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Background: Proteinuria is broadly classified into glomerular and tubular proteinuria. Urinary beta-2-microglobulin (β2-MG) is known as a marker for detecting tubulointerstitial diseases. However, tubulointerstitial damage can also lead to an increase in urinary β2-MG level in some patients with glomerular diseases. This study aimed to determine the ratio of urinary β2-MG to total protein (TP) concentration in patients with both isolated tubulointerstitial and glomerular disease. Methods: This multicenter, retrospective study included children with Dent disease or lupus nephritis in five facilities. Their urinary β2-MG levels were > 1000 µg/L. Urinary β2-MG and TP concentrations were obtained, and the ratio of urinary β2-MG to TP concentration (µg/mg) was calculated. The Mann–Whitney U test was performed to compare this ratio between these children. The optimal cutoff value of the ratio for considering the presence of glomerular disease was obtained from the receiver operating characteristic (ROC) curve. Results: We obtained information on 23 children with Dent disease and 14 children with lupus nephritis. The median ratios of urinary β2-MG to TP concentrations in children with Dent disease and lupus nephritis were 84.85 and 1.59, respectively. The ROC curve yielded the optimal cutoff value of this ratio for distinguishing between these diseases, and the cutoff value was found to be 22.3. Conclusion: In children with tubulointerstitial diseases, the urinary β2-MG concentration may be approximately 8.5% of the TP concentration. The possibility of presenting with glomerular disease should be considered in patients with a ratio of urinary β2-MG to TP concentration of < 22.3 (µg/mg). [ABSTRACT FROM AUTHOR]

Background: Some pediatric patients on maintenance dialysis may need end-of-life care in the future because of being excluded from the indication of kidney transplantation and experiencing difficulty in continuation of their dialysis. This study aimed to thoroughly elucidate mortality outcomes of children on maintenance dialysis including the cause of death and clinical background of exclusion from indication of transplantation. Patients and methods: This single-center retrospective study enrolled 53 children who received kidney transplantation (5) or maintenance peritoneal dialysis (PD, 48) as initial renal replacement therapy (RRT). We examined the selected RRT modalities, mortality outcomes, clinical backgrounds of cause of death, and risk factors of excluding from future the indication of transplantation. Results: Nine (17%) of all 53 patients, all receiving PD (9/48, 19%), were finally excluded from next RRT indication—7 were excluded due to severe extrarenal complications that indicated high risk for transplantation and 2 were excluded due to severe psychomotor retardation and at the guardians' discretion. Patients who were excluded from the indication had a younger age at PD induction and higher proportion of cerebral and cardiac complications or psychomotor retardation than patients who were included in the indication. Of the nine patients, seven died; of which, one patient died due to fatal progression of extrarenal complications and six died due to infectious or noninfectious dialysis-related complications. Conclusion: Patients with severe extrarenal complications or psychomotor retardation tend to be excluded from the indication of transplantation. Their condition becomes fatal because of the complications of long-term dialysis and progression in extrarenal complications. [ABSTRACT FROM AUTHOR]

Background: Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. This study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS. Methods: We sequentially measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 NS patients. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin incuding 51 control subjects. Results: The median of total serum adiponectin levels in patients were 36.7, 36.7, and 20.2 μg/mL at the onset, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects. The median values of %HMW, %MMW, and %LMW values were 56.9/27.0/14.1 at the onset, 62.0/21.8/13.4 at the initial remission, and 58.1/21.7/17.5 at during the remission period of NS, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset were high, and the %LMW values at the onset and at initial remission were low. Conclusions: In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms change. [ABSTRACT FROM AUTHOR]

Background: Only a few studies have investigated epidemiological and clinicopathological information regarding pediatric and adolescent and young adult (AYA) patients with renal disease. The purpose of this study was to clarify the differences and relationship of clinicopathological findings between pediatric and AYA patients using the Japan Renal Biopsy Registry (J-RBR). Methods: This cross-sectional study analyzed data from patients registered in the J-RBR between 2007 and 2017. Clinicopathological findings at diagnosis were analyzed for 3,463 pediatric (age < 15 years) and 6,532 AYA (age 15–30 years) patients. Results: Although chronic nephritic syndrome was the most common clinical diagnosis at age > 5 years, nephrotic syndrome was the most frequent diagnosis at age < 4 years. The most common pathological diagnosis as classified by pathogenesis in pediatric patients was primary glomerular disease (except IgA nephropathy), whereas IgA nephropathy was increased in AYA patients. Mesangial proliferative glomerulonephritis was the most common pathological diagnosis as classified by histopathology in both pediatric and AYA patients. Minor glomerular abnormalities were the most frequent histopathologic diagnoses of nephrotic syndrome in childhood, but their frequency decreased with age. Conclusion: To the best of our knowledge, this is the first report of clinicopathological features of pediatric and AYA patients in a large nationwide registry of renal biopsy. There were differences of clinical, pathological and histopathologic findings between pediatric and AYA patients. [ABSTRACT FROM AUTHOR]

Background: The suitable dosage regime of mycophenolate mofetil (MMF) based on the pharmacokinetics of mycophenoric acid (MPA) for pediatric patients with idiopathic nephrotic syndrome (INS) is controversial. The pharmacokinetics of MPA is influenced by renal function, serum albumin concentration, and concomitant medications, especially calcineurin inhibitors. This study analyzed the pharmacokinetics of MPA in clinically stable children with INS receiving cyclosporine (CyA). Methods: This retrospective study enrolled children with INS receiving MMF (Cellcept) (30-40 mg/kg/day in two divided doses) combined with CyA (Neoral) without relapse and renal dysfunction. Pharmacokinetic parameters, including the area under the concentration-time curve (AUC) calculated by the trapezoid method, were calculated from seven serial blood samples. Results: Thirty-two patients (22 males) of median age 11.0 years were included; 32 pharmacokinetic studies were performed. The median MMF dose was 16.2 mg/kg/time or 470.4 mg/m/time. The median AUC0-12 was 44.3 ng h/mL. AUC0-12 of all patients showed excellent correlations with C2 ( r = 0.6405, P < 0.0001), resulting in a regression formula of AUC0-12 = 21.971 + 2.6059 C2. Comparisons of dose/body weight-normalized AUC0-12 values among age groups showed a lower value in the youngest group (≤5 years). Conclusion: In children with clinically stable INS receiving CyA, C2 monitoring was the most useful single parameter for estimating MPA pharmacokinetics. Younger children required higher MMF doses. [ABSTRACT FROM AUTHOR]

Background: Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. Methods: Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. Results: Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. Conclusion: Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients. [ABSTRACT FROM AUTHOR]