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Background Home-based dialysis therapies, home hemodialysis (HHD) and peritoneal dialysis (PD) are underutilized in many countries and significant variation in the uptake of home dialysis exists across dialysis centers. This study aimed to evaluate the patient- and center-level characteristics associated with uptake of home dialysis. Methods The Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry was used to include incident dialysis patients in Australia and New Zealand from 1997 to 2017. Uptake of home dialysis was defined as any HHD or PD treatment reported to ANZDATA within 6 months of dialysis initiation. Characteristics associated with home dialysis uptake were evaluated using mixed effects logistic regression models with patient- and center-level covariates, era as a fixed effect and dialysis center as a random effect. Results Overall, 54 773 patients were included. Uptake of home-based dialysis was reported in 24 399 (45%) patients but varied between 0 and 87% across the 76 centers. Patient-level factors associated with lower uptake included male sex, ethnicity (particularly indigenous peoples), older age, presence of comorbidities, late referral to a nephrology service, remote residence and obesity. Center-level predictors of lower uptake included small center size, smaller proportion of patients with permanent access at dialysis initiation and lower weekly facility hemodialysis hours. The variation in odds of home dialysis uptake across centers increased by 3% after adjusting for the era and patient-level characteristics but decreased by 24% after adjusting for center-level characteristics. Conclusion Center-specific factors are associated with the variation in uptake of home dialysis across centers in Australia and New Zealand.

Background and Aims In the era of organ shortage, home hemodialysis (HHD) has been identified as the possible preferential bridge to kidney transplantation. Data are conflicting regarding the comparability of HHD and transplantation outcomes. This study aimed to compare patient and treatment survival between HHD patients and kidney transplant recipients. Method The Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry was used to include incident HHD patients on day 90 after initiation of kidney replacement therapy and first kidney-only transplant recipients in Australia and New Zealand from 1997 to 2017. Survival times were analyzed using the Kaplan-Meier product limit method comparing HHD patients to subtypes of kidney transplant recipients using the log-rank test. Adjusted analyses were performed with multivariable Cox proportional hazards regression models for time to all-cause mortality. Time-to-treatment failure or death was assessed as a composite secondary outcome. Results The study compared 1411 HHD patients to 4960 living donor (LD) recipients, 6019 standard criteria donor (SCD) recipients and 2427 expanded criteria donor (ECD) recipients. While LD and SCD recipients had reduced risks of mortality compared to HHD patients (LD adjusted hazard ratio [HR] 0.57, 95%CI 0.46-0.71; SCD HR 0.65 95%CI 0.52-0.79), the risk of mortality was comparable between ECD recipients and HHD patients (HR 0.90, 95%CI 0.73-1.12). LD, SCD and ECD kidney recipients each experienced superior time-to-treatment failure or death compared to HHD patients. Conclusion This large registry study showed that kidney transplant offers a survival benefit compared to HHD but that this advantage is not significant for ECD recipients.

Background and Aims Impaired physical fitness is prevalent across the spectrum of kidney disease and is associated with an increased risk of mortality, progression to end-stage kidney disease, falls and hospitalisation. Physical fitness outcomes have been extensively reported in randomised trials involving patients with kidney disease. This study aimed to assess the scope and consistency of physical fitness outcomes and outcome measures reported in kidney disease trials. Method A systematic review of randomised trials reporting physical fitness outcomes in adults with chronic kidney disease not requiring kidney replacement therapy, receiving maintenance haemodialysis or peritoneal dialysis, and kidney transplant recipients was conducted. The scope, frequency and characteristics of physical fitness outcome measures were categorised and analysed. Trials were identified from MEDLINE, Embase and the Cochrane Library from March 2000 to March 2019. Results From 115 relevant trials, 171 outcome measures for 32 outcomes were identified and categorised into five domains of physical fitness: exercise capacity (reported in 83% of trials), physiological-metabolic (57%), neuromuscular fitness (52%), body composition (45%) and cardiorespiratory fitness (19%). Exercise capacity had 53 different outcome measures and at 15 separate time points. The most common outcome measures were the 6-minute walk test (29%), peak oxygen uptake (20%), 1-repetition maximum (19%) and hand-grip strength (11%), with marked inconsistency in the reporting of outcomes between trials. Outcomes were assessed by field-based tests (65%), lab-based tests (31%) and patient-reported measures (4%). Conclusion There is large heterogeneity in the reporting of physical fitness outcomes, with inconsistencies in the use of validated, relevant and patient-important outcome measures.

Objectives: This study aims to investigate how immunosuppression influences the protein expression of antiapoptotic members of the Bcl-2 family—namely, Bcl-xL and Mcl-1—in nonmelanoma skin cancer (NMSC) and the peritumoral epidermis of renal transplant recipients. Methods: NMSC and peritumoral epidermis protein expression of Bcl-xL and Mcl-1 were assessed by immunohistochemistry in renal transplant recipients receiving tacrolimus or sirolimus and the general population not receiving immunosuppression. Results: NMSC from renal transplant recipients compared with patients not receiving immunosuppressant medications had a reduced Bcl-xL expression intensity ( P = .042). Mcl-1 expression intensity in NMSC was decreased in tacrolimus-treated patients compared with sirolimus-treated patients and the nonimmunosuppressed population ( P = .024). Bcl-xL expression intensity was increased in peritumoral epidermis compared with NMSC ( P = .002). Conclusions: It was shown for the first time that Bcl-xL and Mcl-1 expression are widespread in the peritumoral epidermis and NMSC of renal transplant recipients. Importantly in NMSC, Bcl-xL expression was reduced with immunosuppression exposure, and Mcl-1 expression was reduced in tacrolimus-treated compared with sirolimustreated patients.

Background. Preliminary clinical evidence suggests that heme iron polypeptide (HIP) might represent a promising, novel oral iron supplementation strategy in chronic kidney disease. The aim of this multi-centre randomized controlled trial was to determine the ability of HIP administration to augment iron stores in darbepoetin (DPO)-treated patients compared with conventional oral iron supplementation. Methods. Adult peritoneal dialysis (PD) patients treated with DPO were randomized 1:1 to receive two capsules daily of either HIP or ferrous sulphate per os for 6 months. The primary outcome measure was transferrin saturation (TSAT). Secondary outcomes comprised serum ferritin, haemoglobin, DPO dose and responsiveness, and adverse events. Results. Sixty-two patients were randomized to HIP (n= 32) or ferrous sulphate (n= 30). On intention-to-treat analysis, the median (inter-quartile range) TSAT was 22% (16–29) in the HIP group compared with 20% (17–26 )i n controls (P = 0.65). HIP treatment was not significantly associated with TSATat 6 months on multivariable analysis (P = 0.95). Similar results were found on per-protocol analysis and subgroup analysis in iron-deficient patients. Serum ferritin levels at 6 months were significantly lower in the HIP group (P = 0.003), while the cost of HIP was 7fold higher than that of ferrous sulphate. No other differences in secondary outcomes were observed. Conclusions. HIP showed no clear safety or efficacy benefit in PD patients compared with conventional oral iron supplements. The reduction in serum ferritin levels and high costs associated with HIP therapy suggest that this agent is unlikely to have a significant role in iron supplementation in PD patients.

High cardiovascular risk in chronic kidney disease (CKD) patients appears only partly attributable to atherosclerosis, with much of the remaining risk being ascribed to other vasculature abnormalities, including endothelial dysfunction, arterial stiffness and vascular calcification (VC). To date, these factors have been primarily studied in isolation or in dialysis patients. This study performed a global vascular assessment in moderate CKD and assessed the relationships with both traditional and novel risk factors.This was a prospective cross-sectional analysis of 120 patients (age 60 ± 10 years; estimated glomerular filtration rate 25-60 mL/min/1.73m(2)). Demographic, clinical and biochemical characterization was performed. VC was characterized by lateral lumbar radiograph; arterial stiffness by aortic pulse-wave velocity (PWV); atheroma burden by carotid intima-media thickness (cIMT) and endothelial function by flow-mediated dilation (FMD) of the brachial artery.VC was highly prevalent (74%), and FMD generally poor (FMDΔ 3.3 ± 3.3%). There were significant correlations between all vascular parameters; although these were predominantly explained by age. cIMT was independently associated with classical risks and also PWV (adjusted standardized β = 0.31, P = 0.001). However, traditional risks showed almost no independent associations with other vascular measurements. In contrast, serum phosphate and 1,25-dihydroxyvitamin D (1,25-OHD) correlated with PWV and the presence of VC, respectively. After adjustment, every 1 pg/mL increase in 1,25-OHD was related to a 3% reduction in the chance of VC (odds ratio 0.97; 95% confidence interval 0.94-1.00, P = 0.03). Medication use, HOMA-IR and C-reactive protein did not correlate with any of the vascular measures.This study demonstrates extensive vascular disease across multimodality imaging in moderate CKD. Atherosclerotic burden correlated with traditional risks and PWV, while higher 1,25-OHD was associated with less VC. The lack of association between renal function and imaging indices raises the possibility of a threshold, rather than graded uraemic effect on vascular health that warrants further exploration.

Background. Serum creatinine concentration is an unreliable and insensitive marker of chronic kidney disease (CKD). To improve CKD detection, the Australasian Creatinine Consensus Working Committee recommended reporting of estimated glomerular filtration rate (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD) formula with every request for serum creatinine concentration. The aim of this study was to evaluate the impact of automated laboratory reporting of eGFR on the quantity and quality of referrals to nephrology services in Southeast Queensland, Australia. Methods. Outpatient referrals to a tertiary and regional renal service, and a single private practice were prospectively audited over 3–12 months prior to and 12 months following the introduction of automated eGFR reporting and concomitant clinician education. The appropriateness of referrals to a nephrologist was assessed according to the Kidney Check Australia Taskforce (KCAT) criteria. Significant changes in the quantity and/or quality of referrals over time were analysed by exponentially weighed moving average (EWMA) charts with control limits based on ±3 standard deviations. Results. A total of 1019 patients were referred to the centres during the study period. Monthly referrals overall increased by 40% following the introduction of eGFR reporting, and this was most marked for the tertiary renal service (52% above baseline). The appropriateness of nephrologist referrals, as adjudicated by the KCAT criteria, fell significantly from 74.3% in the 3 months pre-eGFR reporting to 65.2% in the 12 months thereafter (P < 0.05). Nevertheless, a greater absolute number of CKD patients were appropriately being referred for nephrologist review in the post-eGFR period (24 versus 15 per month). Patients referred following the introduction of eGFR were significantly more likely to be older (median 63.2 versus 59.3 years, P < 0.05), diabetic (25 versus 18%, P = 0.05) and have stage 3 CKD (48% versus 36%, P < 0.01). Conclusion. The introduction of automated eGFR calculation has led to an overall increase in referrals with a small but significant decrease in referral quality. The increase in referrals was seen predominantly in older and diabetic patients with stage 3 CKD and appeared to result in net benefit.

Background. The aim of the present study was to determine whether the deceased donor kidney side (left or right kidney) was predictive of subsequent kidney transplant outcomes. Methods. A retrospective analysis was undertaken of the left–right deceased donor kidney pairs transplanted into recipients with end-stage renal failure in Queensland between 1 April 1994 and 31 March 2004. Results. A total of 201 left–right deceased donor kidney pairs were transplanted into 402 patients. The baseline characteristics of the recipients in the two groups were comparable, except that the patients receiving right kidneys had lower body mass indices and shorter cold ischaemic times. No differences were seen between the left and right kidney recipient groups with respect to operative duration (3.02 � 0.67 vs 3.12 � 0.72 h, P ¼ 0.16), warm ischaemic time (0.62 � 0.18 vs 0.65 � 0.21, P ¼ 0.09), delayed graft function (4 vs 6%, respectively, P ¼ 0.26) or a composite vascular, haemorrhagic, ureteric and infective post-operative complication end-point (22 vs 22%, P ¼ 0.90). Estimated glomerular filtration rates were almost identical at 1 month (52.7 � 39.6 vs 51.0 � 24.0 ml/min/1.73 m 2 , P ¼ 0.34) and remained comparable thereafter. Respective death-censored graft survival rates for left and right kidney recipients were 100 and 100% at 1 year, 99.4 and 96.4% at 3 years and 96.3 and 95.5% at 5 years, respectively (P ¼ 0.67). Conclusions. Although left and right deceased donor kidneys present different operative challenges, the present results suggest that the probability of early post-operative complications, delayed graft function, impaired early and medium-term renal allograft function or death-censored graft failure is comparable between left and right kidney recipients.

Cardiovascular disease is the major cause of death in the end-stage renal disease population. Novel risk factors such as homocysteine (Hcy) are of considerable interest in this group as hyperhomocysteinaemia is highly prevalent in the setting of renal impairment. Folic acid-vitamin B group therapies are only partially effective treatments. Hcy is highly protein-bound and thus poorly dialysed. Dialyzers with albumin-leaking properties have been shown to result in lowering of plasma Hcy. As the FX-class (Advanced Fresenius Polysulfone dialyzer) has greater clearance of larger molecular weight substances but is non-albumin-leaking, we explored the capacity of this new technology membrane to reduce plasma Hcy levels.A prospective randomized cross-over trial in 35 prevalent haemodialysis patients, one group receiving 12 weeks dialysis using FX dialyzer then 12 weeks with standard high flux dialysis (SHF) and the other group SHF followed by FX dialyzer. All patients received vitamin B(6) 25 mg and folic acid 5 mg daily throughout the study.The primary outcome was plasma Hcy pre-dialysis at week 12. FX vs SHF showed no significant difference, 25+/-6.6 vs 25.9+/-5.8 microg/l, Delta95% CI = -2.77 to 4.59, P = 0.31. There was a non-significant trend toward a decrease in Hcy in both groups (27.43+/-7.68 to 25.91+/-5.78 micromol/l for SHF, P = 0.23 and 26.0+/-4.58 to 25.0+/-6.61 micromol/l for FX, P = 0.28). Analysis by repeated measures method demonstrated a statistically significantly lower Hcy with FX vs SHF dialyzer (adjusted beta = -1.30, 95% CI = -2.41 to -0.19, P = 0.022). K(t)/V(urea) was higher in FX vs SHF (1.35+/-0.18 vs 1.22+/-0.2; P = 0.013). Folate and B(6) levels did not change.The primary outcome analysis did not show any significant difference in pre-Hcy comparing FX and SHF membranes. Although our secondary analysis demonstrated a statistically significant difference between membranes, the magnitude of the difference (1.3 mumol/l) is not clinically significant. Thus the use of the FX dialyzer did not result in a clinically significant benefit in relation to improving pre-dialysis Hcy compared with standard high-flux dialysis.

Background. Macrophage accumulation is a prominent feature in many forms of glomerulonephritis. Local proliferation of macrophages within the kidney has been described in human and experimental glomerulonephritis and may have an important role in augmenting the inflammatory response. The current study examined the relationship between local macrophage proliferation and renal expression of macrophage colony-stimulating factor (M-CSF). Methods. A total of 118 renal biopsies of patients with a wide range of glomerulonephridities were examined for M-CSF protein and macrophage proliferation (KP1 + PCNA + cells) by single and double immunohistochemistry staining, respectively. Results. Biopsies of thin membrane disease (TMD) with histologically normal kidney showed M-CSF protein expression by 33% of cortical tubules, while glomerular M-CSF expression was limited to resident macrophages and some podocytes. Glomerular M-CSF expression increased significantly in proliferative forms of glomerulonephritis, with M-CSF staining of infiltrating macrophages, podocytes and some mesangial cells. Segmental areas of strong M-CSF expression, particularly in crescents, co-localized with KP1 + PCNA + proliferating macrophages. There was also an increase in tubular M-CSF expression in most types of glomerulonephritis. Tubular M-CSF staining was strongest in areas of tubular damage and co-localized with KP1 + macrophages, including KP1 + PCNA + proliferating macrophages. Many interstitial macrophages and α-smooth muscle actin-positive myofibroblasts showed strong M-CSF staining. Statistical analysis showed a highly significant correlation between M-CSF expression and local macrophage proliferation in both the glomerulus and tubulointerstitium. Glomerular and tubular M-CSF expression gave a significant correlation with renal dysfunction. Conclusions. Glomerular and tubulointerstitial M-CSF expression is up-regulated in human glomerulonephritis, being most prominent in proliferative forms of disease. This correlated with local macrophage proliferation, suggesting that increased renal M-CSF production plays an important role in regulating local macrophage proliferation in human glomerulonephritis.

Background. No conventional immunosuppressive agent preferentially inhibits antibody production. Studies in experimental animals and in human cells in vitro suggested mycophenolate mofetil (MMF) might have such an effect. If this was the case in vivo it could have significant implications in terms of both MMF toxicity and the rational design of immunotherapeutic regimens. Methods. Subjects were renal transplant recipients (25 patients treated with prednisolone, cyclosporine and azathioprine, and 13 treated with prednisolone, cyclo­ sporine and MMF) and 20 normal controls. The three groups received influenza vaccination, and the anti­ body response to it was measured 4-6 weeks later using a standard haemagglutination assay. Results. MMF profoundly suppressed the humoral immune response to influenza vaccination when added to prednisolone and cyclosporine. This effect could be seen when comparing the rise in the mean titre of antibody after vaccination. It was also reflected in the number of patients mounting responses deemed to be clinically protective by either demonstrating a 4-fold rise in titre or an increase in titre to ~ 40. Conclusions. Suppression of the humoral immune response by MMF has implications for the design of immunization protocols to protect the immuno­ suppressed, and raises the possibility that MMF use may be accompanied by more or different infections than complicate more conventional immunosuppres­ sion. More importantly, consideration should be given to harnessing the relatively specific effect of MMF on antibody production to treat antibody-mediated diseases.

SUMMARY Although macrophages play an important role in lipid-induced glomerular injury, we know little of the mechanisms by which hyperlipidaemia induces monocyte recruitment. This study investigated the role of M-CSF and macrophage MIF in monocyte recruitment during the development of lipid-induced glomerular injury in the susceptible ExHC rat strain. Groups of five ExHC rats were fed a high cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate and 15% olive oil, and killed after 3 days, 1, 2 or 6 weeks. Control animals were killed on day 0 or after 6 weeks on a normal diet. Animals were hypercholesterolaemic 3 days after the induction of the HCD, but showed no change in plasma triglycerides over the 6-week period. Glomerular macrophage accumulation was first evident at 1–2 weeks and increased up to week 6, when macrophage-derived foam cells were seen in almost all glomeruli, and segmental lesions and mild proteinuria were also evident. Combined in situ hybridization and immunohistochemistry staining demonstrated that, coincident with the induction of hypercholesterolaemia on day 3, there was marked up-regulation of M-CSF and MIF mRNA expression by intrinsic glomerular cells (mostly mesangial cells and podocytes) which preceded monocyte recruitment. There was a highly significant correlation between the number of M-CSF and MIF-positive cells and glomerular macrophage accumulation over the 6-week period. Although some glomerular macrophages and foam cells exhibited M-CSF and MIF expression, the major source of these molecules was intrinsic glomerular cells. No local macrophage proliferation was observed during the development of glomerular lesions. In conclusion, hypercholesterolaemia caused marked up-regulation of M-CSF and MIF expression by intrinsic glomerular cells, which correlated with monocyte recruitment and the development of lipid-induced glomerular injury. This is the first study to implicate local synthesis of MIF in the pathogenesis of lipid-induced lesions.