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Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy of unknown etiology. The underlying mechanisms are highly heterogeneous, often including genetic backgrounds. Variants of LARS1, encoding the leucyl‐tRNA synthetase 1, are responsible for infantile liver failure syndrome 1. We describe two siblings with ANE caused by compound heterozygous variants of LARS1. Patient 1 was a 17‐month‐old girl. She presented with generalized seizure and liver dysfunction due to influenza type A infection. Brain magnetic resonance imaging on day 4 of onset showed diffuse high‐intensity signals consistent with ANE. She died on day 10. Patient 2, a younger male sibling of patient 1, had mild to moderate developmental delay and growth failure at the age of 18 months. He showed a markedly elevated level of transaminases triggered by infection with human herpesvirus 6. On day 4 of onset, he had generalized seizures. Brain computed tomography showed a diffuse symmetrical hypodensity consistent with ANE. He died on day 7. Whole exome sequencing identified the compound heterozygous variants in LARS1 (NM_020117.11) as c.83_88delinsAATGGGATA, p.(Arg28_Phe30delinsLysTryAspIle) and c.1283C>T, p.(Pro428Leu) in both siblings. The severe neurologic phenotype, found in our patients, reflects the complicated pathogenesis of LARS1‐related disorder. [ABSTRACT FROM AUTHOR]

Background: The clinical spectrum of Henoch–Schönlein purpura nephritis (HSPN), now known as IgA vasculitis‐associated nephritis (IgAVN), ranges from isolated microscopic haematuria to nephrotic syndrome, progressive glomerulonephritis, and kidney failure. The outcome also varies, and the management of IgAVN is controversial. The presence of nephrotic state at disease onset is thought to be a risk factor of a poor prognosis. However, not all patients with nephrotic state have a poor prognosis, and it is unclear whether they need early treatment. Methods: We herein retrospectively examined the clinical course of paediatric IgAVN cases with nephrotic state (serum albumin [sAlb]<3.0 g/dL and urine protein–creatinine ratio of >2.0 g/ gCr) without kidney injury treated at our hospital between 2010 and 2018. Results: Of the 216 patients with IgAVN identified, 17 met the inclusion criteria. The median follow‐up period from disease onset to the last observation was 40.5 months (IQR:31.0–74.2). Eleven patients were male, the median age at onset was 5 years, the minimum serum Alb level was 1.9 g/dL, the maximum proteinuria value was 12.3 g/gCr, and the median minimum eGFR was 86.0 mL/min/1.73 m2 in the acute phase. Eight patients (47%) achieved resolution of nephrotic state within 3 months and complete remission without treatment by the last observation. The patients with spontaneous resolution of nephrotic state had less severe hypoalbuminaemia (Alb<2.0 g/dL) and tended to show a quick increase in the serum albumin level. Conclusions: Our study found that half of paediatric patients with IgAVN with nephrotic state achieved spontaneous resolution without treatment and enjoyed a favourable short‐term outcome. Consideration of the duration of nephrotic state and trends in the serum albumin level in children with IgAVN may allow unnecessary kidney biopsies and immunosuppressive therapy to be avoided. SUMMARY AT A GLANCE: In this retrospective study, eight patients (47%) out of 17 paediatric IgA vasculitis‐associated nephritis with nephrotic state achieved spontaneous resolution without treatment and enjoyed a favourable short‐term outcome. [ABSTRACT FROM AUTHOR]

Aim: Accurate and precise estimation of glomerular filtration rate (GFR) is essential in kidney disease. We evaluated the usefulness of the mean of creatinine clearance (CCr) and urea clearance (CUN) examined over a 1‐h urine collection period (1‐h (CCr + CUN)/2) in a retrospective, cross‐sectional study across two centres, as a relatively simple method for estimating GFR in children. Methods: Children aged ≤18 years who underwent inulin clearance (CIn) tests were eligible. Two clearance values were obtained during a 2‐h test consisting of two periods of 1 h each. The mean clearance in two periods was defined as 1‐h clearance. 1‐h (CCr + CUN)/2, 1‐h CCr, 1‐h CUN and GFR estimated by Cr‐based and cystatin C (CysC)‐based formulas for Japanese children were compared with CIn. Bland–Altman plots were used to evaluate correlations. The primary outcome measure was the correlation between 1‐h (CCr + CUN)/2 and CIn. Results: Fifty‐three children were analysed. Their median age was 10.9 (interquartile range [IQR] 5.3–14.2) years, and median CIn and 1‐h (CCr + CUN)/2 were 77.0 (IQR: 51.5–95.1) and 81.0 (IQR: 64.1–97.7) ml/min/1.73 m2, respectively. Percentage difference of CIn and 1‐h (CCr + CUN)/2 in the Bland–Altman plot was −11.2% (95% confidence interval − 15.3% – −7.1%), with 95% lower and upper limits of agreement of −40.3% and 18.0%, respectively. Thus, 1‐h (CCr + CUN)/2 was 1.12 times CIn. Conclusion: 1 h (CCr + CUN)/2 was almost concordant with CIn. 1‐h (CCr + CUN)/2 can estimate GFR accurately and precisely, making it a simple and speedy test for use in clinical practice. SUMMARY AT A GLANCE: The importance of better measures of kidney function in children is highlighted in this cross‐sectional study, which evaluated the use of a 1‐h urine collection for the determination of the mean of creatinine clearance and urea clearance, and showed a good agreement with measured inulin clearance. The authors propose this urine collection as a quick and reliable measure of kidney function in children and suggest that it may be more accurate than other endogenous clearance methods. [ABSTRACT FROM AUTHOR]

Background: Despite advances in non‐invasive vascular imaging, detection of renal artery stenosis via catheter angiography is the criterion standard for the diagnosis of renovascular hypertension (RVH). However, because of lack of evidence, the utility of various blood tests and imaging modalities remains unclear. Methods: We retrospectively analyzed the utility of blood tests (plasma renin activity [PRA], aldosterone, and renal vein renin [RVR] values) and imaging studies (computed tomography angiography [CTA], kidney ultrasonography [US]) by comparing them with catheter angiography. Ten pediatric patients with RVH at two institutions from January 2008 to December 2017 were recruited. The sensitivities for diagnosing RVH via imaging and blood tests (kidney [US], PRA, and aldosterone) were derived by examining patient records. Furthermore, the sensitivity and specificity of CT angiography were calculated by considering both the affected and non‐affected renal arteries of the patients. Results: A high sensitivity for diagnosing RVH via kidney US (89%) and PRA (80%) was observed. The sensitivity and specificity of CTA were 100%, each. RVR sampling did not aid in the diagnosis of RVH; only two of six patients with unilateral RVH showed significant laterality of RVR boundary ratios. Renal scintigraphy facilitated detection of a non‐functional kidney (split renal function <5%). Conclusions: RVH in children could be diagnosed utilizing non‐invasive blood and imaging tests, without catheter angiography. We recommend kidney length measurement along with measurement of PRA level, as a simple and highly useful screening test, followed by CTA as a diagnostic test. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) infection is one of the major factors that affect morbidity and mortality in kidney transplant (KTx) patients. The rate of CMV seropositivity in children before KTx is lower than that in adults; therefore, pediatric KTx patients have a higher risk of CMV infection. In Japanese pediatric KTx patients, preemptive therapy for CMV infection is a main conventional therapy. This study investigated whether this preemptive treatment would affect kidney function at 2 years post‐KTx. Methods: A total of 163 patients, that is approximately half of the Japanese pediatric KTx patients nationwide, were recruited to participate in our study. We compared the values of the sequential estimated glomerular filtration rate (eGFR) at two years post‐KTx and other influencing factors in CMV viremia, CMV disease, and no‐infection groups. Results: Cytomegalovirus infection after KTx occurred in 75 patients (46.0%), 38.7% of whom developed CMV disease. The sequential eGFR values post‐KTx did not differ significantly between the three groups. CMV infection was not significantly correlated with other factors, other infections (including Epstein‐Barr [EB] virus infection), acute rejection (AR), or adverse events. Only prolonged duration of total hospitalization was significantly associated with CMV infection (P =.002). In the multivariate analysis, younger age, CMV infection, and adverse effects were independently significantly related to prolonged total hospitalization. Conclusion: Preemptive therapy for CMV infection evidenced by viremia and disease did not significantly influence kidney function in Japanese pediatric KTx patients at two years after the operation. [ABSTRACT FROM AUTHOR]

Bartter syndrome (BS) and Gitelman syndrome (GS) are syndromes associated with congenital tubular dysfunction, characterized by hypokalemia and metabolic alkalosis. Clinically, BS is classified into two types: the severe antenatal/neonatal type, which develops during the fetal period with polyhydramnios and preterm delivery; and the relatively mild classic type, which is usually found during infancy with failure to thrive. GS can be clinically differentiated from BS by its age at onset, usually after school age, or laboratory findings of hypomagnesemia and hypocalciuria. Recent advances in molecular biology have shown that these diseases can be genetically classified into type 1 to 5 BS and GS. As a result, it has become clear that the clinical classification of antenatal/neonatal BS, classic BS, and GS does not always correspond to the clinical symptoms associated with the genotypes in a one‐to‐one manner; and there is clinically no clear differential border between type 3 BS and GS. This has caused confusion among clinicians in the diagnosis of these diseases. It has been proposed that the disease name "inherited salt‐losing tubulopathy" can be used for cases of tubulopathies accompanied by hypokalemia and metabolic alkalosis. It is reasonable to use this term prior to genetic typing into type 1–5 BS or GS, to avoid confusion in a clinical setting. In this article, we review causative genes and phenotypic correlations, diagnosis, and treatment strategies for salt‐losing tubulopathy as well as the clinical characteristics of pseudo‐BS/GS, which can also be called a "salt‐losing disorder". [ABSTRACT FROM AUTHOR]

Objectives: To evaluate long‐term outcomes and risk factors for graft loss in pediatric kidney transplantation over a 30‐year period. Methods: We retrospectively assessed 400 consecutive kidney transplants carried out in 377 children during 1975–2009. Patients were stratified according to the immunosuppressive regimen (era 1: methylprednisolone and azathioprine; era 2: calcineurin inhibitor‐based therapy, including methylprednisolone and azathioprine or mizoribine; era 3: basiliximab induction therapy, including calcineurin inhibitors, methylprednisolone and mycophenolate mofetil). Results: The median age and bodyweight at transplantation were 9.7 years and 20.6 kg, respectively. In total, 364 (91.0%) children received a living related donor transplantation. The acute rejection rate within 1 year post‐transplant decreased significantly from 61.0% in era 1 to 14.5% in era 3 (P < 0.001). For transplant eras 1–3, 1‐year graft survival was 81%, 93% and 95%; 5‐year graft survival was 66%, 86% and 93%; and 10‐year graft survival was 47%, 79% and 89%, respectively. The overall 5‐, 10‐ and 20‐year patient survival rates were 96%, 93% and 88%, respectively. A Cox multivariate analysis identified cold ischemia time (hazard ratio 1.385, 95% confidence interval 1.251–1.603), acute rejection (hazard ratio 1.682, 95% confidence interval 1.547–3.842), re‐transplant (hazard ratio 2.680, 95% confidence interval 1.759–3.982) and donor type (hazard ratio 2.957, 95% confidence interval 1.754–4.691) as independent risk factors for graft loss at 10 years post‐transplant. Conclusions: The progress of immunosuppressive therapy has led to a low incidence of acute rejection and a high graft survival rate across 30 years of pediatric transplantation. [ABSTRACT FROM AUTHOR]

ABSTRACT: Children with systemic lupus erythematosus (SLE) generally undergo a pretreatment kidney biopsy. However, some of these patients, especially those with antiphospholipid syndrome (APS), may experience serious coagulopathic complications. We report herein two cases of paediatric SLE with APS in which, despite normal blood test results, the disparate coagulopathic complications of haemorrhage and embolism developed following a kidney biopsy. Case 1 was, an 8‐year‐old male in whom, primary APS was initially diagnosed. Fourteen months later SLE was diagnosed. Based on a percutaneous kidney biopsy, International Society of Nephrology and the Renal Pathology Society (ISN/RPS) class III‐A lupus nephritis was histologically diagnosed. On post‐biopsy Day 9, a giant haematoma in the fascia of the left kidney developed and was accompanied by changes in the vital signs. Case 2, a 13‐year‐old male, initially received the diagnosis of SLE with APS and underwent two courses of pulse methylprednisolone therapy. His coagulation abnormalities improved, and a percutaneous needle kidney biopsy was performed, leading to the histological diagnosis of ISN/RPS class III‐A lupus nephritis. Furthermore, thrombotic microangiopathy was also detected in the renal histopathology. On post biopsy Day 6, the patient experienced right leg pain. A contrast CT and lower extremity ultrasonography detected a massive deep vein thrombosis and partial left pulmonary artery thrombosis. A kidney biopsy in children with SLE and APS can cause lethal coagulopathic complications, and the risks to such patients should be weighed carefully before the procedure is performed. [ABSTRACT FROM AUTHOR]

WDR19 has been reported as a causative gene of nephronophthisis-related ciliopathies. Patients with WDR19 mutations can show various extrarenal manifestations such as skeletal disorders, Caroli disease, and retinal dystrophy, and typically display nephronophthisis as a renal phenotype. However, there is limited information on the renal phenotypes of patients with WDR19 mutations. We report two Japanese infants with Sensenbrenner syndrome caused by WDR19 mutations who demonstrated different features in renal ultrasound and histopathological results, despite several common extrarenal manifestations. Patient 1 had normal sized and hyperechogenic kidneys with several small cysts and histopathological findings compatible with infantile nephronophthisis. Renal ultrasound of Patient 2 showed enlarged kidneys with diffuse microcysts resembling those of autosomal recessive polycystic kidney disease. Her renal histopathology revealed dysplastic kidney with diffuse glomerular cysts. Genetic testing identified compound heterozygous mutations in WDR19 in both patients (Patient 1: c.953delA, c.3533G > A, Patient 2: c.2645 + 1G > T, c.3533G > A). Our patients suggest that WDR19 mutations can cause dysplastic kidney in addition to nephronophthisis pathologically. In addition, differences in pathology of the kidneys from WDR19 mutations may result in heterogeneous features in renal ultrasound findings. Renal phenotypes from WDR19 mutations may thus be more diverse than previously reported. Extrarenal manifestations and genetic testing can therefore help to diagnosis this disease more precisely. [ABSTRACT FROM AUTHOR]

There are two different Japanese serum creatinine-based equations for estimated glomerular filtration rate (eGFR), for adults and paediatric patients, with both equations deemed applicable to 18-year-old subjects. This study assessed the relative accuracy of the two equations in assessing eGFR in patients aged 18 years with chronic kidney disease. A total of 3042 patients (1679 males and 1363 females), aged 2-20 years, who were registered in the Japan Renal Biopsy Registry or the Japan Kidney Disease Registry between 2007 and 2013 were evaluated. eGFR values derived from formulas for children (Uemura's formula) and adults (the 3-variable Japanese formula) were calculated and compared, especially in patients aged 18 years. At all ages, but especially at younger ages, eGFR was significantly higher when calculated with the adult than the paediatric formula. This finding was also observed in 18-year-old adolescents with eGFR <90 mL/min per 1.73 m2 ( P = 0.026). However, the mean difference between the two calculated eGFRs was only 2.79 mL/min per 1.73 m2. These findings indicate that both creatinine-based equations used to calculate eGFR rate in Japanese children and adults with chronic kidney disease could be used to determine eGFR in 18-year-old subjects, with the difference between the two within permissible levels for clinical use. [ABSTRACT FROM AUTHOR]

Children with ESRD in need of RRT are commonly managed by PD due to difficulty with vascular access for HD and the relatively large extracorporeal blood volume required. Major abdominal surgery may result in injury to the peritoneum and consequent adhesion, thereby resulting in a reduction in the anatomical capacity and transport capability across the peritoneal membrane. Here, we report successful resumption of PD after LDLT in two pediatric patients. The causes of ESRD were PH1 and juvenile nephronophthisis, respectively. Both patients were managed by PD prior to LDLT. PD was converted to HD starting three days before LDLT and was continued postoperatively until resumption of PD on days 13 and 28, respectively. The PD weekly Kt/V urea was maintained before and after LDLT. The patients continued to do well on PD without complications. Meticulous intra-operative techniques during LDLT allow postoperative PD resumption by preservation of peritoneal integrity with effective transport capability and without added risk of peritonitis. [ABSTRACT FROM AUTHOR]

Histopathological findings can play an important role in the management of atypical haemolytic uraemic syndrome ( aHUS). We report a case of aHUS that did not recover from anuria, despite the administration of eculizumab, with impressive histopathological findings. A 3-month-old girl was admitted because of poor feeding, vomiting, and diarrhoea without haemorrhage. She had anuria and severe hypertension, and laboratory results showed haemolytic anaemia with schizocytes, thrombocytopenia, and renal impairment. Although no mutations in the complement system or diacylglycerol kinase epsilon were detected, she was diagnosed with a HUS owing to the clinical course and by the exclusion of E scherichia coli infection and thrombotic thrombocytopenic purpura. Plasma exchange was performed once at day 2 and eculizumab therapy was started from day 18, with a severe infusion reaction at the first administration. After the initiation of eculizumab, although the serum lactate dehydrogenase level improved gradually, she did not recover from anuria. Pathological findings of the kidney biopsy at day 37 included diffuse arteriolar and arterial luminal stenosis with remarkable thickness and sclerotic changes of the media and intima, which are suggestive of aHUS. In addition, most glomeruli had global sclerosis and were collapsed, and 80% of the tubulointerstitial compartment showed atrophic changes with infiltration of inflammatory cells. The present case is possibly a kidney-specific fulminant type of aHUS. Although showing efficacy against thrombotic microangiopathy, eculizumab did not improve kidney function. The pathological findings reflected the severe and irreversible kidney injury. [ABSTRACT FROM AUTHOR]

In Japan, urinary screening for preschool children has been obligatory since 1961. The system was reconsidered and has been under review since 2012, because many problems in the system had been identified, and its usefulness was uncertain. In the process, the following were analyzed: (i) frequency of urinary abnormalities identified on screening; (ii) diseases identified from urinary abnormalities; (iii) clinical course of children found to have urinary abnormalities; and (iv) screening for asymptomatic urinary tract infection (UTI) as a way of screening for congenital anomalies of the kidney and urinary tract. A computerized literature search was conducted, and study reports issued by the Ministry of Health, Labour and Welfare study group, and data of Akita City and Chiba City were reviewed. The prevalence of abnormal results at the first urinalysis was high, but at the second urinalysis the prevalence decreased in the range 1/6-1/20. The prevalence of tentative diagnosis at the third urinalysis was similar to the school urinary screening results. Serious illness was not found in children who had hematuria alone. In contrast, diseases requiring immediate attention were found in children with proteinuria, although the prevalence of proteinuria was not high. The dipstick method for leukocyturia was inefficient. The importance of two consecutive urinalyses before detailed examination, the lack of usefulness of screening for hematuria in 3-year-old children, and the importance of proteinuria were confirmed. Screening for asymptomatic UTI using urinary leukocytes was very inefficient. [ABSTRACT FROM AUTHOR]

Aim C3 glomerulonephritis ( C3GN) is a recently described disease that is related to membranoproliferative glomerulonephritis ( MPGN). We retrospectively compared the frequencies, clinical characteristics, treatment modalities, and outcomes of C3GN and MPGN in a cohort of Japanese children. Methods Children who were pathologically diagnosed with MPGN (type I or III) in our hospital were divided into two groups based on immunofluorescence imaging of renal biopsies: children with MPGN induced by classical complement pathway activation (classical MPGN) and children with C3GN. Results Of 14 children with MPGN (five boys), four had classical MPGN, eight had C3GN, and two had unclassifiable glomerulonephritis. Four children with classical MPGN and seven with C3GN received methylprednisolone pulse therapy followed by oral prednisolone for 2 years ( MPT+ PSL therapy). Subsequently, six of seven children with C3GN received combined therapy (prednisolone, azathioprine, and anticoagulants) for 2 years because they responded poorly to MPT+ PSL therapy. At the last follow-up visit, two children with classical MPGN and seven with C3GN had not achieved remission. One child with classical MPGN and five with C3GN had hypocomplementaemia at the last follow-up. None of the children had renal impairment. Conclusion More than half of the patients previously diagnosed with MPGN fulfilled the criteria for C3GN in children. C3GN may be more refractory than classical MPGN to immunosuppressant therapy. [ABSTRACT FROM AUTHOR]

6p duplication syndrome is a rare chromosomal disorder that frequently manifests renal complications, including proteinuria, hypoplastic kidney, and hydronephrosis. We report a girl with the syndrome, manifesting left hydronephrosis, proteinuria/hematuria, and focal segmental glomerular sclerosis (FSGS) resulting in chronic end-stage renal failure, successfully treated with renal transplantation. Microarray comparative genomic hybridization showed the derivative chromosome 6 to have a 6.4-Mb duplication at 6p25.3-p25.1 with 32 protein-coding genes and a 220-Kb deletion at 6p25.3 with two genes of no possible relation to the renal pathology. Review of the literature shows that variation of renal complications in the syndrome is compatible with congenital anomalies of the kidney and urinary tract (CAKUT). FSGS, observed in another patient with 6p duplication syndrome, could be a non-coincidental complication. FOXC1, located within the 6.4-Mb duplicated region at 6p25.3-p25.2, could be a candidate gene for CAKUT, but its single gene duplication effect would not be sufficient. FSGS would be a primary defect associated with duplicated gene(s) albeit no candidate could be proposed, or might occur in association with CAKUT. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Recurrence of focal segmental glomerulosclerosis ( FSGS) in pediatric kidney allografts is associated with poor graft survival. Several therapeutic regimens have been proposed, with conflicting results. Methods Ten pediatric patients with recurrent FSGS after kidney transplantation were treated with a protocol of methylprednisolone ( MP) infusions in combination with cyclosporine ( Cs A)-based immunosuppression. The patients received a drug regimen with infusions of 20 mg/kg MP on three consecutive days at week 1, week 3, and week 5, and then monthly until six months after transplantation. If a complete or partial remission ( PR) was obtained, MP pulse continued every three months until 24 months after transplantation. The Cs A dose was adjusted according to AUC0-4. Results Seven of 10 patients (70%) achieved complete remission ( CR) with stable renal function within 18 months of beginning of treatment. One of two patients with PR entered CR 3.5 yr after transplantation. One patient lost her graft due to recurrence four months after transplantation. After observation for 26-119 months, seven patients maintained remission with normal glomerular filtration rate. Few major side effects were observed in association with the high-dose MP infusion therapy. Conclusions MP infusion therapy in combination with Cs A-based immunosuppression could be safe and effective in treating recurrent FSGS after kidney transplantation. [ABSTRACT FROM AUTHOR]

Mutations of GATA1, leading to aberrant expression of a truncated form of GATA1 (called GATA1s), are present in transient leukaemia (TL) in neonates with Down syndrome. Using these molecular markers of TL, we investigated the growth and differentiation potential of TL blasts in the presence of hematopoietic growth factors (HGFs). Interleukin-3, stem cell factor and granulocyte-macrophage colony-stimulating factor potently stimulated the growth of TL blast progenitors and induced differentiation towards basophil/mast cell lineages, whereas thrombopoietin induced differentiation towards megakaryocytes. GATA1s was expressed in TL blasts in all five patients examined but was down-regulated during differentiation induced by these HGFs, while full-length GATA1 was not expressed throughout the culture. GATA1 mutations were detected in TL blasts in four patients, including one patient with two distinct mutations. The cells of this patient exhibited identical and only mutated sequences both before and after culture with HGFs, confirming the leukemic cell origin of these differentiated cells. Erythroid differentiation of TL blasts was not evident with any HGFs. These data indicate that TL blasts have the potential to grow and differentiate towards particular hematopoietic lineages in the presence of specific HGFs and that the down-regulation of GATA1s might be involved in blast cell differentiation. [ABSTRACT FROM AUTHOR]

Antibody-mediated rejection is an important cause of chronic allograft dysfunction. We report a case of chronic antibody-mediated rejection 13 yr after transplantation. This patient is a 19-yr-old man who had renal insufficiency since infancy because of bilateral polycystic kidneys. Peritoneal dialysis was started when he was four yr old and he received a renal allograft from his mother at the age of six yr. Donor and recipient were ABO compatible and immunosuppressive treatment was started with cyclosporine, mizoribine, and methylprednisolone. No acute rejection was experienced and histological acute rejection was not proven on any subsequent protocol biopsies. Ten yr after transplantation, a protocol biopsy revealed moderate chronic allograft nephropathy and severe cyclosporine-associated arteriolopathy. His allograft function was preserved at this time and the cyclosporine dose was tapered to 125 mg/d. His renal function gradually deteriorated starting 12 yr after transplantation. Although mizoribine was changed to mycophenolate mofetil, he required dialysis one yr later. A diagnosis of antibody-mediated rejection was made based upon the renal biopsy findings (including C4d staining) and circulating anti-human leukocyte antigen (HLA) antibody levels (12 yr after transplantation). We conclude that it is necessary to pay attention to antibody-mediated rejection, even in allograft cases with good function for over 10 yr and no risk factors for the development of de novo anti-HLA antibodies. [ABSTRACT FROM AUTHOR]

Several studies suggested that the incidence of new-onset diabetes following pediatric kidney transplantation has increased markedly in recent years, with reported incidence of up to 20%. However, limited information is available regarding the incidence and features of pretransplant status of abnormal glucose tolerance in pediatric kidney transplant recipients. We assessed the risk of 55 non-diabetic pediatric transplant recipients developing PTDM by performing OGTT prior to transplantation. For post-transplant immunosuppression, each patient received either a CsA- or a TAC-based regimen. However, recipients who had abnormal glucose tolerance in the pretransplant OGTT were allocated to the CsA-based regimen. The mean age of the patients was 9.7 ± 5.4 yr while mean BMI was 16.5 ± 3.3 kg/m2. FPG level before transplantation was within the normal limit in all patients, while the mean HbA1C value was 4.5. However, 18 of the 55 patients (32.7%) had abnormal glucose tolerance in the pretransplant OGTT, 13 (23.6%) had impaired glucose tolerance, and 5 (9.4%) had DM. PTDM developed in two patients on the TAC-based regimen with these patients having normal glucose tolerance prior to the transplant. In contrast, the 18 patients with abnormal glucose tolerance did not develop PTDM under CsA-based immunosuppression. Our results demonstrated an unexpectedly high prevalence of abnormal glucose tolerance in pretransplant OGTT even in a pediatric population. We believe that modification of post-transplant immunosuppression by the identification of high-risk patients using the pretransplant OGTT may minimize the development of new onset of PTDM. [ABSTRACT FROM AUTHOR]

Posterior reversible encephalopathy syndrome ( PRES) has been thought to be a benign disease, but recently severe cases have been reported with increasing recognition. A 3-year-old girl with congenital nephrotic syndrome had rapidly progressed to coma. Computed tomography ( CT) of the head showed striking swelling of the brainstem and transtentorial herniation. Emergency decompressive craniectomy was performed. Consecutively, blood pressure was optimally controlled. The patient gradually recovered to the previous state before onset of PRES. Rapid improvement of clinical symptoms and rapid resolution of abnormal findings on serial CT led to diagnosis of PRES. In severe PRES with unstable vital signs, surgical intervention should be considered as well as appropriate blood pressure management. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Recently eculizumab, a monoclonal antibody to C5, was found to improve the disease course of atypical haemolytic uraemic syndrome (aHUS) and has been recommended as the first line treatment by an international consensus guideline. However, several practical issues in the use of eculizumab for the acute phase of aHUS have yet to be resolved. Methods: Children who received eculizumab with diagnosis of aHUS between March 2010 and December 2015 at Tokyo Metropolitan Children's Medical Center were enrolled. aHUS was diagnosed according to the haemolytic uraemic syndrome (HUS) criteria after excluding Shiga toxin‐inducing Escherichia coli (STEC) ‐associated HUS and thrombocytopaenic purpura. We retrieved and analyzed data from the electronic medical records at our institution. Results: We reviewed four patients with suspected aHUS. Eculizumab was discontinued in one patient in whom STEC‐HUS was later diagnosed. Treatment was continued in the remaining three patients without recurrence. Practical issues included difficulty in diagnosing aHUS, particularly in the acute phase, risk of infection by encapsulated organisms, especially Neisseria meningitis, and infusion reaction. In addition to issues relating to the acute phase, discontinuing eculizumab in stable patients in the chronic phase must be considered. Conclusion: Eculizumab, the first line treatment for children with aHUS, is usually effective. However, certain problems associated with its use require caution to be exercised. As clinical information on eculizumab are still very limited, and the rationale for its long‐term use has yet to be established, physicians are advised to exercise care when using eculizumab to manage aHUS. [ABSTRACT FROM AUTHOR]