Symptom Burden and Its Impact on Quality of Life in Patients With Moderate to Severe CKD: The International Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps).

RATIONALE & OBJECTIVE: Recent evidence suggests substantial burden of symptoms experienced by people with non-dialysis chronic kidney disease (ND-CKD), but informative large-scale studies are scarce. We aimed to assess the prevalence of symptoms, and the association of overall symptom burden with quality of life in patients with moderate to severe CKD. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 4430 patients with ND-CKD stages 3-5 enrolled into the CKDopps Study in Brazil, France, and the US between 2013 and 2021. EXPOSURES: 13 individual patient-reported symptoms from the KDQOL-SF questionnaire and an overall symptom burden score (low, intermediate, and high). OUTCOMES: Physical and mental component summary scores (PCS, MCS) of the KDQOL-SF. ANALYTICAL APPROACH: Adjusted prevalence ratios and generalized estimating equations. RESULTS: Patients (mean age: 68 years; 40% women; mean baseline eGFR: 30 mL/min/1.73m2) were very much to extremely bothered by numerous symptoms ["soreness in muscles" (23%), "washed out or drained" (21%), "cramps, shortness of breath, dry skin, diminished sex life, or numbness in hands or feet" (14-17%)]. The adjusted prevalences of "cramps", "washed out or drained", "lack of appetite", "nausea/upset stomach", and "sex life" were greater with more severe CKD, and, except for "sex life", in women. A high overall symptom burden was more common in women, in France, and in patients with severe albuminuria and various comorbidities, but not with lower eGFR. PCS and MCS scores were 13.4 and 7.7 points lower, respectively, for high vs. low overall symptom burden. LIMITATIONS: Generalizability limited to patients under nephrology care, residual confounding and inaccurate Brazilian translation of some symptoms. CONCLUSIONS: The high symptom burden observed in this large cohort of ND-CKD patients across three diverse countries and its strong association with poorer HRQOL should inform clinical management of and clinical research in CKD.

CKD-Associated Pruritus and Clinical Outcomes in Nondialysis CKD.

Rationale & Objective: Itching is a frequent symptom experienced by people with chronic kidney disease (CKD). We investigated the associations of CKD-associated pruritus (CKD-aP) with clinical outcomes. Study Design: This was a longitudinal cohort study. Setting & Participants: Patients from Brazil, France, and the United States enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) from 2013 to 2021, an international prospective cohort study of adults with nondialysis dependent CKD, and an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 were included. Exposure: CKD-aP was self-reported by response to the question: "During the past 4 weeks, to what extent were you bothered by itchy skin?" Outcomes: The outcomes were as follows: CKD progression, kidney replacement therapy (KRT) initiation, mortality, hospitalization, cardiovascular events, infection events. Analytical Approach: Associations with time-to-event outcomes were investigated using Cox proportional hazards models adjusted for potential confounders. Results: There were 4,410 patients from 91 clinics with a median age of 69 years and a median eGFR at patient questionnaire completion of 29 (21-38) mL/min/1.73 m2. The proportion of patients not at all, somewhat, moderately, very much, and extremely bothered by itchy skin was 49%, 27%, 13%, 7%, and 3%, respectively. Patients with more advanced stages of CKD, older age, and greater comorbidities reported to be more likely bothered by itchy skin. Among patients at least moderately bothered, 23% were prescribed at least 1 pharmacotherapy (35% in the United States, 19% in France, 4% in Brazil), including antihistamine (10%), gabapentin (6%), topical corticosteroids (4%), pregabalin (3%), or sedating antihistamine (3%). The HR (95% CI) for patients extremely (vs not at all) bothered was 1.74 (1.11-2.73) for all-cause mortality, 1.56 (1.11-2.18) for all-cause hospitalization, and 1.84 (1.22-2.75) for cardiovascular events. As CKD-aP severity increased, patients also had higher rates of infection events (P = 0.04); CKD-aP severity was not associated with KRT initiation (P = 0.20) or CKD progression (P = 0.87). Limitations: The limitations were 25% nonresponse rate, recall bias, and residual confounding factors. Conclusions: These results demonstrate a strong association between severe itch and clinical outcomes, providing the nephrology community new insights into the possible adverse consequences of CKD-aP in individuals with nondialysis CKD, and warrant further exploration. Plain-Language Summary: Chronic kidney disease-associated pruritus (CKD-aP) is a common disturbing symptom of chronic kidney disease (CKD). This article analyzes longitudinal data from the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) to describe prevalence of CKD-aP in 4,410 individuals with nondialysis CKD, and its association with clinical outcomes. We found that 51% of the surveyed population were bothered by pruritus. CKD-aP was more prevalent in those with more advanced stages of CKD, older age, and with more comorbid conditions. Compared to those not at all bothered by pruritus, those who were extremely bothered had a higher risk of all-cause mortality, hospitalizations, and cardiovascular events. Severity of CKD-aP was not associated with CKD progression or initiation of kidney replacement therapy.