Susan P. Y. Wong, MD, MS; Tamara Rubenzik, MD; Leila Zelnick, PhD; et alSara N. Davison, MD; Diana Louden, MLib; Taryn Oestreich, MPH, MCHES; Ann L. Jennerich, MD, MS Author AffiliationsArticle Information JAMA Netw Open. 2022;5(3):e222255. doi: 10.1001/jamanetworkopen.2022.2255editorial comment icon Editorial Comment
Key Points
Question What are the long-term outcomes of patients with advanced kidney disease who do not pursue maintenance dialysis?
Findings In this systematic review of 41 cohort studies comprising 5102 adults with advanced kidney disease who did not pursue dialysis, limited available evidence suggests that many patients survived several years and experienced sustained quality of life until late in their illness course. However, use of acute care services was common, and there was substantial disparity in access to supportive care near the end of life across cohorts.
Meaning These findings suggest that advances in research and health care delivery are needed to optimize outcomes among patients who are not treated with dialysis.Abstract
Importance An understanding of the long-term outcomes of patients with advanced chronic kidney disease not treated with maintenance dialysis is needed to improve shared decision-making and care practices for this population.
Objective To evaluate survival, use of health care resources, changes in quality of life, and end-of-life care of patients with advanced kidney disease who forgo dialysis.
Evidence Review MEDLINE, Embase (Excerpta Medica Database), and CINAHL (Cumulative Index of Nursing and Allied Health Literature) were searched from inception through December 3, 2021, for all English language longitudinal studies of adults in whom there was an explicit decision not to pursue maintenance dialysis. Two investigators independently reviewed all studies and selected those reporting survival, use of health care resources, changes in quality of life, or end-of-life care during follow-up. Studies of patients who initiated and then discontinued maintenance dialysis and patients in whom it was not clear that there was an explicit decision to forgo dialysis were excluded. One author abstracted all study data, of which 12% was independently adjudicated by a second author (<1% error rate).
Findings Forty-one cohort studies comprising 5102 patients (range, 11-812 patients) were included in this systematic review (5%-99% men; mean age range, 60-87 years). Substantial heterogeneity in study designs and measures used to report outcomes limited comparability across studies. Median survival of cohorts ranged from 1 to 41 months as measured from a baseline mean estimated glomerular filtration rate ranging from 7 to 19 mL/min/1.73 m2. Patients generally experienced 1 to 2 hospital admissions, 6 to 16 in-hospital days, 7 to 8 clinic visits, and 2 emergency department visits per person-year. During an observation period of 8 to 24 months, mental well-being improved, and physical well-being and overall quality of life were largely stable until late in the illness course. Among patients who died during follow-up, 20% to 76% had enrolled in hospice, 27% to 68% died in a hospital setting and 12% to 71% died at home; 57% to 76% were hospitalized, and 4% to 47% received an invasive procedure during the final month of life.
Conclusions and Relevance Many patients who do not pursue dialysis survived several years and experienced sustained quality of life until late in the illness course. Nonetheless, use of acute care services was common and intensity of end-of-life care highly variable across cohorts. These findings suggest that consistent approaches to the study of conservative kidney management are needed to enhance the generalizability of findings and develop models of care that optimize outcomes among conservatively managed patients.Introduction
Conservative kidney management is a planned, holistic, and person-centered approach to care for patients with stages 4 to 5 advanced chronic kidney disease (CKD) who do not wish to pursue maintenance dialysis. It includes “interventions to delay progression of kidney disease and minimize risk of adverse events or complications; shared decision making; active symptom management; detailed communication including advance care planning; psychological support; social and family support; [and] cultural and spiritual domains of care.”Desire for a more conservative approach to treating patients with advanced CKD has galvanized efforts around the world to develop the evidence base to support the care of these patients.
Toward this end, several systematic reviews and meta-analyses have been conducted comparing outcomes between patients treated with dialysis and those treated conservatively. They show that dialysis is associated with longer survival compared with conservative approaches but that these survival advantages are attenuated with increasing age and comorbidity.7 Patients treated conservatively also spend less time in the hospital and die there less often compared with patients receiving dialysis,6 and early changes in quality of life appear similar between treatment groups.7,8
Although the findings of these prior studies help to inform shared decision-making about treatment of advanced CKD, they are restricted to studies comparing groups treated with dialysis and those treated conservatively. As a result, prior systematic reviews and meta-analyses reflect only a small fraction of the patients who forgo dialysis described in the literature and provide only a limited view of the clinical course of patients to guide ongoing management and anticipatory guidance to patients who have already decided that they will not pursue dialysis. To support a deeper understanding of the long-term outcomes of patients with advanced CKD who do not pursue dialysis, we performed a systematic review of longitudinal studies reporting survival, use of health care resources, quality of life, and end-of-life care of patients with advanced CKD who did not pursue dialysis.MethodsData Sources
This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and is registered in PROSPERO (CRD42020156086). An experienced medical librarian (D. L.) performed a comprehensive search of MEDLINE, Embase (Excerpta Medica Database), and CINAHL (Cumulative Index of Nursing and Allied Health Literature) for all English language publications pertaining to patients with advanced CKD who did not pursue maintenance dialysis from inception through January 27, 2020, with a search update through December 3, 2021. We used database-specific subject heading terms and a range of text words (conservative, non-dialysis, palliative, supportive, and medical management) previously used in the literature to describe this approach to care9 (eMethods in the Supplement) to locate all potentially relevant articles.Study Selection
We included all longitudinal studies that enrolled patients 18 years or older with advanced CKD in whom an explicit decision was made not to pursue maintenance dialysis. We selected studies reporting survival, use of health care resources (ie, all-cause hospitalization and in-hospital days, emergency department visits, and clinic visits), changes in quality of life, or end-of-life care (ie, hospice enrollment, place of death, and hospitalization and invasive procedures during the final month of life) during follow-up and a baseline measure of estimated glomerular filtration rate (eGFR) from which outcomes were measured. We excluded studies of patients who initiated and then discontinued maintenance dialysis, those that did not include information on baseline eGFR, and those of patients in whom it was unclear that an explicit decision to forgo dialysis was made. Case reports, qualitative studies, and the gray literature were excluded.
The results of search queries were imported into Covidence (Veritas Health Innovation Ltd) for screening and study selection. Two authors (S.P.Y.W. and T.R.) independently screened titles and abstracts and reviewed full-text articles to determine study eligibility. Disagreements were resolved through consensus by another author (L.Z. or A.L.J.).Data Extraction
Data extraction was performed by 1 reviewer (S.P.Y.W.) using a standardized data extraction form. For studies comparing multiple treatment groups, we collected information only on groups of patients in whom there was a decision not to pursue dialysis from each study. From each study, we collected information on study design, year of publication, country of origin, sample size, study inclusion criteria, clinical setting, and whether patients were cared for in a dedicated care pathway for those not planning to be treated with dialysis or in usual nephrology care settings. Because nearly all the studies did not report information on the race and ethnicity of its study participants, this information was not collected. We recorded baseline age, sex, eGFR, and distribution of comorbidities of study participants. We recorded measures of survival, use of health care resources, and changes in quality of life. We also collected information on patterns of end-of-life care for study participants who died during study follow-up. We contacted study authors by email to obtain any missing data. One investigator (T.O.) independently reviewed the full text of 5 randomly selected studies (12%) to confirm accuracy of data extraction (<1% errors found).Data Synthesis and Analysis
Owing to the heterogeneity in study designs, patient populations, approaches to care, and measures used across studies, we opted not to meta-analyze collected data; we herein provide a narrative synthesis of reported outcomes. For our primary outcome, we evaluated the median (IQR) survival of patients and the baseline mean eGFR from which survival was measured. For studies reporting only a threshold eGFR value (eg, <20 mL/min/1.73 m2), the closest value (ie, 19 mL/min/1.73 m2) was used in place of mean values. Median eGFR values were used in place of mean values when the latter were not reported. For studies that did not report median and/or IQR measures of survival, these values were abstracted from reported Kaplan-Meier survival curves, estimated using reported mortality rates assuming an exponential distribution, and/or calculated using reported means of survival and their SDs.1 Studies that had insufficient information to estimate median survival or were limited to only patients who died during follow-up were not included in survival analyses. Preplanned subgroup assessment of survival by study region (Asia, Australia, continental Europe, North America, and the UK), year of study publication (before 2010, 2010-2015, and after 2015), mean age of the study cohort (70-79 and ≥80 years), and approach to care (as part of general nephrology care vs a dedicated care pathway) were also performed.
As secondary outcomes, we assessed use of health care resources, trajectories of quality of life, and end-of-life care of patients. Evaluation of these secondary measures by study region, publication date, age of cohort, and approach to care could not be performed owing to the low number of studies in each category.ResultsStudy Characteristics
The literature search yielded 5653 references, of which the full text was reviewed in 132 (Figure 1). A total of 41 cohort studies comprising 5102 patients (study size range, 11-812 patients; 5%-99% men; mean age range, 60-87 years) were included in this review (eTable 1 in the Supplement).1 No clinical trials were identified in our search.
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