Effect of the proton-pump Inhibitor pantoprazole on MycoPhenolic ACid exposure in kidney and liver transplant recipienTs (IMPACT study): a randomized trial.

BACKGROUND: Mycophenolic acid (MPA) is widely utilized as an immunosuppressant in kidney and liver transplantation, with reports suggesting an independent relationship between MPA concentrations and adverse allograft outcome. Proton-pump inhibitors (PPIs) may have variable effects on the absorption of different MPA formulations leading to differences in MPA exposure. METHODS: A multicentre, randomized, prospective, double-blind placebo-controlled cross-over study was conducted to determine the effect of the PPI pantoprazole on the MPA and its metabolite MPA-glucuronide (MPA-G) area under the curve (AUC) >12 h (MPA-AUC12 h) in recipients maintained on mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). We planned a priori to examine separately recipients maintained on MMF and EC-MPS for each pharmacokinetic parameter. The trial (and protocol) was registered with the Australian New Zealand Clinical Trials Registry on 24 March 2011, with the registration number of ACTRN12611000316909 ('IMPACT' study). RESULTS: Of the 45 recipients screened, 40 (19 MMF and 21 EC-MPS) were randomized. The mean (standard deviation) recipient age was 58 (11) years with a median (interquartile range) time post-transplant of 43 (20-132) months. For recipients on MMF, there was a significant reduction in the MPA-AUC12 h [geometric mean (95% confidence interval) placebo: 53.9 (44.0-65.9) mg*h/L versus pantoprazole: 43.8 (35.6-53.4) mg*h/L; P = 0.004] when pantoprazole was co-administered compared with placebo. In contrast, co-administration with pantoprazole significantly increased MPA-AUC12 h [placebo: 36.1 (26.5-49.2) mg*h/L versus pantoprazole: 45.9 (35.5-59.3) mg*h/L; P = 0.023] in those receiving EC-MPS. Pantoprazole had no effect on the pharmacokinetic profiles of MPA-G for either group. CONCLUSIONS: The co-administration of pantoprazole substantially reduced the bioavailability of MPA in patients maintained on MMF and had the opposite effect in patients maintained on EC-MPS, and therefore, clinicians should be cognizant of this drug interaction when prescribing the different MPA formulations.

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.

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.

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.

Impact of early conversion from cyclosporin to everolimus on left ventricular mass index: A randomized controlled trial.

This is an 18-month prospective, randomized controlled trial (RCT) designed to compare the effect of early conversion from cyclosporin to everolimus/mycophenolic acid (E-MPA) between 3 and 4 months post-transplant to cyclosporin/mycophenolic acid (CsA-MPA) on left ventricular mass index (LVMI) at 3 and 18 months post-transplant (primary outcome). Secondary outcomes included estimated glomerular filtration rate (eGFR), viral infection, and adverse events. Twenty-four patients were randomized in a 1:1 ratio to E-MPA or CsA-MPA groups. There were no significant differences in mean (SD) LVMI at 3 (51.6±18.5 vs 53.7±15.7 g/m2.7 ) and 18 months (52.7±16.3 vs 51.7±16.8 g/m2.7 ) between CsA-MPA and E-MPA groups. The incidence of viral infections was reduced in E-MPA compared to CsA-MPA treatment groups (8% vs 50%, P=.02), but the incidences of acute rejection, adverse events, and drug discontinuation were similar between groups. There was an overall increase in eGFR with time (0.04 log- mL/min/1.73 m2 per 6 months, P=.012) but no significant difference between the two groups across time (0.11 log- mL/min/1.73 m2 , P=.311). Immunosuppressive regimen comprising early conversion from cyclosporine to everolimus was not associated with a regression of LVMI, but a lower risk of viral infections was observed.

Recurrent podocytopathy in a patient with systemic lupus erythematosus.

Podocytopathy in systemic lupus erythematosus is characterised by diffuse foot process effacement without significant peripheral capillary wall immune deposits as seen on electron microscopy. Lupus podocytopathy falls outside the scope of the current International Society of Nephrology and the Renal Pathology Society classification of lupus nephritis. We present a case of relapsing podocytopathy with nephrotic syndrome occurring simultaneously with two extra-renal and serological disease flares, which makes it likely that podocytopathy was related to systemic lupus erythematosus activity. This case adds to the growing body of evidence that lupus podocytopathy must be considered in the differential diagnosis of systemic lupus erythematosus patients presenting with nephrotic syndrome.

Insulin resistance and vascular dysfunction in chronic kidney disease: mechanisms and therapeutic interventions.

Insulin resistance (IR) is a novel cardiovascular risk factor that has been implicated in the pathogenesis of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Beyond its metabolic effects, insulin can potentially mediate the increased risk for CVD through its vasoactive properties. This review examines key clinical data and potential mechanisms linking IR and cardiovascular risk in CKD. While lifestyle interventions and pharmacotherapies with known insulin-sensitizing properties are promising therapeutic targets to reduce the CVD burden in this population, clinical trial data on the effect of insulin sensitization on vascular function in CKD are either lacking or conflicting and are limited by small sample size and short duration of intervention. Affirming the role of IR in lowering CVD risk in CKD will require prospective randomized controlled studies with sufficient sample size and hard clinical outcomes. Future research efforts should be directed at assessing the efficacy, safety and mechanisms by which novel insulin sensitizers such as bile acid sequestrant, selective and dual peroxisome proliferator-activated receptor modulators and modulators of gut microbiota and uraemic toxins alter vascular function in patients with CKD.

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 chronic kidney disease and short-term treatment with rosiglitazone on plasma cell-free DNA levels.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease. Circulating free nucleic acids, known as cell-free DNA (cfDNA), have been proposed as a novel biomarker of cardiovascular risk. The impact of renal impairment on cfDNA levels and whether cfDNA is associated with endothelial dysfunction and inflammation in CKD has not been systematically studied. We analysed cfDNA concentrations from patients with varying degrees of CKD. In addition, to determine whether there is a relationship between cfDNA, inflammation, and endothelial dysfunction in CKD, levels of proinflammatory cytokines and von Willebrand Factor (vWF) were measured in patients treated with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone or placebo for 8 weeks. cfDNA levels were not increased with renal impairment or associated with the degree of renal dysfunction (P = 0.5). Treatment with rosiglitazone for 8 weeks, but not placebo, was more likely to lead to a reduction in cfDNA levels (P = 0.046); however, the absolute changes in cfDNA concentrations during treatment were not statistically significant (P > 0.05). cfDNA levels correlated with markers of endothelial dysfunction (hsCRP P = 0.0497) and vWF (P = 0.0005). In conclusion, cell-free DNA levels are not influenced by renal impairment but do reflect endothelial dysfunction in patients with CKD.

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.

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.

Insulin resistance and the metabolic syndrome are associated with arterial stiffness in patients with chronic kidney disease.

BACKGROUND: Insulin resistance (IR) and the metabolic syndrome (MetS) may contribute to cardiovascular risk in chronic kidney disease (CKD). We examine the association between IR and vascular function in CKD. Furthermore, we define the prevalence of MetS and examine the association between defining MetS and vascular function. METHODS: This cross-sectional study of 71 stage 3-4 CKD subjects assessed arterial stiffness (pulse wave velocity (PWV) and endothelial dysfunction (ED). IR was assessed using Homeostasis Model Assessment-IR (HOMA-IR). MetS was defined by the unified International Diabetes Federation and American Heart Association/National Heart Lung and Blood Institute criteria. RESULTS: CKD subjects with HOMA-IR score above the median had significantly higher body mass index and waist circumference. They also had higher PWV, higher triglycerides with lower high-density lipoprotein concentration (P < 0.05). Age, systolic blood pressure, and HOMA-IR were independently associated with PWV, even after exclusion of diabetic subjects (n = 16) (P ≤ 0.05). MetS was more prevalent in CKD (78.9%) than controls (2.5%). MetS in CKD was associated with increased PWV (MetS(+) geometric mean = 9.5 m/s, 95% confidence interval (95% CI) = 8.9-10.2 m/s; vs. MetS(-) 8.1 m/s, 95% CI = 7.1-9.3 m/s; P = 0.03) but not ED. In a multiple logistic regression analysis, PWV higher than the median was independently associated with dysglycemia. CONCLUSIONS: IR is independently associated with arterial stiffness, even in nondiabetic CKD. MetS is common and identified a subgroup of CKD patients with increased arterial stiffness, which is associated with dysglycemia.

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.

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.

Patients' perceptions of subcutaneous delivery of darbepoetin alfa by autoinjector prefilled pen versus prefilled syringe: a randomized, crossover study.

BACKGROUND: Subcutaneous injection of erythropoiesis-stimulating agents for the correction of anemia associated with chronic kidney disease is well recognized. Different delivery devices are available, although their impact on patient-reported outcomes is limited. OBJECTIVES: Subcutaneous delivery of darbepoetin alfa via an autoinjector prefilled pen (PFP) and prefilled syringe (PFS) were compared and assessed according to patient-rated preferences and perceptions. METHODS: In this single-center, randomized, open-label, double-crossover study, patients continued using the PFS for 4 injections or were switched to the PFP for the same number of injections, after which they were switched to the alternative device. Following further 4 injections using the new device, patients were switched back to the initial device. Questionnaires were administered at the end of each series of injections for each device and at the start and end of the study. RESULTS: For overall device preference, the majority (62%) of patients responded with PFP, whereas 32% preferred the PFS mode of delivery. This preference for PFP was driven by a perception of increased convenience and ease of use compared with PFS. No significant differences in pain scores were noted between the 2 devices. Most patients rated both devices as being "easy" or "extremely easy" to use and were either "satisfied" or "extremely satisfied." CONCLUSION: When given the choice, most patients preferred the PFP mode of administration compared with PFS due to convenience and ease of use. ClinicalTrials.gov identifier: ACTRN12611000839909.

Association between initial and pretransplant dialysis modality and graft and patient outcomes in live- and deceased-donor renal transplant recipients.

The association between pretransplant dialysis modality and transplant outcomes remains inconsistent. The aim of this study is to address the association between alteration in dialysis modality and post-transplant outcomes. Using Australia and New Zealand Dialysis and Transplant Registry, primary live- and deceased-donor renal transplant recipients (RTR) between 1997 and 2009 were examined. Pre-emptive and multiple-organ transplants were excluded. The association between initial and pretransplant dialysis modality and transplant outcomes were examined. Of the 6701 RTR, 18.6% were initiated-maintained on peritoneal dialysis pretransplant (PD-PD), 9.2% were initiated on PD, but maintained on haemodialysis (HD) pretransplant (PD-HD), 63.3% were HD-HD and 8.9% were HD-PD. PD-HD [odds ratio(OR)1.44, 95% CI 1.21,1.72] and HD-HD (OR1.25, 95% CI 1.12,1.41) were associated with a significantly greater risk of slow graft function compared with the overall mean of the groups, whereas a change in initial dialysis modality from HD to pretransplant PD was associated with higher risk of overall graft failure [hazard ratio(HR)1.19, 95% CI 1.04,1.36) and recipient death (HR1.34, 95% CI 1.13,1.59). Our registry analysis suggest that dialysis modality pretransplant may affect transplant outcomes and future studies evaluating patient selection, choice of modality and/or potential interventions in the pre and post-transplant period may have a beneficial effect on post-transplant outcomes.

Lack of impact of donor age on patient survival for renal transplant recipients ≥60years.

There has been an increase in the number of older patients on the transplant waiting list and acceptance of older donor kidneys. Although kidneys from older donors have been associated with poorer graft outcomes, whether there is a differential impact of donor age on outcomes in older recipients remains unclear. The aim of this study was to evaluate the effect of donor age on graft and patient survival in renal transplant (RT) recipients ≥60years. Using the Australia and New Zealand Dialysis and Transplant Registry, outcomes of 1,037 RT recipients ≥60years between 1995 and 2009 were analyzed. Donor age groups were categorized into 0-20, >20-40, >40-60, and >60years. Compared with recipients receiving donor kidneys >60years, those receiving donor kidneys >20-40years had lower risk of acute rejection (odds ratio 0.46, 95% CI 0.27, 0.79; P<0.01) and death-censored graft failure (HR 0.37, 95% CI 0.19, 0.72; P<0.01). There was no association between donor age groups and death. With a corresponding growth in the availability of older donor kidneys and the observed lack of association between donor age and patient survival in RT recipients ≥60years, preferential allocation of older donor kidneys to RT recipients ≥60years may not disadvantage the life expectancy of these patients.

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.

Compared with younger peritoneal dialysis patients, elderly patients have similar peritonitis-free survival and lower risk of technique failure, but higher risk of peritonitis-related mortality.

BACKGROUND: The number of elderly patients with end-stage kidney disease (ESKD) is increasing worldwide, but the proportion of elderly patients commencing peritoneal dialysis (PD) is falling. The reluctance of elderly ESKD patients to consider PD may be related to a perception that PD is associated with greater rates of complications. In the present study, we compared outcomes between younger and older PD patients. METHODS: Using Australia and New Zealand Dialysis Registry data, all adult ESKD patients commencing PD between 1991 and 2007 were categorized into under 50, 50 - 64.9, and 65 years of age or older groups. Time to first peritonitis, death-censored technique failure, and peritonitis-associated and all-cause mortality were evaluated by multivariate Cox proportional hazards model analysis. RESULTS: Of the 12 932 PD patients included in the study, 3370 (26%) were under 50 years of age, 4386 (34%) were 50 - 64.9 years of age, and 5176 (40%) were 65 years of age or older. Compared with younger patients (<50 years), elderly patients (≥ 65 years) had a similar peritonitis-free survival and a lower risk of death-censored technique failure [hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.79 to 0.93], but they had higher peritonitis-related (HR: 2.31; 95% CI: 1.68 to 3.18) and all-cause mortality (HR: 2.90; 95% CI: 2.60 to 3.23). CONCLUSIONS: Not unexpectedly, elderly patients have higher peritonitis-related and all-cause mortality, which is likely a consequence of a greater prevalence of comorbid disease. However, compared with younger patients, elderly patients have superior technique survival and similar peritonitis-free survival, suggesting that PD is a viable renal replacement therapy in this group of patients.