TY - JOUR
T1 - Trajectories of Uremic Symptom Severity and Kidney Function in Patients with Chronic Kidney Disease
AU - Wulczyn, Kendra E.
AU - Zhao, Sophia H.
AU - Rhee, Eugene P.
AU - Kalim, Sahir
AU - Shafi, Tariq
N1 - Funding Information:
A condensed version of the primary results of this paper were presented as a poster at the 2021 American Society of Nephrology Annual Kidney Week. The CRIC Study was conducted by the CRIC Study Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from the CRIC Study reported here were supplied by the NIDDK Central Repository. This manuscript was not prepared in collaboration with Investigators of the CRIC Study and does not necessarily reflect the opinions or views of the CRIC Study, the NIDDK Central Repository, or the NIDDK.
Funding Information:
T. Shafi reports grants from the National Institutes of Health during the conduct of the study; consultancy agreements with Siemens; research funding from Baxter (clinical trial site investigator), CVS (clinical trial site investigator), and Natera (clinical trial site investigator); honoraria from Cara Therapeutics, the National Institutes of Health, Siemens, University of Virginia, and State University of New York, Downstate; personal consulting fees from Cara Therapeutics and Siemens; and serving in an advisory or leadership role for the American Journal of Kidney Diseases, American Journal of Medicine, CJASN, and Kidney360. All remaining authors have nothing to disclose.
Funding Information:
S. Kalim is supported by National Institutes of Health (NIH) grant R01DK124453. E.P. Rhee and T. Shafi are supported by NIH grant R01-NR017399. K.E. Wulczyn is supported by NIH grant T32DK007540-34.
Publisher Copyright:
© 2022 by the American Society of Nephrology.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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.
AB - 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.
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U2 - 10.2215/CJN.13010921
DO - 10.2215/CJN.13010921
M3 - Article
C2 - 35246460
AN - SCOPUS:85128249692
VL - 17
SP - 496
EP - 506
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
SN - 1555-9041
IS - 4
ER -