a |
| Female | 9.12 (6.90 to 11.33) | 9.36 (7.15 to 11.56) | 9.60 (7.40 to 11.81) | 10.09 (7.86 to 12.32) | 10.57 (8.28 to 12.86) | 11.06 (8.68 to 13.43) | 0.49 (0.22 to 0.75)a | <0.001a |
| Difference | 1.14 (0.33 to 1.96)a | 1.20 (0.40 to 2.00)a | 1.25 (0.43 to 2.07)a | 1.36 (0.39 to 2.33)a | 1.47 (0.27 to 2.67)a | 1.58 (0.10 to 2.06)a | 0.11 (−0.24 to 0.46) | 0.54 |
| Black | ||||||||
| All other racial/ethnic groupsb | 7.98 (5.82 to 10.13) | 8.13 (5.99 to 10.28) | 8.29 (6.14 to 10.44) | 8.60 (6.44 to 10.77) | 8.92 (6.72 to 11.12) | 9.23 (6.97 to 11.49) | 0.31 (0.09 to 0.54)a | 0.006a |
| Non-Hispanic Black | 7.61 (5.36 to 9.86) | 7.90 (5.66 to 10.14) | 8.19 (5.95 to 10.43) | 8.77 (6.51 to 11.03) | 9.35 (7.03 to 11.66) | 9.93 (7.53 to 12.33) | 0.58 (0.31 to 0.85)a | <0.001a |
| Difference | −0.37 (−1.26 to 0.52) | −0.24 (−1.11 to 0.64) | −0.10 (−1.00 to 0.80) | 0.16 (−0.87 to 1.20) | 0.43 (−0.82 to 1.69) | 0.70 (−0.83 to 2.22) | 0.27 (−0.08 to 0.62) | 0.13 |
| Education | ||||||||
| <High school | 7.61 (5.43 to 9.79) | 8.14 (6.00 to 10.29) | 8.68 (6.52 to 10.85) | 9.76 (7.39 to 12.12) | 10.83 (8.10 to 13.57) | 11.91 (8.69 to 15.12) | 1.07 (0.38 to 1.77)a | 0.002a |
| ≥High school | 6.66 (5.40 to 7.92) | 6.85 (5.60 to 8.09) | 7.03 (5.79 to 8.28) | 7.41 (6.16 to 8.67) | 7.79 (6.50 to 9.08) | 8.17 (6.81 to 9.52) | 0.38 (0.20 to 0.56)a | <0.001a |
| Difference | −0.95 (−2.76 to 0.85) | −1.30 (−3.07 to 0.47) | −1.65 (−3.46 to 0.16) | −2.35 (−4.42 to −0.27)a | −3.04 (−5.57 to −0.52)a | −3.74 (−6.82 to −0.66)a | −0.70 (−1.41 to 0.02) | 0.06 |
| Partnership | ||||||||
| Partnered | 8.05 (5.89 to 10.20) | 8.20 (6.05 to 10.35) | 8.35 (6.21 to 10.50) | 8.66 (6.50 to 10.81) | 8.96 (6.78 to 11.15) | 9.27 (7.04 to 11.50) | 0.31 (0.10 to 0.51)a | 0.004a |
| Nonpartnered | 8.87 (6.64 to 11.10) | 9.17 (6.95 to 11.39) | 9.47 (7.26 to 11.68) | 10.07 (7.84 to 12.29) | 10.66 (8.40 to 12.92) | 11.26 (8.94 to 13.58) | 0.60 (0.35 to 0.84)a | <0.001a |
| Difference | 0.83 (0.07 to 1.58)a | 0.97 (0.25 to 1.69)a | 1.12 (0.41 to 1.82)a | 1.41 (0.63 to 2.18)a | 1.70 (0.76 to 2.64)a | 1.99 (0.83 to 3.14)a | 0.29 (−0.01 to 0.59) | 0.05 |
| Smoking | ||||||||
| Previous/current | 7.98 (5.81 to 10.14) | 8.17 (6.02 to 10.32) | 8.37 (6.23 to 10.51) | 8.76 (6.61 to 10.92) | 9.16 (6.95 to 11.36) | 9.55 (7.26 to 11.84) | 0.39 (0.12 to 0.68)a | 0.006a |
| Never | 6.44 (4.30 to 8.58) | 6.66 (4.53 to 8.79) | 6.88 (4.74 to 9.01) | 7.31 (5.17 to 9.46) | 7.75 (5.57 to 9.93) | 8.19 (5.95 to 10.42) | 0.44 (0.23 to 0.65)a | <0.001a |
| Difference | −1.54 (−2.24 to −0.83)a | −1.51 (−2.17 to −0.86)a | −1.49 (−2.13 to −0.86)a | −1.45 (−2.18 to −0.72)a | −1.41 (−2.34 to −0.48)a | −1.36 (−2.56 to −0.17)a | 0.04 (−0.29 to 0.37) | 0.80 |
| Preemptive KT | ||||||||
| Yes | 7.97 (5.79 to 10.15) | 8.18 (6.01 to 10.35) | 8.39 (6.23 to 10.56) | 8.82 (6.66 to 10.99) | 9.25 (7.06 to 11.43) | 9.67 (7.45 to 11.89) | 0.43 (0.24 to 0.62)a | <0.001a |
| No | 7.85 (5.66 to 10.04) | 7.78 (5.59 to 9.97) | 7.71 (5.50 to 9.92) | 7.57 (5.23 to 9.91) | 7.43 (4.89 to 9.98) | 7.29 (4.47 to 10.11) | −0.14 (−0.61 to 0.33) | 0.57 |
| Difference | −0.12 (−0.62 to 0.38) | −0.40 (−0.89 to 0.08) | −0.68 (−1.26 to −0.11)a | −1.25 (−2.18 to −0.32)a | −1.82 (−3.17 to −0.46)a | −2.38 (−4.18 to −0.58)a | −0.57 (−1.04 to −0.09)a | 0.02a |
| Donor type | ||||||||
| Living | 7.94 (5.78 to 10.09) | 8.16 (6.01 to 10.31) | 8.38 (6.24 to 10.53) | 8.83 (6.66 to 11.01) | 9.28 (7.05 to 11.52) | 9.73 (7.40 to 12.06) | 0.45 (0.17 to 0.73)a | 0.001a |
| Deceased | 8.34 (6.25 to 10.43) | 8.54 (6.46 to 10.62) | 8.74 (6.66 to 10.82) | 9.14 (7.04 to 11.24) | 9.55 (7.41 to 11.68) | 9.95 (7.75 to 12.15) | 0.40 (0.18 to 0.63)a | <0.001a |
| Difference | 0.40 (−0.48 to 1.29) | 0.38 (−0.49 to 1.25) | 0.36 (−0.54 to 1.25) | 0.31 (−0.72 to 1.34) | 0.26 (−0.99 to 1.52) | 0.21 (−1.31 to 1.74) | −0.05 (−0.40 to 0.31) | 0.80 |
Mixed-effect linear regression model with random effect for person (intercept) and time (slope) was used to estimate the baseline (at kidney transplant admission [pre-kidney transplant]) and trajectories of score. Model adjusted for at-admission age, sex, race/ethnicity, partnership status, smoking status, education, cause of ESKD, donor type, Charlson Comorbidity Index, and dialysis time. No adjustments for time (slope). Recipients were enrolled at transplantation admission. Reference population is set to >60 years, all other racial and ethnic groups, male, partnered, previous/current smoking, <high school, GN-caused ESKD, living donor, Charlson Comorbidity Index of 1.0 (median at kidney transplant admission), and dialysis vintage of 2.4 years (median at kidney transplant admission). CES-D, Center for Epidemiologic Studies Depression; CI, confidence interval; KT, kidney transplant.
Statistically significant (P value < 0.05).
All other racial/ethnic groups include non-Hispanic White, Hispanic, American Indian/Alaska Native, Asian, Native Hawaiian or Pacific Islander, other or multiracial.
Over 4 years, the score was 0.42 points/yr higher (95% CI, 0.25 to 0.60; Table 4) in the reference population. After adjusting for recipient characteristics, high depressive symptoms at admission was statistically significantly associated with changes in depressive symptoms (slope=−0.66 points/yr, 95% CI, −1.23 to −0.08). Depressive symptoms among those without initial symptoms slightly worsened but remained under clinical threshold (slope=0.53 points/yr, 95% CI, 0.34 to 0.71). The difference in the change in depressive symptoms between these two groups was statistically significant (difference=−1.18 points/yr, 95% CI, −1.79 to −0.58), The trajectory over 4 years also differed by preemptive KT status (difference=−0.57 points/yr, 95% CI, −1.04 to −0.09). CES-D scores remained the same over time in recipients on dialysis (slope=−0.14, 95% CI, −0.61 to 0.33) but were 0.43 points/yr higher (95% CI, 0.24 to 0.62) in preemptive KT recipients. The trajectory did not differ by other recipient characteristics (Table 4 and Supplemental Table 5).
Sensitivity Analysis
The inferences for all sensitivity analyses remained consistent with the primary analysis. Specifically, trajectories also differed between recipients with high depressive symptoms at admission and those without when we used a CES-D threshold of nine (difference=−0.61 points/yr, 95% CI, −0.98 to −0.24) or 11 (difference−0.80 points/yr, 95% CI, −1.21 to −0.39), corresponding to the highest tertile and quartile within the cohort, respectively (Supplemental Table 1), and in the GEE model (difference=−1.21 points/yr, 95% CI, −1.95 to −0.48; Supplemental Table 2). The direction of the estimates and group differences was consistent across the primary analysis and both missing-data approaches, indicating that the findings were robust to the method used for handling attrition. Results of logistic regressions and longitudinal models adjusted for additional socioeconomic covariates were also comparable with the primary analyses (Supplemental Tables 3 and 4).
Discussion
In this prospective cohort study of potential KT candidates and recipients, we found that depressive symptoms slightly worsened over the first 4 years post-KT, but remained below the clinical threshold for depression diagnosis. Changes in CES-D scores post-KT differed by pre-KT depressive symptom status, with symptoms improving among those with high pre-KT depressive symptoms but worsening among those without. CES-D score changes also differed by preemptive KT status.
Our cohort had a higher prevalence of depressive symptoms at evaluation than pre-KT (19% versus 15%), which may reflect that some individuals undergoing evaluation were not yet suitable candidates for listing because of medical or psychosocial barriers. In addition, our cohort reported a lower prevalence (15%) of high depressive symptoms in KT recipients than previous studies that have used the CES-D, including Novak et al., which found a 22% prevalence of high depressive symptoms despite a higher threshold of CES-D ≥18, among 840 KT recipients between 2002 and 2003.29 The observed difference may also be attributable to variations in population age and study period (i.e., era effects); younger adults are more likely to experience depression.30 Furthermore, although the prevalence of depression among the general population has increased over the decades, the trajectory of depression prevalence among KT recipients was inconsistent between studies.1,30 Longitudinal studies on changes in depressive symptoms more than 1 year post-KT are also limited. Although depressive symptoms do not necessarily indicate clinical depression, our finding parallels with previous study, which reported the cumulative incidence of clinical depression increasing post-KT, of 5.1%, 7.3%, and 9.1% at 1, 2, and 3 years post-KT, respectively.31
Several mechanisms may explain why we found that depressive symptoms change was associated with pre-KT depressive symptoms status. Restoration of kidney function via KT lessens uremia, inflammation, sleep disturbance, and fatigue, all of which are drivers strongly implicated in depression.32,33 KT also reduces psychosocial stressors linked to dialysis, including treatment burden, dietary and fluid restrictions, and loss of independence, thus likely improving health-related quality of life and mood.34,35 However, patients without existing high depressive symptoms at KT may have less room to improve, while also experiencing new stressors, including medical and/or surgical complications of KT, fear of graft loss, or financial strain.36,37 Finally, the absence of improvement among recipients without high pre-KT depressive symptoms may also reflect regression to the mean, whereby individuals with initially low symptom burden are less likely to demonstrate measurable improvement over time independent of true changes.
Several clinically relevant factors, including donor type and cause of ESKD, may influence depressive symptoms in KT patients, with previous studies suggesting that recipients of deceased-donor transplants may experience greater psychological distress than living-donor recipients,38 and diabetic kidney disease may adversely affect mental health through chronic vascular complications.39 However, neither donor type nor cause of ESKD was significantly associated with depressive symptoms in our study. This may reflect improvements in quality of life after KT that attenuate a potential impact from these factors, as well as the complex nature of depressive symptoms, which are also influenced by graft function, medication effects, social support, and psychiatric history.40,41 Overall, these findings suggest that depressive symptoms after KT are shaped by a multifactorial interplay of medical and psychosocial factors rather than any single transplant characteristic.40,41
As such, we also examined the impact of psychosocial and social factors on depressive symptoms in our cohort. In this study, the association of higher educational attainment with lower depressive symptom scores after KT was of borderline statistical significance. Previous research among KT recipients in China has similarly reported lower depressive symptom burden among individuals with greater educational attainment. It may be that education provides advantages in health literacy, coping abilities, and access to socioeconomic resources that facilitate post-KT self-management and mitigate psychological distress.42 In addition, we examined marital status as a potential marker of social support and found that partnered patients (married or cohabitating) had a slower annual increase in CES-D scores after KT than nonpartnered patients, suggesting that partner support may provide modest protection against worsening depressive symptoms after transplantation. Furthermore, the risk of high depressive symptoms at KT admission differed significantly by levels of neighborhood social cohesion. Overall, our findings suggest that psychosocial and social determinants—including education, partnership status, and neighborhood social cohesion—may play an important role in shaping depressive symptoms at or after KT, with greater social and socioeconomic support potentially offering protective effects.43
Depressive symptoms after KT have significant clinical implications. Recipients with depressive symptoms are more likely to demonstrate medication nonadherence, which can be associated with a higher risk of rejection and graft loss.44,45 Depressive symptoms are also associated with reduced observance of lifestyle recommendations such as diet, exercise, and precautionary measures against infection.46 Furthermore, previous studies demonstrate that post-KT depression is associated with higher rates of cardiovascular events and all-cause mortality.33,47 Thus, our findings underscore the need for systematic screening and timely treatment of depressive symptoms in potential KT candidates and recipients to improve their depression and possibly their medication adherence, graft survival, and overall patient health outcomes.
To our knowledge, this is the largest prospective study regarding post-KT depression change with the longest follow-up time of 4 years. Other strengths include the use of CES-D, which could capture the underdiagnosed population.8 In addition, we performed sensitivity analyses using internal thresholds to confirm the study results. Study limitations include potential bias from attrition over the extended follow-up period and restricted result generalizability because of the two-center design, despite a diverse study population. Post-transplant complications may affect longitudinal results; however, the low event rates in our cohort limit evaluation of their impact, suggesting any effect on CES-D trajectories is likely minimal. Information on comas was not available in our dataset. Furthermore, we may have misclassified depressive symptom severity because of the absence of data on diagnoses as well as pharmacologic or nonpharmacologic treatments. Finally, while all transplant centers are required to provide psychosocial support after transplantation, including routine psychosocial assessments and access to mental health services as needed, our cohort study did not collect standardized information on the specific type, intensity, or timing of psychosocial interventions or mental health treatments received by individual participants; this is an opportunity for future study. Nonetheless, CES-D is a validated screening tool for clinical depression and has been widely applied in kidney disease populations.27,41,48,49
To conclude, 19% of potential KT candidates at evaluation, and 15% of recipients at transplant admission had high depressive symptoms, respectively. In the immediate years post-KT, recipients who did not have high depressive symptoms at admission may experience slightly worsening CES-D scores, but these still do not meet the criteria for clinical depression. However, recipients with high depressive symptoms before KT may experience improvement after KT. Pre-KT high depressive symptoms may help identify patients who could benefit from targeted psychosocial support to prevent adverse post-transplant outcomes and further reduce post-KT depressive symptoms. Clinicians should discuss the long-term mental health impact of KT and provide individualized support to preserve psychological well-being throughout the transplant process.
Supplementary Material
Acknowledgments
The authors would like to thank the Frailty Assessment in Renal Disease cohort study participants, as well as the research staff at Johns Hopkins Hospital, University of Michigan, and NYU Langone Health, for their contributions to research. This project was presented as an abstract at the American Transplant Congress 2025; accepted abstracts were published in an online supplement to the American Journal of Transplantation.
Footnotes
N.-S.H. and J.H. shares co-first authorship.
Deceased.
Disclosures
Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/KN9/B694.
Author Contributions
Conceptualization: Mara A. McAdams-DeMarco.
Formal analysis: Jingyao Hong, Nan-Su Huang.
Methodology: Nidhi Ghildayal, Jingyao Hong, Nan-Su Huang, Yiting Li, Mara A. McAdams-DeMarco.
Supervision: Mara A. McAdams-DeMarco.
Writing – original draft: Nidhi Ghildayal, Jingyao Hong, Nan-Su Huang, Yiting Li, Mara A. McAdams-DeMarco, Babak J. Orandi.
Writing – review & editing: Nicole M. Ali, Deidra C. Crews, Daniel Cukor, Nidhi Ghildayal, Jingyao Hong, Nan-Su Huang, Yiting Li, Aarti Mathur, Mara A. McAdams-DeMarco, Silas P. Norman, Babak J. Orandi, Dorry L. Segev.
Funding
None.
Declarative Statements
This study includes clinical experimentation and received IRB or Ethics Committee approval. All patients provided written (including electronic e-consent) or verbal informed consent, with documentation waived for some minimal-risk phone–based procedures per IRB approval. This study includes clinical experimentation and complies with the Declaration of Helsinki. The clinical and research activities being reported are consistent with the Principles of the Declaration of Istanbul as outlined in the Declaration of Istanbul on Organ Trafficking and Transplant Tourism.
Data Availability Statements
Original data cannot be shared. Explanation Why Data Cannot Be Shared: We will not be sharing any clinical data for Frailty Assessment in Renal Disease in concordance with the data sharing policies of the cohort. The data that support this study and its findings are available from the corresponding author upon request.
Supplemental Material
This article contains supplemental material online, published as provided by the authors, at http://links.lww.com/KN9/B695.
Supplemental Table 1. Adjusted estimates of CES-D score at KT admission and posttransplantation among recipients, by high depressive symptoms at admission defined using internal thresholds (N=969).
Supplemental Table 2. Adjusted estimates of CES-D score at KT admission and posttransplantation among recipients (N=969).
Supplemental Table 3. Depressive symptoms among KT candidates at KT evaluation (N=4661) and recipients at KT admission (N=1215). Models were additionally adjusted for individual-level employment status (1% missing), family income (53%–61% missing), and neighborhood deprivation (6%–22% missing).
Supplemental Table 4. Adjusted estimates of CES-D score at KT admission and posttransplantation among recipients (N=920). Models were additionally adjusted for employment status and neighborhood deprivation.
Supplemental Table 5. Adjusted estimates of CES-D score at KT admission and posttransplantation among recipients by neighborhood-level social cohesion tertiles (N=969). Social cohesion (connectedness, supports) was obtained from the Social Capital Atlas estimates (2022) at the ZIP code level, with higher tertiles indicating better social cohesion.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Original data cannot be shared. Explanation Why Data Cannot Be Shared: We will not be sharing any clinical data for Frailty Assessment in Renal Disease in concordance with the data sharing policies of the cohort. The data that support this study and its findings are available from the corresponding author upon request.