Amanda Walker

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.

Socio‐economic status and quality of life in children with chronic disease: A systematic review

Reduced quality of life (QoL) is a known consequence of chronic disease in children, and this association may be more evident in those who are socio‐economically disadvantaged. The aims of this systematic review were to assess the association between socio‐economic disadvantage and QoL among children with chronic disease, and to identify the specific socio‐economic factors that are most influential. MEDLINE, Embase and PsycINFO were searched to March 2015. Observational studies that reported the association between at least one measure of social disadvantage in caregivers and at least one QoL measure in children and young people (age 2–21 years) with a debilitating non‐communicable childhood disease (asthma, chronic kidney disease, type 1 diabetes mellitus and epilepsy) were eligible. A total of 30 studies involving 6957 patients were included (asthma (six studies, n = 576), chronic kidney disease (four studies, n = 796), epilepsy (14 studies, n = 2121), type 1 diabetes mellitus (six studies, n = 3464)). A total of 22 (73%) studies reported a statistically significant association between at least one socio‐economic determinant and QoL. Parental education, occupation, marital status, income and health insurance coverage were associated with reduced QoL in children with chronic disease. The quality of the included studies varied widely and there was a high risk of reporting bias. Children with chronic disease from lower socio‐economic backgrounds experience reduced QoL compared with their wealthier counterparts. Initiatives to improve access to and usage of medical and psychological services by children and their families who are socio‐economically disadvantaged may help to mitigate the disparities and improve outcomes in children with chronic illnesses.

KHA-CARI Guideline: peritonitis treatment and prophylaxis.

Department of Nephrology, Royal Children’s Hospital, Melbourne, Victoria, Renal Unit, Royal Adelaide Hospital, Adelaide, South Australia, Renal Office, Concord Repatriation General Hospital, Renal Service, South Western Sydney Local Health District, Sydney, and Renal Department, The Wollongong Hospital, Wollongong, New South Wales, Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia; and Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand

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.

Spontaneous bacterial peritonitis as a presenting feature of nephrotic syndrome

A previously well 4.5-year-old boy presented to the emergency department (ED) with a 1-day history of fever, abdominal pain, vomiting and diarrhoea. On clinical examination his heart rate was 140 beats per minute, temperature 39°C, respiratory rate 20 breaths per minute and blood pressure 102/62. Abdominal examination revealed generalised tenderness on palpation. Blood investigations showed a leukocytosis (white cell count 23.5 × 10/L) with a predominant neutrophilia (neutrophil count 17.6 × 10/L) and a raised C-reactive protein (CRP) at 70 mg/mL. He was assessed by the ED staff, who made a diagnosis of gastroenteritis, and he was discharged home once tolerating fluids. A positive blood culture that, on smear, identified Grampositive cocci in chains led to recall to the ED. A general paediatric opinion was sought. Since discharge, fever, abdominal pain and diarrhoea had persisted. His heart rate was 110 beats per minute, temperature 35.9°C, respiratory rate 22 breaths per minute and blood pressure 105/52. His abdomen was distended with generalised tenderness and guarding. He had periorbital oedema and pitting oedema to his knees bilaterally. On further history, his mother reported that his urine had been cloudy for a few days prior to the onset of the febrile illness. Urinary dipstick was strongly positive for protein and blood. A presumptive diagnosis of spontaneous bacterial peritonitis as the presenting feature of newly diagnosed nephrotic syndrome was made, with the differential diagnosis of a perforated abdominal viscus. A surgical opinion was sought. Further investigations revealed a normalised leukocyte count, but the CRP had increased to >270 mg/mL. He was hyponatraemic, with a sodium of 132 mmol/L, and hypoalbuminaemic (14 g/dL). An abdominal ultrasound was performed that showed diffuse bowel wall thickening but no intra-abdominal fluid. He was commenced on broad-spectrum intravenous antibiotics (cefotaxime, metronidazole and amoxicillin) to cover resistant pneumococci and bowel organisms. The antibiotics were subsequently rationalised to penicillin monotherapy with confirmation that the isolate from his blood culture was penicillin-susceptible Streptococcus pneumoniae. The diagnosis of nephrotic syndrome was confirmed with a high urinary proteinto-creatinine ratio (0.93 g protein/mmol creatinine) and high serum cholesterol (9.6 mmol/L) and triglyceride (2.3 mmol/L) levels. He was commenced on oral prednisolone and aspirin and completed a 7-day course of intravenous antibiotics. During this time his abdominal pain subsided and the oedema resolved. The S. pneumoniae isolate was typed as 10A, and he was given a single dose of the 13-valent pneumococcal conjugate vaccine (13vPCV) followed by a single dose of the 23-valent pneumococcal polysaccharide vaccine. Since the diagnosis of nephrotic syndrome he has had a frequently relapsing course, requiring a period of cyclophosphamide therapy. He is not on penicillin prophylaxis.

Lifetime risk of end-stage kidney disease in living donors for paediatric kidney transplant recipients in Australia and New Zealand - a retrospective study

Living kidney donors (LKD) for paediatric kidney transplant recipients (KTR) have a heightened motivation to donate for emotional reasons and the clear health benefits to the KTR. We hypothesized that the cohort of LKD for paediatric KTR (LKD‐P) includes motivated young parents with a higher lifetime end‐stage kidney disease (ESKD) risk compared to adult KTR (LKD‐A). Data from the Australia and New Zealand Dialysis and Transplant LKD Registry (2004–2015) was analysed to compare baseline characteristics and predonation ESKD risk in LKD‐P (n = 315) versus LKD‐A (n = 3448). LKD‐P were younger (median age 42 vs. 50 years; P < 0.001) and had a marginally higher lifetime ESKD risk (median 0.44% vs. 0.40%; P < 0.01), with a similar proportion of LKD exceeding 1% risk threshold (5.4% vs. 5.6%; P = NS). Compared to grandparents as LKD‐P, parents (median age 41 vs. 59 years; P < 0.001) had a higher lifetime ESKD (0.44% vs. 0.25%; P < 0.001). Although unique benefits to paediatric KTR justify the minor increase in lifetime ESKD risk in young parents, carefully selected grandparents are an alternative LKD‐P option, allowing parents to donate for subsequent transplants.

Neurocognitive and Educational Outcomes in Children and Adolescents with CKD A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES Poor cognition can affect educational attainment, but the extent of neurocognitive impairment in children with CKD is not well understood. This systematic review assessed global and domain-specific cognition and academic skills in children with CKD and whether these outcomes varied with CKD stage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Electronic databases were searched for observational studies of children with CKD ages 21 years old or younger that assessed neurocognitive or educational outcomes. Risk of bias was assessed using a modified Newcastle-Ottawa scale. We used random effects models and expressed the estimates as mean differences with 95% confidence intervals stratified by CKD stage. RESULTS Thirty-four studies (25 cross-sectional, n=2095; nine cohort, n=991) were included. The overall risk of bias was high because of selection and measurement biases. The global cognition (full-scale intelligence quotient) of children with CKD was classified as low average. Compared with the general population, the mean differences (95% confidence intervals) in full-scale intelligence quotient were -10.5 (95% confidence interval, -13.2 to -7.72; all CKD stages, n=758), -9.39 (95% confidence interval, -12.6 to -6.18; mild to moderate stage CKD, n=582), -16.2 (95% confidence interval, -33.2 to 0.86; dialysis, n=23), and -11.2 (95% confidence interval, -17.8 to -4.50; transplant, n=153). Direct comparisons showed that children with mild to moderate stage CKD and kidney transplants scored 11.2 (95% confidence interval, 2.98 to 19.4) and 10.1 (95% confidence interval, -1.81 to 22.0) full-scale intelligence quotient points higher than children on dialysis. Children with CKD also had lower scores than the general population in executive function and memory (verbal and visual) domains. Compared with children without CKD, the mean differences in academic skills (n=518) ranged from -15.7 to -1.22 for mathematics, from -9.04 to -0.17 for reading, and from -14.2 to 2.53 for spelling. CONCLUSIONS Children with CKD may have low-average cognition compared with the general population, with mild deficits observed across academic skills, executive function, and visual and verbal memory. Limited evidence suggests that children on dialysis may be at greatest risk compared with children with mild to moderate stage CKD and transplant recipients.

Quality of life of children and adolescents with chronic kidney disease: a cross-sectional study

Objective The aim was to compare quality of life (QoL) among children and adolescents with different stages of chronic kidney disease (CKD) and determine factors associated with changes in QoL. Design Cross-sectional. Setting The Kids with CKD study involved five of eight paediatric nephrology units in Australia and New Zealand. Patients There were 375 children and adolescents (aged 6–18 years) with CKD, on dialysis or transplanted, recruited between 2013 and 2016. Main outcome measures Overall and domain-specific QoL were measured using the Health Utilities Index 3 score, with a scale from −0.36 (worse than dead) to 1 (perfect health). QoL scores were compared between CKD stages using the Mann-Whitney U test. Factors associated with changes in QoL were assessed using multivariable linear and ordinal logistic regression. Results QoL for those with CKD stages 1–2 (n=106, median 0.88, IQR 0.63–0.96) was higher than those on dialysis (n=43, median 0.67, IQR 0.39–0.91, p<0.001), and similar to those with kidney transplants (n=135, median 0.83, IQR 0.59–0.97, p=0.4) or CKD stages 3–5 (n=91, 0.85, IQR 0.60–0.98). Reductions were most frequent in the domains of cognition (50%), pain (42%) and emotion (40%). The risk factors associated with decrements in overall QoL were being on dialysis (decrement of 0.13, 95% CI 0.02 to 0.25, p=0.02), lower family income (decrement of 0.10, 95% CI 0.03 to 0.15, p=0.002) and short stature (decrement of 0.09, 95% CI 0.01 to 0.16, p=0.02). Conclusions The overall QoL and domains such as pain and emotion are substantially worse in children on dialysis compared with earlier stage CKD and those with kidney transplants.

A rare cause of pyrexia in a transplant patient: Questions

A 14-year old boy presented to our emergency department with a fever of 39.1 °C, 2 months post-renal transplantation. The fever had begun 2 days prior to presentation. He reported no other associated symptoms. His past medical history included chronic kidney disease (CKD) stage 5 secondary to an obstructive uropathy due to a urethral polyp. This was managed with peritoneal dialysis followed by a deceased donor renal transplant 2 months prior to this presentation. Comorbidities included mineral bone disease and recurrent urinary tract infections (UTIs). Six days beforehand he had been treated with norfloxacin for a pseudomonas-induced UTI, with negative results for urine cultures after 4 days of treatment. He had no other recent symptoms. His regular medications included tacrolimus, mycophenolate mofetil, prednisolone, prophylactic sulfamethoxazole/trimethoprim, aspirin, ranitidine, nystatin and sodium bicarbonate. The patient appeared to be clinically stable, but his temperature fluctuated between 37.5 and 39.2 °C. He was tachypnoeic with a respiratory rate of 26–32 breaths per minute. Examination of his chest and abdomen did not reveal any other remarkable findings, and other haemodynamic parameters were stable. He did not appear to be jaundiced and did not report the appearance of any new rashes. Laboratory tests revealed a rising creatinine concentration of 99 (baseline 80– 85) μmol/L, which is in keeping with an acute kidney injury. He had a mild pancytopenia with a haemoglobin count of 110 g/L, platelet count of 104×10/L and neutrophil count of 1.02×10/L. The fibrinogen level was normal (4.3 g/L); however, the liver function test results indicated increasingly deranged liver function with elevated levels of alanine aminotransferase (69 U/L), lactate dehydrogenase (816 U/L) and gamma-glutamyl transpeptidase (59 U/L). Normal results were obtained for bilirubin and coagulation studies were normal. The C-reactive protein level was 80 mg/L. With these data in mind, the patient was started on empirical antibiotic treatment with ceftazidime. Blood cultures and polymerase chain reaction (PCR) assays for Epstein-Barr virus, cytomegalovirus, adenovirus and human herpes virus in the blood polymerase were performed, as was a chest radiograph. The PCR assay for adenovirus PCR was positive; however, the results of all other investigations, including blood and urine cultures, showed no abnormalities. The serum ferritin level was elevated (6067 g/L), and soluble CD25 count was very elevated at 34,813 pg/mL (normal range 186–2678 mL). Abdominal ultrasound revealed no new changes to the native and graft kidneys; however, it showed a focal hypodense lesion on the liver. The lesions were further investigated 3 days later with computed tomography, which showedmultiple ill-defined hypodense lesions varying between 1.1 and 4.3 cm in diameter in the liver (Fig. 1). The answers to these questions can be found at http://dx.doi.org/10.1007/ s00467-016-3409-2

A rare cause of pyrexia in a transplant patient: Answers.

2. What other tests could lead you towards the diagnosis? Haemophagocytic lymphohistiocytosis is diagnosed based on eight criteria, five of which are needed for a firm diagnosis. These criteria include the presence of a fever, pancytopenia, splenomegaly, high triglyceride or low fibrinogen levels, increased levels of ferritin, an abnormal bone marrow biopsy result and a high soluble CD25 count. In this case, five of the eight criteria were met. The hypodense liver lesions also support the diagnosis, which could have been either adenovirus or HLH-induced. Biopsy of the lesions was planned but deferred when symptoms were resolving.