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Introduction People with chronic kidney disease (CKD) experience reduced quality of life (QoL) because of the high symptom and treatment burden. Limited data exist on the factors associated with overall and domain-specific QoL across all CKD stages. Methods Using data from a prospective, multinational study (Australia, New Zealand, Canada, and Spain) in 1696 participants with CKD, we measured overall and domain-specific QoL (pain, self-care, activity, mobility, anxiety/depression) using the EuroQoL, 5 dimension, 3 level. Multivariable linear regression and logistic modeling were used to determine factors associated with overall and domain-specific QoL. Results QoL for patients with CKD stages 3 to 5 (n = 787; mean, 0.81; SD, 0.20) was higher than in patients on dialysis (n = 415; mean, 0.76; SD, 0.24) but lower than in kidney transplant recipients (n = 494; mean, 0.84; SD, 0.21). Factors associated with reduced overall QoL (β [95% confidence intervals]) included being on dialysis (compared with CKD stages 3–5: –0.06 [–0.08 to –0.03]), female sex (–0.03 [–0.05 to –0.006]), lower educational attainment (– 0.04 [–0.06 to –0.02), lacking a partner (–0.04 [–0.06 to –0.02]), having diabetes (–0.05 [–0.07 to –0.02]), history of stroke (–0.09 [–0.13 to –0.05]), cardiovascular disease (–0.06 [–0.08 to –0.03]), and cancer (–0.03 [–0.06 to –0.009]). Pain (43%) and anxiety/depression (30%) were the most commonly affected domains, with dialysis patients reporting decrements in all 5 domains. Predictors for domain-specific QoL included being on dialysis, presence of comorbidities, lower education, female sex, and lack of a partner. Conclusions Being on dialysis, women with CKD, those with multiple comorbidities, lack of a partner, and lower educational attainment were associated with lower QoL across all stages of CKD., Graphical abstract

Background Patients with kidney failure have a higher cancer risk compared with the age-matched general population. However, the outcomes of incident dialysis patients with a prior cancer history are unknown. Methods Using Australia and New Zealand Dialysis and Transplant Registry data (2000–2019), the outcomes and survival probabilities of incident dialysis patients with prior cancers and having experienced a cancer recurrence or having developed a new cancer after dialysis commencement were described. Results Of 4912 patients with prior cancers before dialysis commencement, 323 (7%) and 343 (7%) patients experienced cancer recurrence or developed new cancers after dialysis initiation, respectively. The median time from dialysis commencement to cancer recurrence was 1.2 years [interquartile range (IQR) 0.5–2.8] and was 2.0 years (IQR 0.7–4.0) for new cancer occurrence. Of those with cancer recurrence, 80% presented with metastatic disease and one in two patients died from cancer, with a median time from cancer recurrence to death of 0.5 years (IQR 0.2–1.7). Of those who developed new cancer, urinary tract and respiratory cancers were the most frequent cancer types, with a median time from new cancer diagnosis to death of 1.3 years (IQR 0.4–3.1). The 3-year survival probabilities on dialysis following cancer recurrence and new cancer were 19% [95% confidence interval (CI) 15–24] and 41% (35–47), respectively. Conclusion Among incident dialysis patients with a prior cancer history, 14% experienced cancer recurrence or developed a new cancer. Patients who experienced cancer recurrence or developed new cancer have poor outcomes, with ˂50% surviving beyond 3 years. These findings suggest the need to have a greater understanding of the characteristics, cancer screening, treatment responses and reasons for commencing dialysis in patients with kidney failure and prior cancer history, which may help in the shared clinical decision-making process when considering dialysis for these patients.

AimTo elucidate the role of mTOR inhibitors on iron, hepcidin and erythropoietin-mediated regulation of hemopoiesis in stable renal transplant recipients (RTR).BackgroundImpaired hemopoiesis is common following renal transplantation managed using mTOR inhibitors. The mechanisms responsible are uncertain but include direct effects on iron, hepcidin or erythropoietin-mediated hemopoiesis.MethodsWe conducted a single center prospective case-control study of 26 adult RTR with stable allograft function. RTR received stable mTOR dosing (cases, 11/26 [42%]) or stable tacrolimus dosing (controls, 15/26 [58%]). Baseline demographics, full blood count, renal function, iron studies, hepcidin-25, Interleukin-6 (IL-6) and erythropoietin (EPO) levels were determined.ResultsThere were no differences in age, gender or allograft function. Mean daily sirolimus dose for cases was 1.72 mg, with mean trough level of 8.46 ng/mL. Mean daily tacrolimus dose for controls was 4.3 mg, with mean trough level of 5.8 ng/mL. There were no differences in mean hemoglobin (143 vs. 147 g/L; p = 0.59), MCV (88 vs. 90 fL; p = 0.35), serum ferritin (150 vs. 85.7 μg/L; p = 0.06), transferrin saturation (26 vs. 23.3%; p = 0.46), IL-6 (11 vs. 7.02 pg/ml; p = 0.14) or hepcidin-25 (3.62 vs. 3.26 nM; p = 0.76) between the groups. EPO levels were significantly higher in the group receiving mTOR therapy (16.8 vs. 8.49 IU/L; p = 0.028). On logistic regression analysis EPO level was the only variable that had a significant impact providing an odds ratio of 0.84 (95%CI 0.66–0.98). The area under the receiver operator characteristic curve (ROC) for the analysis was 0.77 (95%CI 0.54–0.94) with p = 0.04.Conclusion: Higher levels of EPO in the absence of deranged iron biochemistry or hepcidin-25 levels suggest that EPO resistance rather than impaired iron metabolism may contribute to the impaired hemopoiesis previously demonstrated in RTR on mTOR therapy.

Summary Kidney transplant recipients have up to a 100‐fold greater risk of incident cancer compared with the age/sex‐matched general population, attributed largely to chronic immunosuppression. In patients with a prior history of treated cancers, the type, stage and the potential for cancer recurrence post‐transplant of prior cancers are important factors when determining transplant suitability. Consequently, one of the predicaments facing transplant clinicians is to determine whether patients with prior cancers are eligible for transplantation, balancing between the accelerated risk of death on dialysis, the projected survival benefit and quality of life gains with transplantation, and the premature mortality associated with the potential risk of cancer recurrence post‐transplant. The guidelines informing transplant eligibility or screening and preventive strategies against cancer recurrence for patients with prior cancers are inconsistent, underpinned by uncertain evidence on the estimates of the incidence of cancer recurrence and the lack of stage‐specific outcomes data, particularly among those with multiple myeloma or immune‐driven malignancies such as melanomas. With the advent of newer anti‐cancer treatment options, it is unclear whether the current guidelines for those with prior cancers remain appropriate. This review will summarize the uncertainties of evidence informing the current recommendations regarding transplant eligibility of patients with prior cancers.

Rationale & Objective Coronavirus disease 2019 (COVID-19) disproportionately affects people with chronic diseases such as chronic kidney disease (CKD). We assessed the incidence and outcomes of COVID-19 in people with CKD. Study Design Systematic review and meta-analysis by searching MEDLINE, EMBASE, and PubMed through February 2021. Setting & Study Populations People with CKD with or without COVID-19. Selection Criteria for Studies Cohort and case-control studies. Data Extraction Incidences of COVID-19, death, respiratory failure, dyspnea, recovery, intensive care admission, hospital admission, need for supplemental oxygen, hospital discharge, sepsis, short-term dialysis, acute kidney injury, and fatigue. Analytical Approach Random-effects meta-analysis and evidence certainty adjudicated using an adapted version of GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results 348 studies (382,407 participants with COVID-19 and CKD; 1,139,979 total participants with CKD) were included. Based on low-certainty evidence, the incidence of COVID-19 was higher in people with CKD treated with dialysis (105 per 10,000 person-weeks; 95% CI, 91-120; 95% prediction interval [PrI], 25-235; 59 studies; 468,233 participants) than in those with CKD not requiring kidney replacement therapy (16 per 10,000 person-weeks; 95% CI, 4-33; 95% PrI, 0-92; 5 studies; 70,683 participants) or in kidney or pancreas/kidney transplant recipients (23 per 10,000 person-weeks; 95% CI, 18-30; 95% PrI, 2-67; 29 studies; 120,281 participants). Based on low-certainty evidence, the incidence of death in people with CKD and COVID-19 was 32 per 1,000 person-weeks (95% CI, 30-35; 95% PrI, 4-81; 229 studies; 70,922 participants), which may be higher than in people with CKD without COVID-19 (incidence rate ratio, 10.26; 95% CI, 6.78-15.53; 95% PrI, 2.62-40.15; 4 studies; 18,347 participants). Limitations Analyses were generally based on low-certainty evidence. Few studies reported outcomes in people with CKD without COVID-19 to calculate the excess risk attributable to COVID-19, and potential confounders were not adjusted for in most studies. Conclusions The incidence of COVID-19 may be higher in people receiving maintenance dialysis than in those with CKD not requiring kidney replacement therapy or those who are kidney or pancreas/kidney transplant recipients. People with CKD and COVID-19 may have a higher incidence of death than people with CKD without COVID-19.

Our understanding of the pathophysiology of the anaemia of chronic kidney disease (CKD) has improved considerably in the last decade with the discovery of the iron regulatory peptide hepcidin. Reduced clearance of hepcidin and the presence of a chronic inflammatory state contribute to elevated hepcidin levels in kidney disease. The recent discovery of the various factors and signalling pathways regulating hepcidin has opened up an exciting avenue for research into the development of newer agents that could treat anaemia of CKD. This review highlights our current understanding of iron metabolism in health, the regulators of hepcidin, issues associated with the current available therapies for the treatment of anaemia in CKD and potential novel therapies that could be available in the near future targeting the various factors that regulate hepcidin.

A 54-year-old man was diagnosed with atypical haemolytic uraemic syndrome (aHUS) with confirmed complement H mutation in 2012, requiring ongoing dialysis. He was commenced on eculizumab in 2014 once the pharmaceutical board approved this drug. After 4 months, he received a live unrelated donor renal transplant from his wife and continued eculizumab post-transplant. Three months later, there was a rise in his creatinine with no laboratory features of haemolysis and a kidney biopsy confirmed rejection, which was treated with increased immunosuppression. After completing 12 months of treatment with eculizumab, he opted for close monitoring rather than continuation with therapy. Five months post-cessation of the drug, there was a rise in creatinine, and once again, haematological parameters remained within reference range; however, his kidney biopsy showed features consistent with recurrence of aHUS; hence, eculizumab was recommenced with good effect. While there was no evidence of haemolysis, there was a gradual rise in LDH level and a drop in platelet count, although the parameters remained within the normal range. This suggests that aHUS can recur in the allograft in the absence of haematological abnormalities. Clinicians should have a low threshold for allograft biopsy if haematological parameters are not just outside the reference range, but possibly also if there are changes of at least >25% from baseline in platelet count and LDH levels, particularly in those patients who are no longer eligible for eculizumab.

Infection is a serious complication of tunnelled haemodialysis catheters. We aimed to describe the epidemiology of tunnelled haemodialysis central line-associated bloodstream infections (CLABSI) in an Australian centre. We performed a retrospective audit of tunnelled haemodialysis CLABSI from June 2010 to June 2014. From 674 catheter insertions, 70 CLABSI occurred in 55 patients at a rate of 0.95 infections per 1000 catheter days. Aboriginal and Torres Strait Islanders (ATSI) compared to non-ATSI had a higher rate of CLABSI (1.70 vs 0.58 CLABSI per 1000 catheter days, p 0.001). Staphylococcus aureus (n = 22, 31.4%), coagulase negative Staphylococci (n = 14, 17.5%), and Gram negative bacilli (n = 28, 35.0%) were the predominant causative organisms. Two patients who died both had Staphylococcus aureus infection. In conclusion, our infection rate and microbiology are similar to prior reports. Morbidity and mortality are associated with Staphylococcus aureus as the causative organism.

The association between prolonged cold ischemic time (CIT) and graft and patient outcomes in live donor kidney transplant recipients remains unclear. The aims of this study were to examine the association of CIT with delayed graft function and graft loss in live donor kidney transplant recipients and those who participated in the Australian Paired Kidney Exchange program using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Of 3717 live donor transplant recipients between 1997 and 2012 who were followed for a median of 6.6 years (25 977 person-years), 224 (25%) experienced CIT >4-8 h. Donor age was an effect modifier between CIT and graft outcomes. In recipients who received kidneys from older donors aged >50 years, every hour of increase in CIT was associated with adjusted odds of 1.28 (95% confidence interval [CI] 1.07-1.53, p = 0.007) for delayed graft function, whereas CIT >4-8 h was associated with adjusted hazards of 1.93 (95% CI 1.21-3.09, p = 0.006) and 1.91 (95% CI 1.05-3.49, p = 0.035) for overall and death-censored graft loss, respectively, compared with CIT of 1-2 h. Attempts to reduce CIT in live donor kidney transplants involving older donor kidneys may lead to improvement of graft outcomes.

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 3-4 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±15.7g/m2.7) and 18 months (52.7±16.3 vs. 51.7±16.8g/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=0.02), 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/1.73m2 per 6 months, p=0.012) but no significant difference between the two groups across time (0.11 log- ml/min/1.73m2, p=0.311). Immunosuppressive regimen comprising of early conversion from cyclosporine to everolimus was not associated with a regression of LVMI, but a lower risk of viral infections was observed. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000320055). This article is protected by copyright. All rights reserved.