Fiona E. Mackie

Successful transplantation of adult-sized kidneys into infants requires maintenance of high aortic blood flow.

BACKGROUND Nationally, results of renal transplantation in infants are inferior to those in older children and adults. Within the infant group, best results are obtained with adult-sized kidneys (ASKs) rather than size-compatible pediatric kidneys. However, transplantation of ASKs into infants has an increased risk of acute tubular necrosis and graft loss from vascular thrombosis and primary nonfunction. The aim of this study was to define and understand the hemodynamic changes induced by ASK transplantation, so that outcomes of transplantation in infants can be improved. METHODS Nine hemodynamically stable and optimally hydrated infants were studied under a controlled sedation with cine phase-contrast magnetic resonance at three time periods: before transplantation, 8-12 days after transplantation, and 4-6 months after transplantation. Cross-sectional images of both the infant aorta and the adult transplant renal artery were obtained and blood flow was quantitated. Renal volumes were also obtained, and expected renal artery blood flow based on early posttransplant volume was calculated. In addition, renal artery blood flow was determined in 10 in situ native adult kidneys prior to donor nephrectomy. Supplemental nasogastric or gastrostomy tube feeding was carried out during the blood flow study period to optimize intravascular volume. RESULTS Mean infant aortic blood flows were 331+/-148 ml/min before transplantation, 761+/-272 ml/ min at 8-12 days after transplantation (P=0.0006 with pretransplant flow), and 665+/-138 ml/min at 4-6 months after transplantation (P=0.0001 with pretransplant flow). Mean transplanted renal artery flows were 385+/-158 ml/min at 8-12 days and 296+/-113 ml/min at 4-6 months after transplantation. Transplanted renal artery flows were less than prenephrectomy in situ donor renal artery blood flow (618+/-130 ml/min; P=0.02 and P=0.0003) and expected normal renal artery blood flow (666+/-87 ml/min; P=0.003 and P=0.001) at both 8-12 days and 4-6 months after transplantation. A 26% reduction in renal volume (P=0.003) occurred between the two postoperative time periods, and this paralleled the decrease in posttransplant renal artery flow. One-year graft and patient survival in the nine infants was 100%. The mean serum creatinine levels at 3, 6, and 12 months were 0.43+/-0.10, 0.48+/-0.15, and 0.49+/-0.16 mg/dl. CONCLUSIONS This study is the first to quantitatively document the blood flow changes occurring after ASK transplantation in infants. There was a greater than two-fold increase in aortic blood flow after ASK transplantation, and this increase was sustained for at least 4 months and appeared to be driven by the blood flow demand of the ASK. However, actual posttransplant renal artery blood flow was significantly less than normal renal artery flow. Our study suggests that aggressive intravascular volume maintenance may be necessary to achieve and maintain optimum aortic blood flow, so as not to further compromise posttransplant renal artery flow and to avoid low-flow states that could induce acute tubular necrosis, vascular thrombosis, or primary nonfunction.

Waiting time and outcome of kidney transplantation in adolescents.

Background. The major cause of late graft failure in adolescent kidney transplant recipients is thought to be nonadherence with medications. Delaying transplantation in adolescents may lead to improved adherence but at the cost of longer time on dialysis. To determine if waiting time on dialysis is a risk factor for graft survival in adolescents, we compared the outcomes of kidney transplants according to age and time on dialysis. Methods. We analyzed data from the Australian and New Zealand Dialysis and Transplant Registry on 2,739 primary kidney transplants performed between 1980 and 2004 in recipients less than 30 years old. Outcomes according to age at transplantation and waiting time were analyzed by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard tests. Results. Overall five- and 10-year graft survival rates were significantly worse in adolescents (65% and 50%, respectively) compared to recipients aged two to 10 years (74% and 58%) and 20 to 29 years (72% and 57%). Waiting time on dialysis was an independent risk factor for failure of living donor grafts in adolescents (hazard ratio 0.53, P=0.03). Five- and 10-year graft survival of preemptive grafts in adolescents were 82% and 70%, respectively, which were similar to survival rates of preemptive grafts in other age groups. Conclusions. Reduced graft survival rates in adolescent recipients are not seen after preemptive transplants. Preemptive grafts are associated with a 50% reduction in the risk of graft failure. Delaying transplantation in adolescents may expose them to increased risk of poorer outcomes.

Quality of Life of Young Adults and Adolescents with Chronic Kidney Disease

OBJECTIVE To elicit utility-based quality of life (QOL) in adolescents and young adults with chronic kidney disease (CKD). STUDY DESIGN A cross-sectional study was conducted among patients aged 12-25 years with CKD stage 3-5 and 5D from 6 centers in Australia. QOL was measured using a visual analogue scale, and 3 utility-based QOL measures: Health Utilities Index Mark 2 and 3 (HUI2/3), Kidney Disease Quality of Life, incorporating the short form (SF)-12 transformed to SF-6D, and time trade-off (TTO). Multiple linear regression was used to define predictors for TTO QOL weights, SF-6D, and visual analogue scale scores. RESULTS On a utility scale, with extremes of 0 (death) to 1 (full health), the 27 participants had a mean TTO QOL weight of 0.59 (SD = 0.40), HUI2 of 0.73 (SD = 0.28), HUI3 of 0.74 (SD = 0.26), and SF-6D of 0.70 (SD = 0.14). QOL weights were consistently low across the 4 utility-based instruments with widest variability in TTO responses. Mean QOL weights were higher among predialysis participants. The HUI2 indicated variability in the domain of emotion. From the Kidney Disease Quality of Life measures, decrements were observed in all QOL domains though dialysis patients reported a significantly higher burden attributed to kidney disease. CONCLUSIONS Adolescent and young adults with CKD report low QOL values. Their utility-based QOL scores imply they are willing to trade considerable life expectancy for perfect health. Holistic care to improve QOL and minimize disease burden are imperative for optimizing health outcomes in young people with CKD, particularly those on dialysis.

BK viral infection in an Australian pediatric renal transplant population

Abstract: BK virus (BKV) is recognized as a significant cause of renal allograft dysfunction in adults, and there is growing awareness of its importance in the pediatric population. Eighteen pediatric renal transplant recipients and 18 age‐matched controls were prospectively studied. Anti‐BKV immunoglobulin G (IgG) and IgM titres were assayed in all subjects at entry to the study. Polymerase chain reaction (PCR) for BKV DNA was performed on urine and serum at entry, and prospectively tested again at 4, 8 and 12 months. Mean age ± s.d. of transplant recipients and controls was 14.6 ± 3.3 and 13.9 ± 0.33 yr respectively [not significant (NS)]. Transplant patients were studied at a mean time of 5.6 ± 4.2 yr post‐transplant. 56% of transplant patients and 39% of controls were seropositive (+ve BKV IgG) (NS). Plasma BKV PCR was positive in one transplant patient (who also had positive urine PCR) and in none of the controls. The prevalence of positive urine PCR in transplant patients was greater than in controls (33% vs. 0%, p = 0.02). Positive urine BKV PCR was more commonly found in patients treated with mycophenolate than azathioprine (p = 0.04). We conclude that the prevalence of BKV seropositivity and viral activation in this Australian pediatric renal transplant population is similar to that reported in adult and pediatric populations in other countries. BK viruria was more common in children with greater immunosuppression, suggesting that this group is at higher risk of BKV induced nephropathy.

Experiences and Perspectives of Adolescents and Young Adults With Advanced CKD

BACKGROUND Young people with advanced chronic kidney disease experience delayed growth and poor psychosocial outcomes. This study aims to elicit the experiences and perspectives of young people waiting for a kidney transplant. METHODS We conducted semistructured interviews with people aged 12-24 years from 6 Australian renal units. Participants also were asked to complete a journal. Interview transcripts and journal entries were analyzed thematically. RESULTS 27 individuals participated in the study. 5 major themes were identified: inferiority (impaired body image, failing expectations, sick identity, and being a burden), insecurity (contending with prognostic uncertainty, vulnerability, and doubtful future), injustice (deprived of freedom, victimhood, and lost opportunity), resilience (autonomy and empowerment and maturity), and adjustment mentality (self-blame, reserved optimism, focusing on normality, and self-efficacy). CONCLUSIONS Young dialysis- and non-dialysis-dependent patients with chronic kidney disease have an impaired sense of self-worth, perceive a precarious future, and feel limited in their physical and psychosocial capacities to have the same potential and opportunity as their healthy peers. Strategies to increase patient autonomy and self-efficacy in treatment management and to manage the emotional burdens of future uncertainties and lifestyle disruptions are needed to protect and promote the health and well-being of young people waiting for a kidney transplant.

Atorvastatin treatment for hyperlipidemia in pediatric renal transplant recipients

Abstract: The objective of this prospective study was to determine the prevalence of hyperlipidemia in our pediatric renal transplant patients and to treat those with persistently elevated cholesterol and/or low‐density lipoprotein (LDL) levels. All patients with a functioning renal allograft for greater than 6 months were studied (n = 18). Patients with cholesterol and/or LDL levels greater than the 95th percentile (n = 9) were commenced on an HMG‐CoA reductase inhibitor, Atorvastatin and monitoring was performed for efficacy and adverse effects. Total serum cholesterol was elevated in 11 of 18 (61%) and triglyceride (TG) was elevated in 12 of 18 (67%) patients. Atorvastatin treatment was effective with a mean percentage reduction of total cholesterol of 41 ± 10% (p < 0.01 vs. before treatment), LDL 57 ± 7% (p < 0.01 vs. before treatment) and TG 44 ±25% (p = 0.05 vs. before treatment). No adverse effects on allograft function or cyclosporin levels were experienced. Hyperlipidemia is a common problem and Atorvastatin is a safe and effective treatment in pediatric renal transplant recipients.

Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance

OBJECTIVES To evaluate the efficacy, tolerability, and compliance of 3 ketogenic diets, the classical ketogenic diet, medium-chain triglyceride (MCT), and modified Atkins diet. STUDY DESIGN A single-center, retrospective study of 48 children with intractable epilepsy receiving ketogenic diets from 2003 to 2012. Patient demographics, epilepsy history, nutritional management, and side effects were collated. Compliance and tolerability were assessed by recording reasons for diet modification and cessation. The value of potassium citrate supplementation for preventing nephrolithiasis was reviewed. RESULTS Median age at ketogenic diet initiation was 3.8 years (IQR: 2.3-7 years). The majority had intractable epilepsy, and 33 of the 48 children (69%) had epileptic encephalopathies. Three (6%) patients became seizure free, 35 (73%) reported <50%-90% reduction, and 10 (21%) had 0%-50% reduction during a 2-year period. Diet duration or ketogenic diet type did not predict reduction in seizures (P = .381; P = .272). Constipation (n = 31, 65%) was very common. Food refusal (n = 3, 6%) and poor parental compliance (n = 5, 10%) were common reasons cited for cessation. There were lower rates of side effects for modified Atkins diet. Diet cessation was greatest for MCT; however, 3 patients on MCT ceased therapy because adequate seizure control was achieved. Nephrolithiasis was reported in 1 patient before potassium citrate was used and 2 patients noncompliant with potassium citrate supplementation developed hypercalciuria. CONCLUSION The 3 ketogenic diets were comparably effective in seizure control and generally well-tolerated. Potassium citrate supplementation is an effective prophylactic supplement for the prevention of nephrolithiasis.

Lupus Means Sacrifices: Perspectives of Adolescents and Young Adults With Systemic Lupus Erythematosus

Disease activity, organ damage, and treatment burden are often substantial in children and adolescents with systemic lupus erythematous (SLE), and the complex interplay among the developing child, parents, and peers makes effective management difficult. We aimed to describe the experiences and perspectives of adolescents and young adults diagnosed with juvenile‐onset SLE to inform strategies for improving treatment and health outcomes.

The national incidence and clinical picture of SLE in children in Australia - a report from the Australian Paediatric Surveillance Unit

Objectives The objectives of this paper are to prospectively determine the incidence of paediatric systemic lupus erythematosus (pSLE) in Australia as well as describe the demographics, clinical presentation and one-year outcome. Study design Newly diagnosed cases of pSLE were ascertained prospectively from October 2009 to October 2011 through the Australian Paediatric Surveillance Unit (a national monthly surveillance scheme for notification of childhood rare diseases) as well as national subspecialty groups. Questionnaires were sent to notifying physicians at presentation and at one year. Results The annual incidence rate was 0.32 per 105 children aged less than 16 years. The incidence was significantly higher in children of Asian or Australian Aboriginal and Torres Strait Islander parents. Approximately one-third of children underwent a renal biopsy at presentation and 7% required dialysis initially although only one child had end-stage kidney disease (ESKD) at one-year follow-up. Conclusion The incidence of pSLE in Australia is comparable to that worldwide with a significantly higher incidence seen in children of Asian and Australian Aboriginal and Torres Strait Islander backgrounds. Renal involvement is common but progression to ESKD, at least in the short term, is rare.

Pulmonary capillary leak syndrome with intravenous cyclosporin A in pediatric renal transplantation

Abstract: Despite frequent use of intravenous (i.v.) cyclosporin A (CsA) in the early post‐operative course of transplant recipients, allergic reactions have been infrequently described. Of 134 transplants, we report four pediatric renal transplant recipients with severe reaction to i.v. CsA with pulmonary capillary leak syndrome. Pulmonary edema developed at a mean time of 3.5 h after commencement of i.v. CsA, with two patients requiring mechanical ventilation. Discontinuation of i.v. CsA and conversion to oral CsA was followed by rapid resolution of pulmonary edema, suggesting that cremaphor, the solubilizing agent in the i.v. formulation, is likely to be responsible for this adverse response. Skin prick testing with cremaphor was negative in all patients and alternative mechanisms for the cremaphor response are proposed. It is likely that inadequate mixing of the i.v. CsA solution triggered this reaction, by delivering a higher concentration of cremaphor at the start of the CsA infusion. Pulmonary edema in the early post‐transplant course in the absence of obvious fluid overload should prompt the diagnosis of an i.v. CsA reaction. This life‐threatening reaction is easily reversible if recognized, and can be managed easily without compromise to the allograft, by discontinuing i.v. CsA and switching early to an oral CsA formulation.