Worsening Long-Term Post-Traumatic Stress Disorder (PTSD) Symptom Trajectory and Risk of Kidney Function Decline

Background: Post-traumatic stress disorder (PTSD) is a common condition noted in World Trade Center (WTC) responders. We previously reported that PTSD was associated with accelerated decline in estimated glomerular filtration rate (eGFR). However, the long-term effects of PTSD symptom trajectories on kidney function remain unclear. Methods: This study was a prospective cohort analysis of WTC responders, followed for a median of 5.6 years since 2015 with annual protocolized eGFR assessments. PTSD symptoms were measured using the PCL-17 questionnaire. Symptom trajectories over 20 years since 9/11 were modeled using mixed effects, latent class growth, and growth mixture models to identify distinct patterns. The associations between WTC-related PTSD symptom trajectory and kidney outcomes (rapid eGFR decline - defined as a loss of >5 mL/min/1.73 m2 per year, annual eGFR change, and incident CKD) were analyzed using multivariable Poisson and Cox regression models. Secondary analyses included participants of European ancestry with polygenic risk scores (PRS) for PTSD and kidney decline. Models included PTSD symptom levels, and linear and quadratic rates of change, demographics, comorbidities, exposure severity, baseline eGFR, genetic principal components, and relevant PRSs. The outcomes were also assessed after stratification by race: ‘White’ versus ‘Non-white’ Results: Among 9308 WTC responders (mean age: 54.1 ± 8.3 years), 6% of responders had rapid eGFR decline. In the fully adjusted multivariable model, a one standard deviation increase in the linear slope of PTSD symptoms was significantly associated with increased risk of developing rapid eGFR decline in both the overall cohort (RR: 1.11 (95% CI: 1.00 – 1.22), p = 0.042) and PRS sub-group. A similar association was noted with greater eGFR decline per year. Among 9043 individuals without baseline CKD, 670 (7%) developed incident CKD. In a fully adjusted multivariable model, worsening of linear slope of PTSD was associated with risk of incident CKD (HR: 1.13 (95% CI: 1.02 – 1.24), p = 0.016). When stratified by race, non-Whites had a relatively higher risk of kidney outcomes compared to Whites. Conclusion: Among 9/11 responders, worsening symptom trajectory of PTSD is associated with significantly increased risk of rapid kidney function decline and incident CKD, possibly influenced by race.