Despite the difficult times of the Corona disaster, we hosted the 56th Annual Meeting of the Japanese Society for Pediatric Nephrology with the tremendous support of all of pediatric nephrologists. In this article, I would like to express my gratitude and thank all the doctors who took care of me while looking back on my life as a clinician, and to send a heartfelt ale to the precious pediatric nephrologists who will be active in the next generation. To sum up the message: 1) Get in the habit of thinking with the time axis (historical axis) and the spatial axis (world axis) in mind; 2) Doubt common sense once; 3) Start investigating and acting from a familiar place. You can make friends and make a big activity. And 4) I would like you to be interested in deseases and symptoms from the fetal period to the adulthood and to actively express your opinions as a pediatric nephrologist.

Decoding human genetic information and applying it to medical treatment is called “genomic medicine”. Genetic analysis was mainly conducted as research so far, but recently clinical genetic analyses are beginning to be covered by health insurance. Hereditary kidney diseases include various diseases such as Alport syndrome, nephronophthisis, and congenital anomalies of the kidney and urinary tract. Knowing the genomic information of the patients is important not only for accurate diagnosis of the patient, but also for predicting prognosis, diagnosing comorbid extrarenal symptoms, deciding treatment strategy, estimating intrafamilial recurrence rate, and developing specific treatments. On the other hand, there are many issues to promote genomic medicine. Few hereditary kidney diseases can be analyzed using health insurance. To promote genomic medicine in the field of nephrology, it is necessary to build a cooperative system in a wide range of professionals such as clinical geneticists, genetic counselors, and basic researchers as well as nephrologists.

Live attenuated vaccines are generally contraindicated for patients receiving immunosuppressive therapy. However, these patients are at risk of severe infection. In 21 previous reports, 400 patients under immunosuppressive therapy received 816 live attenuated vaccines. No life-threatening adverse events were observed. In our center, we conducted prospective studies of live attenuated vaccines in patients under immunosuppressive therapy for seven years. Patients who met specific immunological criteria (CD4 cell count≥500/mm³, lymphocyte blast transformation by phytohemagglutinin (PHA)≥101.6, and serum IgG level≥300 mg/dL) could receive live attenuated vaccines. The seroconversion rate for measles, rubella, varicella, and mumps was 80.0-95.7%, 100.0%, 59.1-61.9%, and 40.0-69.2%, respectively. In nationwide study, two-thirds of physicians wished to administer live vaccines for patients under immunosuppressants. Only two patients contracted vaccine-strain varicella in 781 immunizations. We demonstrated that live attenuated vaccines could be effective and safe even in patients with immunosuppressive agents, if their immunological parameters are within the acceptable level. We think that medical package inserts and several guidelines should be revised in the near future.

For light microscopic observation of renal pathology, Periodic acid Schiff (PAS) staining and Periodic acid methenaminesilver (PAM) staining are often used. Understanding the characteristics of these and other staining techniques makes us appreciate their significance and utility. Although beginners tend to start observing specimens at higher power, it is recommended to observe the whole specimen first at low power and then switch to high power, if necessary, in order to prevent tiredness and not to miss lesions. Because most of the renal diseases that require biopsy are of glomerular etiology, tubule-interstitial and vascular lesions are usually examined only superficially. To prevent overlooking rare but critical renal diseases, it is necessary to carefully examine all areas. In case glomeruli were not included in the specimen for immunofluorescence or electron microscopy, knowledge of alternative methods could be advantageous.

The long-term renal prognosis of Henoch-Schönlein purpura nephritis (HSPN) in children and the pathological changes before and after treatment has not yet been clarified, and the optimal treatment for HSPN remains unclear. In Japan, children with HSPN are treated according to the treatment guidelines for childhood immunoglobulin A nephropathy. Our study included 8 patients with HSPN who received multidrug combination therapy with azathioprine. All patients underwent renal biopsy at presentation, and 7 patients underwent follow-up biopsy after therapy. Four years after initiating treatment, no patients had decreased renal function compared to that pretreatment and 2 patients had proteinuria (urine protein-tocreatinine ratio: 0.15–0.5 g/gCr). Follow-up renal biopsy revealed chronic lesions in 3 patients, but there was no correlation between chronic lesions and remnant proteinuria. Multidrug combination therapy with azathioprine has certain therapeutic efficacy in alleviating HSPN in children.

Onconephrology is a new specialized field, and pediatric nephrologists should initiatively and professionally take part in the treatment of children with malignant disease along with the pediatric oncologist and other health care providers. Case: A 3-year-old female patient with advanced neuroblastoma and systemic metastasis, which had a poor prognosis, underwent autologous hematopoietic stem cell transplantation (auto-HSCT) with massive chemotherapy. The complications resulted in acute kidney injury (AKI) requiring continuous hemodiafiltration (CHDF). Although the systemic condition of the patient partially recovered, her renal function did not fully recover and intermittent hemodialysis (IHD) was required. However, she was intolerant to IHD, and sustained low-efficiency dialysis (SLED) was performed for 3 months. Remaining metastases in the bones and end stage kidney disease (ESKD) requiring renal replacement therapy (RRT) made her parents anxious and fearful, which was assisted by much discussion about care and treatment of the patient with healthcare providers including pediatric nephrologist. Her parents eventually chose palliative home care, with peritoneal dialysis (PD) using cycler, due to a small abdominal cavity, after the removal of the neuroblastoma. In pediatric patients with coexisting malignant disease and ESKD, the modalities of RRT should be selected based on the status of the malignant disease and the systemic condition, and should be undertaken with family-centered shared decision-making that respects the rights of pediatric patients.

Atypical hemolytic uremic syndrome (aHUS) is one of the thrombotic microangiopathies caused by uncontrolled complement activation. In recent years, eculizumab therapy has significantly improved its prognosis, and early administration is recommended after diagnosis. A 4-month-old girl whose sister had already been diagnosed with aHUS presented with poor feeding 9 days after her vaccination. On the next day, she became pale and had hematuria detected in a home dipstick urine test; thus, she was brought to her physician. She presented with hemolytic anemia and acute kidney injury and was suspected to have aHUS based on her family history and clinical course. She also had thrombocytopenia when she was referred to our hospital on the following day and was diagnosed with aHUS. She was immediately treated with eculizumab, and her symptoms resolved immediately. Thereafter, she was found to have the same complement factor H (CFH) mutation as her sister. Due to her family history of aHUS, home screening for aHUS was performed on her using a dipstick urinalysis, which allowed early detection and treatment. We believe that home urinalysis is useful in detecting the onset of aHUS, especially after events that can trigger the disease such as vaccination.

Infantile hemangioma is common in childhood, but rarely occurs in the urinary bladder. Most cases of childhood bladder hemangioma are cavernous hemangioma, and infantile hemangioma in the urinary bladder is rare. A 7-year-old boy was examined for gross hematuria following an injury to the buttocks. Abdominal ultrasound revealed no abnormalities other than Society of Fetal Urology (SFU) grade 1 left hydronephrosis, and the hematuria resolved after 5 days. Eleven months later, gross hematuria reappeared, and ultrasound and computed tomography (CT) scans revealed not only left lower ureteral dilation and SFU grade 2 left hydronephrosis but also a mass (maximum diameter 18 mm) around the left ureteral orifice within the urinary bladder. Cystoscopy was therefore performed, and a submucosal mass around the left ureteral orifice was identified and resected. Pathological testing showed that the vascular endothelium within the mass was glucose transporter 1-positive, and infantile hemangioma was diagnosed. Ultrasound is useful for the detection of hemangioma in the urinary bladder, but the difficulty of obtaining a sufficiently distended bladder to enable bladder observation in children means that it may have to be repeated several times.

Kidney involvement in IgA vasculitis (IgAV) is the most serious complication and renal biopsy findings in patients are mainly graded according to the criteria of the International Study of Kidney Disease in Children (ISKDC). Case 1 was a 3-year-old girl presented with nephrotic syndrome 1 month after initial presentation with IgAV, in whom pathologic renal biopsy revealed membranoproliferative-like lesions. Urinary findings gradually improved treated with intravenous methylprednisolone (IVMP), followed by multiple-drug therapy. Case 2 was a 6-year-old boy who underwent renal biopsy for nephritic-nephrotic syndrome on the 3 weeks after the onset of IgAV. Pathologic findings showed membranoproliferative-like lesions, and tuft necrosis and cellular crescents in about half of the glomeruli. IVMP and plasma exchange, followed by multiple-drug therapy, were performed. At the time of relapse about 2 years later, re-biopsy showed only new active lesions, and additional treatment with IVMP led to clinical remission after 4 years after the start of treatment. Patients in IgAV nephritis of ISKDC grade 6, membranoproliferative-like lesions, have diverse clinical and pathological features, but not necessarily with a bad prognosis. Hence, it may be important to perform stratified treatment by reclassification and semiquantification based on clinical symptoms and histological findings at the time of onset.