A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

What is the climate footprint of therapeutic diets for people with chronic kidney disease? Results from an Australian analysis.

BACKGROUND: Immediate action is needed to stabilise the climate. Dietitians require knowledge of how the therapeutic diets they prescribe may contribute to climate change. No previous research has quantified the climate footprint of therapeutic diets. This study sought to quantify and compare the climate footprint of two types of therapeutic diets for people with chronic kidney disease (CKD) with two reference diets. METHODS: A usual diet for an individual with CKD and a novel plant-based diet for CKD were compared with the current Australian diet and the Australian-adapted EAT Lancet Planetary Health Diet (PHD). The climate footprint of these diets was measured using the Global Warming Potential (GWP*) metric for a reference 71-year-old male. RESULTS: No diets analysed were climate neutral, and therefore, all contribute to climate change. The novel plant-based diet for CKD (1.20 kg carbon dioxide equivalents [CO2 e] per day) produced 35% less CO2 e than the usual renal diet for an individual with CKD (1.83 kg CO2 e per day) and 50% less than the current Australian diet (2.38 kg CO2 e per day). The Australian-adapted EAT Lancet PHD (1.04 kg CO2 e per day) produced the least amount of CO2 e and 56% less than the current Australian diet. The largest contributors to the climate footprint of all four diets were foods from the meats and alternatives, dairy and alternatives and discretionary food groups. CONCLUSIONS: Dietetic advice to reduce the climate footprint of therapeutic diets for CKD should focus on discretionary foods and some animal-based products. Future research is needed on other therapeutic diets.

Calcium isotopes as a biomarker for vascular calcification in chronic kidney disease.

Calcium balance is abnormal in adults with chronic kidney disease (CKD) and is associated with the development of vascular calcification. It is currently not routine to screen for vascular calcification in CKD patients. In this cross-sectional study, we investigate whether the ratio of naturally occurring calcium (Ca) isotopes, 44Ca and 42Ca, in serum could be used as a noninvasive marker of vascular calcification in CKD. We recruited 78 participants from a tertiary hospital renal center: 28 controls, 9 subjects with mild-moderate CKD, 22 undertaking dialysis and 19 who received a kidney transplant. For each participant, systolic blood pressure, ankle brachial index, pulse wave velocity, and estimated glomerular filtration rate were measured, along with serum markers. Calcium concentrations and isotope ratios were measured in urine and serum. While we found no significant association between urine Ca isotope composition (noted δ44/42Ca) between the different groups, δ44/42Ca values in serum were significantly different between healthy controls, subjects with mild-moderate CKD and those undertaking dialysis (P < 0.01). Receiver operative characteristic curve analysis shows that the diagnostic utility of serum δ44/42Ca for detecting medial artery calcification is very good (AUC = 0.818, sensitivity 81.8% and specificity 77.3%, P < 0.01), and performs better than existing biomarkers. Although our results will need to be verified in prospective studies across different institutions, serum δ44/42Ca has the potential to be used as an early screening test for vascular calcification.

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.

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.

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.

Temporal changes and risk factors for death from early withdrawal within 12 months of dialysis initiation-a cohort study.

BACKGROUND: Mortality risk is high soon after dialysis initiation in patients with kidney failure, and dialysis withdrawal is a major cause of early mortality, attributed to psychosocial or medical reasons. The temporal trends and risk factors associated with cause-specific early dialysis withdrawal within 12 months of dialysis initiation remain uncertain. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the temporal trends and risk factors associated with mortality attributed to early psychosocial and medical withdrawals in incident adult dialysis patients in Australia between 2005 and 2018 using adjusted competing risk analyses. RESULTS: Of 32 274 incident dialysis patients, 3390 (11%) experienced death within 12 months post-dialysis initiation. Of these, 1225 (36%) were attributed to dialysis withdrawal, with 484 (14%) psychosocial withdrawals and 741 (22%) medical withdrawals. These patterns remained unchanged over the past two decades. Factors associated with increased risk of death from early psychosocial and medical withdrawals were older age, dialysis via central venous catheter, late referral and the presence of cerebrovascular disease; obesity and Asian ethnicity were associated with decreased risk. Risk factors associated with early psychosocial withdrawals were underweight and higher socioeconomic status. Presence of peripheral vascular disease, chronic lung disease and cancers were associated with early medical withdrawals. CONCLUSIONS: Death from dialysis withdrawal accounted for >30% of early deaths in kidney failure patients initiated on dialysis and remained unchanged over the past two decades. Several shared risk factors were observed between mortality attributed to early psychosocial and medical withdrawals.

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.

Peritoneal dialysis-related peritonitis as a risk factor for cardiovascular events.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in peritoneal dialysis (PD) patients. Infection is known to increase the risk of cardiovascular events (CVE); however, no studies have examined the association between PD peritonitis and CVE. AIM: To examine peritonitis as a risk factor for CVE in PD patients. METHODS: This retrospective cohort study included all adults undertaking PD for ≥3 months in one Australian health district from 2001 to 2015. Baseline characteristics and peritonitis event information was obtained from the Australian and New Zealand Dialysis and Transplant registry. The Centre for Health Research Illawarra Shoalhaven Population facilitated data linkage using ICD10 coding to capture CVE information. RESULTS: A total of 211 patients was included, with median age of 66 years (interquartile range 54.49-74.45); 64% were male. Peritonitis occurred in 114 (54%) patients and 65 (30.8%) patients experienced a CVE. Identified risk factors for CVE included: cerebrovascular disease (hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.36-5.47), diabetes (HR 2.41, 95% CI 1.47-3.96), coronary artery disease (HR 1.67, 95% CI 1.01-2.77) and age (HR 1.03, 95% CI 1.01-1.06). There was no significant increase in risk of CVE following peritonitis (HR 1.37, 95% CI 0.81-2.32, P = 0.24), even when accounting for age, cerebrovascular disease, diabetes and existing coronary artery disease (HR 1.32, 95% CI 0.78-2.23, P = 0.30). CONCLUSIONS: We did not find an increase in the risk of CVE following a peritonitis episode in PD patients. This result may be due to small sample size or rapid peritonitis treatment mitigating cardiovascular risk.

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.

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.

High-Sensitivity Troponin T and C-Reactive Protein Have Different Prognostic Values in Hemo- and Peritoneal Dialysis Populations: A Cohort Study.

BACKGROUND: Dialysis patients have an exceedingly high mortality rate. Biomarkers may be useful tools in risk stratification of this population. We evaluated the prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) and CRP (C-reactive protein) in predicting adverse outcomes in stable hemodialysis and peritoneal dialysis (PD) patients. Variability in hs-cTnT was also examined. METHODS AND RESULTS: A retrospective cohort study included 574 dialysis patients (hemodialysis 347, PD 227). Outcomes examined included mortality and major adverse cardiovascular events, with median follow-up of 3.5 years. hs-cTnT was an independent predictor of both outcomes in hemodialysis and PD patients. Increased risk only became significant when hs-cTnT reached quintile 3 (>49 ng/L). Area under the receiver operating curve analysis showed that the addition of hs-cTnT to clinical parameters significantly improved its prognostic performance for mortality in PD patients (P=0.002). CRP was an independent predictor of both outcomes in PD patients only. Only CRP in the highest quintile (>16.8 mg/L) was associated with increased risk. hs-cTnT remained relatively stable for the whole follow-up period for hemodialysis patients, whereas for PD patients, hs-cTnT increased by 23.63% in year 2 and 29.13% in year 3 compared with baseline (P<0.001). CONCLUSIONS: hs-cTnT and CRP are useful tools in predicting mortality and major adverse cardiovascular events in hemodialysis and PD patients. Given that hs-cTnT levels increase over time in PD patients, interval monitoring may be valuable for risk assessment. In contrast, hs-cTnT in hemodialysis patients has little interval change and progress monitoring is not indicated.

The Utility of Sonographic Assessment in Selecting Patients for Percutaneous Insertion of Peritoneal Dialysis Catheter.

BACKGROUND: Percutaneous insertion of peritoneal dialysis (PD) catheters by nephrologists is a safe and effective alternative to open surgical techniques. These patients are usually carefully selected due to anatomical considerations and medical comorbidities, with the current literature suggesting exclusion of patients with prior abdominal surgery. METHOD: We conducted a retrospective cohort study of pre-dialysis patients who attended a preprocedural clinic in a tertiary center over 6 years. Procedural complications and catheter survival were assessed. Chi-squared test and Kaplan-Meier survival analysis were undertaken. Inpatient assessments were excluded. RESULTS: A total of 217 patients were assessed, of whom 171 (78.8%) were accepted for percutaneous PD catheter insertion by a nephrologist. The key exclusion criteria were: (1) the clinical presence of abdominal hernia (p < 0.001), (2) ultrasound findings of skin to peritoneum depth of > 5.5 cm (p < 0.001) and (3) ultrasound findings of impaired visceral slide test (p < 0.001). Prior abdominal surgery was not a default exclusion criterion (p = 0.1), as 63 patients (37%) with prior abdominal surgery, average of 1.3 prior surgeries per patient, were assessed as appropriate for the percutaneous procedure. There was no difference in the procedural complication rate and catheter survival between patients with and without prior abdominal surgery. CONCLUSION: A comprehensive preprocedural assessment utilizing ultrasound permits an objective selection of patients for percutaneous insertion of PD catheters by nephrologists. This allowed for successful and safe percutaneous insertion of PD catheters in patients who may have otherwise been excluded, e.g., prior abdominal surgery, patients with large bilateral polycystic kidneys, and central obesity.

The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality.

BACKGROUND: Prognosis in chronic kidney disease (CKD) for adverse outcomes differs substantially based on the etiology of CKD. We examined whether the biomarker profile differed based on CKD etiology and whether they were associated with mortality. METHODS: Prospective observational study of 1,157 patients, 663 with diabetic kidney disease (DKD), 273 with glomerulonephritis (GN), and 221 with cystic/interstitial disease (polycystic kidney disease, pyelonephritis or chronic tubulointerstitial nephritis [PCK/TIN]) were identified in the Canadian Study of Prediction of Dialysis, Death and Interim Cardiovascular events over Time cohort. The outcome of interest was mortality before commencing dialysis. The biomarker profile consisted of N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, high sensitivity C-reactive protein, fibroblast growth factor-23 (FGF23), transforming growth factor-beta, 25-hydroxylvitamin D, and cystatin C (CysC). RESULTS: The mean estimated glomerular filtration rate was 27 mL/min/1.73 m2 and median follow-up time was 44 months. Mortality before dialysis commencement was the greatest in DKD (20%), followed by PCK/TIN (13%), and was least in those GN (8%). The majority of deaths were cardiovascular in nature, 17, 9, and 5.5% for DKD, PCK/TIN, GN, respectively. Those with DKD had higher hazard for mortality, unadjusted (hazard ratio [HR] 2.7, 95% CI 1.7-4.3) and adjusted (HR 1.7, 95% CI 1.1-2.8). The biomarker profiles associated with mortality differed significantly by CKD etiology as follows: DKD was associated with CysC (HR 1.3, 95% CI 1.0-1.6), ADMA (HR 1.3, 95% CI 1.1-1.6), and NT-proBNP (HR 1.7, 95% CI 1.4-2.1), GN was associated with FGF23 (HR 1.8, 95% CI 1.1-2.8), TnI (HR 3.6, 95% CI 1.3-9.5), and transforming growth factor-beta (HR 0.6, 95% CI 0.4-0.9) and PCK/TIN was associated with ADMA (HR 1.5, 95% CI 1.3-1.8) and IL-6 (HR 2.1, 95% CI 1.5-3.1). CONCLUSIONS: Biomarkers profiles differ according to the etiology of CKD and are associated with mortality.

Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events, end-stage kidney disease and mortality.

The risk of infection in advanced chronic kidney disease (CKD) and its subsequent impact on adverse outcomes are not well established. Therefore, we determined the association of an infectious episode with the subsequent risk of cardiovascular ischemia, congestive heart failure, end-stage kidney disease or mortality in a Canadian prospective cohort (CanPREDDICT) of patients with advanced CKD (eGFR: 15-45 ml/min/1.73m(2)) followed by nephrologists for up to 5 years. Infectious episodes were classified by anatomic location and identified by positive culture, hospital admission, or use of antibiotics. Competing risk models were used to examine the time-varying risk of infection and the risk of cardiovascular ischemia, congestive heart failure, or end-stage kidney disease accounting for the competing risk of mortality. All outcomes were independently adjudicated. Of 2370 patients (mean age, 68 years; mean baseline eGFR, 28.2 mL/min/1.73m(2)), 575 patients (24.3%) had recorded infections; 378 had 1 infection episode, whereas 197 had 2 or more episodes, the most common being urinary and respiratory. An infectious episode was independently associated with an increased risk of cardiovascular ischemia (hazard ratio 1.80, 95% confidence interval 1.24-2.60), congestive heart failure (hazard ratio, 3.2; confidence interval, 2.25-4.61), end-stage kidney disease (hazard ratio, 1.58; confidence interval, 1.22-2.05) or mortality (hazard ratio, 3.39; confidence interval, 2.65-4.33). Thus, there is a high risk of infection in advanced CKD being associated with subsequent adverse outcomes.

Efficacy and safety of gabapentin for uremic pruritus and restless legs syndrome in conservatively managed patients with chronic kidney disease.

CONTEXT: Pruritus and restless legs syndrome (RLS) frequently affect patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), impacting the quality of life. Gabapentin (1-aminomethyl cyclohexane acetic acid) alleviates these symptoms in hemodialysis (HD) patients, but data are lacking for patients on the conservative pathway. OBJECTIVES: To determine the safety and effectiveness of gabapentin for pruritus or RLS in conservatively managed patients (n = 34) with CKD and ESKD. METHODS: This was a single-center retrospective cohort study. We compared dosing and side effects in 34 CKD/ESKD patients with similar patients receiving HD (n = 15). RESULTS: Forty-four percent of conservatively managed patients complained of RLS and/or pruritus; 18% were excluded for a nonuremic cause of symptom. Thirty-four patients were included in the final analysis. The most common starting daily dose of gabapentin was the equivalent of 50 mg (44.1%) or 100 mg (38.2%) daily, with the median daily dose of 100 mg (range 39-455 mg). Side effects occurred in 47% of patients, with 17% discontinuing gabapentin. Gabapentin reduced symptoms of pruritus (P < 0.001) and RLS (P < 0.05). There was no statistical difference when comparing HD and conservatively managed patients for daily starting dose (P = 0.88), median dose (P = 0.84), and final dose (P = 0.18). Patients conservatively managed were more likely to manifest side effects compared with HD patients (47.1% vs. 14.3%, P = 0.023). Dose was not found to be a factor associated with side effects in univariate analysis. CONCLUSION: Gabapentin is a viable treatment for conservatively managed CKD and ESKD patients with pruritus and/or RLS, but side effects are common. Gabapentin should be used with caution although higher doses do not appear to be a factor associated with side effects.