Weekend effect: analysing temporal trends in solid organ donation

Background: Research suggests patients treated over weekends experience poorer outcomes. Only one US-based study explored this weekend effect in organ donation, specifically the kidney discard rate. In Australia potential donors are referred to a donation service, and donation proceeds if family consent is granted and the donor is deemed medically suitable to donate. Organ procurement occurs when utilization is almost certain hence discard rates are much lower than in the USA. We aimed to characterize the effect of weekend referral on organ donation in Australia. Methods: We retrospectively reviewed all New South Wales Organ and Tissue Donation Service logs from 2010 to 2016. Our primary outcome was progression to organ procurement, and secondary outcomes were family consent and meeting medical suitability thresholds. We used logistic regression with random effects adjusting for clustering of referral hospitals. Results: Of 3496 potential donors referred for consideration, 694 (20%) progressed to organ procurement. There were fewer referrals on weekends (average 415 versus 588 for weekdays). However, donation rates were no lower for weekend compared to weekday referrals (adjusted OR 1.17; 95% CI 0.95, 1.44). Family consent (adjusted OR 1.20; 95% CI 1.00, 1.44) and medical suitability (adjusted OR 1.15; 95% CI 0.96, 1.38) were not lower for weekend compared to weekday referrals. Similar results were found for all sensitivity analyses conducted. Conclusions: In Australia, the donation pathway operates consistently throughout the week, with donation no less likely to proceed on weekends and holidays. This finding contrasts with findings in the USA

Sex differences in mortality among binational cohort of people with chronic kidney disease: population based data linkage study

Objective To evaluate sex differences in mortality among people with kidney failure compared with the general population. Design Population based cohort study using data linkage. Setting The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which includes all patients receiving kidney replacement therapy in Australia (1980-2019) and New Zealand (1988-2019). Data were linked to national death registers to determine deaths and their causes, with additional details obtained from ANZDATA. Participants Of 82 844 people with kidney failure, 33 329 were female (40%) and 49 555 were male (60%); 49 376 deaths (20 099 in female patients; 29 277 in male patients) were recorded over a total of 536 602 person years of follow-up. Main outcome measures Relative measures of survival, including standardised mortality ratios, relative survival, and years of life lost, using general population data to account for background mortality (adjusting for country, age, sex, and year). Estimates were stratified by dialysis modality (haemodialysis or peritoneal dialysis) and for the subpopulation of kidney transplant recipients. Results Few differences in outcomes were found between male and female patients with kidney failure. However, compared with the general population, female patients with kidney failure had greater excess all cause deaths than male patients (female patients: standardised mortality ratio 11.3, 95% confidence interval 11.2 to 11.5, expected deaths 1781, observed deaths 20 099; male patients: 6.9, 6.8 to 6.9, expected deaths 4272, observed deaths 29 277). The greatest difference was observed among younger patients and those who died from cardiovascular disease. Relative survival was also consistently lower in female patients, with adjusted excess mortality 11% higher (95% confidence interval 8% to 13%). Average years of life lost was 3.6 years (95% confidence interval 3.6 to 3.7) greater in female patients with kidney failure compared with male patients across all ages. No major differences were found in mortality by sex for haemodialysis or peritoneal dialysis. Kidney transplantation reduced but did not entirely remove the sex difference in excess mortality, with similar relative survival (P=0.83) and years of life lost difference reduced to 2.3 years (95% confidence interval 2.2 to 2.3) between female and male patients. Conclusions Compared with the general population, female patients had greater excess deaths, worse relative survival, and more years of life lost than male patients, however kidney transplantation reduced these differences. Future research should investigate whether systematic differences exist in access to care and possible strategies to mitigate excess mortality among female patients

Hepatitis transmission risk IN kidney Transplantation (the HINT study); a cross-sectional survey of transplant clinicians in Australian and New Zealand

Background Interpreting hepatitis serology and virus transmission risk in transplantation can be challenging. Decisions must balance opportunity to transplant against potential infection transmission. We aimed to survey understanding among the Australian and New Zealand medical transplant workforce of hepatitis risk in kidney donors and recipients. Methods An anonymous, self-completed, cross-sectional survey was distributed via electronic mailing lists to Australian and New Zealand clinicians involved in kidney transplantation (2014-2015). We compared interpretation of clinical scenarios with paired donor and recipient hepatitis B virus and hepatitis C virus serology to recommendations in clinical practice guidelines. We used logistic regression modeling to investigate characteristics associated with decisions on transplant suitability in scenarios with poor (<50%) guideline concordance (odds ratios [OR]). Results One hundred ten respondents had representative workforce demographics: most were male (63%) nephrologists (74%) aged 40 to 49 years. Although donor and recipient hepatitis status was largely well understood, transplant suitability responses varied among respondents. For a hepatitis B virus surface antigen-positive donor and vaccinated recipient, 44% suggested this was unsuitable for transplant (guideline concordant) but 35% suggested this was suitable with prophylaxis (guideline divergent). In 4 scenarios with transplant suitability guideline concordance less than 50%, acute transplant care involvement predicted guideline concordant responses (OR, 1.69; P = 0.04). Guideline concordant responses were chosen less by hepatologists, intensive care doctors (OR, 0.23, 0.35, respectively; P = 0.01), and New Zealanders (guideline concordant responses OR, 0.17; P < 0.01; alternative responses OR, 4.31; P < 0.01). Conclusions Despite broadly consistent interpretations of hepatitis serology, transplant suitability decisions varied and often diverged from guidelines. Improved decision support may reduce clinician variability

Macrophage-derived interleukin-18 in kidney injury

Macrophage accumulation is a hallmark of kidney injury; this versatile cell has a central role in the development of kidney diseases, facilitating both tissue injury and in some cases repair. Interleukin-l8 (IL-18) is predominantly a macrophage-derived cytokine that plays a key role in inflammation and a broad range of immune responses. It has a role in both innate and adaptive immunity and is strategically placed in the hierarchy of the inflammatory cascade to be a potential therapeutic target. The aim ofthis work was to further elucidate the role of macrophages in models of kidney disease, specifically glomerulonephritis and acute allograft rejection, by focusing on lL-18, and furthermore to determine the potential clinical application of anti—lL-l 8 therapies. Glomerulonephritis accounts for a quarter of patients that develop end stage renal failure in Australia and focal segmental glomerulosclerosis (FSGS) is one ofthe most common forms ofthe disease. In this thesis, lL-l 8 expression was upregulated in Adriamycin nephropathy (AN), an experimental model of FSGS, while the administration of neutralising IL—1 8 binding protein ameliorated kidney damage. This study demonstrates the pathological significance of lL—18 in this model and raises the possibility of an attractive, clinically applicable therapy, potentially also relevant to other types of glomerulonephritis or macrophage-driven inflammatory diseases. Transplantation is a life-saving therapeutic option for patients with kidney failure, but its success is still hindered by acute rejection (AR). The alloimmune response relies on numerous effectors including macrophages and as lL-l8 is largely derived from macrophages we examined its role in the acute rejection process. In a rat model of acute rejection, lL-l8 expression was upregulated; depletion of macrophages resulted in a reduction of IL-18 and protection from rejection, while macrophage isolation experiments demonstrated specific intragraft macrophage upregulation of lL-l8. The functional significance of IL-1 8 upregulation was then examined utilising lL-l 8 knock-out mice and animals treated with neutralising lL-l8 binding protein. While these interventions significantly diminished the local pro-inflammatory allograft response and lL-l 8+ recipients revealed a Th2 biased response, there was no significant protection afforded against the development of acute rejection. In summary, lL—l 8 is involved in the pathogenesis ofinflammatory kidney disease. Kidney injury in an experimental model of GN was lL-l 8 dependent and importantly could be ameliorated by lL-18 blockade; an intervention with clear therapeutic potential. In the alloimmune response, lL-l 8 plays an active but non-essential role and blocking strategies alone are not protective against the development of acute rejection. The results of this thesis expand on the current understanding of local cytokine expression in acute rejection and support further exploration of IL-1 8BP therapies in inflammatory kidney disease

Peritoneal dialysis in pregnancy : a case series

Patients with significant renal impairment have difficulties maintaining a viable pregnancy due to maternal and fetal complications. Both peritoneal dialysis and hemodialysis support throughout pregnancy has been reported to assist in these pregnancies. We report our experience with the use of peritoneal dialysis in five cases leading to successful deliveries with minimal complications

Weekend effect: analysing temporal trends in solid organ donation

Background: Research suggests patients treated over weekends experience poorer outcomes. Only one US-based study explored this weekend effect in organ donation, specifically the kidney discard rate. In Australia potential donors are referred to a donation service, and donation proceeds if family consent is granted and the donor is deemed medically suitable to donate. Organ procurement occurs when utilization is almost certain hence discard rates are much lower than in the USA. We aimed to characterize the effect of weekend referral on organ donation in Australia. Methods: We retrospectively reviewed all New South Wales Organ and Tissue Donation Service logs from 2010 to 2016. Our primary outcome was progression to organ procurement, and secondary outcomes were family consent and meeting medical suitability thresholds. We used logistic regression with random effects adjusting for clustering of referral hospitals. Results: Of 3496 potential donors referred for consideration, 694 (20%) progressed to organ procurement. There were fewer referrals on weekends (average 415 versus 588 for weekdays). However, donation rates were no lower for weekend compared to weekday referrals (adjusted OR 1.17; 95% CI 0.95, 1.44). Family consent (adjusted OR 1.20; 95% CI 1.00, 1.44) and medical suitability (adjusted OR 1.15; 95% CI 0.96, 1.38) were not lower for weekend compared to weekday referrals. Similar results were found for all sensitivity analyses conducted. Conclusions: In Australia, the donation pathway operates consistently throughout the week, with donation no less likely to proceed on weekends and holidays. This finding contrasts with findings in the USA

Transplant-associated penile Kaposi sarcoma managed with single agent paclitaxel chemotherapy: a case report

Abstract Background Kaposi’s sarcoma is an uncommon complication in renal transplant patients, and typically presents with cutaneous lesions on the lower extremities. Penile involvement has been reported only rarely. Management of cutaneous-limited disease is primarily reduction of immunosuppression and conversion to an mTOR-inhibitor, whereas the treatment of disseminated disease in transplant patients is more variable. Case presentation A 75-year-old male, originally from Somalia, received a deceased-donor kidney transplant for diabetic and hypertensive nephropathy. Seven months post-transplant he presented with lower limb lesions, oedema and bilateral deep vein thromboses. He then developed a fast-growing painful lesion on his penile shaft. A biopsy of this lesion confirmed KS, and a PET scan demonstrated disseminated disease in the lower extremities, penis and thoracic lymph nodes. His tacrolimus was converted to sirolimus, and his other immunosuppression was reduced. He was treated with single agent paclitaxel chemotherapy in view of his rapidly progressing, widespread disease. The penile lesion completely resolved, and the lower extremity lesions regressed significantly. His kidney allograft function remained stable throughout treatment. Conclusion This case illustrates a rare presentation of an uncommon post-transplant complication and highlights the need for a high index of suspicion of KS in transplant patients presenting with atypical cutaneous lesions. It serves to demonstrate that the use of single agent paclitaxel chemotherapy, switch to an mTORi and reduction in immunosuppression where possible produces excellent short-term outcomes, adding to the body of evidence for this management strategy in disseminated Kaposi’s sarcoma

IL-18 Contributes to Renal Damage after Ischemia-Reperfusion

IL-18 is a proinflammatory cytokine produced by macrophages and other cell types present in the kidney during ischemia-reperfusion injury (IRI), but its role in this injury is unknown. Here, compared with wild-type mice, IL-18−/− mice subjected to kidney IRI demonstrated better kidney function, less tubular damage, reduced accumulation of neutrophils and macrophages, and decreased expression of proinflammatory molecules that are downstream of IL-18. For determination of the relative contributions of leukocytes and parenchymal cells to IL-18 production and subsequent kidney damage during IRI, bone marrow–chimeric mice were generated. Wild-type mice engrafted with IL-18−/− hemopoietic cells showed less kidney dysfunction and tubular damage than IL-18−/− mice engrafted with wild-type bone marrow. In vitro, macrophages produced IL-18 mRNA and protein in response to ischemia. These data suggest bone marrow–derived cells are the key contributors to IL-18–mediated effects of renal IRI. Finally, similar to IL-18−/− mice, pretreatment of wild-type mice with IL-18–binding protein was renoprotective in this model of IRI. In conclusion, IL-18, derived primarily from cells of bone marrow origin, contributes to the renal damage observed during IRI. IL-18–binding protein may have potential as a renoprotective therapy