Trajectories of Uremic Symptom Severity and Kidney Function in Patients with Chronic Kidney Disease

Background and objectives Uremic symptoms, including fatigue, anorexia, pruritus, nausea, paresthesia, and pain, are attributed to the accumulation of organic waste products normally cleared by the kidneys, but whether kidney function is the primary driver of changes in symptom severity over time is not known. The goal of our study was to evaluate the association between eGFR and uremic symptom severity score in patients with CKD.

Design, setting, participants, and measurements We identified 3685 participants with CKD not on dialysis in the prospective, observational Chronic Renal Insufficiency Cohort (CRIC) Study with baseline assessment of eGFR and uremic symptom severity. Symptoms were assessed by separate questions on the Kidney Disease Quality of Life-36 instrument (zero- to 100-point scale). The longitudinal association between eGFR and uremic symptom severity score was examined with multivariable adjusted linear mixed-effects models with random intercepts and random slopes.

Results The mean±SD eGFR at baseline was 44±15 ml/min per 1.73 m², and participants had a median of six (interquartile range 3–11) simultaneous assessments of eGFR and uremic symptoms over the duration of follow-up. The most prevalent symptoms at baseline were pain (57%), fatigue (52%), paresthesia (45%), and pruritus (42%). In adjusted models, a decrease in eGFR of 5 ml/min per 1.73 m² was associated with a worsening of the symptom severity score by two points or less for each uremic symptom (P<0.01; zero- to 100-point scale). The association between eGFR and uremic symptom severity score was nonlinear. When starting from a lower initial eGFR, a 5 ml/min per 1.73 m² decrease in eGFR was associated with a greater magnitude of uremic symptom worsening.

Conclusions The prevalence of uremic symptoms in CKD is high, with significant variability in patient symptom change over time. Declines in eGFR were associated with worsening of uremic symptom severity, but the magnitude of these changes is small and of uncertain clinical significance.