Papers of the Week

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 estimated glomerular filtration rate (eGFR) and uremic symptom severity score in patients with chronic kidney disease (CKD). We identified 3,685 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 (0- 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. The mean (±SD) eGFR at baseline was 44±15 mL/min/1.73 m2, and participants had a median 6 (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/1.73 m2 was associated with a worsening of the symptom severity score by 2 points or less for each uremic symptom (p<0.01; 0 to 100-point scale). The association between eGFR and uremic symptom severity score was non-linear. When starting from a lower initial eGFR, a 5 mL/min/1.73 m2 decrease in eGFR was associated with a greater magnitude of uremic symptom worsening. 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.