Eculizumab in STEC-HUS a paradigm shift in the management of pediatric patients with neurological involvement

Background: Eculizumab for the treatment of atypical hemolytic uremic syndrome (HUS) is a standard of care. Central nervous system (CNS) involvement in Shiga toxin-producing Escherichia coli (STEC)-HUS is associated with increased morbidity and mortality. There is no consensus on the use of plasma exchange and/or eculizumab. We report a series (n = 4) of children with CNS involvement in STEC-HUS with excellent outcomes after treatment with eculizumab only and supportive therapies. Methods: A retrospective chart review of patients with CNS involvement in STEC-HUS is managed with supportive therapies and eculizumab only. Results: Four patients (75% female) with a median age of 5 years and 11 months (IQR: 23.5-105.5 months) were admitted to a tertiary pediatric nephrology center with CNS involvement in STEC-HUS. Neurological symptoms presented between days 2 and 7 of illness and included ataxia, altered mental status, visual symptoms, and seizures. All had an abnormal MRI brain. All received two doses of eculizumab, 1 week apart (dosing according to weight). Resolution of neurological symptoms was evident at a mean of 60 h post-administration (range: 24-72 h). All patients have complete kidney and neurological recovery at 12-month follow-up. Conclusion: We present a case series of four children with STEC-HUS and CNS involvement, managed with eculizumab only, in lieu of plasma exchange (as per our previous policy). The marked improvement in symptoms in our cohort supports the use of eculizumab, rather than plasma exchange in the CNS involvement of STEC-HUS.</p

Longitudinal analysis of the impact of rituximab on circulating EBV miRNAs in three paediatric kidney transplant recipients

Background: EBV DNA monitoring is currently the main strategy to identify renal transplant recipients potentially at risk of EBV complications. EBV miRNA expression is markedly altered in different disease presentations associated with EBV. We performed a longitudinal assessment of the impact of rituximab on circulating EBV miRNA in 3 paediatric kidney transplant recipients. Methods: Forty-two miRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined over a 28-month period using miRNA qPCR custom panels. EBV DNA was measured using qPCR and lymphocyte subsets were measured by flow cytometry. Results: Patients were 3 years post kidney transplant and received cycles of rituximab infusions. Treatment with rituximab caused an immediate depletion of the circulating B cells and reduced the expression of the miRNAs and EBV DNA levels. About 4 months post treatment, as the circulating B cells repopulated, EBV miRNAs levels increased. A total of 29 plasma samples were studied and between 4 and 34 EBV miRNAs were detected. A significant correlation was observed between the numbers of EBV miRNAs expressed and the EBV DNA level (r = 0.63, p = 0.001). Conclusion: We provide an in-depth longitudinal assessment of the impact of rituximab on specific circulating EBV miRNA expression in three paediatric kidney transplant recipients. Rituximab treatment resulted in the reduction of EBV miRNA expression and EBV DNA viral loads. Larger studies are required to determine whether EBV miRNA levels could be useful biomarkers to predict transplant recipients at risk of developing post-transplant lymphoproliferative disease.</p

Transitional care models in adolescent kidney transplant recipients - a systematic review

Background: Adolescence is a time of significant change for patients, guardians and clinicians. The paediatrician must ensure patients develop the necessary skills and knowledge required to transition and to function as an independent entity, with autonomy over their own care. The transfer from paediatric to adult care carries an increased risk of graft-related complications attributable to a multitude of reasons, particularly non-adherence to immunosuppressive medicines and poor attendance at scheduled appointments. This systematic review was conducted to ascertain the transitional care models available to clinicians caring for kidney transplant recipients and to compare the approach in each respective case. Methods: A systematic review was performed, in a methodology outlined by the PRISMA guidelines. OVID MEDLINE and EMBASE databases were searched for studies that outlined valid, replicable models pertaining to transitional care of paediatric kidney transplant recipients between 1946 and Quarter 3 of 2021. The reference lists of selected articles were also perused for further eligible studies and experts in the field were consulted for further eligible articles. Two investigators assessed all studies for eligibility and independently performed data extraction. Any discrepancies were settled by consensus. Results: A total of 1121 abstracts were identified, which was reduced to 1029 upon removal of duplicates. A total of 51 articles were deemed appropriate for full-text review and critical appraisal. A total of 12 articles that described models for transition pertaining to kidney transplant patients were included in qualitative synthesis. Every paper utilized a different transition model. All but one model included a physician and nurse at minimum in the transition process. The involvement of adult nephrologists, medical social work, psychology and psychiatry was variable. The mean age for the initiation of transition was 13.4 years (range: 10-17.5 years). The mean age at transfer to adult services was 18.3 years (range: 16-20.5 years). Conclusions: Despite the well-established need for good transitional care for paediatric solid-organ transplant recipients, models tailored specifically for kidney transplant recipients are lacking. Further research and validation studies are required to ascertain the best method of providing effective transitional care to these patients. Transitional care should become a standardized process for adolescents and young adults with kidney transplants.</p

Clinical practice recommendations for recurrence of focal and segmental glomerulosclerosis/steroid-resistant nephrotic syndrome

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence

Clinical practice recommendations for recurrence of focal and segmental glomerulosclerosis/steroid-resistant nephrotic syndrome

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence

Management of bone disease in cystinosis: Statement from an international conference

Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Virtually all individuals with classical, nephropathic cystinosis suffer from cystinosis metabolic bone disease (CMBD), related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life. Manifestations of CMBD include hypophosphatemic rickets in infancy, and renal osteodystrophy associated with CKD resulting in bone deformities, osteomalacia, osteoporosis, fractures, and short stature. Assessment of CMBD involves monitoring growth, leg deformities, blood levels of phosphate, electrolytes, bicarbonate, calcium, and alkaline phosphatase, periodically obtaining bone radiographs, determining levels of critical hormones and vitamins, such as thyroid hormone, parathyroid hormone, 25(OH) vitamin D, and testosterone in males, and surveillance for nonrenal complications of cystinosis such as myopathy. Treatment includes replacement of urinary losses, cystine depletion with oral cysteamine, vitamin D, hormone replacement, physical therapy, and corrective orthopedic surgery. The recommendations in this article came from an expert meeting on CMBD that took place in Salzburg, Austria, in December 2016.status: publishe

Management Of Bone Disease In Cystinosis: Statement From An International Conference

Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Virtually all individuals with classical, nephropathic cystinosis suffer from cystinosis metabolic bone disease (CMBD), related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life. Manifestations of CMBD include hypophosphatemic rickets in infancy, and renal osteodystrophy associated with CKD resulting in bone deformities, osteomalacia, osteoporosis, fractures, and short stature. Assessment of CMBD involves monitoring growth, leg deformities, blood levels of phosphate, electrolytes, bicarbonate, calcium, and alkaline phosphatase, periodically obtaining bone radiographs, determining levels of critical hormones and vitamins, such as thyroid hormone, parathyroid hormone, 25(OH) vitamin D, and testosterone in males, and surveillance for nonrenal complications of cystinosis such as myopathy. Treatment includes replacement of urinary losses, cystine depletion with oral cysteamine, vitamin D, hormone replacement, physical therapy, and corrective orthopedic surgery. The recommendations in this article came from an expert meeting on CMBD that took place in Salzburg, Austria, in December 2016.WoSScopu

Hyperparathyroidism is an independent risk factor for allograft dysfunction in pediatric kidney transplantation

INTRODUCTION: Little is known about the consequences of deranged chronic kidney disease–mineral and bone disorder (CKD-MBD) parameters on kidney allograft function in children. We examined a relationship between these parameters over time and allograft outcome. METHODS: This registry study from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) collected data at baseline, months 1, 3, 6, 9, and 12 after transplant; and every 6 months thereafter up to 5 years. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤30 ml/min per 1.73 m(2) or a ≥50% decline from eGFR at month 1 posttransplant was performed. Associations of parathyroid hormone (PTH), calcium, phosphate, and 25-hydroxyvitamin D (25(OH)D) with allograft outcome were investigated using conventional stratified Cox proportional hazards models and further verified with marginal structural models with time-varying covariates. RESULTS: We report on 1210 patients (61% boys) from 16 European countries. The composite end point was reached in 250 grafts (21%), of which 11 (4%) were allograft losses. In the conventional Cox proportional hazards models adjusted for potential confounders, only hyperparathyroidism (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.82–4.74) and hyperphosphatemia (HR, 1.94; 95% CI, 1.28–2.92) were associated with the composite end point. Marginal structural models showed similar results for hyperparathyroidism (HR, 2.74; 95% CI, 1.71–4.38), whereas hyperphosphatemia was no longer significant (HR, 1.35; 95% CI, 0.87–2.09), suggesting that its association with graft dysfunction can be ascribed to a decline in eGFR. CONCLUSION: Hyperparathyroidism is a potential independent risk factor for allograft dysfunction in children