Acute kidney injury increases risk of kidney stones-a retrospective propensity score matched cohort study.

BACKGROUND: Acute kidney injury (AKI) is common. An episode of AKI may modify the risk of developing kidney stones by potential long-term effects on urine composition. We aimed to investigate the association between AKI and the risk of kidney stone presentations. METHODS: The retrospective cohort study used patient data (1 January 2008-31 December 2017), from an Australian Local Health District, which included AKI diagnosis, demographics, comorbidities and kidney stone admissions. Time-varying Cox proportional hazards and propensity-matched analysis were used to determine the impact of AKI on the risk of kidney stones. To address possible population inhomogeneity in comparisons between no AKI and hospitalized AKI, sub-group analysis was done comparing inpatient and outpatient AKI versus no AKI, to assess consistency of association with future stones. Sensitivity analysis was undertaken to capture the impact of a known AKI status and AKI severity. RESULTS: Out of 137 635 patients, 23 001 (17%) had an AKI diagnosis and 2295 (2%) had kidney stone presentations. In the unadjusted analysis, AKI was associated with kidney stones, with AKI used as a time-varying exposure, [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.16-1.50)]. Both inpatient-AKI (HR 1.19, 95% CI 1.01-1.39) and outpatient-AKI (HR 1.59, 95% CI 1.30-1.94) were significantly associated with future stones compared to no AKI subjects. This association persisted in the adjusted analysis (HR 1.45, 95% CI 1.26-1.66), propensity-matched dataset (HR 1.67, 95% CI 1.40-1.99) and sensitivity analysis. There was a dose-response relationship with higher stages of AKI being associated with a greater risk of kidney stones. CONCLUSIONS: In a large cohort of patients, AKI is associated with a greater risk of kidney stones, which increases with higher stages of AKI. This association should be examined in other cohorts and populations for verification.

Elevated renal resistive index is independently predicted by older age, but not by the presence of chronic kidney disease: a retrospective cohort study.

BACKGROUND: Renal resistive index (RRI), which reflects intrarenal arterial impedance, is routinely measured when undertaking renal Doppler ultrasonography (RDU). Increased RRI has been suggested to reflect renal parenchymal disease and imply risk of kidney disease progression. But this has been disputed and extra-renal haemodynamic factors rather than intra-renal factors have been proposed to determine RRI. AIMS: To investigate the relationship between elevated RRI and presence of chronic kidney disease (CKD), and examine whether elevated RRI at baseline is associated with decline in estimated glomerular filtration rate (eGFR) on follow up. METHODS: This retrospective observational study examined the association of elevated RRI (>0.7) with the presence of CKD (eGFR < 60 mL/min for >3 months), demographic and clinical factors in multivariable models. We also examined the effect of elevated RRI on eGFR decline on follow up using mixed models. RESULTS: Of the 346 patients undergoing RDU (median age 69.7 years; 46.2% male), 180 had elevated RRI. There was a strong inverse association between RRI and eGFR at baseline, 1 and 2 years (rho = -0.53, -0.51, -0.53, all P < 001). Elevated RRI was independently predicted by older age (odds ratio 3.29; 95% confidence interval 2.25-4.8; P < 0.001) and diabetes (odds ratio 2.65; 95% confidence interval 1.21-5.80; P = 0.015), but not CKD using multivariate logistic regression. Decline of eGFR was not different between RRI categories on follow up. CONCLUSION: Elevated RRI was predicted by older age and diabetes, but not by the presence of CKD. Baseline RRI was not associated with eGFR decline.

Breaking the adherence barriers: Strategies to improve treatment adherence in dialysis patients.

Nonadherence to therapy (dietary/fluid restrictions, medications, and dialysis treatment), is common in patients with end-stage kidney disease (ESKD) undergoing dialysis. It is associated with a higher risk of mortality and adverse outcomes. Clinical trials evaluating adherence improvement interventions have largely addressed patient-related factors by employing educational/cognitive, counselling/behavioral, psychological strategies, or combinations thereof. A major barrier to progress in addressing ESKD-related adherence is the difficulty in comparing these trials due to the highly diverse nature of interventions and adherence outcomes. Surrogate outcomes like changes in inter-dialysis weight gain or phosphate levels are frequently used without adjusting for confounders, with the potential for biased efficacy estimates. A majority of trials reported improvement in some adherence measures, but some of the same studies showed no improvement in other adherence markers, questioning the validity of outcome measurement. Among the interventions, cognitive/behavioral strategies, combination strategies, and individually delivered interventions may have some advantages. Relapse of nonadherence, which is common on follow-up, should be managed to sustain long-term adherence. Technology-based interventions hold great future potential for addressing ESKD nonadherence. Streamlining intervention strategies and standardizing outcome measures in future clinical trials will provide reliable guidance to manage nonadherence effectively, which may improve clinical outcomes in dialysis patients.

Incidence and factors associated with geographical relocation in patients receiving renal replacement therapy.

BACKGROUND: Renal replacement therapy (RRT) places a burden on patients, and geographical relocation for easier access to healthcare facilities is a necessity for some. Incidence and factors associated with relocation has not been comprehensively examined at a national level. We aimed to determine proportion, incidence, characteristics of RRT patients who relocate and relocation rate by remoteness of residence and dialysis modality. METHODS: Retrospective cohort analysis using Australian and New Zealand Dialysis and Transplant Registry to examine RRT patients in Australia from January 2005 to December 2015. Relocation incidence was calculated for remoteness of residence and RRT modality as rate per 100 patient years. Factors associated with relocation were examined using competing risk regression models with death as a competing event. RESULTS: Of 24,676 incident patients on RRT, 5888 (23.9%) relocated with a median time of 1.6 years [IQR 0.7-3.4] years. Relocation incidence was 7.9 per 100 patient years and increased from major cities to very remote regions (7.2 to 48.8 per 100 patient years respectively, p < 0.001). Remoteness of residence was associated with geographical relocation in competing risk analysis especially in remote (SHR 1.20, 95%CI 1.01, 1.41 p = 0.034) and very remote regions (SHR 3.51 95% 3.05, 4.04 p < 0.001). Aboriginal or Torres Strait Islander ethnicity, compared to Caucasian, was independently associated with relocation (SHR 1.18, 95% CI 1.06,1.31, p = 0.002) while transplant patients were less likely to relocate compared to haemodialysis patients (HR 0.37, 95%CI 0.34, 0.39, p < 0.001). CONCLUSIONS: Relocation in patients receiving RRT is associated with remoteness of residence, RRT modality and ethnicity. Reasons for relocation and its impact on patient wellbeing and outcome should be further explored.

Medication adherence in randomized controlled trials evaluating cardiovascular or mortality outcomes in dialysis patients: A systematic review.

BACKGROUND: Medication 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. METHODS: Electronic 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. RESULTS: Of 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. CONCLUSIONS: Reporting 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.

Survival of Indigenous Australians receiving renal replacement therapy: closing the gap?

OBJECTIVES: To compare mortality rates for Indigenous and non-Indigenous Australians commencing renal replacement therapy (RRT) over time and by categories of remoteness of place of residence. DESIGN, SETTING AND PARTICIPANTS: An observational cohort study of Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data on Indigenous and non-Indigenous Australians registered with ANZDATA who commenced RRT from 1 January 1995 to 31 December 2009 and were followed until 31 December 2011. MAIN OUTCOME MEASURES: Five-year all-cause mortality for Indigenous and non-Indigenous patients in three cohorts (1995-1999, 2000-2004 and 2005-2009) and five remoteness (of place of residence) categories. RESULTS: Indigenous patients were younger, more likely to have diabetes, be referred late and be from a more remote area than non-Indigenous patients. Age and comorbid conditions increased with successive cohorts for both groups. Unadjusted analysis (using the log-rank test) showed an increased risk of death for Indigenous patients in the 1995-1999 (P = 0.02) and 2000-2004 (P = 0.03) cohorts, but not for the 2005-2009 cohort (P = 0.7). However, a Cox proportional hazards model adjusted for covariates (age, sex, late referral and comorbid conditions [diabetes, coronary artery disease, peripheral vascular disease, cerebrovascular disease, lung disease], and body mass index < 18.5 kg/m(2) and > 30 kg/m(2)) showed the following Indigenous:non-Indigenous hazard ratios (with 95% CIs) for major capital cities: 1995-1999, 1.47 (1.21-1.79); 2000-2004, 1.35 (1.12-1.63); and 2005-2009, 1.37 (1.14-1.66). CONCLUSIONS: Although unadjusted analysis suggests that the survival gap between Indigenous and non-Indigenous patients receiving RRT has closed, there remains a significant disparity in survival after adjusting for the variables considered in our study.

Associations between acute kidney injury and bone fractures: a retrospective cohort study.

Background: Acute kidney injury (AKI) is common. An AKI episode may disrupt the normal mineral bone balance maintained by normal kidney function, thereby modifying the risk of developing bone fractures. However, it remains unclear whether an AKI episode is associated with the risk of bone fractures. Methods: Using retrospective cohort study from an Australian Local Health District, we examined the association between an AKI episode and bone fractures using patient data between 2008 and 2017. Time-varying Cox proportional hazards and propensity-matched analysis were used to examine the association. Sensitivity analyses were undertaken to capture the impact of confirmed AKI status and AKI severity. Results: Of 123 426 included patients, 14 549 (12%) had an AKI episode and 12 505 (10%) had a bone fracture. In the unadjusted analysis, AKI was associated with bone fractures [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.88-2.11]. This association persisted in the adjusted analysis (HR 1.50, 95% CI 1.41-1.59) and propensity-matched dataset (HR 1.71, 95% CI 1.59-1.83). The sensitivity analysis yielded similar results, with the AKI patients having a higher risk of fractures compared with no AKI patients in the adjusted analysis (HR 1.34, 95% CI 1.25-1.43) and in the propensity-matched dataset (HR 1.44, 95% CI 1.33-1.55). Similar results were seen in the subsidiary sensitivity analysis excluding patients without baseline creatinine. We did not find an increased risk of bone fractures with increasing AKI severity (P = .7). Interaction tests demonstrated a significant association between sex and age category with AKI status and fractures, but not CKD stage or osteoporosis. Conclusions: AKI is associated with a greater risk of bone fractures. This could have implications for managing and screening for bone disease in patients post-AKI episode. This association should be examined in other cohorts and populations for verification.

Exploring the Agreement Between Self-Reported Medication Adherence and Pharmacy Refill-Based Measures in Patients with Kidney Disease.

Aim: To assess the quantitative and categorical agreement between two methods of measuring medication adherence: pharmacy refill-based medication possession rates and self-reported medication adherence scale. Background: Categorisation of adherence metrics using empirical cut-off scores can lead to misclassification, which can be overcome by expressing adherence as a continuous variable. Pharmacy refill-based adherence can be reported as actual rates, but the validity of expressing self-reported medication adherence scores as a continuous variable to reflect adherence is unknown and its quantitative agreement with refill-based adherence rates untested. Methods: Patients with kidney disease, including dialysis patients, from Illawarra Shoalhaven region of New South Wales, Australia were recruited between January 2015 and June 2016 to this cross-sectional study. Medication adherence was assessed using the self-reported Morisky Medication Adherence Scale (MMAS) and two pharmacy refill-based measures, Medication Possession Ratio (MPR) and Proportion of Days Covered (PDC) for antihypertensives and cardiometabolic drugs. Categorical and quantitative agreement between self-reported adherence and pharmacy refill-based adherence were assessed using tests of trend, analysis of covariance (ANCOVA), Cohen's kappa and Bland-Altman analysis. Results: We recruited 113 patients. There was a significant declining trend of MPR (p < 0.001) and PDC (<0.001 for antihypertensives, p = 0.004 for cardiometabolic) scores among categories with worsening MMAS adherence. Adjusted ANCOVA showed significant association between self-report and pharmacy refill-based adherence (p < 0.001). Weighted Cohen's kappa statistics showed fair agreement between the self-report and pharmacy refill-based categories. Bland-Altman's analysis showed less than 5% of cases were outside the limits of agreement (-0.36 to 0.27) and the bias for MMAS was negative (-0.05 to -0.09), indicating MMAS did not overestimate adherence. Conclusion: There is modest agreement between pharmacy refill-based measures and self-report MMAS measures when assessed categorically or quantitatively. Assessing adherence as a continuous variable should be considered to overcome the challenges associated with categorization of adherence based on arbitrary thresholds.

Association of Peritonitis With Cardiovascular Mortality Over Time in the Peritoneal Dialysis Population: An Australia and New Zealand Dialysis and Transplant Registry Study.

Introduction: Though peritonitis is associated with increased mortality in patients receiving peritoneal dialysis (PD), its association with cardiovascular mortality remains uncertain. Methods: The study participants included adult patients (≥18 years old) commencing PD in Australia (from October 2003 to December 2019) using the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Association between peritonitis and cardiovascular mortality was evaluated using Cox proportional hazards analysis and competing risks analysis. Associations between peritonitis rates between different eras and cardiovascular mortality were also compared using Jointpoint regression model to determine the time point when a significant change in peritonitis trend occurred to define the era for cardiovascular mortality. Subgroup analysis dividing the groups into 0, 1 and ≥2 episodes of peritonitis and sensitivity analysis censoring at 90 days post-transfer to hemodialysis (HD) were performed. Results: The study included 9699 incident PD patients. The overall peritonitis rate was 0.37 episodes per patient-year and declined by 4.7% (95% confidence interval [CI] 3.6-5.8%) during the study period. Peritonitis was associated with increased cardiovascular mortality risk (subdistribution hazard ratio [SHR] 1.53, 95% CI 1.39-1.69, P < 0.001) with increasing peritonitis episodes associated with higher risk (1 episode of peritonitis SHR 1.41, 95%CI 1.24-1.61; ≥2 episodes of peritonitis SHR 1.69, 95% CI 1.47-1.93, P < 0.001). Patients who commenced PD between 2012 and 2019 had a lower risk of cardiovascular mortality (SHR 0.60, 95% CI 0.50-0.72, P < 0.001), compared to patients who commenced between 2003 and 2011. Results were consistent in the sensitivity analysis. Conclusion: Peritonitis is independently associated with an increased risk of cardiovascular mortality, and the association is episode-dependent. Prevention and adequate treatment of PD peritonitis may improve cardiovascular outcomes among patients receiving PD.

Systematic Review and Meta-analysis of Herpes Zoster Vaccine in Patients With CKD.

INTRODUCTION: Chronic kidney disease (CKD) is a risk factor for herpes zoster (HZ) infection. Few studies have examined HZ vaccine (HZV) in this population. We conducted a systematic review and meta-analysis investigating the efficacy and safety of HZV in patients with renal disease (CKD, dialysis, and transplant). METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases (up to May 2020) were searched for randomized controlled trials and nonrandomized controlled studies evaluating HZV in patients with CKD for effectiveness and adverse event risks. Studies without a control group (placebo or no vaccine) were excluded. Extraction of prespecified data and risk of bias assessments using the Newcastle-Ottawa scale for cohort studies and the Cochrane Risk of Bias Tool for randomized controlled trials were done by 3 authors. Random-effects meta-analysis was used to generate pooled treatment effects and 95% confidence intervals. RESULTS: Included were 404,561 individuals from 8 studies (3 randomized controlled trials and 5 nonrandomized). All 8 studies examined HZ as an outcome, with 3 reporting adverse events. Risk of HZ was lower in patients who received HZV compared with controls (hazard ratio, 0.55; 95% confidence interval, 0.37-0.82; P < 0.01); however, heterogeneity was high (I 2 = 88%, P < 0.01). There was no significant difference in adverse events associated with HZV (hazard ratio, 1.03; 95% confidence interval, 0.54-1.28; P = 0.8). CONCLUSIONS: HZV compared with control significantly lowers the risk of HZ without an increase in adverse events in CKD patients. However, significant heterogeneity was present. HZV should be actively considered in CKD patients because the prevalence of HZ is higher in this population.

Changes in measures of cognitive function in patients with end-stage kidney disease on dialysis and the effect of dialysis vintage: A longitudinal cohort study.

INTRODUCTION: Prevalence of cognitive impairment increases with worsening severity of chronic kidney disease (CKD) and majority of end-stage kidney disease (ESKD) patients on dialysis have cognitive impairment. Trends of cognitive function (CF) in this population are less well known with published studies reporting conflicting results. METHODS: We assessed CF in a cohort of non-dialysis CKD and ESKD patients undergoing dialysis using modified mini-mental state examination (3MS), trail-making test (TMT-A & B) scores and Stroop task, and evaluated demographics, comorbidities and depression using Beck depression inventory at baseline. We repeated tests of CF and depression ≥ 1-year after baseline in both groups and compared change scores in CF and depression between ESKD/ CKD sub-groups. Among ESKD patients we compared change scores between patients with dialysis vintage of <1-year and >1-year. Analysis of covariance was used to adjust for the effect of age on these change scores. RESULTS: At baseline (N = 211), compared to CKD (N = 108), ESKD (N = 103) patients had significantly worse CF based on 3MS and TMT-A & B scores, and depression scores. On follow-up (N = 160) 3MS scores, especially the memory subscale significantly improved in ESKD, but worsened in CKD, with no significant changes in TMT A /TMT-B, or depression scores after adjusting for age. Among ESKD patients, 3MS, especially memory subscale improved in patients with dialysis vintage <1-year compared to >1-year. The 51 patients who discontinued after baseline assessment had worse baseline CF scores suggesting differential attrition. CONCLUSION: Though baseline cognitive scores were worse in ESKD patients on dialysis, compared to CKD, their 3MS, especially memory subscale improved on follow-up. Among ESKD patients, the improvement was significant only in patients who have been on dialysis for less than one-year which may indicate a beneficial effect of clearance of uraemic toxins. Differential attrition of study subjects may have impacted the observed results.

Comparison of health literacy profile of patients with end-stage kidney disease on dialysis versus non-dialysis chronic kidney disease and the influencing factors: a cross-sectional study.

OBJECTIVES: Lower health literacy (HL) is associated with poor outcomes in patients with kidney disease. Since HL matches the patient's competencies with the complexities of the care package, the level of HL sufficient in earlier stages of chronic kidney disease (CKD) may be inadequate for patients with end-stage kidney disease (ESKD) on dialysis. We aimed to analyse the HL profile of patients with ESKD and non-dialysis CKD and examine if there were significant associations with covariates which could be targeted to address HL deficits, thereby improving patient outcomes. DESIGN AND SETTING: Cross-sectional study of patients with CKD and ESKD from a single Australian health district. METHODS: We assessed the HL profile of 114 patients with CKD and 109 patients with ESKD using a 44-item multidomain Health Literacy Questionnaire (HLQ) and examined its association with demographic factors (age, gender, race), smoking, income, education, comorbidities, carer status, cognitive function and depression. Using multivariable logistic regression models, HL profiles of patients with CKD and ESKD were evaluated after adjusting for covariates. RESULTS: Patients with ESKD had similar demographics and educational levels compared with patients with CKD. ESKD had significantly higher frequency of vascular disease, cognitive impairment and depression. Patients with ESKD had better HL scores for the social support domain (37.1% vs 19.5% in higher HLQ4 tertile, p=0.004), whereas all other HL domains including engagement with healthcare providers were comparable to CKD. Depression was independently associated with nearly all of the HL domains (HLQ1: OR 2.6, p=0.030; HLQ2: OR 7.9, p=<0.001; HLQ3: OR 7.6, p<0.001; HLQ4: OR 3.5, p=0.010; HLQ5: OR 8.9, p=0.001; HLQ6: OR 3.9, p=0.002; HLQ7: OR 4.8, p=0.001; HLQ8: OR 5.3, p=0.001) and education with HL domains relevant to processing health-related information (HLQ8: OR 2.6, p=0.008; HLQ9: OR 2.5, p=0.006). CONCLUSIONS: Despite very frequent interactions with health systems, patients with ESKD on dialysis did not have higher HL in engagement with health providers and most other HL domains, compared with patients with CKD. Strategies promoting patient-provider engagement and managing depression which strongly associates with lower HL may address the impact of HL deficits and favourably modify clinical outcomes in renal patients.

Strategies to improve dietary, fluid, dialysis or medication adherence in patients with end stage kidney disease on dialysis: A systematic review and meta-analysis of randomized intervention trials.

BACKGROUND: In 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. METHODS: We 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. RESULTS: From 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. CONCLUSIONS: Interventions 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. LIMITATIONS: Poor methodological quality of trials. Frequent use of surrogate outcomes measures. Low certainly of evidence.