Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder to the upper urinary tract due to an abnormality at the ureterovesical junction (UVJ). It is one of the major causes of febrile urinary tract infections (fUTIs) in children. While VUR is often diagnosed following an episode of fUTI, it is also observed in 10–20% of the cases of congenital hydronephrosis detected on prenatal ultrasonography. Primary VUR, which results from a congenital defect in the formation of the UVJ in the absence of any other predisposing pathology, frequently resolves spontaneously. Therefore, initial management typically involves continuous antibiotic prophylaxis. If spontaneous resolution does not occur or if fUTIs are not adequately controlled, surgical intervention may be considered. Although VUR management may appear straightforward, we often encounter challenges in daily clinical practice. This article highlights five particularly challenging aspects of VUR management and provides a practical overview based on current clinical evidence.

Persistent Cloaca (PC) is a congenital disease in which the urethra, vagina, and rectum fail to separate, resulting in a single opening in the perineal area. The surgery involves separating the urethra, vagina, and rectum. However, the surgical approach varies depending on the length of the common canal or the urethra, and the functional outcomes related to the urinary, reproductive, and digestive systems also differ. Clarifying the living conditions of patients with multiple organ dysfunction is essential to improving their quality of life and identifying the necessary support. Based on the patient narratives, we examined what is needed to create a supportive environment for them. As medical professionals, we recognize the importance of “treatment policies that take into account the patient’s suffering,” “the need to provide information to patients and their supporters,” “support from peers and family and along with societal acceptance,” “respect for identity as women,” and “assistance for patients with complex conditions in maintaining their social lives.” We aim to promote the establishment of a continuous and comprehensive support system.

The Career Diversity Committee of the Japanese Society of Pediatric Nephrology (JSPN) disseminated a questionnaire about career development among society members before holding a committee-planned session entitled “Career Development: What Do You Want to Be?”, at the 58th Annual Meeting of the Japanese Society for Pediatric Nephrology. We collected responses from 161 members. The survey responses suggested that “continuation of clinical practice” is important for career development, and that career satisfaction is greatly affected by their workplace and surrounding environment. In addition, 69.5% of respondents were satisfied with the current state of their career development, whereas 25.4% were not fully satisfied for various reasons. The survey findings suggest that to help the members develop their careers, the JSPN should continue listening to members and provide them with programs beneficial for career development while maintaining efforts to support them with knowledge acquisition and upskilling regarding pediatric nephrology.

This article outlines the findings of normal glomeruli on electron microscopy (EM) and outlines the EM terms and definitions for glomerular abnormalities. EM glomerular abnormalities are closely related to clinical findings. In podocytes, severe loss of foot processes, condensation of cytoskeletal material, cellular hypertrophy, and increased intracytoplasmic lysosomes and vacuolation suggest severe damage of podocytes and help to distinguish focal segmental glomerulosclerosis from minimal change disease. Glomerular basement membrane (GBM) changes are seen in not only Alport syndrome but also many other glomerular disease. Especially in IgA nephropathy, GBM changes on EM suggest disease activity and should be observed with caution.

The Kyushu Council for In-School Examination prepared the Standard Manual for School Urinary Screening in Kyushu in 2004 and has since promoted its use. In recent years, congenital anomalies of the kidney and urinary tract (CAKUT) accounted for many cases of pediatric chronic kidney disease in Japan; consequently, in-school urinary screening for CAKUT was proposed nationwide. The 5th edition of the Kyushu manual was revised to allow the introduction of urine beta-2 microglobulin/urine creatinine ratio screening and ultrasonography based on medical circumstances. As the use of ultrasonography, in particular, required training for non-specialized healthcare professionals, simple manuals and instructional video materials for CAKUT screening were prepared. Here we present the history of the Kyushu Council for In-School Examination over approximately 20 years, explaining its current activities, including aggregate results publicly disclosed annually and the role of in-school urinary screening in the detection of immunoglobulin A (IgA) nephropathy. The Kyushu Council for In-School Examination should be enhanced using Personal Health Records (PHRs) that contain school health-examination data to facilitate continued sharing of both examination results and the importance of in-school urinary screening.

Adult porcine xenotransplantation for adult renal failure patients is underway in some countries, but currently requires strong immunosuppression, extensive facilities and large amounts of money to maintain the pigs. Porcine fetal kidney xenotransplantation differs from that of adult in many aspects. Fetal kidneys are hypoimmunogenic and do not require the long-term maintenance of pigs, thus reducing the size and funding of facilities. We are advocating the clinical application of fetal pig kidney transplantation for renal oligohydramnios sequence. The concept is to transplant a fetal porcine kidney into the fetus with renal oligohydramnios sequence to produce urine, avoid renal replacement therapy during the postnatal period of respiratory and circulatory instability, and provide a bridging therapy until renal replacement therapy can be more safely initiated. Xenotransplantation to the fetus requires more careful caution in terms of ethics, and we believe it is important to carefully explore the path to clinical application through multifaceted discussions involving patients’ families, medical professionals, and ethics experts, in parallel with basic research.

For appropriate intravenous infusion therapy, it is important to recognize that volume depletion and dehydration are distinct clinical conditions, and to understand the physiology of total body water distribution in the body fluid compartment. Traditionally, early rapid infusion with an isotonic crystalloid fluid has been used for severely dehydrated children and those in shock; however, in recent years, restrictive intravenous fluid therapy has become the preferred practice because of concerns regarding the safety of early rapid infusion. Historically, hypotonic solutions, based on the Holliday-Segar (HS) formula, have been used for maintenance intravenous fluid therapy. However, isotonic solutions with a more restricted infusion volume than that calculated using the HS formula have become the treatment of choice in view of iatrogenic hyponatremia associated with the syndrome of inappropriate antidiuretic hormone secretion in pediatric patients. Overall, it is important to recognize that infusion therapy can cause serious complications in children. As there is no firm consensus on the best approach for intravenous fluid resuscitation and maintenance therapy, it is necessary to repeatedly assess changes in the child’s clinical presentation related to infusion therapy, and modify the infusion approach for a more appropriate therapy.

IgA vasculitis is clinically characterized by skin, joint, and abdominal symptoms, and is a disease that is often encountered in general pediatric practice. IgA vasculitis nephritis is an important complication observed in approximately 30% of cases with IgA vasculitis and determines the long-term prognosis. Kidney biopsy is necessary in severe cases with IgA vasculitis nephritis, and the severity of IgA vasculitis nephritis is important in determining the subsequent treatment approach. However, there are no clinical practice guideline for pediatric IgA vasculitis in Japan, and in response to a request for their creation, this guideline was created with the aim of clarifying the treatment policy based on the evidence accumulated to date and supporting the provision of uniform medical care with a high level of evidence throughout Japan. In this article, an overview of clinical practice guideline for pediatric IgA vasculitis in Japan 2023 was shown, focusing on the main points.

Intravenous fluid therapy is often prescribed in pediatrics. It can effectively cure children who are dehydrated and/or suffer from poor oral intake. But inappropriate fluids could lead to adverse outcomes, because fluids are directly administered into patients’vessels without the patient being able to adjust it. Clinicians should continually assess the patients’ state, e.g. severity of dehydration, improvement in oral intake, body temperature, etc. and correct prescription of intravenous fluid therapy.

Background and Purpose: In recent years, the number of patients with eating disorders has been increasing, and general pediatricians who are not specialists in this field are seeing more cases. Renal dysfunction is one of complications of eating disorder, but the frequency and prognosis in the pediatric field are unknown. Methods: We investigated the frequency of renal dysfunction, patient background and test values, and the time it takes for renal function to recover of fifteen patients with eating disorders who visited at our hospital, which is a secondary medical institution. Results: Of the fifteen patients, a median age at the diagnosis of 9.0 (5.4–15.2) years, and the type of disease was avoidant/restrictive food intake disorder in 10 cases (66.7%). The median estimated glomerular filtration rate at the time of admission was 91.8 (57.4–123.4) mL/min/1.73m², and 7 of the 15 patients (46.7%) had decreased renal function. The median time required for renal function to normalize in patients with decreased renal function was 88 days (34–114). Conclusion: Renal dysfunction is a frequent complication in patients with eating disorders, even in children, and requires long-term follow-up.

Background: Membranoproliferative glomerulonephritis (MPGN) is classified into immune complex-associated MPGN (IC- MPGN), C3 glomerulonephritis (C3GN), and dense deposit disease (DDD). These diseases are rare and not fully understood. Objectives and Methods: To clarify the clinicopathological characteristics of MPGN, we retrospectively studied childhood-onset MPGN cases pathologically diagnosed and followed for more than 2 years in our division. Results: A total of 9 patients were included: 3 with IC- MPGN, 5 with C3GN, and 1 with DDD. The most common detection method was school urinalysis. At the time of diagnosis, two patients had nephrotic syndrome, and one patient had renal dysfunction in the IC-MPGN group. However, no patients in the C3GN or DDD groups presented with these symptoms. At the last follow-up, none of the patients had nephrotic syndrome or renal dysfunction, but 8 patients still required medication. Conclusions: Most childhood-onset MPGN cases were identified through school urinalysis. Despite persistent hypocomplementemia in serum C3 levels, short-term renal function was preserved.

Background and Purpose: In Japan, estimated glomerular filtration rate (eGFR) based on creatinine (Cr), cystatin C (CysC), and β2-microglobulin (β2MG) is commonly used to evaluate kidney function in children. However, discrepancies between these eGFR values have been observed in clinical practice. This study aimed to investigate the consistency between the measured glomerular filtration rate (mGFR) using the inulin clearance test (Cin), eGFR values derived from Cr, CysC, and β2MG, as well as eGFR based on 24-hour creatinine clearance (CCr).

Methods: This retrospective study included 120 patients (83 boys) aged 3 months to 18 years with chronic kidney disease who underwent Cin testing at our hospital between 2016 and 2023. The mGFR values were compared with Cr-eGFR, CysC-eGFR, β2MG-eGFR, and CCr-eGFR for each subject. The mean error (ME) was calculated through Bland-Altman analysis to evaluate the validity of each estimate.

Results: A total of 167 Cin tests were conducted. The mean values (ml/min/1.73 m²) of each test were as follows: mGFR 63.5±32.6, Cr-eGFR 63.3±26.2, CysC-eGFR 68.8±28.3, β2MG-eGFR 87.3±40.5, and CCr-eGFR 57.4±26.9. The Cr-eGFR showed the greatest similarity to mGFR, with Bland-Altman analysis confirming that Cr-eGFR was the most valid and reliable method for estimating mGFR.

Conclusion: Cr-eGFR provides the most accurate estimate of mGFR compared to other methods. The reasons for the observed discrepancies and the potential need for new estimation formulas warrant further discussion.

Background and Purpose: In 2014, we developed the cystatin C (cysC)-based eGFR (cysC-eGFR) for Japanese children, using inulin clearance as the gold standard. However, there have been recent reports that the cysC-eGFR overestimates GFR, and we reviewed the validity of the cysC-eGFR at the time of its creation. Methods: The cysC-eGFR was created using company A’s prestandardized cysC values multiplied by a standardization factor, but the cysC values of three other companies at that time existed, and the cysC-eGFRs of four companies were compared by multiplying by each standardization factor. Results: The four equations were not in agreement with each other. The validity of the standardization coefficients of company A was demonstrated when the cysC-eGFR was created. The validity of the currently used eGFR=104.1/cysC-7.80 in Japan was shown to be equivalent to the creatinine-based eGFR in data collected from 2012 to 2016 from the pediatric CKD study group in Japan. Conclusion: The recent GFR overestimation of cysC-eGFR is considered to be issues after 2017, and these need to be discussed in the future.

Background and Purpose: Although clinical practice guidelines recommend that angiotensin system (RAS) inhibitors be considered for children with mild IgA nephropathy, the spontaneous remission rate of IgA nephropathy in children with mild proteinuria is not high, around 20%. Methods: In this retrospective study, we investigated the efficacy and safety of tonsillectomy combined with steroid pulse therapy as initial treatment in 59 children (median age, 13.0 years) with IgA nephropathy and mild proteinuria (urinary protein/creatinine ratio, <1.0 g/gCr). Results: After the initiation of steroid pulse therapy, proteinuria disappeared in 57 patients (97%) at a median of 8.0 days; hematuria disappeared in 57 patients (97%) at a median of 6.8 months. During the follow-up period (median, 6.0 years), relapse occurred in three patients (5%). However, there were no serious adverse events due to steroid pulse therapy or tonsillectomy. At the last follow-up (median age 18.3 years), one patient (2%) had mild proteinuria and six patients (10%) had hematuria. Although one patient received RAS inhibitors, none developed CKD stage 3 or higher. Conclusion: Tonsillectomy combined with steroid pulse therapy should be considered as initial therapy in children with undeniable future progression to CKD.

Background and Purpose: Differentiating acute pyelonephritis from acute focal bacterial nephritis (AFBN) in cases of febrile urinary tract infection (fUTI) is crucial for determining therapeutic strategy. Currently, the gold standard for diagnosing AFBN is the detection of a localized low-absorption area on contrast-enhanced CT. The purpose of this study was to evaluate the utility of ultrasonography (US) in the diagnosing AFBN, with a particular focus on its positive predictive value (PPV). Methods: A retrospective study was conducted on 103 children hospitalized with first-episode fUTI between September 2020 and August 2023. Results: Of the 10 patients who met the US diagnostic criteria for AFBN—defined by an indistinct focal mass and local blood flow defects—contrast-enhanced CT was performed in 9. In all cases, a mass-like heterogeneous contrast-impaired area was observed in the region identified on US. The PPV of US for diagnosing AFBN was found to be 100%. Conclusion: These findings suggest that contrast-enhanced CT may not be necessary when AFBN is suspected based on US findings.

Background and Purpose: In our department, tacrolimus is administered by continuous intravenous infusion (FK civ) to achieve a blood concentration of 10 ng/mL following pediatric kidney transplantation until oral administration becomes possible. To stabilize blood concentrations after surgery, we developed a formula to estimate the FK civ dosage. Methods: This study included 36 patients (18 males and 18 females) aged <20 yrs. who underwent kidney transplantation at our hospital between January 2016 and August 2023 and received FK civ with blood concentration monitoring. Multivariate analysis was performed using FK civ dosage to achieve a target blood concentration of 10 ng/mL as the dependent variable. Results: The median FK civ dosage was 0.48 mg/day (interquartile range: 0.35–0.64), with a median blood concentration of 12.5 ng/mL (interquartile range: 10.8–15.0). Blood concentrations were measured in 33 patients the day after surgery. The formula for FK civ dosage (mg/day) targeting blood concentration 10 ng/mL is: 1.358 * body surface area (m²)−0.04809 * age (yrs.)−0.27774, with an R² value of 0.38. Conclusion: In the case of FK civ after pediatric kidney transplantation, the formula for FK civ dosage (mg/day) targeting blood concentration 10 ng/mL is: 1.358 * body surface area (m²)−0.04809 * age (yrs.)−0.27774.

We encountered CUBN variants in two children with asymptomatic proteinuria, which showed minor glomerular abnormalities. Despite initiating renin-angiotensin system (RAS) inhibitors, proteinuria did not decrease. Genetic testing was conducted, diagnosing a CUBN gene abnormality. After genetic diagnosis, RAS inhibitors were discontinued, and no renal dysfunction was observed at the final observation point. Depending on the mutation site of the CUBN gene, it can either lead to vitamin B12 malabsorption in the intestines or asymptomatic proteinuria. Abnormalities in cubilin present as tubular proteinuria, which is usually less severe than proteinuria from other glomerular gene abnormalities, and often show minor glomerular abnormalities in renal pathology. Even if the pathology shows minor glomerular abnormalities in cases of asymptomatic proteinuria, genetic test should be performed to avoid unnecessary treatments and to predict renal prognosis in cases where proteinuria does not improve with RAS inhibitors.

A 16-year-old male patient was diagnosed with systemic lupus erythematosus and class IV-G(A) lupus nephritis 2 years before presentation. He was treated with methylprednisolone pulse therapy, oral prednisolone (PSL), hydroxychloroquine (HCQ), and mycophenolate mofetil (MMF), which resulted in remission; however, he decided to discontinue his treatment after 7 months. One year later, the patient presented to our hospital with fever and generalized edema, as well as hypertension, renal dysfunction, and severe proteinuria. Renal histopathology revealed class IV-G(A), thrombosis and fibrinoid necrosis in the vascular pole and loop walls. Although there was no hemolytic anemia, the findings were characteristic of thrombotic microangiopathy or antiphospholipid antibody syndrome nephropathy. He was started on PSL and received three courses of methylprednisolone pulse therapy. HCQ and MMF were included to maintain remission, and the patient was administered PSL, HCQ, and MMF for approximately 18 months after relapse. He experienced persistent renal dysfunction, and there was concern that the disease might progress to chronic kidney disease.

A 15-year-old girl was first diagnosed with occult blood and protein in her urine at the age of 10 during a school urinalysis. She was admitted to the hospital with nephrotic syndrome with generalized edema at the age of 13 years. Renal pathology revealed membranoproliferative glomerulonephritis (MPGN) type 3. Although proteinuria decreased with combination therapy of methylprednisolone pulses and cyclosporine, her kidney function gradually declined. A second renal biopsy revealed chronic nephrotoxicity, which prompted us to switch from cyclosporine to mycophenolate mofetil. Subsequently, nephrotic syndrome developed again. For refractory MPGN, IgG subclass and light chain staining were performed, and only IgG3 (lambda chain predominant) was found to be deposited, leading to a diagnosis of proliferative glomerulonephritis with monoclonal IgG deposits. In children with refractory nephrotic MPGN, staining for IgG subclasses and light chains should be considered.

A 10-year-old female patient without significant prior medical history was evaluated by ultrasound-guided percutaneous renal biopsy for persistent, significant proteinuria initially noted during routine school urine screening. Following the biopsy, she developed gross hematuria, which resolved the next day, and perirenal hematoma, which subsequently declined in size; she was discharged three days after the procedure. However, 2 days later, she was readmitted with lower abdominal pain and gross hematuria. Contrast-enhanced computed tomography revealed hemorrhage originating from a renal arteriovenous fistula. Coil embolization was performed 2 days later, 7 days after the initial biopsy, resolving the symptoms. The arteriovenous fistula was presumed to have arisen from an inadvertent puncture near the renal hilum. Subsequent delayed-phase renal scintigraphy confirmed the preserved split renal function. Renal histopathology revealed minor glomerular abnormality, and she was finally diagnosed with orthostatic proteinuria. Although severe hemorrhagic complications requiring intervention are uncommon in pediatric patients undergoing renal biopsy, preparedness for prompt intervention is essential.

Lupus peritonitis, a condition that can develop during the active phase of systemic lupus erythematosus (SLE), is characterized by abdominal pain, vomiting, diarrhea, and ascites effusion. Reports of pediatric cases are few. Blood tests in a 14-year-old girl with no history of cutaneous rashes who presented with abdominal distention, pedal edema, and abdominal pain revealed hypoalbuminemia, hyponatremia, and thrombocytopenia. After hospital admission for further evaluation and treatment, hypocomplementemia was detected; however, the ds-DNA antibody and urinary protein test results were negative. Imaging revealed severe ascites. Steroid administration alleviated the ascites over time, and the patient’s laboratory values improved. A subsequent renal biopsy revealed lupus nephritis International Society of Nephrology/Renal Pathology Society class III(A), and SLE was diagnosed. The patient then received steroid pulse therapy, hydroxychloroquine, and mycophenolate mofetil, achieving remission. This case was challenging to diagnose because some SLE diagnostic criteria were not met. Understanding lupus peritonitis and performing a renal biopsy are crucial for early diagnosis.

We report a 12-year-old boy with stage 3 chronic kidney disease who developed metabolic acidosis and growth retardation after augmentation enterocystoplasty for neurogenic bladder. In infancy, he was diagnosed with recurrent urinary tract infections, bilateral complete duplication of the renal pelvis and ureterobladder transitional stenosis, and underwent bilateral ureterobladder neoanastomosis. He subsequently had repeated urinary tract infections. He was undergoing clean intermittent catheterization for vesicoureteral reflux and neurogenic bladder. However, due to difficulties in managing his urinary incontinence, he underwent bowel use bladder enlargement at the age of 12 years. As a postoperative complication, he repeated anion gap normal hyperchloremic metabolic acidosis, thought to be caused by the contact of urine with the intestinal wall, requiring alkalizing agents for more than 5 years. The growth curve, which had temporarily stagnated postoperatively, showed a trend towards improvement after the start of acidosis management. It is important to recognize that metabolic acidosis can occur after augmentation enterocystoplasty and that acidosis can affect growth.