ObjectiveTo systematically identify and describe self-management interventions for adult patients with chronic kidney disease (CKD).SettingCommunity-based.ParticipantsAdults with CKD stages 1–5 (not requiring kidney replacement therapy).InterventionsSelf-management strategies for adults with CKD.Primary and secondary outcome measuresUsing a scoping review, electronic databases and grey literature were searched in October 2016 to identify self-management interventions for adults with CKD stages 1–5 (not requiring kidney replacement therapy). Randomised controlled trials (RCTs), non-RCTs, qualitative and mixed method studies were included and study selection and data extraction were independently performed by two reviewers. Outcomes included behaviours, cognitions, physiological measures, symptoms, health status and healthcare.ResultsFifty studies (19 RCTs, 7 quasi-experimental, 5 observational, 13 pre-post intervention, 1 mixed method and 5 qualitative) reporting 45 interventions were included. The most common intervention topic was diet/nutrition and interventions were regularly delivered face to face. Interventions were administered by a variety of providers, with nursing professionals the most common health professional group. Cognitions (ie, changes in general CKD knowledge, perceived self-management and motivation) were the most frequently reported outcome domain that showed improvement. Less than 1% of the interventions were co-developed with patients and 20% were based on a theory or framework.ConclusionsThere was a wide range of self-management interventions with considerable variability in outcomes for adults with CKD. Major gaps in the literature include lack of patient engagement in the design of the interventions, with the majority of interventions not applying a behavioural change theory to inform their development. This work highlights the need to involve patients to co-developed and evaluate a self-management intervention based on sound theories and clinical evidence.
Defects in protein folding and the proteasomal pathway have been linked with many neurodegenerative diseases. PLIC-1 (protein linking IAP to the cytoskeleton) is a ubiquitin-like protein that binds to the ubiquitin-interacting motif (UIM) of the proteasomal subunit S5a. Here, we show that PLIC-1 also binds to the UIM proteins ataxin 3-a deubiquitinating enzymeHSJ1a-a co-chaperone-and EPS15 (epidermal growth factor substrate 15)-an endocytic protein. Using a polyglutamine (polyQ) disease model, we found that both endogenous PLIC-1 and EPS15 localize to perinuclear aggresomes, and that polyQ enhances their in vivo interaction. We show that knockdown of PLIC-1 and EPS15 by RNA interference reduces aggresome formation. In addition, PLIC-1 DUBL functions as a dominantnegative mutant, blocking both polyQ transport to aggresomes and the association of EPS15 with dispersed aggregates. We also show that PLIC-1 is upregulated by arsenite-induced protein misfolding. These results indicate a role for PLIC-1 in the protein aggregation-stress pathway, and we propose a novel function for the ubiquitin-like (UBL) domain-by means of UBL-UIM interactions-in transport to aggresomes.
IMPORTANCE Using the same level of estimated glomerular filtration rate (eGFR) to define chronic kidney disease (CKD) regardless of patient age may classify many elderly people with a normal physiological age-related eGFR decline as having a disease. OBJECTIVE To compare the outcomes associated with CKD as defined by a fixed vs an age-adapted eGFR threshold. DESIGN, SETTING, AND PARTICIPANTSThis population-based cohort study was conducted in Alberta, Canada and used linked administrative and laboratory data from adults with incident CKD from April 1, 2009, to March 31, 2017, defined by a sustained reduction in eGFR for longer than 3 months below a fixed or an age-adapted eGFR threshold. Non-CKD controls were defined as being 65 years or older with a sustained eGFR of 60 to 89 mL/min/1.73 m 2 for longer than 3 months and normal/mild albuminuria. The follow-up ended on March 31, 2019. The data were analyzed from February to April 2020.EXPOSURES A fixed eGFR threshold of 60 vs thresholds of 75, 60, and 45 mL/min/1.73 m 2 for age younger than 40, 40 to 64, and 65 years or older, respectively. MAIN OUTCOMES AND MEASURESCompeting risks of kidney failure (kidney replacement initiation or sustained eGFR <15 mL/min/1.73 m 2 for >3 months) and death without kidney failure. RESULTSThe fixed and age-adapted CKD cohorts included 127 132 (69 546 women [54.7%], 57 586 men [45.3%]) and 81 209 adults (44 582 women [54.9%], 36 627 men [45.1%]), respectively (537 vs 343 new cases per 100 000 person-years). The fixed-threshold cohort had lower risks of kidney failure (1.7% vs 3.0% at 5 years) and death (21.9% vs 25.4%) than the age-adapted cohort. A total of 53 906 adults were included in both cohorts. Of the individuals included in the fixed-threshold cohort only (n = 72 703), 54 342 (75%) were 65 years or older and had baseline eGFR of 45 to 59 mL/min/1.73 m 2 with normal/mild albuminuria. The 5-year risks of kidney failure and death among these elderly people were similar to those of non-CKD controls, with a risk of kidney failure of 0.12% or less in both groups across all age categories and a risk of death at 69, 122, 279, and 935 times higher than the risk of kidney failure for 65 to 69, 70 to 74, 75 to 79, and 80 years or older, respectively.CONCLUSIONS AND RELEVANCE This cohort study of adults with CKD suggests that the current criteria for CKD that use the same eGFR threshold for all ages may result in overestimation of the CKD burden in an aging population, overdiagnosis, and unnecessary interventions in many elderly people who have age-related loss of eGFR.
We identified the top 10 research priorities for patients with CKD that can be used to guide researchers, as well as inform funders of health-care research.
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