Long-Term Outcomes, Including Fetal and Neonatal Prognosis, of Renal Oligohydramnios: A Retrospective Study over 22 Years.

OBJECTIVE: To assess the long-term outcome of renal oligohydramnios and risk factors for fetal, neonatal, and postneonatal death. STUDY DESIGN: This retrospective cohort study included fetuses with prenatally detected renal oligohydramnios between 2002 and 2023. Patients who were lost to follow-up were excluded. Fetal, neonatal, and long-term outcomes were evaluated, and their risk factors were analyzed. RESULTS: Of 131 fetuses with renal oligohydramnios, 46 (35%) underwent a termination of pregnancy, 11 (8%) had an intrauterine fetal death, 26 (20%) had a neonatal death, nine (7%) had a postneonatal death, and 39 (30%) survived. Logistic regression analyses showed that an earlier gestational age at onset (OR 1.16, 95% CI 1.01-1.37) was significantly associated with intrauterine fetal death; anhydramnios (OR 12.7, 95% CI 1.52-106.7) was significantly associated with neonatal death as a prenatal factor. Although neonatal survival rates for bilateral renal agenesis, bilateral multicystic dysplastic kidney (MCDK), and unilateral MCDK with contralateral renal agenesis were lower than for other kidney diseases, 1 case of bilateral renal agenesis and two of bilateral MCDK survived with fetal intervention. Kaplan-Meier overall survival rates were 57%, 55%, and 51% for 1, 3, and 5 years, respectively. In the Cox proportional hazards model, birth weight <2000 g (hazard ratio 7.33, 95% CI 1.48-36.1) and gastrointestinal comorbidity (hazard ratio 4.37, 95% CI 1.03-18.5) were significant risk factors for postneonatal death. CONCLUSION: Long-term survival following renal oligohydramnios is a feasible goal and its appropriate risk assessment is important.

Living-donor liver transplantation for methylmalonic acidemia patient with hepatocellular carcinoma: A case report and literature review.

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive disorder caused by defects in propionyl-CoA (P-CoA) catabolism; of note, liver neoplasms rarely occur as a long-term complication of the disorder. Herein, we report the case of a patient with MMA and hepatocellular carcinoma (HCC) who was successfully treated with a living-donor liver transplant (LDLT) following prior kidney transplantation. CASE REPORT: A 25-year-old male patient with MMA underwent LDLT with a left lobe graft because of metabolic instability and liver neoplasms. He had presented with chronic symptoms of MMA, which had been diagnosed by genetic testing. Additionally, he had undergone living-donor kidney transplantation with his father as the donor due to end-stage kidney disease 6 years before the LDLT. He had an episode of metabolic decompensation triggered by coronavirus disease in 2019. Imaging studies revealed an intrahepatic neoplasm in the right hepatic lobe. Due to concerns about metabolic decompensation after hepatectomy, LDLT was performed using a left lobe graft obtained from the patient's mother. Pathological findings were consistent with the characteristics of well-to-moderately differentiated HCC. The postoperative course was uneventful, and the patient was discharged 48 days after the LDLT without any complications. At the 9-month follow-up, the patient's condition was satisfactory, with sufficient liver graft function and without metabolic decompensation. CONCLUSION: This case indicates that although HCC is a rare complication in patients with MMA, clinicians should be aware of hepatic malignancies during long-term follow-up.

Association between the time of initial relapse and subsequent relapses in patients with childhood-onset idiopathic nephrotic syndrome.

BACKGROUND: Nephrotic syndrome relapse within 6 months is a known risk factor for steroid-dependent nephrotic syndrome/frequently relapsing nephrotic syndrome (SDNS/FRNS), but the risk of early development of SDNS/FRNS and initiation of immunosuppression therapy remains unknown. METHODS: Patients with childhood-onset idiopathic nephrotic syndrome who had the first relapse within 6 months were enrolled. We analyzed the relationship between the time of the first relapse or the time of initial remission and incidence of SDNS/FRNS or initiation of immunosuppression therapy. RESULTS: Forty-five patients were enrolled. Twenty out of 23 patients (87%) with the first relapse within 30 days after discontinuing initial steroid therapy experienced a second relapse within 30 days after discontinuing steroid therapy. Additionally, most patients in this group (96%) experienced a second relapse within 6 months after the onset and were diagnosed as SDNS/FRNS at this time. In this group, the incidence of SDNS/FRNS development within 6 months was 96%. In contrast, the incidence of SDNS/FRNS development within 6 months was 18% in patients with the first relapse more than 30 days after steroid discontinuation. The incidence of initiation of immunosuppressive agents within 6 months was 83% in the former group and 14% in the latter group. CONCLUSIONS: Most patients with the first relapse within 30 days after discontinuing steroid therapy developed SDNS/FRNS and were administered immunosuppressive agents within 6 months. Thus, it might be reasonable to start immunosuppression therapy in this group without waiting for the second relapse.

Efficacy of rituximab and risk factors for poor prognosis in patients with childhood-onset steroid-resistant nephrotic syndrome: a multicenter study.

BACKGROUND: The efficacy of rituximab in steroid-resistant nephrotic syndrome (SRNS) is controversial. We previously reported that rituximab in combination with methylprednisolone pulse therapy (MPT) and immunosuppressants was associated with favorable outcomes. We determined risk factors for poor response following rituximab treatment, which remains unknown. METHODS: This retrospective study included 45 patients with childhood-onset SRNS treated with rituximab across four pediatric kidney facilities. Treatment effects were categorized as complete remission (CR), partial remission (PR), and no remission (NR) at one year after rituximab treatment. The primary outcome was the rate of CR, PR, and NR. Risk factors for non-CR were calculated with multivariate logistic regression. Adverse events and the relationship between disease status at one year and long-term prognosis were also evaluated. RESULTS: The rates of CR, PR, and NR at one year were 69%, 24%, and 7%, respectively. The median time from rituximab administration to CR was 90 days. The median follow-up period after rituximab administration was 7.4 years. In multivariate analysis, significant risk factors for poor response were the pathologic finding of focal segmental glomerular sclerosis and a long interval between SRNS diagnosis and rituximab administration. The rates of CR were 90.3% and 21.4% in patients receiving rituximab within and after 6 months following SRNS diagnosis, respectively (p < 0.001). Five patients developed chronic kidney disease stage G5, including 2 of the 11 patients with PR and all 3 patients with NR, whereas none of the 31 patients with CR developed chronic kidney disease stage G5. CONCLUSION: Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS.

Feasibility of discontinuing immunosuppression in children with idiopathic nephrotic syndrome.

BACKGROUND: Despite adverse events associated with the long-term use of immunosuppressants, their long-term discontinuation remains challenging in children with idiopathic nephrotic syndrome. Relapse and resumption of immunosuppressants after discontinuation and associated risk factors were analyzed. METHODS: This single-center retrospective cohort study included children with frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS) or steroid-resistant nephrotic syndrome (SRNS) who initiated immunosuppressant treatment between 2010 and 2020. Patients treated with immunosuppressants for less than two years, those with genetic SRNS, and those with continuation of immunosuppressants were excluded. RESULTS: Sixty-eight patients with FRNS/SDNS or SRNS discontinued immunosuppressants. Discontinuation of immunosuppressants was more frequently tried in patients with less relapse on initial immunosuppressants and less rituximab administration. Of 68 patients who discontinued immunosuppressants, 45 (66%) relapsed and 31 (46%) resumed immunosuppressants with a median follow-up of 39.8 months (IQR 24.6-71.2 months) after discontinuation. The relapse-free survival rates were 40.0%, 35.3%, and 35.3% in 1, 2, and 3 years from discontinuation of immunosuppressants, respectively. Relapse on initial immunosuppressants (HR 2.038, 95%CI 1.006-4.128, P = 0.048) and the relapse-free interval before discontinuation of immunosuppressants (HR 0.971, 95%CI 0.944-0.998, P = 0.037) were significant risk factors associated with relapse after the discontinuation of immunosuppressants, adjusting for sex, age at immunosuppressant treatment initiation, SRNS, and rituximab use. CONCLUSIONS: Long-term discontinuation of immunosuppressants can be feasible in patients without a relapse on initial immunosuppressants, those with longer relapse-free interval before discontinuation of immunosuppressants, and those without a relapse for one year after discontinuation of immunosuppressants. TRIAL REGISTRATION: Not applicable.

Frequency and prognosis of peritoneal dialysis-associated peritonitis in children.

BACKGROUND: Peritonitis is the leading cause of peritoneal dialysis (PD) discontinuation. However, few data concern risk factors of peritonitis development and catheter removal caused by treatment failure in pediatric patients. METHODS: This single-center, retrospective study analyzed data from pediatric patients who underwent chronic PD between March 2002 and June 2022. The incidence rates of peritonitis by the person-year method were calculated, and they were stratified by patient age groups. Risk factors for peritonitis development and catheter removal were also analyzed by multivariate analysis using logistic regression model. RESULTS: Ninety patients were enrolled, and 62 peritonitis episodes were observed in 41 (46%) patients. The incidence rate of peritonitis was 0.21 episodes per patient-year, which was the highest in children aged under 2 years old (0.26 episodes per patient-year). Moreover, 44 (71%) cases were successfully cured by antibiotics alone, although 17 (27%) cases required catheter removal, and 4 (6%) cases transitioned to chronic hemodialysis because of peritoneal dysfunction. One patient died. The risk factor for peritonitis development and catheter removal caused by treatment failure was PD insertion at under 2 years old (odds ratio = 2.5; P = 0.04) and Pseudomonas aeruginosa (odds ratio = 11.0; P = 0.04) in the multivariate analysis. P. aeruginosa was also a risk factor for difficulty in re-initiating PD (P = 0.004). CONCLUSIONS: The incidence rate of peritonitis was the highest in children under 2 years old. P. aeruginosa peritonitis is a risk factor for catheter removal and peritoneal dysfunction.

Changes in Patterns of Infection Associated with Pediatric Idiopathic Nephrotic Syndrome: A Single-Center Experience in Japan.

OBJECTIVE: We studied infection rates and risk factors for infection in current patients with idiopathic nephrotic syndrome (INS). STUDY DESIGN: This retrospective cohort study included the clinical data for children with diagnosed INS in our center between January 2010 and December 2020. The infection rates and risk factors were analyzed. RESULTS: We enrolled 187 patients, including 85 cases with steroid-dependent/frequently relapsing nephrotic syndrome and 45 with steroid-resistant nephrotic syndrome. Infection was observed a total of 84 times in 55 patients (95.5 per 1000 person-years). Pneumonia was the most common infection (21 cases, 23.9 per 1000 person-years), followed by febrile neutropenia (12 cases, 13.7 per 1000 person-years), whereas peritonitis and bacteremia were observed in only 3 and 2 cases, respectively. The multivariate analyses by logistic regression showed that rituximab treatment was significantly associated with infections in pediatric INS (P = .001). The infection rate during the B-cell-depleted state with immunosuppressants (318 per 1000 person-years) was greater than that with normal B-cell count with immunosuppressants (109 per 1000 person-years) or without immunosuppressants (76 per 1000 person-years). CONCLUSION: Common infections, such as peritonitis and bacteremia, decreased, whereas infections associated with medication (eg, rituximab) increased. The rate of infection increases during B-cell depletion after treatments with rituximab and other immunosuppressants.

The association between hypogammaglobulinemia severity and infection risk in rituximab-treated patients with childhood-onset idiopathic nephrotic syndrome.

BACKGROUND: Hypogammaglobulinemia is a major adverse effect from rituximab. However, the association between rituximab-induced hypogammaglobulinemia and infection frequency is unknown. METHODS: Patients who received rituximab for complicated nephrotic syndrome between February 2006 and October 2020 were enrolled in this retrospective observational study. Infections requiring antibacterial or antiviral agents or hospitalization were identified, and the characteristics of infections were compared according to infection type. RESULTS: One hundred and forty patients were enrolled. Fifty infection events were detected in 36 patients, 45 infection events in 32 patients required hospitalization, and 1 severe infection event required intensive care unit admission. In eight patients who developed severe hypogammaglobulinemia (serum IgG level < 200 mg/dL) for more than 1 year after rituximab treatment, eight infections occurred in six patients; six of these infections did not occur during the period of severe hypogammaglobulinemia. Febrile neutropenia accounted for 54.2% (13/24) of all infections among the patients with hypogammaglobulinemia. The incidence of infections was 0.028 (95% confidence interval = 0.017-0.448), 0.071 (95% [CI] = 0.041-0.114), and 0.096 (95% [CI] = 0.019-0.282) patient-years in patients with normal serum IgG levels and those with mild and severe hypogammaglobulinemia, respectively. Immunoglobulin replacement therapy was not administered to any patients except for the treatment of infection. CONCLUSIONS: Our results showed no statistically significant association between hypogammaglobulinemia severity and infection rate. In addition, the frequency of infection was relatively low even in patients with severe hypogammaglobulinemia, suggesting that immunoglobulin replacement therapy may not be necessary for rituximab-treated patients with severe hypogammaglobulinemia. A higher resolution version of the Graphical abstract is available as Supplementary information.

Immunogenicity and safety of SARS-CoV-2 mRNA vaccine in patients with nephrotic syndrome receiving immunosuppressive agents.

BACKGROUND: As there are no large-scale reports of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with nephrotic syndrome using immunosuppressive agents, we conducted the prospective study. METHODS: SARS-CoV-2 mRNA vaccines were administered to patients with nephrotic syndrome receiving immunosuppressive agents. The titers of SARS-CoV-2 spike protein receptor-binding domain antibodies were measured before and after vaccination. We evaluated factors associated with antibody titers after vaccination and analyzed adverse events. RESULTS: We enrolled 40 patients and evaluated vaccine immunogenicity in 35 of them. Seroconversion (> 0.8 U/mL) was achieved in all patients, and the median antibody titer was 598 U/mL (interquartile range, 89-1380 U/mL). Patients using mycophenolate mofetil (MMF) showed lower antibody titers than those who were not (median: 272 U/mL vs. 2660 U/mL, p = 0.0002), and serum immunoglobulin G (IgG) levels showed a weak linear relationship with antibody titers (R2 = 0.16). No breakthrough infections were noted. Three patients (7.5%) suffered from a relapse of nephrotic syndrome (2 and 3 days, respectively, after the first dose and 8 days after the second dose), two of whom had a history of relapse within 6 months before the vaccination. CONCLUSIONS: The SARS-CoV-2 mRNA vaccine was immunogenic in patients with nephrotic syndrome using immunosuppressive agents, although the use of MMF and low levels of serum IgG were associated with lower antibody titers after vaccination. Patients with high disease activity may experience a relapse of nephrotic syndrome after vaccination. A higher resolution version of the Graphical abstract is available as Supplementary information.

Postoperative management and complications after abdominal surgery in children receiving peritoneal dialysis.

BACKGROUND: Patients on peritoneal dialysis (PD) may develop PD-related complications that necessitate abdominal surgery. However, when to resume PD and how to prescribe PD fluid after surgery in pediatric patients are unknown. METHODS: Patients on PD who underwent small-incision abdominal surgery between May 2006 and October 2021 were included in this retrospective observational study. The complications after surgery and characteristics of patients with PD fluid leakage were analyzed. RESULTS: Thirty-four patients were included. They underwent 45 surgical procedures, including 23 inguinal hernia repairs, 17 PD catheter repositioning or omentectomy, and 5 others. The median time to resume PD was 1.0 (IQR, 1.0-3.0) days, and the median PD exchange volume at the initiation of PD after surgery was 25 (IQR, 20-30) ml/kg/cycle. PD-related peritonitis occurred in two patients after omentectomy and one after inguinal hernia repair. There was no PD fluid leakage or hernia recurrence among the 22 patients who had a hernia repair. Peritoneal leakage occurred in 3 of the 17 patients who had PD catheter repositioning or an omentectomy and was treated conservatively. No patients who resumed PD 3 days after small-incision abdominal surgery with less than half of PD volume had fluid leakage. CONCLUSIONS: Our findings demonstrated that PD could be resumed within 48 h of inguinal hernia repair with no PD fluid leakage or hernia recurrence in pediatric patients. In addition, resuming PD 3 days after a laparoscopic procedure with less than half of the usual dialysate volume might reduce the risk of PD fluid leakage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Early predictive factors for progression to kidney failure in infants with severe congenital anomalies of the kidney and urinary tract.

BACKGROUND: Severe congenital anomalies of the kidney and urinary tract (CAKUT) progress to infantile kidney failure with replacement therapy (KFRT). Although prompt and precise prediction of kidney outcomes is important, early predictive factors for its progression remain incompletely defined. METHODS: This retrospective cohort study included patients with CAKUT treated at 12 centers between 2009 and 2020. Patients with a maximum serum creatinine level ≤ 1.0 mg/dL during the first 3 days, patients who died of respiratory failure during the neonatal period, patients who progressed to KFRT within the first 3 days, and patients lacking sufficient data were excluded. RESULTS: Of 2187 patients with CAKUT, 92 were finally analyzed. Twenty-five patients (27%) progressed to KFRT and 24 (26%) had stage 3-5 chronic kidney disease without replacement therapy during the median observation period of 52.0 (interquartile range, 22.0-87.8) months. Among these, 22 (24%) progressed to infantile KFRT. The kidney survival rate during the infantile period was significantly lower in patients with a maximum serum creatinine level during the first 3 days (Cr-day3-max) ≥ 2.5 mg/dL (21.8%) compared with those with a Cr-day3-max < 2.5 mg/dL (95.2%) (log-rank, P < 0.001). Multivariate analysis demonstrated Cr-day3-max (P < 0.001) and oligohydramnios (P = 0.025) were associated with higher risk of infantile KFRT. Eighty-two patients (89%) were alive at the last follow-up. CONCLUSIONS: Neonatal kidney function, including Cr-day3-max, was associated with kidney outcomes in patients with severe CAKUT. Aggressive therapy for severe CAKUT may have good long-term life outcomes through infantile dialysis and kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Risk factors for early dialysate leakage around the exit site after catheter placement in pediatric peritoneal dialysis: a single-center experience.

BACKGROUND: Dialysate leakage, a major complication in peritoneal dialysis (PD), causes difficulty in continuing PD. However, literature evaluating risk factors for leakage in detail and the appropriate break-in period to avoid leakage in pediatric patients is scarce. METHODS: We conducted a retrospective study on children aged < 20 years who underwent Tenckhoff catheter placement between April 1, 2002, and December 31, 2021, at our institution. We compared clinical factors between patients with and without leakage within 30 days of catheter insertion. RESULTS: Dialysate leakage occurred in 8 of 102 (7.8%) PD catheters placed in 78 patients. All leaks occurred in children with a break-in period of < 14 days. Leaks were significantly more frequent in patients with low body weight at the catheter insertion, single-cuffed catheter insertion, a break-in period ≤ 7 days, and a long PD treatment time per day. Only one patient who had leakage with a break-in period > 7 days was neonate. PD was suspended in four of the eight patients with leakage and continued in the others. Two of the latter had secondary peritonitis, one of whom required catheter removal, and leakage improved in the remaining patients. Three infants had serious complications from bridge hemodialysis. CONCLUSIONS: A break-in period of > 7 days and if possible 14 days is recommended to avoid leakage in pediatric patients. Whereas infants with low body weight are at high risk of leakage, their difficulty in inserting double-cuffed catheter, hemodialysis complications, and possible leakage even under long break-in period make prevention of leakage challenging.

CD4 + and CD8 + T-lymphocyte number as predictive marker of relapse after rituximab treatment in childhood-onset refractory nephrotic syndrome.

BACKGROUND: Rituximab is a promising option for refractory idiopathic nephrotic syndrome. However, no simple predictive markers for relapse after rituximab have been established. To determine such markers, we investigated the relationship between CD4 + and CD8 + cell counts and relapse after rituximab administration. METHODS: We retrospectively investigated patients with refractory nephrotic syndrome who received rituximab followed by immunosuppressive as maintenance therapy. Patients were divided into no relapse in 2 years after rituximab treatment or relapse group. After rituximab treatment, CD4 + /CD8 + cell counts were measured monthly, at prednisolone discontinuation, and at B-lymphocyte recovery. To predict relapse, these cell counts were analyzed using receiver operating characteristic (ROC). Additionally, relapse-free survival was reevaluated based on the result of ROC analysis for 2 years. RESULTS: Forty-eight patients (18 in the relapse group) were enrolled. At prednisolone discontinuation (52 days after rituximab treatment), the relapse-free group showed significantly lower cell counts than the relapse group (median CD4 + cell count: 686 vs. 942 cells/µL, p = 0.006; CD8 + : 613 vs. 812 cells/µL, p = 0.005). In the ROC analysis, CD4 + cell count > 938 cell/µL and CD8 + cell count > 660 cells/µL could predict relapse in 2 years (sensitivity, 56% and 83%; specificity, 87% and 70%). The patient group with both lower CD4 + and CD8 + cell counts showed significantly longer 50% relapse-free survival (1379 vs. 615 days, p < 0.001 and 1379 vs. 640 days, p < 0.001). CONCLUSIONS: Lower CD4 + and CD8 + cell counts in the early phase after rituximab administration may predict a lower risk of relapse.

Incidence and risk factors of rituximab-associated hypogammaglobulinemia in patients with complicated nephrotic syndrome.

BACKGROUND: Hypogammaglobulinemia is a major adverse event after rituximab treatment; however, the precise incidence and risk factors are unclear in complicated steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS) patients. METHODS: This was a single-center, retrospective, observational study. Patients who received a single dose of rituximab for complicated SDNS or FRNS between February 2007 and May 2019 were enrolled. Serum IgG levels were plotted, and their trends were evaluated after rituximab treatment. The incidence of transient and persistent hypogammaglobulinemia was examined, and risk factors were calculated by multivariate analysis using logistic regression. RESULTS: We enrolled 103 patients who received 238 single doses of rituximab. Hypogammaglobulinemia was observed in 58.4% of the patients at least once after a single dose of rituximab treatment and 22.3% developed persistent hypogammaglobulinemia. Serum IgG levels gradually increased during B-cell depletion, and patients with low serum IgG levels at rituximab treatment had persistent hypogammaglobulinemia. Repeated courses of rituximab treatment increased the incidence of hypogammaglobulinemia. A past history of steroid-resistant nephrotic syndrome (SRNS) (odds ratio [OR] = 10.02; 95% confidence interval [CI] = 2.65-37.81; P < 0.001) and low serum IgG levels at rituximab treatment (OR = 7.63; 95% CI = 2.10-27.71; P = 0.002) was significantly associated with hypogammaglobulinemia in multivariate analysis. CONCLUSIONS: Hypogammaglobulinemia is a frequent adverse event after rituximab treatment, although IgG levels slightly increase during B-cell depletion. Low serum IgG levels at rituximab treatment and a past history of SRNS are significant risk factors for the development of hypogammaglobulinemia after rituximab treatment.

Glucocorticoid discontinuation in pediatric-onset systemic lupus erythematosus: a single-center experience.

BACKGROUND: Glucocorticoid discontinuation, a challenge in systemic lupus erythematosus (SLE), might be achievable with the advent of new therapeutic options. METHODS: This single-center study included 31 children with newly diagnosed pediatric SLE between 2002 and 2021, after the exclusion of patients who were followed for less than 1 year after treatment initiation and those lost to follow-up. Patient characteristics, clinical course including flares, treatment, glucocorticoid discontinuation, and outcomes were retrospectively analyzed. RESULTS: Glucocorticoids could be discontinued in 19 (61%) patients during a median observation period of 105.5 (range, 17-221) months. Of these, 5 (26%), 12 (63%), and 18 (95%) patients could discontinue glucocorticoids in 3, 5, and 10 years from treatment initiation, respectively. Additionally, 18 of the 19 patients did not experience flares after glucocorticoid discontinuation during a median duration of 37.2 (7.2-106.8) months. Three of the nineteen patients achieved drug-free remission. At last follow-up, all patients achieved low disease activity with or without glucocorticoids and 19, 8, and 1 patient were receiving mycophenolate mofetil (MMF), MMF plus tacrolimus, and MMF plus ciclosporin A, respectively. Flares were observed in 15 patients during the observation period. MMF as initial immunosuppressant (P = 0.01) and shorter interval between therapy initiation and achieving maintenance prednisolone dose of 0.1-0.15 mg/kg/day (P = 0.001) were associated with significantly reduced flare risk. Femoral head necrosis was observed in two patients. CONCLUSION: Despite the small sample size, these results support glucocorticoid discontinuation as a therapeutic target in pediatric SLE.

Trajectory of kidney recovery in pediatric patients requiring continuous kidney replacement therapy for acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is commonly seen in the PICU and is associated with poor short-term and long-term outcomes, especially in patients who required continuous kidney replacement therapy (CKRT). However, as the trajectory of kidney recovery in these patients remain uncertain, determination of the timing to convert to permanent kidney replacement therapy (KRT) remains a major challenge. We aimed to examine the frequency and timing of kidney recovery in pediatric AKI survivors that required CKRT. METHODS: We performed a retrospective study of patients under 18 years old who received CKRT for AKI in a tertiary-care PICU over 6 years. Primary outcomes were the rate of KRT withdrawal due to kidney recovery and KRT-dependent days for those who survived to hospital discharge. Secondary outcomes were all-cause mortality, dialysis dependence, and occurrences of estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 and eGFR < 60 mL/min/1.73m2 one year after initiation of the index CKRT in survivors. RESULTS: Thirty-nine patients were included. Of the 28 children who survived to hospital discharge, 26 (93%) withdrew from dialysis due to kidney recovery, all within 30 days. Twenty-three patients were followed up. One had died, five had an eGFR of 60 mL/min/1.73m2 or more but less than 90 mL/min/1.73m2, and two had an eGFR < 60 mL/min/1.73m2, of which one required peritoneal dialysis. CONCLUSIONS: Over 90% of the survivors withdrew CKRT within 30 days. However, the frequency of abnormal eGFR one year after initiation of CKRT in survivors exceeded 30% and supports the recommendation of post-AKI follow-up.

Ultrasonographic reference values and a simple yet practical formula for estimating average kidney length in Japanese children.

BACKGROUND: The assessment of kidney size is essential for treating kidney disease. However, there are no reliable and sufficiently robust ultrasonographic reference values or prediction formulas for kidney length in Japanese children, based on a sufficient number of participants. METHODS: We retrospectively analyzed kidney measurements by ultrasonography in children aged 18 years or younger from eight facilities throughout Japan between January 1991 and September 2018. Detailed reference values were developed by aggregating the left and right kidneys of boys and girls separately. Simple and practical reference values were developed by combining all the data from left and right kidneys and boys and girls. The estimation formulas for the average value and lower limit of the normal range for kidney length were developed based on regression analysis. RESULTS: Based on the aggregated kidney length data of 1984 participants (3968 kidneys), detailed reference values and simple reference values for kidney length were determined. From the regression analysis, the formula for calculating the average kidney length was generated as "kidney length (cm) = body height (m) × 5 + 2", and that for predicting the lower limit of normal kidney length in children under 130 cm was calculated as "lower limit (cm) = 0.85 × [body height (m) × 5 + 2]". CONCLUSION: Detailed ultrasonographic reference values of kidney length for Japanese children and simple reference values and estimation formulas for daily practice have been established.

Risks and renal outcomes of severe acute kidney injury in children with steroid-resistant nephrotic syndrome.

BACKGROUND: Risks and renal outcomes of severe acute kidney injury (AKI) in children with steroid-resistant nephrotic syndrome (SRNS), particularly those who require dialysis, have not been fully explored. METHODS: This retrospective cohort study enrolled children who had been diagnosed with idiopathic nephrotic syndrome at the National Center for Child Health and Development between March 2002 and December 2018. Children with steroid-sensitive nephrotic syndrome or SRNS-related gene mutations were excluded. RESULTS: Sixty-two children with SRNS (37 boys; median age, 3.6 years [interquartile range (IQR) 2.0-10.3]) were enrolled. Sixteen patients (25.8%) had severe AKI, including nine patients (14.5%) who received dialysis. The period from nephrotic syndrome (NS) onset to partial remission (median [IQR]) was not significantly influenced by dialysis status, but tended to be longer in the dialysis group (125 days [74-225] vs. 40 days [28-113]; p = 0.09); notably, no patient developed chronic kidney disease during the follow-up period. Infection and posterior reversible encephalopathy (PRES) were significantly associated with AKI. Patients with AKI tended to require dialysis in the presence of infection, undergo treatment with cyclosporine A, and have PRES. The period from onset of NS to AKI was significantly longer in the dialysis group (26 days [15.5-46.0] vs. 4 days [0.0-14.0]; p = 0.01). CONCLUSION: Dialysis was commonly required among children with SRNS who exhibited severe AKI. The period from onset of NS to partial remission tended to be longer in patients receiving dialysis, whereas renal prognosis was satisfactory during subsequent follow-up.

Unilateral nephrectomy for young infants with congenital nephrotic syndrome of the Finnish type.

BACKGROUND: The management of congenital nephrotic syndrome of the Finnish type (CNF) is challenging. It is difficult to withdraw intravenous albumin infusions, resulting in long-term hospitalization. In addition, fatal hypotension after bilateral nephrectomy has been reported. In our center, we have performed unilateral nephrectomy during early infancy. METHODS: Infants diagnosed with CNF between 2011 and 2020 in our institution were enrolled. We examined the clinical course before and after unilateral nephrectomy and evaluated the effectiveness of this strategy. RESULTS: Seven patients (all showing NPHS1 mutations) were enrolled. All required daily intravenous albumin infusion via central venous catheter (CVC). Unilateral nephrectomy was performed at a median of 76 days of age (59-208 days). Surgical complications did not occur in any of patients. The mean albumin dose was decreased after unilateral nephrectomy (2.0 vs 0.4 g/kg/day; p = 0.02). Intravenous albumin infusion could be withdrawn at a median of 17 days, the CVC removed at a median of 21 days, and they discharged at a median of 82 days after unilateral nephrectomy. Although bacterial infections were noted seven times before unilateral nephrectomy, only one episode occurred after surgery. Four patients initiated peritoneal dialysis at two to three years of age and all of them underwent kidney transplantation thereafter. CONCLUSIONS: Unilateral nephrectomy during early infancy may be an effective treatment allowing for withdrawal from albumin infusion, prevention of complications, withdrawal from CVCs and shortening hospital stay for patients with CNF.

Immunogenicity and safety of SARS-CoV-2 vaccine with immunosuppressive agents.

BACKGROUND: We conducted a prospective study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination in children and adolescents who were taking immunosuppressive agents. METHODS: Two doses of SARS-CoV-2 mRNA vaccine were administered to patients taking immunosuppressive agents. Titers of SARS-CoV-2 spike protein receptor-binding domain antibodies were measured before and after vaccination. Vaccine failure was defined as a postvaccination antibody titer of <0.8 U/mL. Seroconversion rates, factors associated with antibody titers after vaccination, clinical effectiveness against breakthrough infection, and adverse events were evaluated. RESULTS: A total of 42 patients (median age, 18.1 years) were enrolled. Immunogenicity was measured in 34 patients. The median SARS-CoV-2 spike antibody titer was 329 U/mL (interquartile range [IQR] 50-812 U/mL). Seroconversion (≥0.8 U/mL) was achieved in 29 patients (85%), whereas vaccine failure was diagnosed in five (15%). All patients with vaccine failure were recipients of solid organ transplants (SOTs) and were taking two immunosuppressants. The median antibody titer in SOT recipients (57 U/mL) was significantly lower than that in non-recipients (653 U/mL, P = 0.0002); that of patients taking two immunosuppressive agents (93 U/mL) was lower than that of patients taking one (506 U/mL, P = 0.003). Breakthrough infection occurred in three patients (7%). Adverse events were non-specific, and no flares of primary disease or acute rejection in SOT recipients occurred. CONCLUSIONS: SARS-CoV-2 mRNA vaccine was immunogenic in children and adolescents taking immunosuppressive agents, although SOT recipients and patients taking two immunosuppressive agents tended to show lower postvaccination antibody titers.