Opioid Analgesic Use among Patients with Kidney Disease: A Systematic Review.

INTRODUCTION: Opioid analgesics are often used to manage moderate to severe pain. A significant proportion of patients taking opioids have compromised kidney function. This systematic review aimed to examine the available evidence on the safety and analgesic effect of opioid use in adults with kidney disease. METHODS: We searched eight electronic databases from inception to January 26, 2023. Published original research articles in English reporting on opioid use and pharmacokinetic data among adults with reduced renal function were included. Article screening, data extraction, and quality assessment were conducted by at least two investigators independently. This review was registered prospectively on PROSPERO (ID: CRD42020159091). RESULTS: There were 32 observational studies included, 14 of which reported on morphine use, three involved fentanyl use, two involved hydromorphone use, and 13 articles reported on other opioids including codeine, dihydrocodeine, and buprenorphine. CONCLUSION: There is limited and low-quality evidence to inform the safety and analgesic effect of opioid use in reduced renal function. Morphine remains the opioid for which there is the most evidence available on safety and analgesic effect in the context of renal disease. Greater caution and consideration of potential risks and benefits should be applied when using other opioids. Further high-quality studies examining clinical outcomes associated with the use of different opioids and opioid doses in renal disease are warranted.

The impact of coronavirus-19 vaccination on anti-nuclear cytoplasmic antibody vasculitis hospitalisations in a Sydney health network.

There have been reports of COVID-19 vaccination triggering anti-nuclear cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but no robust studies have examined the link. This retrospective cohort study assessed the impact of COVID vaccination on the rate of denovo and relapsed AAV in a Sydney Local Health District from 2018 to 2022. Despite more than 95% of the population receiving vaccination, the case rate of AAV was stable. These findings do not support a relationship between COVID vaccination and AAV.

The Controversies of Coronary Artery Disease in End-Stage Kidney Disease Patients: A Narrative Review.

Cardiovascular disease (CVD) accounts for more than 50% of deaths among patients with end-stage kidney disease (ESKD). Approximately 40-50% of ESKD patients have clinically significant coronary artery disease (CAD) due to atherosclerosis which accounts for a significant proportion of CVD risk. However, other CVD pathologies including myocardial fibrosis, vascular calcification and arterial stiffening play important contributory roles. The pathophysiology of CAD in ESKD is distinct from the general population. ESKD patients is typically have diffuse multi-vessel involvement with increased calcification that involves both intimal and medial layers of the arterial wall. There is a complex interplay between an increased burden of traditional Framingham risk factors and exposure to non-traditional risk factors including chronic inflammation and dialysis per se. Established treatments for CAD risk factors including cholesterol lowering with statin therapy have attenuated effects and ESKD patients also have worse outcomes after revascularisation. Recent trials such as the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) have established that direct modulation of inflammation improves CVD outcomes in the general population, which may prove to be a potential attractive therapeutic target in ESKD patients. Multiple retrospective observational studies comparing mortality outcomes between haemodialysis (HD) and peritoneal dialysis (PD) patients have been inconclusive. Randomised trials on this issue of clinical equipoise are clearly warranted but are unlikely to be feasible. Screening for stable CAD in asymptomatic ESKD patients remains a clinical dilemma which is unique to chronic dialysis patients being assessed for kidney transplantation. This has become particularly relevant in light of the recent ISCHEMIA-CKD trial which demonstrated no difference between optimal medical therapy and revascularisation upon CVD outcomes or mortality. The optimal strategy for screening is currently being investigated in the ongoing large international multi-centre CARSK trial. Here we discuss the pathophysiology, risk modification, treatment, screening and future directions of CAD in ESKD.

The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration.

AIMS: The aim is to report the results of Australia's first uterus transplantation (UTx). METHODS: Following long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team. RESULTS: This is the first UTx procedure to occur in Australia, involving a mother donating her uterus to her daughter. The total operative time for the donor was 9 h 54 min. Concurrently, recipient surgery was synchronised to minimise graft ischaemic time, and the total operative time for the recipient was 6 h 12 min. Surgery was by laparotomy in the LD and recipient. The total warm ischaemic time of the graft was 1 h 53 min, and the cold ischaemic time was 2 h 17 min (total ischaemic time 4 h 10 min). The patient's first menstruation occurred 33 days after the UTx procedure. CONCLUSION: Twenty-five years of Swedish and Australian collaboration has led to Australia's first successfully performed UTx surgery at The Royal Hospital for Women, Sydney, Australia.

Retrospective study on the epidemiology of antineutrophil cytoplasmic autoantibodies-associated vasculitis in two Australian health districts.

BACKGROUND: Antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV) is more prevalent in rural Australia compared with metropolitan areas, suggesting a role of environment in disease pathogenesis. However, the prevalence of environmental risk factors in Australian AAV patients has not been described. AIMS: To compare the incidence of AAV between two health districts (Illawarra Shoalhaven Local Health District (ISLHD), a mixed rural/metropolitan region, and South Eastern Sydney Local Health District (SESLHD), a metropolitan region) in Australia and its relationship to environmental exposures. METHODS: Cases of AAV from 2002 to 2017 were retrospectively identified from ISLHD and SESLHD using electronic medical records. Eligible participants were invited to complete a standardised questionnaire examining their exposure to silica, solvents, metal, dust, farming, gardening and sunlight. RESULTS: One hundred and fifty-six cases of AAV were identified from 2002 to 2017. A higher cumulative incidence of AAV was observed in the ISLHD (184.2 (95% confidence interval (CI) 143.6-232.7) per million) compared with SESLHD (102.6 (95% CI 82.1-126.8) per million). Over 50% of the cohort had high levels of silica and solvents exposure, based on self-reported questionnaires. There was no significant relationship between region and exposure to silica (P = 0.96), solvents (P = 0.44), metal (P = 0.33), dust (P = 0.25), farming (P = 0.90), gardening (P = 0.93) or sunlight (P = 0.55). CONCLUSIONS: We found a higher incidence of AAV in ISLHD compared with SESLHD with high levels of exposure to silica and solvents in both regions based on self-reported questionnaires. Prospective systematic collection of data, such as a registry of AAV, is warranted to further explore the relationship between environmental exposures and AAV.

Relationship between pulse pressure and inflammation with left ventricular diastolic dysfunction in chronic kidney disease patients.

BACKGROUND: Diastolic dysfunction (DD) is an important cause of cardiovascular disease (CVD) mortality in chronic kidney disease (CKD) patients. Non-traditional risk factors, such as arterial stiffness and inflammation, are implicated in the pathogenesis of DD in CKD patients. AIM: To determine the association between inflammatory markers (interleukin (IL)-12, IL-18, highly sensitive C-reactive protein (hsCRP)) and non-invasive markers of arterial stiffness (24-h pulse pressure (PP)) with DD in stages 3-4 CKD patients. METHODS: We performed a sub-analysis of 78 non-diabetic stages 3-4 CKD subjects to determine the relationship between 24-h PP, IL-12, IL-18 and hsCRP with DD. RESULTS: DD was present in 38 subjects (49%). Subjects with DD were significantly older (61.0 ± 1.9 vs 50.2 ± 2.0 years; P < 0.001) and had higher 24-h PP (48(95% confidence interval 45, 52) vs 43(95% confidence interval 41, 45) mmHg; P < 0.005); 24-h PP was associated with DD (P = 0.02), but this was no longer significant after adjustment for age (P = 0.31). Serum IL-12, IL-18 and hsCRP levels were not significantly different between subjects with or without DD. CONCLUSION: Asymptomatic subclinical DD was present in 50% of a cohort of stages 3-4 CKD patients but was not associated with IL-12, IL-18 or hsCRP. The association between 24-h PP and DD was no longer apparent following adjustment for age, but given the small sample size, our findings will need to be explored in larger-sized cohorts of individuals with moderate-stage CKD.

The Effects of OMEGA-3 Fatty Acid Supplementation Upon Interleukin-12 and Interleukin-18 in Chronic Kidney Disease Patients.

OBJECTIVE(S): Cardiovascular disease (CVD) remains a leading cause of mortality in chronic kidney disease (CKD) patients. Interventions targeting traditional risk factors have largely proven ineffective in CKD patients in part because of the increased role of nontraditional risk factors such as chronic inflammation. Omega-3 fatty acids (ω3FA) are inexpensive and safe natural agents, which target inflammation and have potential cardioprotective benefits. The aim of the study was to determine the effects of ω3FA supplementation upon serum interleukin (IL)-12, IL-18, and highly sensitive C-reactive protein (hsCRP) in patients with Stage 3-4 CKD. METHODS: We performed a post-hoc analysis of a randomized placebo-controlled trial in 73 nondiabetic CKD patients to determine the effects of ω3FA supplementation (4 g daily for 8 weeks) upon serum levels of IL-12, IL-18, and hsCRP. RESULTS: There were no preintervention differences in IL-12, IL-18, or hsCRP between treatment groups. Postintervention levels of IL-12, IL-18, and hsCRP were similar between the treatment groups. However, IL-12 and IL-18 increased in both treatment groups over the intervention period, whereas hsCRP remained unchanged. The magnitude of increase in serum IL-18 (ΔIL-18) was significantly less in participants in the ω3FA treatment group compared to placebo (P = .047). CONCLUSION(S): This study has shown that 4 g daily ω3FA supplementation may lower serum IL-18 levels in patients with moderate CKD. Although there were no apparent effects on several other markers of inflammation, this study provides evidence for a specific effect of ω3FA on inflammatory pathways.

Predictive Validity of Intrinsic Capacity Composite Scores for Risk of Frailty at 2 Years: A Comparison of 4 Scales.

OBJECTIVE: Intrinsic capacity (IC) and frailty are complementary constructs that encapsulate functional capacities of older adults. Although earlier studies suggest the utility of composite IC scores in predicting risk of frailty, key gaps remain with the lack of direct comparative studies between different IC scales and lack of a composite score based on the World Health Organization Integrated Care for Older People (ICOPE) tool. We aimed to compare different IC scales, including an ICOPE-based scale, in their predictive ability for risk of frailty at 2 years in healthy community-dwelling older adults. DESIGN: Cohort study. SETTING AND PARTICIPANTS: A total of 230 participants (age: 67.2 ± 7.4 years) from the GeriLABS-2 cohort study. METHODS: We derived composite scores by summing 4 IC domains (locomotion, cognition, vitality, and psychological). We compared composite scores of 4 scales: IC1-Chew 2021, range: 0-8; IC2-Liu 2021, range: 0-4; IC3-ICOPE, range: 0-4; IC4-modified ICOPE, range: 0-8. The primary outcome was risk of frailty using the modified Fried Frailty Phenotype. We performed logistic regression to examine the association of baseline composite IC with risk of frailty. We also examined the impact of individual domains and number of impaired domains on risk of frailty. RESULTS: Among 193 (83.9%) older adults who completed 2-year follow-up, 20 (10.4%) met criteria for risk of frailty. When adjusted for covariates, 2-point per domain scales (IC1/IC4) predicted increased risk of frailty (OR, 4.31; 95% CI, 1.55-11.96; OR, 5.00; 95% CI, 1.75-14.26). When further adjusted for baseline frailty, only IC4 remained significant (OR, 4.28; 95% CI, 1.45-12.60). Among the domains, impaired locomotion and vitality were associated with risk of frailty. Greater number of impaired domains predicted increased risk of frailty (IC1/IC2: ß = 0.18-0.19, P < .05). CONCLUSIONS AND IMPLICATIONS: Baseline composite IC score using 2-point per domain scales better predicted risk of frailty at 2 years, predicated on impaired locomotion/vitality and greater number of impaired domains. For early identification of healthy older adults at risk of frailty, an ICOPE-based scale should be considered, as it is effective and accessible.

Elevated interleukin-12 and interleukin-18 in chronic kidney disease are not associated with arterial stiffness.

BACKGROUND: Chronic kidney disease (CKD) patients are at increased risk of cardiovascular disease (CVD) mortality compared to the general population. Evidence suggests inflammation is important in the pathogenesis of CVD in CKD and inflammatory bio-markers such as C-reactive protein (CRP) and pro-atherogenic cytokines such as interleukin(IL)-6, IL-12 and IL-18 are associated with CVD-related outcomes in the general population and CKD. In the general population, IL-12 and IL-18 are implicated in the pathogenesis of atherosclerosis and are associated with acute CVD events, including mortality. Although IL-12 and IL-18 are increased in CKD, extrapolating an equally important role for these cytokines in the pathogenesis of CVD in CKD remains uncertain. In this study we aim to compare serum levels of pro-atherogenic cytokines in non-dialysis CKD patients and healthy individuals. We will also assess the relationship between these cytokines and arterial stiffness, a surrogate marker of CVD. METHODS: We performed a case-control study examining IL-12, IL-18, aortic pulse wave velocity (PWV) and augmentation index (AIx) in healthy volunteers (n=69) and stage 3-4 (n=70) and stage 5 (n=84) CKD subjects. RESULTS: IL12 levels were elevated in stage 3-4 (129 pg/mL; IQR 56-222) and stage 5 (125 pg/mL; IQR 45-240) CKD in comparison to healthy controls (65 pg/mL; IQR 5-229). IL18 was elevated in CKD stage 5 (617 pg/mL; IQR 468-793) in comparison to CKD stage 3-4 (417 pg/mL; IQR 288-494) and healthy controls (359 pg/mL; IQR 238-548). In multivariate analysis, only glomerular filtration rate (GFR) remained an independent predictor of IL-18 (p<0.01). Neither IL-12 nor IL-18 were associated with PWV or AIx. CONCLUSION: IL-12 and IL-18 are elevated during the earlier stages of CKD but are not associated with arterial stiffness. The association with GFR suggests that IL-18 is largely dependent upon renal clearance.

In Vivo Confocal Microscopy in Different Types of Dry Eye and Meibomian Gland Dysfunction.

In vivo confocal microscopy (IVCM) imaging is increasingly popular in ocular surface disease diagnosis and management. We conducted a systematic review to update the use of IVCM in the diagnosis and treatment of dry eye and meibomian gland dysfunction (MGD). A literature review was conducted on IVCM studies in MGD, dry eye disease, systemic disease causing dry eye, dry eye in glaucoma patients, contact lens-associated ocular conditions, graft-versus-host disease, and Sjogren's syndrome-related dry eye. The articles were identified through PubMed and a total number of 63 eligible publications were analyzed in detail. All primary research studies on confocal microscopy on dry eye and related conditions from 2017 onwards were included. The reports were reviewed for their contribution to the existing literature as well as potential biases and drawbacks. Despite limitations such as small field of view, lack of population-based norms, and lack of standardization of image acquisition, interpretation, and quantification, IVCM is useful as a complementary technique for clinical diagnosis in various ocular surface disorders related to dry eye. With advances in hardware and software in the near future, it has the potential for further practical impact.

Treatment decision-making and care among older adults with kidney failure: protocol for a multicentre, prospective observational cohort study with nested substudies and linked qualitative research (the Elderly Advanced CKD Programme).

INTRODUCTION: Shared treatment decision-making and planning of care are fundamental in advanced chronic kidney disease (CKD) management. There are limited data on several key outcomes for the elderly population including survival, quality of life, symptom burden, changes in physical functioning and experienced burden of healthcare. Patients, caregivers and clinicians consequently face significant uncertainty when making life-impacting treatment decisions. The Elderly Advanced CKD Programme includes quantitative and qualitative studies to better address challenges in treatment decision-making and planning of care among this increasingly prevalent elderly cohort. METHODS AND ANALYSIS: The primary component is OUTcomes of Older patients with Kidney failure (OUTLOOK), a multicentre prospective observational cohort study that will enrol 800 patients ≥75 years with kidney failure (estimated glomerular filtration rate ≤15 mL/min/1.73 m2) across a minimum of six sites in Australia. Patients entered are in the decision-making phase or have recently made a decision on preferred treatment (dialysis, conservative kidney management or undecided). Patients will be prospectively followed until death or a maximum of 4 years, with the primary outcome being survival. Secondary outcomes are receipt of short-term acute dialysis, receipt of long-term maintenance dialysis, changes in biochemistry and end-of-life care characteristics. Data will be used to formulate a risk prediction tool applicable for use in the decision-making phase. The nested substudies Treatment modalities for the InfirM ElderLY with end stage kidney disease (TIMELY) and Caregivers of The InfirM ElderLY with end stage kidney disease (Co-TIMELY) will longitudinally assess quality of life, symptom burden and caregiver burden among 150 patients and 100 caregivers, respectively. CONsumer views of Treatment options for Elderly patieNts with kiDney failure (CONTEND) is an additional qualitative study that will enrol a minimum of 20 patients and 20 caregivers to explore experiences of treatment decision-making and care. ETHICS AND DISSEMINATION: Ethics approval was obtained through Sydney Local Health District Human Research Ethics Committee (2019/ETH07718, 2020/ETH02226, 2021/ETH01020, 2019/ETH07783). OUTLOOK is approved to have waiver of individual patient consent. TIMELY, Co-TIMELY and CONTEND participants will provide written informed consent. Final results will be disseminated through peer-reviewed journals and presented at scientific meetings.

Effects of proactive iron and erythropoiesis-stimulating agent protocol implementation on achieving clinical guideline targets for anaemia in a satellite haemodialysis patient cohort.

AIM: Anaemia management with erythropoiesis-stimulating agents (ESA) and i.v. iron replacement in haemodialysis patients poses several clinical challenges, including maintaining stable haemoglobin (Hb) levels within target ranges while achieving lowest effective ESA dose. This manuscript describes the effect of implementing proactive protocol-driven adjustments for iron and ESA in maintenance haemodialysis patients. METHODS: This was a cohort study of 46 satellite haemodialysis patients examined from 2004 to 2006 with protocol implementation in 2005. Baseline haemoglobin, transferrin saturations (TSAT), ferritin values and ESA administration were obtained during 2004. Follow-up data was collected in 2006 and compared to baseline values in reference to specified targets in the 2004 Caring for Australasians with Renal Impairment (CARI) guidelines. RESULTS: Fifty-four percent of patients achieved haemoglobin targets during follow up versus 43% patients during baseline. Seventy-nine percent of patients achieved TSAT targets during follow up versus 67% patients during baseline. Ninety percent of patients achieved ferritin targets during follow up versus 75% patients during baseline. Odds ratios for values falling within target ranges during follow up compared to baseline were 1.63 (Hb: P = 0.037; 95% confidence interval (CI), 1.03-2.57), 1.90 (TSAT: P = 0.006; 95% CI, 1.20-3.01) and 3.72 (ferritin: P = 0.003; 95% CI, 1.57-8.83). There was a trend toward lower average ESA dose (P = 0.07). CONCLUSION: This study demonstrates the successful implementation and efficacy of a proactive protocol for iron and ESA treatment in haemodialysis patients. Benefits include increased concordance with historical guideline targets and decreased haemoglobin variability. Improved iron status and optimizing ESA response allows for lower ESA doses, limiting both potential side-effects of ESA (hypertension) and the burgeoning costs of anaemia management.

Increased Inflammatory Response in Association with the Initiation of Hemodialysis Compared with Peritoneal Dialysis in a Prospective Study of End-Stage Kidney Disease Patients.

BACKGROUND: Large epidemiological studies have demonstrated an early survival advantage with the initiation of peritoneal dialysis (PD) compared to haemodialysis (HD). Chronic inflammation may contribute to atherosclerosis and cardiovascular (CVD) mortality in end-stage kidney disease (ESKD). We hypothesize that the initiation of HD in ESKD patients is associated with a greater inflammatory response compared with PD. AIMS: To examine the effects of initiating HD and PD upon inflammation and CVD risk markers in ESKD patients. METHODS: We performed a pilot prospective study on 75 predialysis CKD stage-5 subjects comparing the effects of HD and PD upon high sensitivity C-reactive protein (hsCRP), interleukin(IL)-12, IL-18 and pulse wave velocity (PWV). Study visits were conducted 3 - 6 months before (baseline) and after (follow-up) initiation of dialysis RESULTS: Thirty-nine and 36 patients were initiated on HD and PD respectively. HD patients were older than PD patients (65.1 ± 2.1 vs 57.7 ± 2.7 years; p = 0.03) but had similar baseline systolic blood pressure (SBP), pulse pressure (PP), hsCRP, IL-12, IL-18, and PWV. At follow-up, HD patients had significantly increased hsCRP levels [5.2(3.7, 7.3) vs 1.7(1.0, 2.8)g/L; p < 0.001] compared to PD. Follow-up blood pressure, IL-12, IL-18, and PWV were similar between groups. A significant association remained between hsCRP and HD after adjustment for age, previous CVD, and residual urine output. CONCLUSION: The initiation of HD was associated with significantly increased hsCRP compared to PD. Further study is required to determine the plausibility of inflammation as a potential underlying contributor to the observed early mortality difference between dialysis modalities.

Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

BACKGROUND: New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. METHODS: This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. RESULTS: Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). CONCLUSIONS: Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

The impact of abnormal glucose regulation on arterial stiffness at 3 and 15 months after kidney transplantation.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) has been associated with an increased risk of cardiovascular disease (CVD) mortality following kidney transplantation, but the association between pre-diabetes (i.e. impaired fasting glucose and impaired glucose tolerance) and CVD mortality remains unclear. The aim of this study was to assess the association between abnormal glucose regulation and arterial stiffness at 3 and 15 months post-transplantation. METHODS: This is a single-centre prospective cohort study of 83 non-diabetic kidney transplant recipients who received a kidney transplant between 2008 and 2011. All patients underwent an oral glucose tolerance test (OGTT - categorised as normal, pre-diabetes or PTDM) and non-invasive measurements of arterial stiffness (aortic pulse wave velocity [PWV] and augmentation index [AIx]) 3 months post-transplantation. A sub-set of patients had repeat OGTT (n = 33) and arterial stiffness measurements (n = 28) at 15 months post-transplant. RESULTS: Of the 83 patients, 52% (n = 43) had normal glucose regulation, 31% (n = 26) had pre-diabetes and 17% (n = 14) developed PTDM. Compared with recipients with normal glucose regulation, recipients with PTDM (adjusted ß = 5.61, 95% confidence interval [CI] 0.09 to 11.13, p = 0.047) but not those with pre-diabetes (adjusted ß = 3.23, 95% CI -1.05 to 7.51, p = 0.137) had significantly higher AIx 3 months after transplantation. No association was found between glucose regulation and PWV at 3 months after transplantation. There was no association between glucose regulation at 3 or 15 months and AIx and PWV at 15 months in a subset of recipients. CONCLUSIONS: Early onset PTDM is associated with increased systemic vascular stiffness (AIx) but not regional stiffness of large arteries (PWV) suggesting that small vessel dysfunction may be the earliest vascular change seen with PTDM. Thus, measurements of arterial stiffness after transplantation may assist in more accurately stratifying future CVD risk of kidney transplant recipients.

Interleukin-12 is associated with arterial stiffness in healthy individuals.

BACKGROUND: Atherosclerotic cardiovascular disease (CVD) is a chronic inflammatory disease mediated by the proinflammatory cytokines interleukin-12 (IL-12) and interleukin-18 (IL-18). Evidence suggests that IL-12 is dominant in early atherosclerosis, while IL-18 is critical in advanced atherosclerosis. In this study, we explore the association between IL-12 and IL-18 and arterial stiffness in healthy individuals. METHODS: We performed a cross-sectional study examining pulse wave velocity (PWV), augmentation index (AIx), IL-12, and IL-18 in healthy individuals (N = 53) without CVD risk factors. RESULTS: In multivariate regression, age (P < 0.01), systolic blood pressure (P = 0.05), and IL-12 (P < 0.01) were positively associated with PWV, and high-density lipoprotein (P = 0.04) was negatively associated with PWV (model R (2) = 0.476, P < 0.01). CONCLUSIONS: IL-12, but not IL-18, is associated with PWV in healthy individuals without clinical CVD, supporting a role for IL-12 in early atherosclerosis as suggested by animal studies.

Association of a change in immunosuppressive regimen with hemodynamic and inflammatory markers of cardiovascular disease after kidney transplantation.

BACKGROUND: Although rejection rates and short-term graft survival have significantly improved in kidney transplantation with the introduction of calcineurin inhibitor (CNI), cardiovascular disease (CVD) and metabolic complications are being increasingly recognized as important causes of morbidity and mortality. We hypothesize that non-CNI proliferation signal inhibitor (PSI)-based immunosuppressive regimen is associated with improved arterial stiffness after kidney transplantation compared with CNI-based immunosuppressive regimens. METHODS: This is a prospective, single-center study of renal transplant (RT) recipients comparing the metabolic, cardiovascular (pulse wave velocity and aortic augmentation index (AI) adjusted for heart rate (AI × 75)), inflammatory cytokines (interleukins (ILs) 6, 12, and 18) and graft-related outcomes at 3 and 15 months posttransplantation between RT recipients maintained on CNI- (CNI-CNI) or PSI-based (CNI-PSI) regimens including sirolimus and everolimus. RESULTS: Fifty and 17 RT recipients maintained on CNI-CNI and CNI-PSI, respectively, were included in this study. Median time to PSI conversion from CNI was 5 months. Compared with CNI-CNI recipients, CNI-PSI recipients had significantly lower fasting blood glucose in nondiabetics (coefficient = -16.2; 95% confidence interval (CI) = -14.4 to -18.0; P < 0.01), lower IL-18 levels (coefficient = -229.16; 95% CI = -343.94 to -114.38; P < 0.01), and lower AI × 75 (coefficient = -5.14; 95% CI = -9.99 to -0.28; P = 0.04) at 15 months posttransplant in the multivariable models. CONCLUSIONS: Our study suggests from the elimination of CNI for PSI may lower AIx75 and IL-18, both surrogate markers of CVD, but adequately powered, randomized, controlled studies are required to establish the causal relationship between immunosuppressive agents and CVD risk.

Acute kidney injury: controversies revisited.

This paper addresses the epidemiology of AKI specifically in relation to recent changes in AKI classification and revisits the controversies regarding the timing of initiation of dialysis and the use of peritoneal dialysis as a renal replacement therapy for AKI. In summary, the new RIFLE/AKIN classifications of AKI have facilitated more uniform diagnosis of AKI and clinically significant risk stratification. Regardless, the issue of timing of dialysis initiation still remains unanswered and warrants further examination. Furthermore, peritoneal dialysis as a treatment modality for AKI remains underutilised in spite of potential beneficial effects. Future research should be directed at identifying early reliable biomarkers of AKI, which in conjunction with RIFLE/AKIN classifications of AKI could facilitate well-designed large randomised controlled trials of early versus late initiation of dialysis in AKI. In addition, further studies of peritoneal dialysis in AKI addressing dialysis dose and associated complications are required for this therapy to be accepted more widely by clinicians.