Joshua Kausman

Association of renal adenocarcinoma and BK virus nephropathy post transplantation.

While most BK virus infections are asymptomatic, immunosuppression has been associated with BK virus reactivation and impaired graft function or ureteric ulceration in renal transplant patients and hemorrhagic cystitis in bone marrow transplant patients. Oncogenicity is also postulated and this is the first report of a child with a carcinoma of the donor renal pelvis following BK virus allograft nephropathy. Removal of the primary tumor and cessation of immunosuppression led to regression of secondary tumors and a return to health.

Application of an epitope-based allocation system in pediatric kidney transplantation

Donor–recipient HLA mismatch remains a leading cause for sensitization and graft loss in kidney transplantation. HLA compatibility at an epitope level is emerging as an improved method of matching compared with current HLA antigen allocation. A novel epitope‐based allocation approach to prospectively exclude donors with high‐level mismatches was implemented for pediatric KTRs on the DD waiting list. Nineteen consecutive transplants were followed for 12 months, including eight DD KTRs listed with eplet exclusions, as well as three DD KTRs and eight LD KTRs without exclusions. KTRs with eplet exclusions had estimated GFR of 78.5 mL/min/1.73 m2, no episodes of rejection, and time to transplant 6.55 months. HLA‐A, HLA‐B, HLA‐DR antigen mismatches were similar between all groups. KTRs with exclusions had significantly lower class II eplet mismatches (20.4) than the contemporary DD KTRs without exclusions (63.7) and DD KTRs transplanted in the preceding decade (46.9). dnDSAs were identified in two of eight DD KTRs with exclusions, two of three DD KTRs without exclusions and five of eight LD KTRs. Epitope‐based allocation achieved timely access to transplantation, low class II eplet mismatches, and low rates of dnDSAs in the first year. This strategy requires longer follow‐up and larger numbers, but has the potential to reduce anti‐HLA sensitization and improve both graft survival and opportunities for future retransplantation.

Atypical haemolytic uraemic syndrome treated with the complement inhibitor eculizumab: the experience of the Australian compassionate access cohort.

This study aimed to report the clinical characteristics and outcomes of Australian patients treated with eculizumab for atypical haemolytic uraemic syndrome (aHUS).

KHA‐CARI guideline: Diagnosis and treatment of urinary tract infection in children

Child & Adolescent Renal Service, Royal Children’s and Mater Children’s Hospitals, University of Queensland, Department of Paediatrics and Child Health, The University of Queensland, Brisbane, Queensland, Department of General Medicine, The Royal Children’s Hospital, Vaccine and Immunisation Research Group and Rotavirus Research Group, Murdoch Childrens Research Institute, Department of Paediatrics, The University of Melbourne, Paediatric Imaging, Monash Health, Monash University, Department of Nephrology, Royal Children’s Hospital Melbourne, Murdoch Childrens Research Institute, University of Melbourne, Melbourne, Victoria, Department of Nephrology, Princess Margaret Hospital for Children, Perth, Western Australia, Nephrology, Sydney Children’s Hospital, School of Women’s & Children’s Health, University of New South Wales, and Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, New South Wales, Australia

Optimising Outcomes in Pediatric Renal Transplantation through the Australian Paired Kidney Exchange Program

Kidney paired donation (KPD) programs offer the opportunity to enable living kidney donation when immunological and other barriers prevent safe directed donation. Children are likely to require multiple transplants during their lifetime; therefore, high‐level histocompatibility and organ quality matching are key priorities. Details are given for a cohort of seven pediatric renal transplantations performed through the Australian Kidney Exchange (AKX), including barriers to alternative transplantation and outcomes after KPD. Reasons for entering the KPD program were preformed donor‐specific antibodies to their registered donor in five cases, ABO mismatch, and avoidance of the risk of exposure to hepatitis B virus. Four recipients were highly sensitized. All patients received transplants with organs of lower immunological risk compared with their registered donors. HLA eplet mismatch scores were calculated for donor–recipient pairs; three patients had improved eplet mismatch load with AKX donor compared with their registered donor. All grafts are functioning, with a mean estimated glomerular filtration rate of 77 mL/min/1.73 m2 (range 46–94 mL) and a follow‐up range of 8–54 months, and no patient experienced clinical or histological rejection. KPD is a viable strategy to overcome many barriers to living donation for pediatric patients who have an otherwise suitable donor and provides an opportunity to minimize immunological risks.

Childhood nephrotic syndrome in the 21st century: What's new?

Childhood nephrotic syndrome is a condition managed by general paediatricians and paediatric nephrologists. Whether treating a first presentation or a relapse, the clinician requires expertise in order to minimise the risk of serious complications and optimise long‐term care. Indeed, many children suffer a difficult relapsing course in their disease, warranting consideration of second‐line therapies. The last two decades have witnessed a growing knowledge of the condition and increased complexity of diagnostic and therapeutic options, which poses a challenge for the general paediatrician, given the conditions relative rarity in daily practice. This review aims to familiarise the reader with some of the most important recent developments and particularly to provide an insight into what management options are available and when it may be appropriate to seek advice from a nephrologist.

HLA epitope matching in pediatric renal transplantation

Chronic graft loss due to antibody-mediated rejection (AMR) and the difficulty of re-transplanting highly sensitized patients are two of the major long-term challenges in pediatric renal transplantation. Treatments for AMR are often ineffective and desensitization protocols can be a high risk, making prevention a highly appealing strategy. Insights into the structural determinants of humoral alloantigenicity present an exciting opportunity to reassess our current paradigm of tissue matching and potentially preventing these complications. We review the theory behind human leukocyte antigen (HLA) B cell epitopes and the various systems that have been proposed to define them, including eplets. There is a growing body of clinical evidence suggesting that epitope-based tissue matching may be superior to traditional HLA antigen matching at predicting a range of clinical outcomes. However, additional studies are required to better understand the biological relevance of these systems of defining epitopes and their role in pediatric transplantation.

Complicated Henoch–Schönlein purpura

We present a case of Henoch Schonlein pupura in a 6‐year‐old boy demonstrating some of the diagnostic pitfalls, complications and management challenges of this common paediatric condition.

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand: Thrombotic microangiopathy in Aust/NZ

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4–8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin‐associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC‐HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC‐HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement‐related mutation in a significant proportion of aHUS cases. The presence of other TMA‐associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

Long-term remission with eculizumab in atypical haemolytic uraemic syndrome

The understanding of the role of complement dysregulation in atypical haemolytic uraemic syndrome (aHUS) has led to major changes in therapeutic approaches and outcomes. Eculizumab is a humanized anti‐C5 monoclonal antibody that inhibits the terminal complement pathway and has revolutionized the treatment and prognosis of aHUS. However, published reports to date have had relatively short‐term follow‐up. We report two paediatric cases of aHUS successfully treated with eculizumab longer than 6 years with no serious adverse events and preservation of renal function.