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. 2022 Apr;17(4):496-506.
doi: 10.2215/CJN.13010921. Epub 2022 Mar 4.

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

Kendra E Wulczyn  1 , Sophia H Zhao  2 , Eugene P Rhee  1   3 , Sahir Kalim  2 , Tariq Shafi  4   5   6
Affiliations

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

Kendra E Wulczyn et al. Clin J Am Soc Nephrol. 2022 Apr.

Abstract

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.

Keywords: chronic kidney disease; clinical epidemiology; depression; quality of life; uremia.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Severity of uremic symptoms at the baseline evaluation, stratified by baseline CKD stage. The severity of symptoms experienced by patients with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study was assessed in the preceeding 4 weeks by the Kidney Disease Quality of Life-36 instrument.
Figure 2.
Figure 2.
Longitudinal relationship of eGFR and uremic symptom severity score over a median of 7 years of follow-up in 3685 CRIC Study participants. (A) Fatigue. (B) Anorexia. (C) Pruritus. (D) Nausea. (E) Paresthesia. (F) Pain. (G) KDQOL symptom domain. Each point and associated confidence interval represent the average adjusted uremic symptom severity at a given eGFR. The line represents the slope of symptom change as eGFR decreases over time. Higher symptom scores represent greater symptom severity.
See this image and copyright information in PMC

Comment in

  • Symptoms with or because of Kidney Failure?
    Abdel-Kader K. Abdel-Kader K. Clin J Am Soc Nephrol. 2022 Apr;17(4):475-477. doi: 10.2215/CJN.02050222. Epub 2022 Mar 4. Clin J Am Soc Nephrol. 2022. PMID: 35246459 Free PMC article. No abstract available.

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