BackgroundIn patients with end stage kidney disease (ESKD) on dialysis, treatment non-adherence is common and results in poor health outcomes. However, the clinical benefits of interventions to improve adherence in dialysis patients are difficult to evaluate since trialled interventions and reported outcomes are highly diverse/ heterogeneous. This review summarizes existing literature on randomized controlled trials (RCTs) evaluating adherence interventions in ESKD patients focusing on the intervention category, outcome efficacy and persistence of benefit beyond the intervention.MethodsWe performed electronic database searches in Medline, Embase & Cochrane CENTRAL upto 1st July 2018 for RCTs evaluating interventions to improve diet, fluid, medication or dialysis adherence in ESKD patients. Study characteristics including category of interventions, outcomes, efficacy and follow-up were assessed. Meta-analysis was used to compute pooled estimates of the effects on the commonest reported outcome measures.ResultsFrom 1311 citations, we included 36 RCTs (13 cluster-randomized trials), recruiting a total of 3510 dialysis patients (mean age 55.1 ± 5.8 years, males 58.1%). Overall risk of bias was ‘high’ for 24 and of ‘some concern’ for 12 studies. Most interventions (33 trials, 92%) addressed patient related factors, and included educational/cognitive (N = 11), behavioural / counselling (N = 4), psychological/affective (N = 4) interventions or a combination (N = 14) of the above. A majority of (28/36) RCTs showed improvement in some reported outcomes. Surrogate measures like changes in phosphate (N = 19) and inter-dialytic weight gain (N = 15) were the most common reported outcomes and both showed significant improvement in the meta-analysis. Sixteen trials reported follow-up (1–12 months) beyond intervention and the benefits waned or were absent in nine trials within 12 months post-intervention.ConclusionsInterventions to improve treatment adherence result in modest short-term benefits in surrogate outcome measures in dialysis patients, but significant improvements in trial design and outcome reporting are warranted to identify strategies that would achieve meaningful and sustainable clinical benefits.LimitationsPoor methodological quality of trials. Frequent use of surrogate outcomes measures. Low certainly of evidence.

The latest Caring for Australians with Renal Impairment (CARI) guideline detailing renal transplant care, developed as a local modification of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines.

BackgroundMedication non-adherence is common among renal dialysis patients. High degrees of non-adherence in randomized controlled trials (RCTs) can lead to failure to detect a true treatment effect. Cardio-protective pharmacological interventions have shown no consistent benefit in RCTs involving dialysis patients. Whether non-adherence contributes to this lack of efficacy is unknown. We aimed to investigate how medication adherence and drug discontinuation were assessed, reported and addressed in RCTs, evaluating cardiovascular or mortality outcomes in dialysis patients.MethodsElectronic database searches were performed in MEDLINE, EMBASE & Cochrane CENTRAL for RCTs published between 2005–2015, evaluating self-administered medications, in adult dialysis patients, which reported clinical cardiovascular or mortality endpoints, as primary or secondary outcomes. Study characteristics, outcomes, methods of measuring and reporting adherence, and data on study drug discontinuation were analyzed.ResultsOf the 642 RCTs in dialysis patients, 22 trials (12 placebo controlled), which included 19,322 patients, were eligible. The trialed pharmacological interventions included anti-hypertensives, phosphate binders, lipid-lowering therapy, cardio-vascular medications, homocysteine lowering therapy, fish oil and calcimimetics. Medication adherence was reported in five trials with a mean of 81% (range: 65–92%) in the intervention arm and 84.5% (range: 82–87%) in the control arm. All the trials that reported adherence yielded negative study outcomes for the intervention. Study-drug discontinuation was reported in 21 trials (mean 33.2%; 95% CI, 22.0 to 44.5, in intervention and 28.8%; 95% CI, 16.8 to 40.8, in control). Trials with more than 20% study drug discontinuation, more often yielded negative study outcomes (p = 0.018). Non-adherence was included as a contributor to drug discontinuation in some studies, but the causes of discontinuation were not reported consistently between studies, and non-adherence was listed under different categories, thereby potentiating the misclassification of adherence.ConclusionsReporting of medication adherence and study-drug discontinuation in RCTs investigating cardiovascular or mortality endpoints in dialysis patients are inconsistent, making it difficult to compare studies and evaluate their impact on outcomes. Recommendations for consistent reporting of non-adherence and causes of drug discontinuation in RCTs will therefore help to assess their impact on clinical outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0449-1) contains supplementary material, which is available to authorized users.

Patients with end-stage kidney disease (ESKD) who are on dialysis have to make significant adaptions to their life, accepting dietary and fluid restrictions, rigorous medication regimens, and complex renal replacement therapy routines. 1 Patients also have to cope with the multiple self-management challenges related to complications and comorbidities associated with ESKD, diminished independence, loss of time spent on dialysis, travel limitations, and financial burden. 2 Adherence to the demanding physical and behavioral adaptions are central to the effective delivery of ESKD care, 1 yet low adherence to all domains of ESKD therapy (diet, fluid, medication, and dialysis) is common. 3-5 Nonadherence to treatment is associated with increased risk of mortality, hospitalizations, complications, and poor quality of life in dialysis patients. 6-8 Given the high baseline risk of adverse outcomes experienced by ESKD patients, it is instinctive to examine whether strategies to promote treatment adherence could improve clinical outcomes. In the context of long-term therapies of chronic diseases, it has been suggested that a more significant impact on the population health outcomes could result from the introduction of effective adherence interventions than any improvement in specific medical treatments. 9 Several randomized and nonrandomized trials have examined the effectiveness of diverse adherence intervention strategies on the direct or indirect markers of adherence in dialysis patients. 10-12 In this review, we plan to explore the nature of these

images in clinical medicineT h e n e w e ng l a n d j o u r na l o f m e dic i n e n engl j med 358;4 www.nejm.org january 24, 2008 e A 31-year-old woman with bilateral nephrectomy due to bleeding angiomyolipomas from tuberous sclerosis received a kidney transplant with good early graft function. Irreversible, oliguric renal allograft failure soon developed from widespread deposition of calcium oxalate crystals, involving 30% of tubules (Panels A and B, hematoxylin and eosin). The patient had abundant oxalate deposits in the skin (resembling tophaceous gout but without hyperuricemia) (Panels C and D); polarizing microscopy confirmed the presence of oxalate in a specimen from these deposits (Panel E). She had a plasma oxalate level of 62 µmol per liter (normal value, <2) and a history of self-medication with vitamin C (2 g per day for 3 years while on dialysis). A diagnosis of secondary oxalosis was established. Excess ascorbate is normally excreted harmlessly in the urine, but in patients with renal failure, it is retained and converted to insoluble oxalate and can accumulate in multiple organs. High-dose vitamin C therapy should be avoided in patients with renal failure.