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.

Management and outcomes of myocardial infarction in people with impaired kidney function in England.

BACKGROUND: Acute myocardial infarction (AMI) causes significant mortality and morbidity in people with impaired kidney function. Previous observational research has demonstrated reduced use of invasive management strategies and inferior outcomes in this population. Studies from the USA have suggested that disparities in care have reduced over time. It is unclear whether these findings extend to Europe and the UK. METHODS: Linked data from four national healthcare datasets were used to investigate management and outcomes of AMI by estimated glomerular filtration rate (eGFR) category in England. Multivariable logistic and Cox regression models compared management strategies and outcomes by eGFR category among people with kidney impairment hospitalised for AMI between 2015-2017. RESULTS: In a cohort of 5 835 people, we found reduced odds of invasive management in people with eGFR < 60mls/min/1.73m2 compared with people with eGFR ≥ 60 when hospitalised for non-ST segment elevation MI (NSTEMI). The association between eGFR and odds of invasive management for ST-elevation MI (STEMI) varied depending on the availability of percutaneous coronary intervention. A graded association between mortality and eGFR category was demonstrated both in-hospital and after discharge for all people. CONCLUSIONS: In England, patients with reduced eGFR are less likely to receive invasive management compared to those with preserved eGFR. Disparities in care may however be decreasing over time, with the least difference seen in patients with STEMI managed via the primary percutaneous coronary intervention pathway. Reduced eGFR continues to be associated with worse outcomes after AMI.

Propensity Score and Instrumental Variable Techniques in Observational Transplantation Studies: An Overview and Worked Example Relating to Pre-Transplant Cardiac Screening.

Inferring causality from observational studies is difficult due to inherent differences in patient characteristics between treated and untreated groups. The randomised controlled trial is the gold standard study design as the random allocation of individuals to treatment and control arms should result in an equal distribution of known and unknown prognostic factors at baseline. However, it is not always ethically or practically possible to perform such a study in the field of transplantation. Propensity score and instrumental variable techniques have theoretical advantages over conventional multivariable regression methods and are increasingly being used within observational studies to reduce the risk of confounding bias. An understanding of these techniques is required to critically appraise the literature. We provide an overview of propensity score and instrumental variable techniques for transplant clinicians, describing their principles, assumptions, strengths, and weaknesses. We discuss the different patient populations included in analyses and how to interpret results. We illustrate these points using data from the Access to Transplant and Transplant Outcome Measures study examining the association between pre-transplant cardiac screening in kidney transplant recipients and post-transplant cardiac events.

A propensity score-matched analysis indicates screening for asymptomatic coronary artery disease does not predict cardiac events in kidney transplant recipients.

Screening for asymptomatic coronary artery disease prior to kidney transplantation aims to reduce peri- and post-operative cardiac events. It is uncertain if this is achieved. Here, we investigated whether pre-transplant screening with a stress test or coronary angiogram associated with any difference in major adverse cardiac events (MACE) up to five years post-transplantation. We examined a national prospective cohort recruited to the Access to Transplant and Transplant Outcome Measures study who received a kidney transplant between 2011-2017, and linked patient demographics and details of cardiac screening investigations to outcome data extracted from the Hospital Episode Statistics dataset and United Kingdom Renal Registry. Propensity score matched groups were analyzed using Kaplan-Meier and Cox survival analyses. Overall, 2572 individuals were transplanted in 18 centers; 51% underwent screening and the proportion undergoing screening by center ranged from 5-100%. The incidence of MACE at 90 days, one and five years was 0.9%, 2.1% and 9.4% respectively. After propensity score matching based on the presence or absence of screening, 1760 individuals were examined (880 each in screened and unscreened groups). There was no statistically significant association between screening and MACE at 90 days (hazard ratio 0.80, 95% Confidence Interval 0.31-2.05), one year (1.12, 0.51-2.47) or five years (1.31, 0.86-1.99). Age, male sex and history of ischemic heart disease were associated with MACE. Thus, there is no association between screening for asymptomatic coronary artery disease and MACE up to five years post-transplant. Practices involving unselected screening of transplant recipients should be reviewed.

Limited health literacy is associated with reduced access to kidney transplantation.

Limited health literacy is common in patients with chronic kidney disease (CKD) and has been variably associated with adverse clinical outcomes. The prevalence of limited health literacy is lower in kidney transplant recipients than in individuals starting dialysis, suggesting selection of patients with higher health literacy for transplantation. We investigated the relationship between limited health literacy and clinical outcomes, including access to kidney transplantation, in a prospective UK cohort study of 2,274 incident dialysis patients aged 18-75 years. Limited health literacy was defined by a validated Single Item Literacy Screener (SILS). Multivariable regression was used to test for association with outcomes after adjusting for age, sex, socioeconomic status (educational level and car ownership), ethnicity, first language, primary renal diagnosis, and comorbidity. In fully adjusted analyses, limited health literacy was not associated with mortality, late presentation to nephrology, dialysis modality, haemodialysis vascular access, or pre-emptive kidney transplant listing, but was associated with reduced likelihood of listing for a deceased-donor transplant (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.51-0.90), receiving a living-donor transplant (HR 0.41; 95% CI 0.19-0.88), or receiving a transplant from any donor type (HR 0.65; 95% CI 0.44-0.96). Limited health literacy is associated with reduced access to kidney transplantation, independent of patient demographics, socioeconomic status, and comorbidity. Interventions to ameliorate the effects of low health literacy may improve access to kidney transplantation.

Health literacy and patient outcomes in chronic kidney disease: a systematic review.

Background: Limited health literacy affects 25% of people with chronic kidney disease (CKD), and may reduce self-management skills resulting in poorer clinical outcomes. By disproportionately affecting people with low socio-economic status and non-white ethnicity, limited health literacy may promote health inequity. Methods: We performed a systematic review of quantitative studies of health literacy and clinical outcomes among adults with CKD. Results: A total of 29 studies (13 articles; 16 conference abstracts) were included. One included non-USA patients. Of the 29 studies, 5 were cohort studies and 24 were cross-sectional. In all, 18 300 patients were studied: 4367 non-dialysis CKD; 13 202 dialysis; 390 transplant; 341 unspecified. Median study size was 127 [interquartile range (IQR) 92-238)], but 480 (IQR 260-2392) for cohort studies. Median proportion of non-white participants was 48% (IQR 17-70%). Six health literacy measures were used. Outcomes included patient attributes, care processes, clinical/laboratory parameters and 'hard' clinical outcomes. Limited health literacy was significantly, independently associated with hospitalizations, emergency department use, missed dialysis sessions, cardiovascular events and mortality (in cohort studies). Study quality was high (1 study), moderate (3 studies) and poor (25 studies), limited by sampling methods, variable adjustment for confounders and reduced methodological detail given in conference abstracts. Conclusions: There is limited robust evidence of the causal effects of health literacy on patient outcomes in CKD. Available evidence suggests associations with adverse clinical events, increased healthcare use and mortality. Prospective studies are required to determine the causal effects of health literacy on outcomes in CKD patients, and examine the relationships between socio-economic status, comorbidity, health literacy and CKD outcomes. Intervention development and evaluation will determine whether health literacy is a modifiable determinant of poor outcomes in CKD.

Limited health literacy in advanced kidney disease.

Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy.

Complex Interventions Across Primary and Secondary Care to Optimize Population Kidney Health: A Systematic Review and Realist Synthesis to Understand Contexts, Mechanisms, and Outcomes.

BACKGROUND: CKD affects 850 million people worldwide and is associated with high risk of kidney failure and death. Existing, evidence-based treatments are not implemented in at least a third of eligible patients, and there is socioeconomic inequity in access to care. While interventions aiming to improve delivery of evidence-based care exist, these are often complex, with intervention mechanisms acting and interacting in specific contexts to achieve desired outcomes. METHODS: We undertook realist synthesis to develop a model of these context-mechanism-outcome interactions. We included references from two existing systematic reviews and from database searches. Six reviewers produced a long list of study context-mechanism-outcome configurations based on review of individual studies. During group sessions, these were synthesized to produce an integrated model of intervention mechanisms, how they act and interact to deliver desired outcomes, and in which contexts these mechanisms work. RESULTS: Searches identified 3371 relevant studies, of which 60 were included, most from North America and Europe. Key intervention components included automated detection of higher-risk cases in primary care with management advice to general practitioners, educational support, and non-patient-facing nephrologist review. Where successful, these components promote clinician learning during the process of managing patients with CKD, promote clinician motivation to take steps toward evidence-based CKD management, and integrate dynamically with existing workflows. These mechanisms have the potential to result in improved population kidney disease outcomes and cardiovascular outcomes in supportive contexts (organizational buy-in, compatibility of interventions, geographical considerations). However, patient perspectives were unavailable and therefore did not contribute to our findings. CONCLUSIONS: This systematic review and realist synthesis describes how complex interventions work to improve delivery of CKD care, providing a framework within which future interventions can be developed. Included studies provided insight into the functioning of these interventions, but patient perspectives were lacking in available literature.

Persistent renal replacement requirement following fulminant psittacosis infection in pregnancy.

Chlamydia psittaci is a zoonotic bacterial infection that most commonly causes mild flu-like symptoms in humans. However, in pregnancy, it can present as fulminant psittacosis associated with systemic illness, disseminated intravascular coagulation, renal and hepatic failure. We describe a case of a veterinary nurse in her 30s who presented at 32 weeks' gestation with rapidly progressive multiorgan failure, with positive, C. psittaci serology. Further history revealed that she had delivered a number of dead lambs in the preceding weeks to her illness, highlighting the importance of a thorough social history. C. psittaci should be suspected in the differential as a causative organism for severe pneumonia with multiorgan failure particularly in pregnant women with animal or bird contacts.

Impact of chronic kidney disease on case ascertainment for hospitalised acute myocardial infarction: an English cohort study.

OBJECTIVES: Acute myocardial infarction (AMI) case ascertainment improves for the UK general population using linked health data sets. Because care pathways for people with chronic kidney disease (CKD) change based on disease severity, AMI case ascertainment for these people may differ compared with the general population. We aimed to determine the association between CKD severity and AMI case ascertainment in two secondary care data sets, and the agreement in estimated glomerular filtration rate (eGFR) between the same data sets. METHODS: We used a cohort study design. Primary care records for people with CKD or risk factors for CKD, identified using the National CKD Audit (2015-2017), were linked to the Myocardial Ischaemia National Audit Project (MINAP, 2007-2017) and Hospital Episode Statistics (HES, 2007-2017) secondary care registries. People with an AMI recorded in either MINAP, HES or both were included in the study cohort. CKD status was defined using eGFR, derived from the most recent serum creatinine value recorded in primary care. Moderate-severe CKD was defined as eGFR <60 mL/min/1.73 m2, and mild CKD or at risk of CKD was defined as eGFR ≥60 mL/min/1.73 m2 or eGFR missing. CKD stages were grouped as (1) At risk of CKD and Stages 1-2 (eGFR missing or ≥60 mL/min/1.73 m2), (2) Stage 3a (eGFR 45-59 mL/min/1.73 m2), (3) Stage 3b (eGFR 30-44 mL/min/1.73 m2) and (4) Stages 4-5 (eGFR <30 mL/min/1.73 m2). RESULTS: We identified 6748 AMIs: 23% were recorded in both MINAP and HES, 66% in HES only and 11% in MINAP only. Compared with people at risk of CKD or with mild CKD, AMIs in people with moderate-severe CKD were more likely to be recorded in both MINAP and HES (42% vs 11%, respectively), or MINAP only (22% vs 5%), and less likely to be recorded in HES only (36% vs 84%). People with AMIs recorded in HES only or MINAP only had increased odds of death during hospitalisation compared with those recorded in both (adjusted OR 1.61, 95% CI 1.32 to 1.96 and OR 1.60, 95% CI 1.26 to 2.04, respectively). Agreement between eGFR at AMI admission (MINAP) and in primary care was poor (kappa (K) 0.42, SE 0.012). CONCLUSIONS: AMI case ascertainment is incomplete in both MINAP and HES, and is associated with CKD severity.

Ethical Duties of Nephrologists: When Patients Are Nonadherent to Treatment.

When providing care, nephrologists are subject to various ethical duties. Beyond the Hippocratic notion of doing no harm, nephrologists also have duties to respect their patients' autonomy and dignity, to meet their patients' care goals in the least invasive way, to act impartially, and, ultimately, to do what is (clinically) beneficial for their patients. Juggling these often-conflicting duties can be challenging at the best of times, but can prove especially difficult when patients are not fully adherent to treatment. When a patient's nonadherence begins to cause harm to themselves and/or others, it may be questioned whether discontinuation of care is appropriate. We discuss how nephrologists can meet their ethical duties when faced with nonadherence in patients undergoing hemodialysis, including episodic extreme agitation, poor renal diet, missed hemodialysis sessions, and emergency presentations brought on by nonadherence. Furthermore, we consider the impact of cognitive impairment and provider-family conflict when making care decisions in a nonadherence context, as well as how the coronavirus disease 2019 pandemic might affect responses to nonadherence. Suggestions are provided for ethically informed responses, prioritizing a patient-narrative approach that is attentive to patients' values and preferences, multidisciplinarity, and the use of behavioral contracts and/or technology where appropriate.

Intravenous drug users who require dialysis: causes of renal failure and outcomes.

BACKGROUND: Intravenous drug use is associated with progressive kidney disease of several aetiologies. It is associated with behavioural and lifestyle characteristics that make the provision of renal replacement therapies (RRTs) challenging. We observed that patients who use intravenous drugs [people who inject drugs (PWID)] present late to renal services and struggle to engage with treatment. We describe the experience of a UK centre providing renal services to a mixed city and rural population. METHODS: A review of electronic patient records (2003-16) was performed to identify patients actively using intravenous drugs at the time of dialysis initiation. Descriptive statistics were used to describe aetiology, treatment, complications and prognosis. RESULTS: Twenty-three patients were identified; 15 had a biopsy-proven diagnosis of AA amyloidosis. The median time from presentation to dialysis initiation was 47 days [interquartile range (IQR) 8-147.5]. Hepatitis C infection, venous thromboembolism and mental health disorders were common comorbidities. Eight patients attempted peritoneal dialysis; all failed after a median of 30 days (IQR 21.75-83). One-year survival was 65% (95% confidence interval 42-80), significantly lower than 2013 UK renal registry statistics for incident haemodialysis patients <65 years of age (94.2%). CONCLUSIONS: PWID who develop end-stage kidney disease in our region predominantly have AA amyloidosis. Most present late to renal services and have poor outcomes on all forms of RRT. Rates of transplantation are low. Management challenges include coexisting alcohol and mental health problems, low socio-economic status, contamination of intravenous dialysis access and chaotic lifestyles. Multidisciplinary management with enhanced social support may be beneficial in improving outcomes for this patient group.

Assessing Consensus Between UK Renal Clinicians on Listing for Kidney Transplantation: A Modified Delphi Study.

BACKGROUND: It is well recognized that there is significant variation between centers in access to kidney transplantation. In the absence of high-grade evidence, it is unclear whether variation is due to patient case mix, other center factors, or individual clinician decisions. This study sought consensus between UK clinicians on factors that should influence access to kidney transplantation. METHODS: As part of the Access to Transplantation and Transplant Outcome Measures project, consultant nephrologists and transplant surgeons in 71 centers were invited to participate in a Delphi study involving 2 rounds. During rounds 1 and 2, participants rated their agreement to 29 statements covering 8 topics regarding kidney transplantation. A stakeholder meeting was used to discuss statements of interest after the 2 rounds. RESULTS: In total, 122 nephrologists and 16 transplant surgeons from 45 units participated in rounds 1 and 2. After 2 rounds, 12 of 29 statements reached consensus. Fifty people participated in the stakeholder meeting. After the stakeholder meeting, a further 4 statements reached agreement. Of the 8 topics covered, consensus was reached in 6: use of a transplant protocol, patient age, body mass index, patient compliance with treatment, cardiac workup, and use of multidisciplinary meetings. Consensus was not reached on screening for malignancy and use of peripheral Doppler studies. CONCLUSIONS: The Delphi process identified factors upon which clinicians agreed and areas where consensus could not be achieved. The findings should inform national guidelines to support decision making in the absence of high quality evidence and to guide areas that warrant future research.

A Systematic Review of the Prevalence and Associations of Limited Health Literacy in CKD.

BACKGROUND AND OBJECTIVES: The self-management and decision-making skills required to manage CKD successfully may be diminished in those with low health literacy. A 2012 review identified five papers reporting the prevalence of limited health literacy in CKD, largely from United States dialysis populations. The literature has expanded considerably since. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used systematic review, pooled prevalence analysis, metaregression, and exploration of heterogeneity in studies of patients with CKD (all stages). RESULTS: From 433 studies, 15 new studies met the inclusion criteria and were analyzed together with five studies from the 2012 review. These included 13 cross-sectional surveys, five cohort studies (using baseline data), and two using baseline clinical trial data. Most (19 of 20) were from the United States. In total, 12,324 patients were studied (3529 nondialysis CKD, 5289 dialysis, 2560 transplant, and 946 with unspecified CKD; median =198.5; IQR, 128.5-260 per study). Median prevalence of limited health literacy within studies was 23% (IQR, 16%-33%), and pooled prevalence was 25% (95% confidence interval, 20% to 30%) with significant between-study heterogeneity (I2=97%). Pooled prevalence of limited health literacy was 25% (95% confidence interval, 16% to 33%; I2=97%) among patients with CKD not on dialysis, 27% (95% confidence interval, 19% to 35%; I2=96%) among patients on dialysis, and 14% (95% confidence interval, 7% to 21%; I2=97%) among patients with transplants. A higher proportion of nonwhite participants was associated with increased limited health literacy prevalence (P=0.04), but participant age was not (P=0.40). Within studies, nonwhite ethnicity and low socioeconomic status were consistently and independently associated with limited health literacy. Studies were of low or moderate quality. Within-study participant selection criteria had potential to introduce bias. CONCLUSIONS: Limited health literacy is common in CKD, especially among individuals with low socioeconomic status and nonwhite ethnicity. This has implications for the design of self-management and decision-making initiatives to promote equity of care and improve quality. Lower prevalence among patients with transplants may reflect selection of patients with higher health literacy for transplantation either because of less comorbidity in this group or as a direct effect of health literacy on access to transplantation.