Burden of Pruritus in Advanced CKD and Hemodialysis: Results From National Kidney Foundation Surveys.

People living with chronic kidney disease (CKD), particularly those in the later stages and those treated with hemodialysis, are at an increased risk of CKD-associated pruritus (CKD-aP), an uncomfortable condition that can negatively affect the quality of life and health outcomes.1Simonsen E. Komenda P. Lerner B. et al.Treatment of uremic pruritus: a systemic review.Am J Kidney Dis. 2017; 70: 638-655Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 2Rayner H.C. Larkina M. Wang M. et al.International comparisons of prevalence, awareness, and treatment of pruritus in people on hemodialysis.Clin J Am Soc Nephrol. 2017; 12: 2000-2007Crossref PubMed Scopus (115) Google Scholar, 3Shirazian S. Aina O. Park Y. et al.Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges.Int J Nephrol Renvasc Dis. 2017; 10: 11-26Crossref PubMed Scopus (57) Google Scholar, 4Sukul N. Karaboyas A. Csomor P. et al.Self-reported pruritus and clinical, dialysis-related, and patient-reported outcomes in hemodialysis patients.Kidney Med. 2020; 3: 42-53.e1Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 5Satti M.Z. Arshad D. Javed H. et al.Uremic pruritus: prevalence and impact on quality of life and depressive symptoms in hemodialysis patients.Cureus. 2019; 11: e5178PubMed Google Scholar, 6Pisoni R.L. Wikström B. Elder S.J. et al.Pruritus in haemodialysis patients: international results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).Nephrol Dial Transplant. 2006; 21: 3495-3505Crossref PubMed Scopus (385) Google Scholar, 7Combs S.A. Teixeira J.P. Germain M.J. Pruritus in kidney disease.Semin Nephrol. 2015; 35: 383-391Abstract Full Text Full Text PDF PubMed Google Scholar, 8Mathur V.S. Lindberg J. Germain M. et al.A longitudinal study of uremic pruritus in hemodialysis patients.Clin J Am Soc Nephrol. 2010; 5: 1410-1419Crossref PubMed Scopus (178) Google Scholar, 9Kim D. Pollock C. Epidemiology and burden of chronic kidney disease-associated pruritus.Clin Kidney J. 2021; 14: i1-i7Crossref PubMed Scopus (11) Google Scholar, 10Mettang T. Kremer A.E. Uremic pruritus.Kidney Int. 2015; 87: 685-691Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar The itch is often chronic and less is known about pruritus in earlier CKD stages.1Simonsen E. Komenda P. Lerner B. et al.Treatment of uremic pruritus: a systemic review.Am J Kidney Dis. 2017; 70: 638-655Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 2Rayner H.C. Larkina M. Wang M. et al.International comparisons of prevalence, awareness, and treatment of pruritus in people on hemodialysis.Clin J Am Soc Nephrol. 2017; 12: 2000-2007Crossref PubMed Scopus (115) Google Scholar, 3Shirazian S. Aina O. Park Y. et al.Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges.Int J Nephrol Renvasc Dis. 2017; 10: 11-26Crossref PubMed Scopus (57) Google Scholar, 4Sukul N. Karaboyas A. Csomor P. et al.Self-reported pruritus and clinical, dialysis-related, and patient-reported outcomes in hemodialysis patients.Kidney Med. 2020; 3: 42-53.e1Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar The patient-reported effect of pruritus is important across the spectrum of kidney diseases risk stratification. We conducted 2 similar online surveys of patient experience with pruritus, both using National Kidney Foundation social media to capture US adults, aged 18 years or older, who met the survey criteria. The first survey, conducted from November 11 to November 27, 2020, enrolled patients who were treated with hemodialysis. The second, conducted from June 16 to 21, 2021, focused on patients who self-reported with CKD stage G2, G3, G4, or G5 (Fig S1). Item S1 reports the detailed methods and Item S2 reports the survey instruments that align with the worst itch numeric rating scale. Among the 1,629 patients who participated in the 2 surveys, 692 patients were receiving hemodialysis and 937 patients with CKD, with a wide range of kidney disease severity (Table 1). The population was broadly distributed across the US census regions, with most being younger than 40 years or younger than the average adult patient with CKD and receiving hemodialysis in the United States.11United States Renal Data System2021 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2021Google Scholar Most of the patients had some college education and were employed. More than 50% of those receiving hemodialysis had education beyond high school and were employed, which is relatively higher than the US surveillance data.11United States Renal Data System2021 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2021Google ScholarTable 1Survey Respondent CharacteristicsCharacteristicPatients not Receiving Dialysis and With CKD G2 (n = 152)Patients Not Receiving Dialysis and With CKD G3 (n = 113)Patients Not Receiving Dialysis and With CKD G4 (n = 258)Patients Not Receiving Dialysis and With CKD G5 (n = 414)Patients With CKD and Receiving Hemodialysis (n = 692)Age, y, n (%) <35108 (71)87 (77)114 (44)182 (44)252 (36) 35-4443 (28)24 (21)130 (51)181 (44)167 (24) 45-541 (1)1 (1)13 (5)41 (10)65 (9) 55-640 (0)0 (0)0 (0)5 (1)31 (5) ≥650 (0)1 (1)0 (0)1 (0)23 (3) Mean ± SD31.3 ± 5.331.2 ± 6.635.2 ± 5.336.0 ± 7.138.5 ± 11.8(1 missing)(4 missing)(154 missing)Female sex, n (%)67 (44)60 (53)139 (54)236 (57)245 (35)(1 missing)(3 missing)(153 missing)Employment status, n (%) Employed or student136 (90)108 (96)221 (86)299 (73)402 (58)(1 missing)(2 missing)(3 missing)(154 missing)Race/ethnicityaMay exceed 100% owing to multiple responses., n (%) White129 (85)89 (79)207 (81)292 (71)375 (54) Black16 (11)15 (13)38 (15)85 (21)80 (12) Other7 (5)9 (8)6 (2)14 (3)68 (10) Hispanic3 (2)8 (7)7 (3)21 (5)49 (7)(3 missing)(4 missing)(155 missing)US Census region, n (%) Northeast13 (9)11 (10)34 (13)27 (7)63 (9) Midwest31 (21)18 (16)38 (15)47 (11)109 (16) South53 (35)41 (36)99 (38)167 (40)190 (28) West54 (36)43 (38)75 (29)161 (39)165 (24)(1 missing)(12 missing)(12 missing)(165 missing)Education, n (%) High school or less33 (22)9 (8)86 (34)75 (18)102 (15) Some college or technical school54 (36)41 (36)57 (22)173 (42)216 (31) College graduate63 (42)63 (56)95 (37)157 (38)200 (29) Postgraduate studies1 (1)0 (0)18 (7)6 (1)20 (3)(1 missing)(2 missing)(3 missing)(154 missing)How long been living with kidney disease, n (%) ≤6 mo8 (5)2 (2)11 (4)14 (3) 7-12 mo22 (14)9 (8)89 (34)77 (19) 1-2 y55 (36)41 (37)72 (28)171 (41) 2-5 y55 (36)53 (47)61 (24)109 (26) >5 y12 (8)7 (6)25 (10)42 (10)(1 missing)(1 missing)How long been on dialysis, n (%) ≤6 mo88 (13) 7-12 mo191 (28) 1-2 y155 (22) 2-5 y159 (23) >5 y99 (14)Abbreviations: CKD, chronic kidney disease; n, number; SD, standard deviation.a May exceed 100% owing to multiple responses. Open table in a new tab Abbreviations: CKD, chronic kidney disease; n, number; SD, standard deviation. In these surveys, ≥87% of the patients with CKD, across the stages of kidney disease or receiving hemodialysis, reported experiencing pruritus (Fig 1). Approximately half of the patients had itchy skin for a year or longer (43%-61%), and some reported being itchy most, if not all, of the time (range across the kidney disease populations, 12%-42%). Approximately half of the patients with CKD G2 or G3 reported their doctor informing them that their pruritus was caused by kidney disease, increasing to 70%-74% among patients with CKD G4 or G5. Patients with CKD G2 or G3 are particularly likely to report that the itch was very intense (39%-42%) compared with patients with both CKD G4 or G5 (16%-19%) and receiving hemodialysis (25%). Many patients with CKD reported being very much affected/bothered by itchy skin (range across the CKD stages, 12%-29%). Similarly, patients treated with hemodialysis reported being very much affected/bothered by itchy skin (23%). Patients described many ways that itchy skin affected them. One example is skipping planned activities because of itchy skin. Patients with CKD G4 or G5 (58%-71%) or those treated with hemodialysis (54%) reported this more often than patients with CKD G2 or G3 (33%-41%). Many patients also reported that the itchy skin sometimes caused sleep problems. More than half of the patients with CKD G4 or G5 (60%-71%) reported that itchy skin interferes with sleeping through the night, and a similar percentage was noted among those who were treated with hemodialysis (61%). This cross-sectional snapshot of the experiences of the US adults suggests that pruritus is a common, chronic symptom in patients with CKD and treated with hemodialysis. When mild, it is uncomfortable and can lead to skin excoriations. However, when severe, sleep and social functioning are affected. This study has several limitations. First, the survey population was self-selected and nonrepresentative. Given that our data were recorded from online surveys, the graphs may not accurately represent the whole population of those who have late-stage CKD and those on hemodialysis. In addition, transplant respondents were potentially included in the CKD survey. Our survey likely had a selection bias for younger, better educated, and mostly employed people who tend to use social media. In the adult population, data are conflicting on whether younger or older patients are more likely to report pruritus.9Kim D. Pollock C. Epidemiology and burden of chronic kidney disease-associated pruritus.Clin Kidney J. 2021; 14: i1-i7Crossref PubMed Scopus (11) Google Scholar The authors also speculate that awareness and education about kidney diseases are likely to be higher among individuals who follow National Kidney Foundation social media. Second, we used a nonvalidated survey tool. Finally, the likely etiology of pruritus in CKD G4, G5, and hemodialysis is uremia, whereas the etiology of pruritus in CKD G2 and G3 is an etiology other than uremia. In CKD G2 and G3, a thorough search of dermatologic, hepatobiliary, hematologic, endocrinologic, and neurologic causes is prudent. Investigation to elucidate the pathogenesis of CKD-aP is ongoing. Histamine and parathyroid hormone have been investigated, but studies have not demonstrated a causal relationship. Recently, the literature has focused on an imbalance of μ-opioid and κ-opioid receptor activation with μ-receptor overactivation as a specific hypothesis in CKD-aP.10Mettang T. Kremer A.E. Uremic pruritus.Kidney Int. 2015; 87: 685-691Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar Our study highlights the importance of detecting pruritus in CKD and hemodialysis. Treatment should address the primary etiology and symptoms. Pruritus is commonly associated with CKD and hemodialysis with frequent chronicity and a significant negative effect on the quality of life. Research idea and study design: GT and LSD; data acquisition: LSD; data analysis/interpretation: DL, JAV, GT and LSD; supervision or mentorship: JAV and LSD. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual’s own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. JAV reports consulting fees for Renalytix, Plc, and AstraZenica, Inc. The remaining authors declare that they have no relevant financial interests. November 5, 2022. Evaluated by 2 external peer reviewers, with direct editorial input from the Statistical Editor and the Editor-In-Chief. Accepted in revised form February 5, 2023. Download .pdf (.52 MB) Help with pdf files Supplementary File (pdf)Figure S1; Item S1; Item S2.