I was in charge of the 57th annual meeting and the theme was “Spinning the evidence of pediatric kidney disease”. The word “spinning” is used to refer to the process of making cotton or cocoons into threads by putting them on a weight and drawing out the fibers, or figuratively connecting words to form a sentence. I chose the theme of this meeting with the idea of connecting evidence and combining evidence to form actual clinical practice. I believe that actual clinical practice, clinical trials, and research are a series of things. When these are organically connected, they create a driving force and lead to better medical care. To move things forward, ability, effort, environment, and luck are all necessary. In the environment, the support of people is one of the most important factors. I have treated many children with kidney disease over the past 30 years. In this article, I would like to look back on my career, describe various aspects of my clinical practice, clinical trials, and research, and convey a message to young physicians as I aim to further my own efforts.

The Division of Medical Safety Management continues to strive for comprehensive improvement of hospital environments assuring high quality and reliable safety in medical care. Our daily activities include various fields. We foster medical safety mind in all hospital staff members and formulate specific and efficient measures for a better management system at our hospital. The Division provides qualified information related medical safety, sets sustainable developmental goals, and promotes research and technological innovation for continuous improvement of the medical safety management system. Since April in 2017, I have been a vice director who is in charge of medical safety management at Okayama University Hospital. Based on my observation and experience, I will report specific details of the daily activities of the Division of Medical Safety Management at University Hospital.

The first renal biopsy in Japan was performed at Niigata University in 1954. Records indicate that pediatric renal biopsy was also performed at Niigata University in 1957. Since there was no pathology atlas for renal biopsy at that time, they did everything themselves, including observing the renal biopsy tissue, interpreting the clinical symptoms and pathology, and deciding on a treatment plan. Seventy years have passed since then, and the roles of clinicians and pathologists have been divided into the technique and diagnosis of renal biopsy, respectively. In addition, many guidelines based on pathological findings have been established, and uniform treatment based on pathological diagnosis has become possible without the observation of the tissue itself. However, there are several cases in which treatment based on guidelines does not work, and in such cases, it is sometimes difficult to determine which direction to take to modify treatment. At such times, the pathological findings of renal biopsies can be a useful source of information to consider the course of treatment. This review describes the basics of renal biopsy procedures and the interpretation of basic pathological findings.

Peritoneal dialysis has long been the most commonly used acute blood purification for neonates. Recently, cases of acute blood purification using extracorporeal circulation have been reported in neonates, especially those with low birth weight. In 2013, the “Japanese Guidelines for Neonatal Acute Blood Purification with Extracorporeal Circulation” were published. In Japan, a blood purification system that can be set at speeds as low as 1 mL/min, anticoagulants with low risk of bleeding, and low-priming-volume columns are available. These may contribute to improved outcomes for critically ill and low-birth-weight infants.

About 10 years have passed since the publication of the aforementioned guidelines. In the future, it will be necessary to consolidate the experience of acute blood purification using extracorporeal circulation for neonates in Japan and disseminate more effective and safer methods nationwide to “equalize” this therapy as a general treatment method.

In Japan, mycophenolate mofetil (MMF) is used off-label for the treatment of nephrotic syndrome; however, there are no clear guidelines regarding the duration of its use in for this condition. In this retrospective study, we evaluated the efficacy and safety of the long-term use of MMF after an initial period of treatment with rituximab (RTX) treatment for refractory nephrotic syndrome (RNS). The study participants were 13 patients with childhood-onset RNS who used MMF as a single therapeutic agent for more than two years after initially using RTX. The median duration of MMF use was 4 years and 2 months. Eleven patients remained “relapse-free” during the observation period, while the remaining two relapsed after cessation of MMF treatment. All 12 patients who underwent renal biopsy diagnosed with minimal change nephrotic syndrome (MCNS). No serious complications necessitating the discontinuation of MMF, such as neutropenia and prolonged hypo-IgG were observed. This study has shown that administration of MMF is a safe and efficacious therapeutic option following treatment with RTX for long-term remission in most patients with RNS. This could have a considerable impact on the quality of life for children with RNS as they advance through their formative years of the education and employment.

We conducted a retrospective study to clarify the clinical features of children with horseshoe kidney in Japan. Of 59 cases, 34 (57.7%) were boys, the median age at diagnosis was 1.2 years (0.0–13.3 years), and the median observation period was 1409 days (2–6134 days). Fourteen patients (23.7%) had malformation syndromes with confirmed diagnoses, and of the other 45 patients, 17 (37.8%) had congenital anomalies. Of the 17 cases, 6 (35.4%) had neurological diseases and 5 (29.4%) had congenital heart diseases, both accounting for more than half of the cases. In this study, 9 cases (15.3%) required surgical treatment, and chronic kidney disease stage 2 was observed in 3 cases (5.1%) during the observation period. In many cases, the horseshoe kidney may be a renal manifestation of various syndromic congenital anomalies of the kidney and urinary tract that requires attention to the presence of extrarenal lesions. In the present study, there were many cases that ended the observation in a short period of time, and further investigation of the prognosis of horseshoe kidney is needed in the future.

A 6-year-old boy started to receive oral prednisolone for an incipient nephrotic syndrome. Two weeks later, he started to receive a calcium antagonist because of hypertension. Another two weeks later, he was still not in complete remission; therefore a renal biopsy was performed, and a pathological diagnosis of focal segmental glomerulosclerosis syndrome was made. The day after the renal biopsy, his systolic blood pressure was in the 120 mmHg range, and he had impaired consciousness and conjugate deviation to the left. We diagnosed him with posterior reversible encephalopathy syndrome. Continuous intravenous infusion of nicardipine and that of midazolam were started, fosphenytoin and phenobarbital were administered, and continuous electroencephalogram monitoring was performed. After an electroencephalogram showed a decreasing tendency of spike-and-wave discharges, his consciousness recovered, and his imaging findings improved. An angiotensin-converting enzyme inhibitor was administered, and his systolic blood pressure fell to around 100 mmHg. Administration of prednisolone was tapered and discontinued, and his urine total protein to creatinine ratio (g/g·Cr) fell under 0.5. It is of note that pediatric patients with renal disease have many risk factors for posterior reversible encephalopathy syndrome and may develop it even in the absence of significant hypertension or immunosuppressive medication.

We experienced a case of multicentric carpotarsal osteolysis (MCTO) diagnosed based on genetic testing at an early stage, leading to useful management. She was a 1-year-old girl with a history of laryngomalacia, short skull, dysphagia, and psychomotor retardation. When she was admitted to the hospital for treatment of pneumonia and bronchial asthma attacks, she met the diagnostic criteria for nephrotic syndrome. Then, steroid therapy was started but she was found to be steroid resistant. Renal ultrasonography revealed the presence of nephronophthisis, and a renal biopsy was performed. Renal pathology showed compatible findings with nephronophthisis and secondary focal segmental glomerulosclerosis (FSGS). On the other hand, genetic testing showed a previously reported heterozygous mutation in the MAFB gene and she was finally diagnosed with MCTO. Radiographic examination revealed osteolysis characteristic of MCTO, and orthopedic management was initiated. During outpatient management, renal dysfunction rapidly progressed and peritoneal dialysis was required at the age of three. There is no report of MCTO with nephrotic state, and early genetic diagnosis was useful for long-term management.

Mixed connective tissue disease (MCTD) is characterized by positivity to anti-U1-ribonucleoprotein (RNP) antibodies and presents with symptoms of systemic lupus erythematosus, dermatomyositis/polymyositis, and scleroderma. MCTD-associated nephropathy unusually precedes extrarenal involvement, although pediatric-onset MCTD complicates nephropathy more frequently than the adult-onset type. We experienced the case of a 13-year-old girl who was diagnosed with membranous nephropathy (MN) without extrarenal involvement following school urine screening, which was subsequently confirmed as MCTD. Her urine was positive for protein and occult blood; further examination revealed positive antinuclear antibodies and strongly positive anti-U1-RNP antibodies. The proteinuria and hematuria worsened; subsequently, thorough examination including kidney biopsy was performed. Although the criterion for MCTD was not fulfilled at that point, the diagnosis was MN based on renal glomerular histology; thereafter, corticosteroid and immunosuppressive therapy commenced. Raynaud’s phenomenon appeared later; therefore, MCTD was diagnosed. It was a rare disease course where nephropathy preceded extrarenal manifestations, such as Raynaud’s phenomenon.

Galloway-Mowat syndrome (GAMOS) is a disorder characterized by mental retardation with microcephaly and steroid-resistant nephrotic syndrome (SRNS). According to previous reports, SRNS defines the prognosis in patients with GAMOS because of its resistance to treatment. We herein describe a patient with GAMOS who achieved long-term remission on cyclosporine. A 1-year-old girl was noted to have mental retardation and microcephaly at a health checkup. She developed proteinuria at 2 years of age; she thereafter met the criteria for SRNS at 5 years of age and was diagnosed with GAMOS based on clinical symptoms. After the introduction of cyclosporine A for SRNS, the proteinuria gradually decreased, and nephrotic remission was achieved at 7 years of age. When the cyclosporine was discontinued after remission, the proteinuria worsened again, suggesting that the cyclosporine had contributed to the decrease in proteinuria. To reduce nephrotoxicity, the cyclosporine was changed to once-daily administration at 8 years of age. Renal biopsy at 14 years of age showed no obvious nephrotoxicity, and remission was maintained. Once-daily administration of cyclosporine may be effective in reducing nephrotoxicity and improving the prognosis in patients with hereditary SRNS such as GAMOS nephropathy.

We hereby report a case of severe Henoch-Schönlein purpura nephritis (HSPN). The patient was treated using a multidrug combination regimen, which included steroid pulse therapy. However, the steroid-induced intraocular pressure increased early on, requiring modification of the treatment. Surgical treatment for steroid-induced intraocular hypertension could be avoided through early reduction of corticosteroids and use of multiple ophthalmic medications. In addition, nephritis was treated by switching to combination of multiple immunosuppressive agents (mizoribine, cyclosporine, and cyclophosphamide), which resulted in negative urine dipstick tests. In this case, it was possible to avoid ocular complications while treating nephritis by administration of appropriate steroid-induced intraocular hypertension medications and concomitant use of effective immunosuppressive agents.

We experienced a boy who presented with steroid-resistant nephrotic syndrome at the age of 2 years and was diagnosed with severe lupus nephritis 1 year later. The first renal biopsy showed secondary membranous nephropathy and fluorescent antibody showed a full house pattern, but he did not meet the diagnostic criteria for systemic lupus erythematosus (SLE). We administered prednisolone, angiotensin converting enzyme inhibitor and angiotensin II receptor blocker to him, the severe proteinuria disappeared. A year later, severe proteinuria and serological findings appeared, and he was diagnosed with SLE. The second renal biopsy showed lupus nephritis type IV+type V, which was already mainly chronic lesion. In the case of type V lupus nephritis, it can be difficult to diagnose SLE. However, delayed SLE has a poor prognosis. This is the importance of renal biopsy for SRNS because there is delayed SLE with SRNS onset. If pathological findings suggest lupus erythematosus type V, we should have regular urinalysis and blood tests for early diagnosis.