Abstract
Abstract
BACKGROUND AND AIMS
The burden of chronic kidney disease-associated pruritus (CKD-aP) in hemodialysis (HD) patients, and its association with adverse clinical events and patient-reported outcomes (PROs) has been well-established. However, most studies focus on a single baseline CKD-aP assessment. In this study, we quantify the extent to which pruritus symptoms vary >1 year, and relationship with associated clinical and patient-reported outcomes.
METHOD
We included 7976 HD patients across 21 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4–6 (2009–18) who had 2 CKD-aP assessments 12 months (±6 months) apart, with concurrent PRO collection. CKD-aP intensity was assessed by a single question in the KDQOL-36 asking about the extent patients were bothered by itch over the past 4 weeks. We categorized patients into 4 groups—those at least moderately (versus somewhat or not at all) bothered by itchy skin in Year 1 only (Yes/No), Year 2 only (No/Yes), neither (No/No), or both (Yes/Yes) time points. Difference-in-difference analyses were used to estimate changes in laboratory values and PROs between Years 1 and 2, by within-patient changes in CKD-aP severity. Cox regression was used to estimate rates of mortality and hospitalization, with follow-up starting after the Year 2 CKD-aP assessment, across the 4 exposure groups, adjusted for confounders.
RESULTS
Half of the patients were at least moderately bothered by pruritus over the course of 1 year: 22% of patients were at least moderately bothered by CKD-aP at each annual assessment (Yes/Yes); 14% each were bothered at Year 1 only (Yes/No) or Year 2 only (No/Yes); 49% were not bothered at either CKD-aP assessment (No/No). These proportions were similar across DOPPS regions. Changes in laboratory values—including calcium, phosphorus, parathyroid hormone (PTH), albumin, hemoglobin, single pool Kt/V—between Years 1 and 2 varied minimally by within-patient changes in CKD-aP. Changes in some targeted PROs (depression, sleep quality, feeling faint or drained) tracked closely with changes in CKD-aP: the proportion of patients reporting > = 3 nights/week of restless sleep increased from 38% to 48% in the No/Yes group, decreased from 48% to 40% in the Yes/No group, and was unchanged between Years 1 and 2 in the No/No and Yes/Yes groups (Table 1). Changes in more general PROs (physical [PCS] and mental [MCS] component summary scores) were modest, and only varied by 2–3 points across the 4 CKD-aP exposure groups. The all-cause mortality HR (95% confidence interval), compared with the No/No reference group, was 1.22 (0.99–1.51) for Yes/No, 1.32 (1.07–1.63) for No/Yes and 1.31 (1.11–1.56) for Yes/Yes. Results for hospitalization and other clinical outcomes are shown in Figure 1.
CONCLUSION
Our findings indicate that half of chronic HD patients were at least moderately bothered by CKD-aP at some point over the course of 1 year, reflecting an unmet medical need, and that CKD-aP symptoms remained unresolved 12 months later for the majority of HD patients who were bothered by itchy skin at baseline, highlighting the chronic nature of the condition. The trend towards worse patient-reported outcomes for those affected in Year 2 but not Year 1 implicates the consequences of patients’ significant adjustment to this new, often unrelenting, symptom. Those with chronic pruritus had higher rates of hospitalization and cardiovascular events, underscoring the impact of patients with chronic pruritus on hospital systems. Moreover, those affected by pruritus at any point in the year had higher rates of mortality, further highlighting the importance of diagnosing pruritus and investigating its effect on cardiovascular events. Future research should investigate potential causes of CKD-aP symptoms more systematically and focus on how potential treatments can aide in patients’ relief.