Holistic care and symptom management for pediatric kidney transplant recipients.

While many aspects of life may improve substantially for children and young people undergoing kidney transplant, there may be new challenges including symptoms that can be detrimental to health-related quality of life. Addressing symptoms requires attention to patient and family perspectives and a holistic approach grounded in symptom management. The interdisciplinary pediatric nephrology transplant team should be attuned to the prevalence of common symptoms including fatigue, anxiety, depression, post-traumatic stress, pain, and sleep disturbances, as well as poor body image and sexual health. These common symptoms require regular assessment with a focus on appropriate interventions and how care may be impacted by transplant status.

2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis.

OBJECTIVE: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN). METHODS: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. RESULTS: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. CONCLUSIONS: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.

Screen of traditional soup broths with reported antipyretic activity towards the discovery of potential antimalarials.

OBJECTIVE: The global impact of artemisinin-based combination therapies on malaria-associated mortality and their origins in ancient Chinese medicine has heightened interest in the natural discovery of future antimalarials. METHODS: A double-blind study to identify potential ingredients with antimalarial activity from traditional remedies with reported antipyretic properties. Recipes of clear broths, passed down by tradition in families of diverse ethnic origin, were sourced by school children. Broths were then tested for their ability to arrest malaria parasite asexual growth or sexual stage development in vitro. Clear broth extract was incubated with in vitro cultures of Plasmodium falciparum asexual or mature sexual stage cultures and assayed for parasite viability after 72 hours. RESULTS: Of the 56 broths tested, 5 were found to give >50% in vitro growth inhibition against P. falciparum asexual blood stages, with 2 having comparable inhibition to that seen with dihydroartemisinin, a leading antimalarial. Four other broths were found to have >50% transmission blocking activity, preventing male parasite sexual stage development. After unblinding, two active broths were found to be from siblings from different classes, who had brought in the same vegetarian soup, demonstrating assay robustness. CONCLUSIONS: This screening approach succeeded in finding broths with activity against malaria parasite in vitro growth, arising from complex vegetable and/or meat-based broths. This represented a successful child education exercise, in teaching about the interface between natural remedies, traditional medicine and evidence-based drug discovery.

Hypomagnesemia and increased risk of new-onset diabetes mellitus after transplantation in pediatric renal transplant recipients.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a significant co-morbidity following kidney transplantation. Lower post-transplant serum magnesium levels have been found to be an independent risk factor for NODAT in adult kidney transplant recipients. METHODS: We undertook a retrospective analysis of risk factors for NODAT in pediatric renal transplant recipients at our institution with the aim of determining if hypomagnesemia confers a significant risk of developing NODAT in this patient population. RESULTS: A total of 173 children with a median age at transplantation of 7.0 (range 1.3-17.5) years were included. Hypomagnesemia was found to be a significant independent risk factor for NODAT (p = 0.01). High trough tacrolimus levels were also independently associated with NODAT (p < 0.001). There was no significant association between NODAT and body mass index at the time of transplantation, monthly cumulative steroid dose or post-transplant cytomegalovirus viremia (p = 0.9, 0.6 and 0.7, respectively). CONCLUSIONS: This study identifies hypomagnesemia as a significant independent risk factor for the development of NODAT in pediatric renal transplant recipients. Given the clear association between hypomagnesemia and NODAT in both adults and children following renal transplantation, further studies are merited to clarify the etiology of this association and to examine the effect of magnesium supplementation on NODAT.

Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis.

OBJECTIVES: To develop recommendations for the management of adult and paediatric lupus nephritis (LN). METHODS: The available evidence was systematically reviewed using the PubMed database. A modified Delphi method was used to compile questions, elicit expert opinions and reach consensus. RESULTS: Immunosuppressive treatment should be guided by renal biopsy, and aiming for complete renal response (proteinuria <0.5 g/24 h with normal or near-normal renal function). Hydroxychloroquine is recommended for all patients with LN. Because of a more favourable efficacy/toxicity ratio, as initial treatment for patients with class III-IV(A) or (A/C) (±V) LN according to the International Society of Nephrology/Renal Pathology Society 2003 classification, mycophenolic acid (MPA) or low-dose intravenous cyclophosphamide (CY) in combination with glucocorticoids is recommended. In patients with adverse clinical or histological features, CY can be prescribed at higher doses, while azathioprine is an alternative for milder cases. For pure class V LN with nephrotic-range proteinuria, MPA in combination with oral glucocorticoids is recommended as initial treatment. In patients improving after initial treatment, subsequent immunosuppression with MPA or azathioprine is recommended for at least 3 years; in such cases, initial treatment with MPA should be followed by MPA. For MPA or CY failures, switching to the other agent, or to rituximab, is the suggested course of action. In anticipation of pregnancy, patients should be switched to appropriate medications without reducing the intensity of treatment. There is no evidence to suggest that management of LN should differ in children versus adults. CONCLUSIONS: Recommendations for the management of LN were developed using an evidence-based approach followed by expert consensus.

Vitamin D deficiency is associated with short stature and may influence blood pressure control in paediatric renal transplant recipients.

Vitamin D deficiency is common in adult renal transplant recipients, but data in children are scarce. Vitamin D is shown to have multiple effects on the cardiovascular system, renal function, and maintenance of bone health. We hypothesized that 25(OH)D deficiency is common in pediatric renal transplant recipients, and may be associated with hyperparathyroidism, short stature, renal function, and blood pressure control. We recruited 106 children during the winter/spring season who had a functioning renal transplant for at least 3 months. Twenty-five hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured and correlated with clinical and biochemical parameters. Of the renal transplant patients, 38% were 25(OH)D deficient, 54% had insufficient levels, and only 8% had adequate 25(OH)D levels. Despite alfacalcidol supplementation in 59 (56%) patients, parathyroid hormone was increased in 58 (55%) and showed an inverse correlation with 25(OH)D (p = 0.0003, r = 0.61) but not with 1,25(OH)(2)D levels. Height standard deviation score (SDS) correlated with 25(OH)D (p = 0.007, r = 0.42) and time post transplantation (p = 0.02, r = 0.23); both were significant and independent predictors of height SDS. 25(OH)D inversely correlated with systolic BP SDS (p = 0.02, r =-0.26); this association was lost on multiple regression analysis, but 25(OH)D was the only modifiable risk factor for hypertension. There was no correlation with estimated GFR or proteinuria. In conclusion, 25(OH)D deficiency is common in pediatric renal transplant recipients and correlates with hyperparathyroidism and short stature. 25(OH)D deficiency may be a modifiable risk factor for hypertension in transplant recipients. Further studies are required to test if routine supplementation with ergo or cholecalciferol is safe and effective in children after renal transplantation.