Haidong Fu

Treatment of tacrolimus or cyclosporine A in children with idiopathic nephrotic syndrome

BackgroundCyclosporine A (CsA) and tacrolimus (TAC) are often alternative treatment choices for patients with nephrotic syndrome.MethodsIn this prospective study, the efficacy and safety of CsA and TAC in inducing and maintaining remission in 74 children with idiopathic nephrotic syndrome (INS) were evaluated.ResultsIn terms of short-term efficacy, TAC was more effective than CsA in children with steroid-resistant nephrotic syndrome (χ2 = 13.75, P = 0.001), although no significant difference in number of episodes of relapse were found in patients with complete remission between the two treatment groups (first year: χ2 = 0.261, P = 0.88; second year: χ2 = 2.685, P = 0.26). In patients with frequently relapsing or steroid-dependent nephrotic syndrome, no significant difference in short-term remission (χ2 = 1.908, P = 0.39) or in relapse frequency during follow-up (within first year: χ2 = 1.046, P = 0.59; within second year: χ2 = 0.587, P = 0.75) were found between the two groups. There was a difference in the rate of adverse effects between the two treatment groups [nephrotoxicity: 4/24 (CsA) vs .0/50 (TAC), P = 0.002; hirsutism: 8/24 (CsA) vs. 0/50 (TAC), P < 0.001].ConclusionsIn our pediatric patient cohort, the treatment of steroid-resistant nephrotic syndrome with tacrolimus was associated with higher efficacy and lower renal toxicity in comparison to CsA, although no favorable outcome in relapse rate during long-term follow-up was seen. On the other hand, tacrolimus was not always the better choice to replace CsA in the treatment of severe frequently relapsing or steroid-dependent nephrotic syndrome.

Fluid management of hypernatraemic dehydration to prevent cerebral oedema: A retrospective case control study of 97 children in China

Aim:  To compare the fluid management of hypernatraemic dehydration in acute gastroenteritis in those who developed cerebral oedema (cases) versus those who did not (controls).

Efficacy of triptolide for children with moderately severe Henoch-Schonlein purpura nephritis presenting with nephrotic range proteinuria: a prospective and controlled study in China.

Objective. To observe the clinical efficacy of the Chinese herb, Triptolide, in children with moderately severe Henoch-Schönlein purpura nephritis (HSPN). Methods. From January 2007 to December 2011, 56 HSPN children manifested by nephrotic range proteinuria with normal kidney function and <50% crescents or sclerosing lesions on biopsy were hospitalized in the Childrens Hospital of Zhejiang University School of Medicine. They were divided into two groups: the treatment group (n = 42; Triptolide at a dosage of 1 mg/kg·d, combined with prednisone at a dosage of 2 mg/kg·d, within a course of medium-to-long-term therapy of 6 to 9 months) and the control group (n = 14; prednisone alone, with the same procedure). Results. Short-term remission was observed in 95% of patients from treatment group and in 72% of patients from control group, respectively. There was a significant difference between both groups (χ 2 = 6.222, P = 0.029) for short-term effects. Meanwhile, no significant difference, as proteinuria, hematuria, hypertension, and decreased eGFR, was observed between the two groups in long-term followup (χ 2 = 3.111, P = 0.097). The Kaplan-Meier plot analysis also revealed no significant difference (χ 2 = 2.633, P = 0.105). Conclusion. Triptolide is effective in relieving short-term symptoms for moderately severe HSPN children, though its long-term effects need to be observed further.

Triple immunosuppressive therapy in steroid-resistant nephrotic syndrome children with tacrolimus resistance or tacrolimus sensitivity but frequently relapsing.

The treatment strategy for steroid‐resistant nephrotic syndrome remains uncertain at present, especially in those with calcineurin inhibitor resistance or intolerance. To date, few studies have been published using multiple combination therapy of immunosuppressive reagents for children with calcineurin inhibitor‐resistant or ‐intolerant nephrotic syndrome.

Overexpression of Myo1e in Mouse Podocytes Enhances Cellular Endocytosis, Migration, and Adhesion

Podocytes are a terminally differentiated and highly specialized cell type in the glomerulus that forms a crucial component of the glomerular filtration barrier. Recently, Myo1e was identified in the podocytes of glomeruli. Myo1e podocyte‐specific knockout mice exhibit proteinuria, podocyte foot process effacement, glomerular basement membrane disorganization, signs of chronic renal injury, and kidney inflammation. After overexpression of Myo1e in a conditionally immortalized mouse podocyte cell line (MPC5), podocyte migration was evaluated via transwell assay, endocytosis was evaluated using FITC‐transferrin, and adhesion was evaluated using a detachment assay after puromycin aminonucleoside treatment. Myo1e overexpression significantly increased the adherence of podocytes. ANOVA analysis indicated significant differences for cell adhesion between the overexpression and control groups (overexpression vs. control, t = 11.3199, P = 0.005; overexpression vs. negative control, t = 12.0570, P = 0.0006). Overexpression of Myo1e inhibited puromycin aminonucleoside‐induced podocyte detachment, and the number of cells remaining on the bottom of the culture plate increased. Cell migration was enhanced in Myo1e‐overexpressing podocytes in the transwell migration assay. Internalization of FITC‐transferrin also increased in Myo1e‐overexpressing podocytes relative to control cells. Overexpression of Myo1e can enhance podocyte migration ability, endocytosis, and attachment to the glomerular basement membrane. Restoration of Myo1e expression in podocytes may therefore strengthen their functional integrity against environmental and mechanical injury. J. Cell. Biochem. 115: 410–419, 2014.

Persistent asymptomatic isolated hematuria in children: clinical and histopathological features and prognosis

BackgroundThis study involving 351 children who had undergone kidney biopsy secondary to persistent asymptomatic isolated hematuria was undertaken to assess histological diagnosis of the disease and its natural history and prognosis.MethodsThe patients were divided into two groups: 215 patients with asymptomatic isolated microhematuria (AIMH; proteinuria <0.1 g/day) and 136 patients with persistent asymptomatic microhematuria, recurrent macrohematuria and/or proteinuria (AMHP; proteinuria 0.1–0.25 g/day). After kidney biopsy, the patients were monitored for 2–10 years.ResultsNormal biopsies or minor abnormalities were more frequent in AIMH patients than those in AMHP patients, who exhibited IgA nephropathy more frequently. During the 2- to 10-year follow-up period, adverse renal events (i.e., development of proteinuria, hypertension, or impaired renal function) were observed in 13/215 (6.0%) patients with AIMH and 31/136 (22.8%) patients with AMHP (χ2=15.521, P<0.001).ConclusionsNormal biopsies or minor abnormalities were more frequently observed in AIMH patients, whereas IgA nephropathy and adverse renal events were more frequent in AMHP. Microscopic hematuria, especially when accompanied by macroscopic hematuria and proteinuria, may represent an important risk factor for the development of chronic kidney disease.

Coenzyme Q10 supplementation therapy for 2 children with proteinuria renal disease and ADCK4 mutation: Case reports and literature review

Rationale: Mitochondrial nephropathy has a poor prognosis and often progresses to the end-stage renal disease. Renal pathology often is focal segmental glomerulosclerosis (FSGS) and does not respond to steroid therapy or immunosuppressive therapy. Some patients are benefited from the therapy of coenzyme Q10, which affect the synthesis pathway of coenzyme Q10. Patient concerns: Herein, we report 2 cases of children with proteinuria renal disease with ADCK4 mutation. Diagnoses: Proteinuria renal disease with ADCK4 mutation. Interventions: Compound heterozygous mutation in ADCK4 gene were detected with next-generation sequencing and confirmed by Sanger sequencing. Both of the patients were given coenzyme Q10 supplementation therapy. Outcomes: The first patient showed a decreased proteinuria after coenzyme Q10 supplementation therapy, while the other was not improved. Lessons: Based on the cases we reported and from the literature, recognition of ADCK4 mutation through early and accurate genetic screening could be helpful in avoiding unnecessary toxicities and in preventing complications arising in mitochondrial nephropathy.

Clinical Characteristics of Concomitant Nephrotic IgA Nephropathy and Minimal Change Disease in Children

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in children and adolescents worldwide. Meanwhile, minimal change disease (MCD) is the most common cause of nephrotic syndrome in children. Recently, several case reports have revealed that IgAN can be complicated by MCD in adults. Here, we report our experience concerning the features of such patients in pediatrics. Methods: The clinical manifestations and pathological features of 197 children who presented with IgAN from December 2007 to November 2013 were analyzed retrospectively based on the criteria for nephrotic syndrome and MCD. Results: Among the 197 children diagnosed with primary IgAN, 25 (12.7%) patients presented with nephrotic syndrome, and 7 patients (2.8%) presented with MCD-like pathological features and nephrotic syndrome simultaneously. The cohort of 7 patients included 5 boys, and the median age was 8.9. All of the patients who were diagnosed with primary nephrotic syndrome were treated initially with corticosteroids. Except for 1 patient with steroid resistance who was lost to follow-up, the other 6 cases presented were steroid sensitive and remained in complete remission for the last follow-up, with median and mean follow-up durations of 30.5 and 34.5 months, respectively (range 10-65 months). Conclusions: This study revealed that IgAN and MCD may also coexist in children. Moreover, most of these patients who presented with nephrotic syndrome responded well to steroids and had a favorable prognosis. Large-scale studies are required, and careful attention should be paid to such complicated cases.

The Value of Monitoring the Serum Concentration of Mycophenolate Mofetil in Children with Steroid-Dependent/Frequent Relapsing Nephrotic Syndrome

Background: Mycophenolate mofetil (MMF) is an alternative treatment strategy in children with steroid sensitivity who have frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). Methods: From January 2009 to January 2015, 31 cases of children with FRNS/SDNS were prospectively recruited and administered MMF and prednisone; then, serum samples were collected, and the area under the curve (AUC) of mycophenolic acid (MPA-AUC) was calculated. Results: A MPA-AUC of 27.99 μg·h/ml had a diagnostic sensitivity of 65.2% and a specificity of 87.5% in discriminating relapsing from non-relapsing patients (receiver operating characteristic-AUC 0.848). The 31 patients were then grouped according to the results of the MPA-AUC as follows: low-AUC group, <30 μg·h/ml and high-AUC group, ≥30 μg·h/ml. The results indicated that there was a significant difference in the remission rate between the groups (χ2 = 6.645, p = 0.01) during the 6 months of follow-up. Compared with the results before MMF therapy, the steroid dosage in both groups was significantly reduced at the 6- and 12-month follow-ups. Furthermore, the steroid dose was reduced more significantly in the high-AUC group than in the low-AUC group (0.447 ± 0.254 vs. 0.219 ± 0.161 mg/kg/day, p = 0.006) at the 6-month follow-up. Compared with the low-AUC group at the 6-month follow-up, the number of patients with relapse and relapse episodes in the high-AUC group were also significantly reduced (7/16 vs. 1/15, p = 0.037, and 15/27 vs. 1/29, p = 0.014, respectively). Conclusions: MMF is a reasonable treatment choice to reduce the number of relapse episodes and steroid administration in children with FRNS/SDNS. Moreover, children in the high-AUC group (MPA-AUC ≥30 μg·h/ml) tended to require lower steroid doses and had greater remission rates than the patients in the low-AUC group (<30 μg·h/ml) at the 6-month follow-up.

Evaluation of mycophenolate mofetil or tacrolimus in children with steroid sensitive but frequently relapsing or steroid‐dependent nephrotic syndrome

Approximately 30–40% of children with steroid sensitive nephrotic syndrome have frequently relapsing nephrotic syndrome (FRNS) or steroid‐dependent nephrotic syndrome (SDNS). Mycophenolate mofetil (MMF) and tacrolimus (TAC) are often alternative treatment choices for these patients.