Symptoms are a subjective feeling that reflect individual physiological disorders. "Symptom burden" is used to describe the number of symptoms a patient has at any stage of the disease, including the incidence, frequency, severity and distress of symptoms, and their impact on the patient's health-related quality of life and other aspects. Symptom burden is an important predictor of reduced quality of life in patients with chronic kidney disease (CKD), and patients with advanced CKD are characterized by significant symptom burden.
Current understanding of symptom changes in CKD patients at different stages is limited. There are few longitudinal studies investigating symptom changes in non-dialysis-dependent CKD patients, and the results of existing studies are inconsistent. To this end, foreign scholars conducted a prospective study based on the French CKD-REIN Kidney Epidemiology and Information Network (CKD-REIN) cohort study data to determine the 5-year symptom change trajectory and characteristics of CKD patients. The study shows that patients with more severe baseline symptoms (31%) tend to have their symptoms worsen over time, and these patients have more risk factors that affect the progression of CKD and have worse quality of life. In contrast, patients with mild baseline symptoms (69%) had overall relatively stable symptoms. The research results were recently published in Clin J Am Soc Nephrol. (impact factor 10.614).
01 Study design
The CKD-REIN study is a prospective cohort study, enrolling adult patients with CKD who were not receiving renal replacement therapy (KRT) and had an eGFR <60>2. Baseline data including sociodemographic data, body mass index, smoking history, medication history, medical history, and laboratory indicators of CKD patients participating in the CKD-REIN study from July 2013 to May 2016 were collected. Patients' symptoms were assessed annually during the study period until December 2020 using the Kidney Disease Quality of Life-36 (KDQOL-36) scale. The KDQOL-36 scale is divided into 5 parts, including physical health score, mental health score, kidney disease burden in the kidney disease section, kidney disease symptoms/problems, and kidney disease impact. The primary endpoint of this study is the score of the kidney disease symptoms/problems subscale of the KDQOL-36 scale , which includes 11 symptom scores including muscle aches, chest pain, cramps, itchy skin, dry skin, shortness of breath, dizziness, loss of appetite, fatigue, numbness of hands and feet, nausea or stomach discomfort. The lower the score, the more severe the symptoms. Score data were recorded at baseline and at 1, 2, 3, and 5 years of follow-up, and at least one piece of data was collected for each patient. A latent class mixed effects model (JLCMM) was used to identify types of symptom score trajectories.
02 Study Results A total of 2787 patients were included in the
study. The mean age (± standard deviation [SD]) was 67±13 years, and 66% were male. The average eGFR was 33±13 ml/min/1.73 m2, and 45% of patients were in CKD stages 4-5. The average symptom score was 75±16 points. The prevalence of symptoms ranged from 24% (chest pain) to 83% (fatigue), with fatigue (83%), muscle aches (82%), cramps (72%), dry skin (60%) and shortness of breath (68%) being the most common. 98% of patients reported at least one symptom.
Over time, the trajectory of symptom scores in non-dialysis-dependent CKD patients tended to be 2 types.
During the median follow-up (interquartile range) of 5.3 years (3.4-6.0), 690 patients initiated KRT and 490 died before KRT. JLCMM analysis identified 2 types of symptom trajectories (Figure 1). 31% (n=875) of the patients had "lower symptom scores, and the trajectory tends to get worse" , which is characterized by more severe symptoms at baseline, and as time goes by, the symptom score decreases by >10 points, indicating worsening of symptoms; 69% (n=1912) of the patients "has high symptom scores, and the trajectory is relatively stable" , which is characterized by mild symptoms at baseline, which over time, the symptoms are generally stable. As expected, patients with "lower symptom scores and worsening trajectories" had a relatively higher risk of KRT and pre-KRT death.
Figure 1 Mean symptom scores (solid lines) and their confidence intervals (shaded bands) for 2 symptom trajectory types
Patient characteristics with different symptom trajectories
Compared with patients with higher symptom scores and stable trajectories, patients with lower symptom scores and worsening trajectories were more likely to have diabetes (48% vs. 40%), obesity (36% vs. 36% vs. 33%), comorbidities (diabetes, cardiovascular disease), anemia (55% vs. 29%) and hypocalcemia (4% vs. 1%); and less physical exercise (57% vs. 44%) and more medication (9±4 vs. 7±4), estimated glomerular filtration rate (eGFR) was lower (26±10 vs. 37±11 ml/min), quality of life was worse and symptoms were more obvious. At the same time, eGFR also declined significantly faster (3.56, 95% confidence interval [CI] 3.80-3.33 vs. 1.15, 95% CI 21.24-21.06) ml/min/1.73 m2/year.
03 Research conclusion and discussion
This study aimed to identify the 5-year symptom change trajectory and characteristics of CKD patients. The results showed that patients with more severe baseline symptoms (31%) tended to have worsening symptoms, and found that such patients have more risk factors that affect the progression of CKD and have worse quality of life. In contrast, patients with mild baseline symptoms (69%) had overall relatively stable symptoms.
In the care of patients with chronic diseases, patients' quality of life and symptom burden have received increasing attention. In the Kidney Disease Standardized Outcomes Initiative, hemodialysis patients identified fatigue as one of the important factors affecting their condition. During the progression of disease, patients with chronic diseases may experience rapid functional decline and increased symptom burden. Understanding the changes in patients' condition is of great significance for formulating treatment strategies.
In addition, in addition to monitoring clinical symptoms and laboratory indicators, scholars also suggest that the KDQOL-36 scale or other valid questionnaires should be used to systematically evaluate patients' symptoms. The results will help doctors more comprehensively understand changes in patients' condition, conduct early therapeutic intervention, and improve patients' clinical outcomes.
Reference: Faye M, Legrand K, Le Gall L, et al. CKD-REIN Study Group. Five-Year Symptom Trajectories in Nondialysis-Dependent CKD Patients[J]. Clin J Am Soc Nephrol. 2022 Nov;17(11):1588-1597. doi: 10.2215/CJN.06140522. PMID: 36307136; PMCID: PMC9718050.
