Self-reported Pruritus and Clinical, Dialysis-Related, and Patient-Reported Outcomes in Hemodialysis Patients.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD)-associated pruritus, generalized itching related to CKD, affects many aspects of hemodialysis patients' lives. However, information regarding the relationship between pruritus and several key outcomes in hemodialysis patients remains limited. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 23,264 hemodialysis patients from 21 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 6 (2009-2018). EXPOSURE: Pruritus severity, based on self-reported degree to which patients were bothered by itchy skin (5-category ordinal scale from "not at all" to "extremely"). OUTCOMES: Clinical, dialysis-related, and patient-reported outcomes. ANALYTICAL APPROACH: Cox regression for time-to-event outcomes and modified Poisson regression for binary outcomes, adjusted for potential confounders. RESULTS: The proportion of patients at least moderately bothered by pruritus was 37%, and 7% were extremely bothered. Compared with the reference group ("not at all"), the adjusted mortality HR for patients extremely bothered by pruritus was 1.24 (95% CI, 1.08-1.41). Rates of cardiovascular and infection-related deaths and hospitalizations were also higher for patients extremely versus not at all bothered by pruritus (HR range, 1.17-1.44). Patients extremely bothered by pruritus were also more likely to withdraw from dialysis and miss hemodialysis sessions and were less likely to be employed. Strong monotonic associations were observed between pruritus severity and longer recovery time from a hemodialysis session, lower physical and mental quality of life, increased depressive symptoms, and poorer sleep quality. LIMITATIONS: Residual confounding, recall bias, nonresponse bias. CONCLUSIONS: Our findings demonstrate how diverse and far-reaching poor outcomes are for patients who experience CKD-associated pruritus, specifically those with more severe pruritus. There is need for change in practice patterns internationally to effectively identify and treat patients with pruritus to reduce symptom burden and improve quality of life and possibly even survival.

Reasons for Underreporting of Uremic Pruritus in People With Chronic Kidney Disease: A Qualitative Study.

CONTEXT: Uremic pruritus, or itch, is common in people with chronic kidney disease (CKD) and has a negative impact on their lives and well-being. However, for reasons currently unknown, itch often remains unreported and therefore untreated. OBJECTIVES: To explore reasons for underreporting of itch to provide pointers for improving itch reporting and management in people with CKD. METHODS: We interviewed adult patients with CKD who self-reported experiencing itching in the last three years (n = 25), nephrologists (n = 10), and nurses (n = 12) from three kidney services in the U.K. Topic guides were informed by previous studies and a theoretical model of self-regulation. We conducted a thematic analysis of verbatim transcripts using framework analysis. RESULTS: We identified the following three main themes reflecting factors that may influence whether itch is reported: knowledge on causes and treatment of itch (lack of awareness of the relationship between itch and CKD, and lack of knowledge of treatment options); attitudes toward importance of itch as a health issue (patients' and clinicians' attitudes); and prompts for itch assessment during consultations (routine practice, itch as a marker, and itch severity). CONCLUSION: Underreporting of itch is related to patients being unaware of its causes, accepting it as something to live with, prioritizing other health issues, and the length and timing of consultations. Health care professionals' assessment and management of itch vary widely and are not necessarily evidence-based. Better patient information, development of clinical practice guidelines, and incorporation of routine symptom assessments into care may improve itch reporting and management in people with CKD.

Pruritus and Patient Reported Outcomes in Non-Dialysis CKD.

BACKGROUND AND OBJECTIVES: Among patients on hemodialysis, pruritus has been associated with poorer mental and physical quality of life, sleep quality, depression, and mortality. We evaluated patients with nondialysis CKD to describe the prevalence of pruritus, identify associated factors, and investigate associations with patient-reported outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using cross-sectional data from patient questionnaires in the CKD Outcomes and Practice Patterns Study (CKDopps), we asked patients with CKD stages 3-5 (nondialysis) from the United States, Brazil, and France to identify how much they were bothered by pruritus. Response options ranged from "not at all" to "extremely." Log-Poisson regression, yielding prevalence ratios, was used to evaluate associations of moderate-to-extreme pruritus with patient characteristics, CKD stage, self-reported depression symptoms, and restless sleep. Mixed linear regression was used to examine associations between pruritus and physical and mental component summary scores, with lower scores indicating poorer quality of life. RESULTS: Of the 5658 CKDopps patients enrolled in the United States, Brazil, and France, 3780 (67%) answered the pruritus question. The prevalence of moderate-to-extreme pruritus was 24%, and more likely in older patients, women, and those with stage 5 CKD, lung disease, diabetes, and physician-diagnosed depression. In adjusted models, patients with moderate pruritus had physical and mental component summary scores 3.5 (95% confidence interval [95% CI], -4.6 to -2.3) and 2.3 (95% CI, -3.2 to -1.5) points lower, respectively, than patients without pruritus, and they also had a higher adjusted prevalence of patient-reported depression (prevalence ratio, 1.83; 95% CI, 1.58 to 2.11) and restless sleep (prevalence ratio, 1.69; 95% CI, 1.49 to 1.91) compared with patients without pruritus. These patient-reported outcomes were progressively worse with increasing severity of pruritus. CONCLUSIONS: Our findings demonstrate high prevalence of pruritus in nondialysis CKD, as well as strong associations of pruritus with poor health-related quality of life, self-reported depression symptoms, and self-reported poor sleep.

Mortality risk in patients on hemodiafiltration versus hemodialysis: a 'real-world' comparison from the DOPPS.

Background: With its convective component, hemodiafiltration (HDF) provides better middle molecule clearance compared with hemodialysis (HD) and is postulated to improve survival. A previous analysis of Dialysis Outcomes and Practice Patterns Study (DOPPS) data in 1998-2001 found lower mortality rates for high replacement fluid volume HDF versus HD. Randomized controlled trials have not shown uniform survival advantage for HDF; in secondary (non-randomized) analyses, better outcomes were observed in patients receiving the highest convection volumes. Methods: In a 'real-world' setting, we analyzed patients on dialysis >90 days from seven European countries in DOPPS Phases 4 and 5 (2009-15). Adjusted Cox regression was used to study HDF (versus HD) and mortality, overall and by replacement fluid volume. Results: Among 8567 eligible patients, 2012 (23%) were on HDF, ranging from 42% in Sweden to 12% in Germany. Median follow-up was 1.5 years during which 1988 patients died. The adjusted mortality hazard ratio (95% confidence interval) was 1.14 (1.00-1.29) for any HDF versus HD and 1.08 (0.92-1.28) for HDF >20 L replacement fluid volume versus HD. Similar results were found for cardiovascular and infection-related mortality. In an additional analysis aiming to avoid treatment-by-indication bias, we did not observe lower mortality rates in facilities using more HDF (versus HD). Conclusions: Our results do not support the notion that HDF provides superior patient survival. Further trials designed to test the effect of high-volume HDF (versus lower volume HDF versus HD) on clinical outcomes are needed to adequately inform clinical practices.

International Comparisons of Prevalence, Awareness, and Treatment of Pruritus in People on Hemodialysis.

BACKGROUND AND OBJECTIVES: Uremic pruritus in patients on hemodialysis is associated with depression, lower quality of life, and mortality. We studied the prevalence, awareness, and treatment of pruritus to assess how well this important condition is currently managed internationally. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from 35,452 patients on hemodialysis in up to 17 countries from the Dialysis Outcomes and Practice Patterns Study were analyzed to describe pruritus prevalence from 1996 to 2015. Data from 6256 patients and 268 medical directors in 17 countries in 2012-2015 were analyzed to describe predictors, effects, medical directors' awareness, and treatment of pruritus. RESULTS: Patients very much or extremely bothered by itching declined from 28% in 1996 to 18% in 2015. In 2012-2015, among patients nearly always or always bothered by itching, pruritus had a major effect on work and social life; 18% used no treatment for pruritus, and 17% did not report itching to health care staff. In total, 69% of medical directors underestimated the prevalence of pruritus in their unit. Managing high serum phosphorus and low Kt/V was ranked as the most important intervention, but no relationship was found between these factors and pruritus; 57% of medical directors used oral antihistamines for first-line chronic treatment of pruritus. Gabapentin was used by 45% as first-, second-, or third-line treatment. Nalfurafine was only used in Japan. CONCLUSIONS: The prevalence of pruritus in people on hemodialysis is decreasing but remains underestimated. Large numbers of patients on hemodialysis with severe pruritus do not receive treatment. There is wide variation in the use of unlicensed medications for the treatment of pruritus. These data provide a benchmark for initiatives to improve the management of uremic pruritus. MULTIMEDIA: This article contains multimedia at https://vimeo.com/49458473This article contains multimedia at vimeo.com/49455976.

A programme to spread eGFR graph surveillance for the early identification, support and treatment of people with progressive chronic kidney disease (ASSIST-CKD): protocol for the stepped wedge implementation and evaluation of an intervention to reduce late presentation for renal replacement therapy.

BACKGROUND: Patients who start renal replacement therapy (RRT) for End-Stage Kidney Disease (ESKD) without having had timely access to specialist renal services have poor outcomes. At one NHS Trust in England, a community-wide CKD management system has led to a decline in the incident rate of RRT and the lowest percentage of patients presenting within 90 days of starting RRT in the UK. We describe the protocol for a quality improvement project to scale up and evaluate this innovation. METHODS: The intervention is based upon an off-line database that integrates laboratory results from blood samples taken in all settings stored under different identifying labels relating to the same patient. Graphs of estimated glomerular filtration rate (eGFR) over time are generated for patients <65 years with an incoming eGFR <50 ml/min/1.73 m2 and patients >65 years with an incoming eGFR <40 ml/min/1.73 m2. Graphs where kidney function is deteriorating are flagged by a laboratory scientist and details sent to the primary care doctor (GP) with a prompt that further action may be needed. We will evaluate the impact of implementing this intervention across a large population served by a number of UK renal centres using a mixed methods approach. We are following a stepped-wedge design. The order of implementation among participating centres will be randomly allocated. Implementation will proceed with unidirectional steps from control group to intervention group until all centres are generating graphs of eGFR over time. The primary outcome for the quantitative evaluation is the proportion of patients referred to specialist renal services within 90 days of commencing RRT, using data collected routinely by the UK Renal Registry. The qualitative evaluation will investigate facilitators and barriers to adoption and spread of the intervention. It will include: semi-structured interviews with laboratory staff, renal centre staff and service commissioners; an online survey of GPs receiving the intervention; and focus groups of primary care staff. DISCUSSION: Late presentation to nephrology for patients with ESKD is a source of potentially avoidable harm. This protocol describes a robust quantitative and qualitative evaluation of a quality improvement intervention to reduce late presentation and improve the outcomes for patients with ESKD.

Association between changes in quality of life and mortality in hemodialysis patients: results from the DOPPS.

Background: Cross-sectional health-related quality of life (HR-QOL) measures are associated with mortality in hemodialysis (HD) patients. The impact of changes in HR-QOL on outcomes remains unclear. We describe the association of prior changes in HR-QOL with subsequent mortality among HD patients. Methods: A total of 13 784 patients in the Dialysis Outcomes and Practice Patterns Study had more than one measurement of HR-QOL. The impact of changes between two measurements of the physical (PCS) and mental (MCS) component summary scores of the SF-12 on mortality was estimated with Cox regression. Results: Mean age was 62 years (standard deviation: 14 years); 59% were male and 32% diabetic. Median time between HR-QOL measurements was 12 months [interquartile range (IQR): 11, 14]. Median initial PCS and MCS scores were 37.5 (IQR: 29.4, 46.2) and 46.4 (IQR: 37.2, 54.9); median changes in PCS and MCS scores were -0.2 (IQR: -5.5, 4.7) and -0.1 (IQR: -6.8, 5.9), respectively. The adjusted hazard ratio (HR) for a 5-point decline in HR-QOL score was 1.09 [95% confidence interval (CI): 1.06-1.12] for PCS and 1.05 (95% CI: 1.03-1.08) for MCS. Adjusting for the second QOL score, the change was not associated with mortality: HR = 1.01 (95% CI: 0.98-1.05) for delta PCS and 1.01 (95% CI: 0.98-1.03) for delta MCS. Categorizing the first and second scores as predictors, only the second PCS or MCS score was associated with mortality. Conclusions: In our study, only the most recent HR-QOL score was associated with mortality. Hence, the predictive power of a measurement of HR-QOL is not affected by changes in HR-QOL prior to that measurement; more frequent HR-QOL measurements are needed to improve the prediction of outcomes in HD. Further studies are needed to determine the optimal frequency and appropriate instrument to be used for serial measurements.

Associations of self-reported physical activity types and levels with quality of life, depression symptoms, and mortality in hemodialysis patients: the DOPPS.

BACKGROUND AND OBJECTIVES: Physical activity has been associated with better health status in diverse populations, but the association in patients on maintenance hemodialysis is less established. Patient-reported physical activities and associations with mortality, health-related quality of life, and depression symptoms in patients on maintenance hemodialysis in 12 countries were examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 5763 patients enrolled in phase 4 of the Dialysis Outcomes and Practice Patterns Study (2009-2011) were classified into five aerobic physical activity categories (never/rarely active to very active) and by muscle strength/flexibility activity using the Rapid Assessment of Physical Activity questionnaire. The Kidney Disease Quality of Life scale was used for health-related quality of life. The Center for Epidemiologic Studies Depression scale was used for depression symptoms. Linear regression was used for associations of physical activity with health-related quality of life and depression symptoms scores. Cox regression was used for association of physical activity with mortality. RESULTS: The median (interquartile range) of follow-up was 1.6 (0.9-2.5) years; 29% of patients were classified as never/rarely active, 20% of patients were classified as very active, and 20.5% of patients reported strength/flexibility activities. Percentages of very active patients were greater in clinics offering exercise programs. Aerobic activity, but not strength/flexibility activity, was associated positively with health-related quality of life and inversely with depression symptoms and mortality (adjusted hazard ratio of death for very active versus never/rarely active, 0.60; 95% confidence interval, 0.47 to 0.77). Similar associations with aerobic activity were observed in strata of age, sex, time on dialysis, and diabetes status. CONCLUSIONS: The findings are consistent with the health benefits of aerobic physical activity for patients on maintenance hemodialysis. Greater physical activity was observed in facilities providing exercise programs, suggesting a possible opportunity for improving patient outcomes.

Recovery time, quality of life, and mortality in hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: There is limited information about the clinical and prognostic significance of patient-reported recovery time. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 6,040 patients in the DOPPS (Dialysis Outcomes and Practice Patterns Study). PREDICTOR: Answer to question "How long does it take you to recover from a dialysis session?" categorized as follows: fewer than 2, 2-6, 7-12, or longer than 12 hours. OUTCOMES & MEASUREMENTS: Cross-sectional and longitudinal associations between recovery time and patient characteristics, hemodialysis treatment variables, health-related quality of life (HRQoL), and hospitalization and mortality. RESULTS: 32% reported recovery time shorter than 2 hours; 41%, 2-6 hours; 17%, 7-12 hours; and 10%, longer than 12 hours. Using proportional odds (ordinal) logistic regression, shorter recovery time was associated with male sex, full-time employment, and higher serum albumin level. Longer recovery time was associated with older age, dialysis vintage, body mass index, diabetes, and psychiatric disorder. Greater intradialytic weight loss, longer dialysis session length, and lower dialysate sodium concentration were associated with longer recovery time. In facilities that used uniform dialysate sodium concentrations for ≥90% of patients, the adjusted OR of longer recovery time, comparing dialysate sodium concentration<140 vs 140 mEq/L, was 1.72 (95% CI, 1.37-2.16). Recovery time was correlated positively with symptoms of kidney failure and kidney disease burden score and inversely with HRQoL mental and physical component summary scores. Using Cox regression, adjusting for potential confounders not influenced by recovery time, it was associated positively with first hospitalization and mortality (adjusted HRs for recovery time>12 vs 2-6 hours 1.22 [95% CI, 1.09-1.37] and 1.47 [95% CI, 1.19-1.83], respectively). LIMITATIONS: Answers are subjective and not supported by physiologic measurements. CONCLUSIONS: Recovery time can be used to identify patients with poorer HRQoL and higher risks of hospitalization and mortality. Interventions to reduce recovery time and possibly improve clinical outcomes, such as increasing dialysate sodium concentration, need to be tested in randomized trials.

Does community-wide chronic kidney disease management improve patient outcomes?

BACKGROUND: The number of patients starting renal replacement therapy (RRT) is increasing in England, as it is worldwide. Improvements in the management of chronic kidney disease (CKD) across communities to alter this trend are a public health priority. We have prospectively studied changes in the incidence and modality of treatment for end-stage renal disease following the introduction of a CKD management programme in the West Midlands region of England. METHODS: Nephrology service to approximately 700 000 adult population of mixed ethnicity in urban and suburban areas, many with social deprivation. The programme was introduced in stages between 2003 and 2006 and comprised primary care education and financial incentives, personal clinical reports written directly to patients following every consultation, routine laboratory estimated glomerular filtration rate (eGFR) reporting, eGFR graph surveillance to identify and monitor patients at risk, multidisciplinary pre-RRT care and conservative care. Prevalent patients: 10 552 with CKD and 8509 without CKD with diabetes. OUTCOMES: access to nephrology care, trends in RRT incidence and starting modality, place of death without RRT. Incident count was adjusted for changes in the local adult population recorded in national censuses. RESULTS: Ninety-one per cent of patients aged ≥75 years with incident CKD stage 5 were known to a nephrologist. The population-adjusted incident RRT rate peaked in 2005 and then declined; the proportion starting with transplant, peritoneal dialysis or haemodialysis by arterio-venous fistula increased to 63% by 2012 (P = 0.001 versus 2005). Fifty-two per cent of patients receiving planned conservative care without dialysis died out of hospital. CONCLUSIONS: Following the introduction of a community-wide systematic CKD management programme, the population-adjusted incidence of RRT reduced, modality of initiation of RRT improved and a majority of patients receiving planned conservative care without dialysis died out of hospital.

Laboratory database population surveillance to improve detection of progressive chronic kidney disease.

BACKGROUND: Some patients with chronic kidney disease are still referred late for specialist care despite the evidence that earlier detection and intervention can halt or delay progression to end-stage kidney disease (ESKD). OBJECTIVES: To develop a population surveillance system using existing laboratory data to enable early detection of patients at high risk of ESKD by reviewing cumulative graphs of estimated glomerular filtration rate (eGFR). METHODS: A database was developed, updated daily with data from the laboratory computer. Cumulative eGFR graphs containing up to five years of data are reviewed by clinical scientists for all primary care patients or out-patients with a low eGFR for their age. For those with a declining trend, a report containing the eGFR graph is sent to the requesting doctor. A retrospective audit was performed using historical data to assess the predictive value of the graphs. RESULTS: In nine months, we reported 370,000 eGFR results, reviewing 12,000 eGFR graphs. On average 60 graphs per week were flagged as 'high' or 'intermediate' risk. Patients with graphs flagged as high risk had a significantly higher mortality after 3.5 years and a significantly greater chance of requiring renal replacement therapy after 4.5 years of follow-up. Five patients (7%) with graphs flagged as high risk had a sustained >25% fall in eGFR without evidence of secondary care referral. Feedback about the service from requesting clinicians was 73% positive. CONCLUSIONS: We have developed a system for laboratory staff to review cumulative eGFR graphs for a large population and identify patients at highest risk of developing ESKD. Further research is needed to measure the impact of this service on patient outcomes.

Associations of frequency and duration of patient-doctor contact in hemodialysis facilities with mortality.

It is unknown whether regular patient-doctor contact (PDC) contributes to better outcomes for patients undergoing hemodialysis. Here, we analyzed the associations between frequency and duration of PDC during hemodialysis treatments with clinical outcomes among 24,498 patients from 778 facilities in the international Dialysis Outcomes and Practice Patterns Study (DOPPS). The typical facility PDC frequency, estimated by facility personnel, was high (more than once per week) for 55% of facilities, intermediate (once per week) for 24%, and low (less than once per week) for 21%. The mean ± SD estimated duration of a typical interaction between patient and physician was 7.7 ± 5.6 minutes. PDC frequency and duration varied across DOPPS phases and countries; the proportion of facilities with high PDC frequency was 17% in the United States and 73% across the other countries. Compared with high PDC frequency, the adjusted hazard ratio (HR) for all-cause mortality was 1.06 (95% confidence interval [CI], 0.96 to 1.17) for intermediate PDC frequency and 1.11 (95% CI, 1.01 to 1.23) for low PDC frequency (P=0.03 for trend). Furthermore, each 5-minutes-shorter duration of PDC was associated with a 5% higher risk for death, on average (HR, 1.05; 95% CI, 1.01 to 1.09), adjusted for PDC frequency and other covariates. Multivariable analyses also suggested modest inverse associations between both PDC frequency and duration with hospitalization but not with kidney transplantation. Taken together, these results suggest that policies supporting more frequent and longer duration of PDC may improve patient outcomes in hemodialysis.

Hemodialysis patient preference for type of vascular access: variation and predictors across countries in the DOPPS.

PURPOSE: Catheters are associated with worse clinical outcomes than fistulas and grafts in hemodialysis (HD) patients. One potential modifier of patient vascular access (VA) use is patient preference for a particular VA type. The purpose of this study is to identify predictors of patient VA preference that could be used to improve patient care. METHODS: This study uses a cross-sectional sample of data from the Dialysis Outcomes and Practice Patterns Study (DOPPS 3, 2005-09), that includes 3815 HD patients from 224 facilities in 12 countries. Using multivariable models we measured associations between patient demographic and clinical characteristics, previous catheter use and patient preference for a catheter. RESULTS: Patient preference for a catheter varied across countries, ranging from 1% of HD patients in Japan and 18% in the United States, to 42% to 44% in Belgium and Canada. Preference for a catheter was positively associated with age (adjusted odds ratio per 10 years=1.14; 95% CI=1.02-1.26), female sex (OR 1.49; 95% CI=1.15-1.93), and former (OR=2.61; 95% CI=1.66-4.12) or current catheter use (OR=60.3; 95% CI=36.5-99.8); catheter preference was inversely associated with time on dialysis (OR per three years=0.90; 95% CI=0.82-0.97). CONCLUSIONS: Considerable variation in patient VA preference was observed across countries, suggesting that patient VA preference may be influenced by sociocultural factors and thus could be modifiable. Catheter preference was greatest among current and former catheter users, suggesting that one way to influence patient VA preference may be to avoid catheter use whenever possible.

Systematic kidney disease management in a population with diabetes mellitus: turning the tide of kidney failure.

PROBLEM: A significant proportion of patients with diabetes mellitus do not get the benefit of treatment that would reduce their risk of progressive kidney disease and reach a nephrologist once significant loss of kidney function has already occurred. DESIGN: Systematic disease management of patients with diabetes and kidney disease. SETTING: Diverse population (approximately 800,000) in and around Birmingham, West Midlands, UK. KEY MEASURES FOR IMPROVEMENT: Number of outpatient appointments, estimated glomerular filtration rate (eGFR) at first contact with nephrologist, number of patients starting kidney replacement therapy (KRT) and mode of KRT at start. STRATEGY FOR CHANGE: Identification of patients with low or deteriorating trend in eGFR from weekly database review, specialist diabetes-kidney clinic, self-management of blood pressure and transfer to multidisciplinary clinic >12 months before end-stage kidney disease. EFFECTS OF CHANGE: New patients increased from 62 in 2003 to 132 in 2010; follow-ups fell from 251 to 174. Median eGFR at first clinic visit increased from 28.8 ml/min/1.73 m(2) (range 6.1-67.0) in 2000/2001 to 35.0 (11.1-147.5) in 2010 (p<0.006). In 2010, the number of patients starting KRT fell 30% below the projected activity using 1993-2003 data as baseline (p<0.003). The proportion starting KRT with either a kidney transplant, peritoneal dialysis or haemodialysis via an arteriovenous fistula increased from 26% in 2000 to 55% in 2010. LESSONS LEARNED: Systematic disease management across a large population significantly improves patient outcomes, increases the productivity of a specialist service and could reduce healthcare costs compared with the current model of care.