Rituximab in combination with cyclosporine and steroid pulse therapy for childhood-onset multidrug-resistant nephrotic syndrome: a multicenter single-arm clinical trial (JSKDC11 trial).

BACKGROUND: Only 80% of children with idiopathic nephrotic syndrome respond well to glucocorticoid therapy. Multidrug-resistant nephrotic syndrome (MRNS) is associated with a poor kidney prognosis. Several retrospective studies have identified rituximab as an effective treatment for MRNS; however, prospective studies are required to assess its efficacy and safety. METHODS: We conducted a multicenter, non-blinded, single-arm trial to investigate the efficacy and safety of rituximab in patients with childhood-onset MRNS who were resistant to cyclosporine and more than three courses of steroid pulse therapy. The enrolled patients received four 375 mg/m2 doses of rituximab in combination with baseline cyclosporine and steroid pulse therapy. The primary endpoint was a > 50% reduction in the urinary protein/creatinine ratio from baseline on day 169. Complete and partial remissions were also evaluated. RESULTS: Six patients with childhood-onset MRNS were enrolled. All patients were negative for pathogenic variants of podocyte-related genes. On day 169, five patients (83.3%) showed a > 50% reduction in the urinary protein/creatinine ratio, two patients showed partial remission, and two patients showed complete remission. No deaths occurred and severe adverse events occurred in two patients (infection in one patient and acute kidney injury in one patient). Three patients needed treatment for moderate-to-severe infection. CONCLUSIONS: The study treatment effectively reduced the urinary protein/creatinine ratio in patients with childhood-onset MRNS. The adverse events in this study were within the expected range; however, attention should be paid to the occurrence of infections.

Postpartum Neonatal Disseminated Herpes Simplex Virus-1 Infection in Which Herpes Simplex Virus-1 Was Detected in Mother's Breast Milk.

A 17-d-old girl was diagnosed with disseminated herpes simplex virus-1 infection-associated hemophagocytic lymphohistiocytosis. The virus was detected in the neonate's blood and mandible. The neonate was treated with dexamethasone and acyclovir and discharged without neurological sequelae. The mother had no history of a herpes simplex virus-1 infection and did not have visible genital herpetic lesions; moreover, the neonate was delivered via an elective cesarean section. However, the day before the delivery, the mother had met with the neonate's grandmother, who had herpes labialis. Viral DNA was detected in bilateral breast milk samples; however, no superficial herpetic lesions were noted on both breasts. The authors speculated that the neonate may have acquired the infection via contaminated breast milk. Thus far, only one neonatal case of this infection contracted via breast milk has been reported. Further studies on breast milk as a transmission route for these infections are required.

Intravenous tocilizumab for Takayasu arteritis with aortic aneurysms, bilateral renal artery stenosis, and atypical aortic coarctation in a 2-year-old girl.

Takayasu arteritis (TAK) is classified as large vessel vasculitis, and continuous inflammation of the vessel results in aneurysm or stenosis, which leads to various serious complications. Recently, a TAKT [TAK treated with tocilizumab (TCZ)] study showed that subcutaneous TCZ, a humanised anti-interleukin-6 receptor monoclonal antibody, is an effective treatment in patients with TAK above 12 years of age; however, the effectiveness of TCZ for juvenile TAK under 12 years old remains unclear. Here, we described the case of a 2-year-old girl with TAK, which was successfully treated with intravenous TCZ. She was diagnosed with TAK type V (Numano's angiographic classification system) with aortic aneurysms, bilateral renal arteries stenosis, and atypical descending aortic coarctation based on contrast-enhanced computed tomography findings. Treatment was started with 2 mg/kg/day prednisolone (PSL) and methotrexate instead of methylprednisolone pulse due to renovascular hypertension. She was immediately afebrile and her C-reactive protein level decreased, although it was elevated 4 weeks after starting PSL. Intravenous TCZ of 8 mg/kg/2 weeks was added because the progression of aneurysms or stenosis might lead to a poor prognosis. PSL was steadily reduced under intravenous TCZ. Magnetic resonance imaging showed that aortic aneurysms, renal arteries stenosis, and aortic coarctation ameliorated 4 months after starting TCZ, with the amelioration maintained at 1 year after starting TCZ. Aneurysms and stenosis improved; therefore, TCZ may be effective for the treatment of inflammation of vessels, aneurysms, and stenosis. It is desirable to examine the effect of TCZ on TAK patients under 12 years of age.

Diagnosis and Treatment for Acute Focal Bacterial Nephritis With Renal Abscess Based on Magnetic Resonance Imaging Evaluation.

A 5-year-old boy was diagnosed with left acute focal bacterial nephritis (AFBN) complicated with renal abscess (RA) on magnetic resonance imaging (MRI). MRI is useful for diagnosing AFBN and RA complications. He was administered antibiotics for 3 weeks on evaluation of MRI findings. Evaluation of apparent diffusion coefficient values over time may be useful as an index of treatment of RA.

Type 3 antenatal Bartter syndrome presenting with mild polyuria.

Bartter syndrome (BS) is a well-recognised inherited tubular dysfunction that causes polyuria, metabolic alkalosis and hypokalaemia. Among BS cases, antenatal/neonatal BS (ABS) usually shows distinct polyhydramnios prenatally and presents features of BS in the early neonatal period. We encountered a premature infant with type 3 ABS presenting with mild polyuria and discuss the pathogenesis of mild polyuria in type 3 ABS. A male infant was born at 31 weeks' gestation. His mother received amniocentesis because of polyhydramnios. Hyponatraemia and hypokalaemia appeared within 3 days after birth. Metabolic alkalosis, hyperreninaemia and hyperaldosteronism were also identified. Temporary polyuria developed at 1 month after birth; however, the mean urine output during hospitalisation was within the normal range. CLCNKB compound heterozygous mutations were confirmed. Polyuria of type 3 ABS may be less severe than in other types of ABS. Lower urine sodium loss may be a characteristic feature of type 3 ABS.

Influenza virus vaccination in children with nephrotic syndrome: insignificant risk of relapse.

BACKGROUND: Immunization with various vaccines is considered desirable for children with idiopathic nephrotic syndrome (NS) because of their high risk of severe infections. Vaccinations may precipitate relapses of NS, but there is no available data regarding inactivated influenza (flu) virus vaccines. METHODS: We retrospectively reviewed the medical records of children with NS who had received flu vaccines between 2002 and 2015. The day of flu vaccination was defined as day 0, and the period between the pre-vaccination and the post-vaccination days was defined as - X to + Y. The risk ratios and their 95% confidence intervals for NS relapse rate were estimated by generalized estimating equation (GEE) Poisson regression. RESULTS: A total of 104 pediatric patients received 208 flu vaccines. The mean age at onset of NS was at 4.85 ± 3.87 years old. There were 261 NS relapses between days - 180 and + 180. Compared with the relapse rate in the - 180 to 0 interval (1.19 times/person-year), those in 0 to + 30 (1.23), + 31 to + 60 (1.58), + 61 to + 90 (1.41), + 91 to + 120 (1.41), and + 121 to + 180 (1.32) days groups were slightly increased, but without significance. Multivariate analysis using GEE Poisson regression also showed no significant increase in relapse rate in each day group compared with days - 180 to 0. Risk ratios for NS relapse were significantly higher in children who were treated with steroids at the first vaccination. CONCLUSIONS: Our results suggest that flu vaccines should not be avoided in children with NS based on the potential for NS relapses.

A simple, refined approach to diagnosing renovascular hypertension in children: A 10-year study.

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.

Treatment of hemolytic uremic syndrome related to Bordetella pertussis infection -is plasma exchange or eculizumab use necessary?

BACKGROUND: Bordetella pertussis infection is a known trigger of atypical hemolytic uremic syndrome (HUS). For patients suspected of having atypical HUS, prompt plasma exchange/infusion (PE/PI) or eculizumab (ECZ) treatment is recommended. CASE PRESENTATION: We report a 1-month-old female infant who was admitted with a severe cough and a B. pertussis-positive sputum culture. She was born at 38 weeks gestation and did not have a family history of renal diseases. Hemophagocytic syndrome was suspected and she was transferred to our hospital 17 days after her initial admission. One day later, she developed acute kidney injury and was diagnosed with HUS triggered by B. pertussis infection. Her plasma complement levels were low and her kidney function continued to worsen over the next few days. However, prior to starting ECZ treatment, her kidney function improved spontaneously; she did not receive PE/PI or ECZ. She was discharged 46 days after her initial hospitalization, without complications. A genetic workup revealed no mutations in CFH, CFI, CFB, C3, MCP, THBD, or DGKE. CONCLUSIONS: This case demonstrates that B. pertussis infection-related HUS may resolve spontaneously. The decision to treat during the acute phase is challenging because B. pertussis often affects infants suspected of having atypical HUS. However, ECZ may not be the first treatment option for patients with B. pertussis infection-related HUS unless they show an indicated genetic abnormality; if ECZ is used, early discontinuation should be considered.

Coagulopathy as a complication of kidney biopsies in paediatric systemic lupus erythematosus patients with antiphospholipid syndrome.

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.