Environmentally sustainable design guide for haemodialysis facilities: An Australian and New Zealand society of Nephrology initiative.

Haemodialysis facilities have a large environmental impact due to high energy, water and consumable usage by haemodialysis equipment. As climate change and natural resource scarcity escalate, all the while the number of people requiring dialysis increases, there is an urgent need for dialysis facilities that meet care needs while minimising environmental impact. To address this, the Australian and New Zealand Society of Nephrology engaged an environmental sustainability consulting practise to develop a best practise guide for the environmentally sustainable design and operation of haemodialysis facilities. Four opportunity areas were considered, namely energy, water, waste and resource recovery, and additional sustainability. A total of 28 environmental improvement initiatives were identified. The majority (n = 23) were general measures that could be applied across all healthcare settings, while five were specific to haemodialysis facilities. Recommendations were made regarding specific measures that should be undertaken and/or standards that must be met to achieve the intent of each initiative. These were stratified to enable their application to both existing dialysis facilities and new builds. The lifecycle stage of a haemodialysis facility to which each initiative applied was highlighted, as was its potential impact. This guide provides a tailored and comprehensive resource for the kidney care community to enable the integration of best practise sustainability considerations into both existing and new facilities. If broadly implemented, it has the potential to markedly improve the environmental impact of haemodialysis provision.

Rituximab Resistance in Glomerular Diseases: A GlomCon Mini Review.

Resistance to rituximab B-cell depletion therapy is a clinically pertinent adverse sequela that can have significant implications for the treatment of immune-mediated glomerular diseases. The true incidence of rituximab resistance remains unknown; however, it is an increasingly recognized treatment complication. Resistance typically presents with suboptimal treatment response, rapid B-cell reconstitution, and a relapsing disease course. Although the diverse mechanisms resulting in rituximab resistance are ongoing topics of research, both primary and secondary mechanisms have been identified as key catalysts. The emergence of human antichimeric antibodies (HACAs) is a major cause of secondary resistance to rituximab therapy and typically appears following repeated drug exposure. Frequently, HACAs develop in the setting of underlying autoimmune disease and contribute to poor B-cell depletion, reduced rituximab therapeutic efficacy, and enhanced drug clearance. The clinical challenge of rituximab resistance necessitates heightened awareness among clinicians. Screening for HACAs should be considered in individuals with poor clinical response to rituximab, more rapid B-cell reconstitution, and relapsing disease. Detection of HACAs may guide treatment alterations, including addition of further immunosuppressive therapy and transitioning to a humanized B-cell depleting monoclonal antibody.

Approach to Pregnancy in Patients With Lupus Nephritis.

Active lupus nephritis (LN) in pregnancy is strongly associated with poor maternal and fetal outcomes and, therefore, has implications on the planning, timing, and management. Prepregnancy evaluation is essential for all LN patients with childbearing potential to ensure pregnancies proceed in a safe and timely manner. Both maternal and fetal risks are communicated to patient during the evaluation. Stratification into different risk profile groups is then made based on disease activity and organ impairment severity. Patients with LN are generally divided into 3 main groups. Patients with LN who become pregnant receive treatments that are nonteratogenic and optimal for fetal and maternal outcomes. Throughout the pregnancy period, these patients are monitored closely under surveillance by a multidisciplinary team of clinicians. The management of patients with LN in pregnancy can be challenging both diagnostically (distinguishing LN from pre-eclampsia and determining the role and timing of kidney biopsy) and therapeutically (LN flares during pregnancy and managing a newly diagnosed LN during pregnancy).

Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors and CKD: Are You a #Flozinator?

Sodium/glucose cotransporter 2 (SGLT2) inhibitors have rapidly emerged as a novel therapy to reduce the rate of progression of chronic kidney disease (CKD). With humble beginnings in the 19th century for treating malaria, this class of drugs initially developed for the treatment of diabetes has now revolutionized the management of heart failure and CKD. SGLT2 inhibitors trigger glucosuria, thus modestly improving glycemic control. In addition, they have pleiotropic effects, such as reducing intraglomerular pressure and improving tubuloglomerular feedback, which lead to their beneficial effects on CKD progression. Recent data from randomized controlled trials have demonstrated the efficacy of this class of drugs in CKD. We briefly review the evidence from major trials on SGLT2 inhibitors in CKD, discuss the mechanisms of action and provide an overview of the safe and successful prescription of these medications.

Management of antineutrophil cytoplasmic antibody-associated vasculitis: a changing tide.

PURPOSE OF REVIEW: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a group of autoimmune disorders of small blood vessels. While outcomes in AAV have improved with the use of glucocorticoids (GC) and other immunosuppressants, these treatments are associated with significant toxicities. Infections are the major cause of mortality within the first year of treatment. There is a move towards newer treatments with better safety profiles. This review reflects on recent advances in the treatment of AAV. RECENT FINDINGS: The role of plasma exchange (PLEX) in AAV with kidney involvement has been clarified with new BMJ guideline recommendations following the publication of PEXIVAS and an updated meta-analysis. Lower dose GC regimens are now standard of care. Avacopan (C5a receptor antagonist) was noninferior to a regimen of GC therapy and is a potential steroid-sparing agent. Lastly, rituximab-based regimens were noninferior to cyclophosphamide in two trials for induction of remission and superior to azathioprine in one trial of maintenance of remission. SUMMARY: AAV treatments have changed tremendously over the past decade with a drive towards targeted PLEX use, increased rituximab use and lower GC dosing. Striking a crucial balance between morbidity from relapses and toxicities from immunosuppression remains a challenging path to navigate.

The incidence of cancer recurrence and new cancer following commencement of dialysis.

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.

The Accuracy of Sequence-Specific Oligonucleotide and Real-Time Polymerase Chain Reaction HLA Typing in Determining the Presence of Pre-Transplant Donor-Specific Anti-HLA Antibodies and Total Eplet Mismatches for Deceased Donor Kidney Transplantation.

High resolution human leukocyte antigen (HLA) typing is important in establishing eplet compatibility and the specificity of donor-specific anti-HLA antibodies (DSA). In deceased donor kidney transplantation, high resolution donor HLA typing may not be immediately available, leading to inaccuracies during the organ allocation process. We aimed to determine the concordance and agreement of HLA-Class I and II eplet mismatches calculated using population frequency based allelic haplotype association (linkage disequilibrium, LD) from sequence-specific oligonucleotide (SSO) and real-time polymerase chain reaction (rtPCR) donor HLA typing (available at time of donor kidney allocation) compared to high-resolution Next Generation Sequencing (NGS) donor typing. NGS high resolution HLA typing were available for all recipients prior to donor kidney allocation. A cohort of 94 deceased donor-recipient pairs from a single Western Australian center were included (77 individual donors typed, 55 local and 22 interstate). The number of class I (HLA-A+B+C) and class II (HLA-DRB1+DRB3/4/5+DQB1+DQA1+DPB1+DPA1) eplet mismatches were calculated using HLAMatchmaker, comparing LD- and NGS-HLA typing. The accuracy in assigning pre-transplant DSA was compared between methods. The concordance correlation coefficient (95%CI) for HLA-class I and II eplet mismatches were 0.994 (0.992 to 0.996) and 0.991 (0.986 to 0.993), respectively. The 95% limits of agreement for class I were -1.3 (-1.6 to -1.1) to 1.4 (1.2 to 1.7) and -4.8 (-5.7 to -3.9) to 5.0 (4.1 to 5.9) for Class II. Disagreement between the two methods were present for 11 and 37 of the Class I and II donor/recipient pairs. Of which, 5 had a difference of ≥5 class II eplet mismatches. There were 34 (36%) recipients with potential pre-transplant DSA, of which 8 (24% of recipients with DSA) had indeterminate and ultimately false positive DSA assigned by donor LD-typing. While the concordance between NGS- and LD-typing was high, the limits of agreement suggest meaningful differences between these two techniques. The inaccurate assignment of DSA from donor LD-typing may result in associated HLA being considered unacceptable mismatches, inappropriately precluding candidates' access to transplantation. Accurate imputation of two-field HLA alleles based on LD from SSO and rtPCR HLA typing remains a substantial challenge in clinical practice in-lieu of widely available, rapid, high-resolution methods.

mTOR Inhibitors Induce Erythropoietin Resistance in Renal Transplant Recipients.

Aim: To elucidate the role of mTOR inhibitors on iron, hepcidin and erythropoietin-mediated regulation of hemopoiesis in stable renal transplant recipients (RTR). Background: Impaired 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. Methods: We 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. Results: There 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.

Incidence and Outcomes of COVID-19 in People With CKD: A Systematic Review and Meta-analysis.

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.

Health-Related Quality of Life in People Across the Spectrum of CKD.

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 (ß [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.

Assessment of kidney transplant suitability for patients with prior cancers: is it time for a rethink?

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.

A retrospective study of tunnelled haemodialysis central line-associated bloodstream infections.

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.

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.

Absence of thrombocytopaenia and/or microangiopathic haemolytic anaemia does not reliably exclude recurrence of atypical haemolytic uraemic syndrome after kidney transplantation.

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.