Conservative kidney management and kidney supportive care: core components of integrated care for people with kidney failure.

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.

Protein Biomarkers and Major Cardiovascular Events in Older People With Advanced CKD: The European Quality (EQUAL) Study.

Rationale & Objective: Cardiovascular disease is the leading cause of morbidity and mortality in chronic kidney disease (CKD). We investigated 184 inflammatory and cardiovascular proteins to determine their potential as biomarkers for major cardiovascular events (MACEs). Study Design: The European Quality (EQUAL) is an observational cohort study that enrolled people aged ≥65 years with an estimated glomerular filtration rate ≤20 mL/min/1.73 m2. Setting & Participants: Recruited participants were split into the discovery (n = 611) and replication cohorts (n = 292). Exposure: Levels of 184 blood proteins were measured at the baseline visit, and each protein was analyzed individually. Outcome: MACE. Analytical Approach: Cox proportional hazard models adjusted for age, sex, estimated glomerular filtration rate, previous MACE, and country were used to determine the risk of MACE. Proteins with false discovery rate adjusted P values of <0.05 in the discovery cohort were tested in the replication cohort. Sensitivity analyses were performed by adjusting for traditional risk factors, CKD-specific risk factors, and level of proteinuria and segregating atherosclerotic and nonatherosclerotic MACE. Results: During a median follow-up of 2.9 years, 349 people (39%) experienced a MACE. Forty-eight proteins were associated with MACE in the discovery cohort; 9 of these were reproduced in the replication cohort. Three of these proteins maintained a strong association with MACE after adjustment for traditional and CKD-specific risk factors and proteinuria. Tenascin (TNC), fibroblast growth factor-23 (FGF-23), and V-set and immunoglobulin domain-containing protein 2 (VSIG2) were associated with both atherosclerotic and nonatherosclerotic MACE. All replicated proteins except carbonic anhydrase 1 and carbonic anhydrase 3 were associated with nonatherosclerotic MACE. Limitations: Single protein concentration measurements and limited follow-up time. Conclusions: Our findings corroborate previously reported relationships between FGF-23, vascular cell adhesion protein-1, TNC, and placental growth factor with cardiovascular outcomes in CKD. We identify 5 proteins not previously linked with MACE in CKD that may be targets for future therapies. Plain-Language Summary: Kidney disease increases the risk of heart disease, stroke, and other vascular conditions. Blood tests that predict the likelihood of these problems may help to guide treatment, but studies are needed in people with kidney disease. We analyzed blood tests from older people with kidney disease, looking for proteins associated with higher risk of these conditions. Nine proteins were identified, of which 3 showed a strong effect after all other information was considered. This work supports previous research regarding 4 of these proteins and identifies 5 additional proteins that may be associated with higher risk. Further work is needed to confirm our findings and to determine whether these proteins can be used to guide treatment.

An introduction to realist evaluation and synthesis for kidney research.

Realist research describes a methodological approach that aims to explore how and why interventions work, for whom, and under what circumstances. Rather than quantifying how well an intervention works under specific conditions, realist theory explores the function of interventions in detail and specifically considers how the contexts in which interventional components are delivered influence the mechanisms that lead to outcomes. Realist methods can be applied to primary data (realist evaluation) or secondary data (realist synthesis). Although realist techniques are increasingly being used in the evaluation of complex interventions, there are relatively few published studies in the field of kidney care. In this review, we outline the theory and principles behind realist methods through discussion of a published realist synthesis describing complex interventions promoting delivery of optimal chronic kidney disease care. We discuss other kidney studies that have used realist methodology and situations where realist techniques could be applied to advance our understanding of how to best deliver care to patients with kidney disease.

CareKnowDo-A Multichannel Digital and Telephone Support Program for People With Chronic Kidney Disease: Feasibility Randomized Controlled Trial.

BACKGROUND: Chronic kidney disease (CKD) is a common, progressive condition. Lifestyle changes and antihypertensive medication can slow the progression to end-stage kidney disease, which requires renal replacement therapy. However, adherence to these recommendations is often low. OBJECTIVE: The aim of CareKnowDo was to assess the feasibility of rolling out a digital self-management support and adherence program integrated with a patient-facing electronic health record, Patient View (PV). METHODS: A 2-arm, parallel, individual-level pragmatic feasibility pilot randomized controlled trial was conducted at 2 National Health Service (NHS) sites in the United Kingdom. A total of 61 patients with CKD were randomized 1:1 into 2 groups and provided with either a new, tailored digital and telephone support program (CareKnowDo: 31/61, 51%) integrated with PV or standard care (PV alone: 30/61, 49%). Quantitative measures included clinical and psychosocial measures. The primary outcomes were feasibility based: recruitment rate, dropout, and the exploration of associations. RESULTS: Of the 1392 patients screened in local kidney clinics, 269 (19.32%) met the basic inclusion criteria; the first 22.7% (61/269) who met the eligibility criteria were recruited to participate in the study. Of the 69 patients, 23 (38%) patients completed the final 6-month follow-up web-based survey. Reasons for the attrition were explored. A higher belief in the ability of the treatment to control CKD was associated with lower blood pressure at baseline (r=0.52; P=.005), and a higher perceived understanding of CKD at baseline was associated with lower blood pressure at follow-up (r=0.66; P<.001). Beliefs about medicines at baseline were associated with blood pressure at baseline but not at follow-up. This was true for both concerns about medicines (r=0.58; P=.001) and perceived necessity of medicines (r=0.42; P=.03). CONCLUSIONS: A tailored digital and nurse call-based program to enhance support for patients with CKD was piloted in 2 NHS sites and found to be feasible and acceptable. However, to maximize the effectiveness of the intervention (and of future trials), consideration should be given to the target audience most likely to benefit, as well as how to help them access the program as quickly and easily as possible. TRIAL REGISTRATION: NHS Health Research Authority, IRAS ID 184206; https://www.hra.nhs.uk/planning-and-improving -research/application-summaries/research-summaries/careknowdo-pilot-version-1/.

Shared decision making: a personal view from two kidney doctors and a patient.

Shared decision making (SDM) combines the clinician's expertise in the treatment of disease with the patient's expertise in their lived experience and what is important to them. All decisions made in the care of patients with kidney disease can potentially be explored through SDM. Adoption of SDM in routine kidney care faces numerous institutional and practical barriers. Patients with chronic disease who have become accustomed to paternalistic care may need support to engage in SDM-even though most patients actively want more involvement in decisions about their care. Nephrologists often underestimate the risks and overestimate the benefits of investigations and treatments and often default to recommending burdensome treatments rather than discussing prognosis openly. Guideline bodies continue to issue recommendations written for healthcare professionals without providing patient decision aids. To mitigate health inequalities, care needs to be taken to provide SDM to all patients, not just the highly health-literate patients least likely to need additional support in decision making. Kidney doctors spend much of their time in the consulting room, and it is unjustifiable that so little attention is paid to the teaching, audit and maintenance of consultation skills. Writing letters to the patient to summarise the consultation rather than sending them a copy of a letter between health professionals sets the tone for a consultation in which the patient is an active partner. Adoption of SDM will require nephrologists to relinquish long-established paternalistic models of care and restructure care around the values and preferences of patients.

Mixed-methods research in nephrology.

Mixed-methods research involves the mixing of at least 1 qualitative and 1 quantitative method in the same research project or set of related projects. Combined use of qualitative and quantitative research methods in nephrology has increased over the last 10 years. In this review, we aim to advance the understanding of mixed-methods research within the kidney community. Qualitative and quantitative techniques provide different but noncompeting representations of what exists in the world; findings from qualitative research do not generalize to a large population, whereas those from quantitative research may not apply to individuals within the diverse and heterogeneous larger population. Mixed-methods research combines these complementary representations, allowing the strengths of each method to be combined and the strengths of 1 method to address the limitations of the other. Mixed-methods approaches can be used to: (i) gain a more complete understanding of a research problem, (ii) explain initial results from one method with results from another, (iii) generate instruments, for example, survey tools and interventions, (iv) evaluate services, and (v) optimize clinical trial design and delivery. There are 3 core mixed-methods designs: explanatory sequential, exploratory sequential, and convergent parallel, which can be combined. We discuss each design in turn before discussing analysis and integration of findings from the different methods. We provide case studies that illustrate the application of these study designs to kidney research questions. We briefly discuss mixed-methods systematic reviews and evidence synthesis before finally highlighting guidance on how to appraise published mixed-methods research.

Converting from face-to-face to postal follow-up and its effects on participant retention, response rates and errors: lessons from the EQUAL study in the UK.

BACKGROUND: Prospective cohort studies are challenging to deliver, with one of the main difficulties lying in retention of participants. The need to socially distance during the COVID-19 pandemic has added to this challenge. The pre-COVID-19 adaptation of the European Quality (EQUAL) study in the UK to a remote form of follow-up for efficiency provides lessons for those who are considering changing their study design. METHODS: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced chronic kidney disease. Initially, patients were invited to complete a questionnaire (SF-36, Dialysis Symptom Index and Renal Treatment Satisfaction Questionnaire) at research clinics every 3-6 months, known as "traditional follow-up" (TFU). In 2018, all living patients were invited to switch to "efficient follow-up" (EFU), which used an abbreviated questionnaire consisting of SF-12 and Dialysis Symptom Index. These were administered centrally by post. Response rates were calculated using returned questionnaires as a proportion of surviving invitees, and error rates presented as the average percentage of unanswered questions or unclear answers, of total questions in returned questionnaires. Response and error rates were calculated 6-monthly in TFU to allow comparisons with EFU. RESULTS: Of the 504 patients initially recruited, 236 were still alive at the time of conversion to EFU; 111 of these (47%) consented to the change in follow-up. In those who consented, median TFU was 34 months, ranging from 0 to 42 months. Their response rates fell steadily from 88% (98/111) at month 0 of TFU, to 20% (3/15) at month 42. The response rate for the first EFU questionnaire was 60% (59/99) of those alive from TFU. With this improvement in response rates, the first EFU also lowered errors to baseline levels seen in early follow-up, after having almost trebled throughout traditional follow-up. CONCLUSIONS: Overall, this study demonstrates that administration of shorter follow-up questionnaires by post rather than in person does not negatively impact patient response or error rates. These results may be reassuring for researchers who are trying to limit face-to-face contact with patients during the COVID-19 pandemic.

Quality assuring early dialysis care: evaluating rates of death and recovery within 90 days of first dialysis using the UK Renal Registry.

Background: Kidney disease registries typically report populations incident to kidney replacement therapy (KRT) after excluding reversible disease. Registry-based audit and quality assurance is thus based on populations depleted of those with the highest early mortality. It is now mandatory for UK kidney units to report all recipients of dialysis, both acute and chronic. This work presents 90-day survival and recovery outcomes for all reported adults. Methods: Seventy adult centres reporting to the UK Renal Registry were included. Those assessed as underreporting death and recovery were excluded. Survival was evaluated using a Kaplan-Meier estimator. Cox regression was used to describe hazard ratios (HRs) for age, sex and acute/chronic dialysis coding on day 1. Analysis of all-cause 90-day mortality with recovery as a competing risk is presented. Results: Twenty-four centres were assessed as underreporting, with rates of death/recovery below the 99.7th centile. Of 5784 dialysis starters in the remaining 46 centres, 2163 (37.4%) were coded as receiving acute dialysis on day 1. Ninety days after starting, 3860 (66.7%) of all starters were receiving KRT, 1157 (20.0%) were alive having stopped, 716 (12.4%) were dead and 51 (0.9%) were lost to follow-up. Mortality was higher among those coded as receiving acute dialysis on day 1 (HR 4.88, P < 0.001). The sub-HR for recovery among those coded as receiving acute compared with chronic dialysis was 56.14 (P < 0.001). Conclusions: Death and recovery rates are substantially higher than reported in conventional incident populations. This work highlights a vulnerable subgroup of patients largely overlooked by most national quality assurance systems.

International prescribing patterns and polypharmacy in older people with advanced chronic kidney disease: results from the European Quality study.

BACKGROUND: People with chronic kidney disease (CKD) are at high risk of polypharmacy. However, no previous study has investigated international prescribing patterns in this group. This article aims to examine prescribing and polypharmacy patterns among older people with advanced CKD across the countries involved in the European Quality (EQUAL) study. METHODS: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced CKD. Baseline demographic, clinical and medication data were analysed and reported descriptively. Polypharmacy was defined as ≥5 medications and hyperpolypharmacy as ≥10. Univariable and multivariable linear regressions were used to determine associations between country and the number of prescribed medications. Univariable and multivariable logistic regression were used to determine associations between country and hyperpolypharmacy. RESULTS: Of the 1317 participants from five European countries, 91% were experiencing polypharmacy and 43% were experiencing hyperpolypharmacy. Cardiovascular medications were the most prescribed medications (mean 3.5 per person). There were international differences in prescribing, with significantly greater hyperpolypharmacy in Germany {odds ratio (OR) 2.75 [95% confidence interval (CI) 1.73-4.37]; P < 0.001, reference group UK}, the Netherlands [OR 1.91 (95% CI 1.32-2.76); P = 0.001] and Italy [OR 1.57 (95% CI 1.15-2.15); P = 0.004]. People in Poland experienced the least hyperpolypharmacy [OR 0.39 (95% CI 0.17-0.87); P = 0.021]. CONCLUSIONS: Hyperpolypharmacy is common among older people with advanced CKD, with significant international differences in the number of medications prescribed. Practice variation may represent a lack of consensus regarding appropriate prescribing for this high-risk group for whom pharmacological treatment has great potential for harm as well as benefit.

A systematically collated library of prescribing safety indicators for people with chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) have high levels of co-morbidity and polypharmacy placing them at increased risk of prescribing-related harm. Tools for assessing prescribing safety in the general population using prescribing safety indicators (PSIs) have been established. However, people with CKD pose different prescribing challenges to people without kidney disease. Therefore, PSIs designed for use in the general population may not include all PSIs relevant to a CKD population. The aim of this study was to systematically collate a library of PSIs relevant to people with CKD. METHODS: A systematic literature search identified papers reporting PSIs. CKD-specific PSIs were extracted and categorised by Anatomical Therapeutic Chemical (ATC) classification codes. Duplicate PSIs were removed to create a final list of CKD-specific PSIs. RESULTS: Nine thousand, eight hundred fifty-two papers were identified by the systematic literature search, of which 511 proceeded to full text screening and 196 papers were identified as reporting PSIs. Following categorisation by ATC code and duplicate removal, 841 unique PSIs formed the final set of CKD-specific PSIs. The five ATC drug classes containing the largest proportion of CKD-specific PSIs were: Cardiovascular system (26%); Nervous system (13.4%); Blood and blood forming organs (12.4%); Alimentary and metabolism (12%); and Anti-infectives for systemic use (11.3%). CONCLUSION: CKD-specific PSIs could be used alone or alongside general PSIs to assess the safety and quality of prescribing within a CKD population.

Supportive care for end-stage kidney disease: an integral part of kidney services across a range of income settings around the world.

A key component of treatment for all people with advanced kidney disease is supportive care, which aims to improve quality of life and can be provided alongside therapies intended to prolong life, such as dialysis. This article addresses the key considerations of supportive care as part of integrated end-stage kidney disease care, with particular attention paid to programs in low- and middle-income countries. Supportive care should be an integrated component of care for patients with advanced chronic kidney disease, patients receiving kidney replacement therapy (KRT), and patients receiving non-KRT conservative care. Five themes are identified: improving information on prognosis and support, developing context-specific evidence, establishing appropriate metrics for monitoring care, clearly communicating the role of supportive care, and integrating supportive care into existing health care infrastructures. This report explores some general aspects of these 5 domains, before exploring their consequences in 4 health care situations/settings: in people approaching end-stage kidney disease in high-income countries and in low- and middle-income countries, and in people discontinuing KRT in high-income countries and in low- and middle-income countries.

Illness as Transformative Experience: Implications of Philosophy for Advance Care Planning.

Advance care planning has been shown to improve patient outcomes and is recommended as part of routine care for people with a life-limiting illness. Nevertheless, developing an advance care plan can be complex and challenging for both patients and family members, and the clinicians who support them. One complexity is that illness and its treatments often cannot be deeply understood without lived experience. In this paper, we explore this idea, highlighting how lived experience can bring about unpredictable changes in an individual's values and preferences. We examine the implications of such "transformative experiences" for advance care planning, using the hypothetical case study of Jean, an older person with advanced kidney disease. Finally, we consider consequences for clinical practice and how an understanding of transformative experience might enhance current approaches to advance care planning.

Treatment of End-stage Kidney Failure without Renal Replacement Therapy.

For the majority of patients with end-stage kidney failure (ESKF) replacement of excretory renal function by dialysis or transplantation (RRT) can extend life and alleviate symptoms. Historically, the availability of RRT has been insufficient and this remains the case for much of the world. However, RRT is now widely available in healthcare systems of higher income countries. Increasing numbers of elderly patients are developing ESKF. RRT in this population is largely by dialysis, comorbidity is high and life expectancy short. Evidence of effectiveness coupled with the burden of treatment among these individuals has raised concerns that health services in high-income countries may have moved from an era of unmet need into one of potential over-treatment. Alongside the requirement to make treatment more patient-centered, this has driven the development of comprehensive conservative care as an alternative approach for older comorbid individuals with ESKF, with the potential for acceptable symptom control and reduced treatment burden. This paper provides a largely UK-perspective on treating ESKF without RRT. Emphasis is on the need for high-quality evidence to inform treatment decisions. Complexities of defining, delivering and improving treatment of ESKF without dialysis care are explored. Quantitative and qualitative evidence are summarized and the relationship with palliative and terminal care examined. A framework is suggested for classifying management of ESKF and recommendations made to improve delivery of nondialysis care in the future. For patients with a poor prognosis, such treatment may not result in significantly different survival or quality of life when compared with dialysis. There is a key need to generate the best possible evidence of person-centered health outcomes associated with the various treatment options for ESKF and to present this to patients in a balanced, personalized way that allows them to make the treatment decision most appropriate for them.