Genetics and clinical features of 15 Asian families with steroid-resistant nephrotic syndrome.
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Adolescent↗
Biomedical subjects
Masataka Honda
Publications and source records attributed to Masataka Honda.
A survey of peritonitis and exit-site and/or tunnel infections in Japanese children on PD.
To obtain data on peritonitis and exit-site and/or tunnel infections (ESI/TI) in Japanese children undergoing peritoneal dialysis (PD) from January 1999 through June 2003, we surveyed 22 members of the Japanese Study Group of Pediatric Peritoneal Dialysis (JSPPD) by questionnaire. One hundred and thirty patients were eligible. Seventy episodes of bacterial peritonitis occurred in 45 patients (0.17 episodes/patient-year), and 123 ESI/TI occurred in 60 patients (0.29 episodes/patient-year). S. aureus and MRSA were found to be the causative organisms in 39% and 13% of the peritonitis episodes, and in 59% and 20% of the ESI/TI, respectively. Tunnel infection was found in 55% of the MRSA peritonitis episodes. Eleven percent of the peritonitis episodes relapsed, and 19% needed hemodialysis. One patient died due to MRSA peritonitis. The PD catheter was removed in all fungal and 78% of MRSA peritonitis. However, the type of organism did not influence the need for catheter-related surgery for ESI/TI. Neither peritonitis nor ESI/TI was prevented by the use of a swan-neck catheter, a downward-pointing exit site, povidone iodine exit-site care, bathing instruments, or nasal mupirocin. In conclusion, MRSA peritonitis was not uncommon in children in Japan, was frequently associated with tunnel infections, and had a poor outcome. No association was found between the occurrence of infection and preventive measures previously reported as effective. Alternative approaches are needed in children, especially for MRSA.
Anti-Bacterial Agents↗
Posterior reversible encephalopathy syndrome in children: its high prevalence and more extensive imaging findings.
BACKGROUND: Posterior reversible encephalopathy syndrome is a distinctive clinicoradiological entity observed in a variety of clinical settings, including pediatric patients. A greater prevalence of this syndrome has been suggested in kidney transplant recipients and patients with kidney disease. Although usually considered benign and reversible, characteristics of this syndrome in pediatric patients remain obscure. The objective of the present study involved disclosing details of imaging findings, as well as the clinical course and prevalence of the syndrome in this field. METHODS: We investigated kidney transplant recipients and pediatric patients with kidney disease in our institution from 1990 to 2004. For these patients, clinical course, imaging findings, blood pressure, concurrent medical illnesses, and administrative condition of calcineurin inhibitors were analyzed. RESULTS: Twenty cases of posterior reversible encephalopathy syndrome were investigated in patients ranging in age from 1.9 to 18.3 years. In most patients, radiological abnormalities extended to the gray matter (17 of 20 patients), frontal and temporal lobes, and even the cerebellum (16 patients). Of 177 kidney transplant recipients (cyclosporine, 127 patients; tacrolimus, 50 patients), 6 patients administered cyclosporine (4.7%) and 4 patients administered tacrolimus (8.0%) developed the syndrome after transplantation. CONCLUSION: Posterior reversible encephalopathy syndrome should be suspected in pediatric kidney transplant recipients and patients with kidney disease if they have a sudden episode of neurological symptoms, even if imaging findings are not restricted to the subcortical white matter of the occipital region.
Adolescent↗
Unexpectedly high prevalence of pretransplant abnormal glucose tolerance in pediatric kidney transplant recipients.
Several studies suggested that the incidence of new-onset diabetes following pediatric kidney transplantation has increased markedly in recent years, with reported incidence of up to 20%. However, limited information is available regarding the incidence and features of pretransplant status of abnormal glucose tolerance in pediatric kidney transplant recipients. We assessed the risk of 55 non-diabetic pediatric transplant recipients developing PTDM by performing OGTT prior to transplantation. For post-transplant immunosuppression, each patient received either a CsA- or a TAC-based regimen. However, recipients who had abnormal glucose tolerance in the pretransplant OGTT were allocated to the CsA-based regimen. The mean age of the patients was 9.7 +/- 5.4 yr while mean BMI was 16.5 +/- 3.3 kg/m2. FPG level before transplantation was within the normal limit in all patients, while the mean HbA1C value was 4.5. However, 18 of the 55 patients (32.7%) had abnormal glucose tolerance in the pretransplant OGTT, 13 (23.6%) had impaired glucose tolerance, and 5 (9.4%) had DM. PTDM developed in two patients on the TAC-based regimen with these patients having normal glucose tolerance prior to the transplant. In contrast, the 18 patients with abnormal glucose tolerance did not develop PTDM under CsA-based immunosuppression. Our results demonstrated an unexpectedly high prevalence of abnormal glucose tolerance in pretransplant OGTT even in a pediatric population. We believe that modification of post-transplant immunosuppression by the identification of high-risk patients using the pretransplant OGTT may minimize the development of new onset of PTDM.
Adolescent↗
Autosomal dominant polycystic kidney disease.
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Alanine Transaminase↗
[Beneficial and adverse effects of high-dosage MZR therapy in the management of children with frequently relapsing nephrotic syndrome].
BACKGROUND: Long-term therapy of mizoribine (MZR 2-5 mg/kg/day) has been reported in the management of children with frequently relapsing nephrotic syndrome(FRNS). It had minimum adverse effects, however, MZR therapy does not sufficiently suppress the relapse of FRNS. Previous reports suggested that modification of MZR therapy with a total dosage and administration schedule may improve the therapeutic effect. To elucidate the issue, we retrospectively evaluated the efficacy and safety of high-dose MZR therapy for children with FRNS. METHODS: The subjects comprised 13 affected children with FRNS (9 boys and 4 girls: median age of 11.7 years, ranging from 7.8 to 20.1 years). They were divided into a high dose group (MZR 7-10 mg/kg/ day; Max 400 mg) and a low dose group (MZR 4-6 mg/kg/day). We compared the therapeutic benefits between both groups, including the incidence of relapse(times/year) and daily dosages of prednisolone (PSL, mg/kg/day). The Wilcoxon test was used for statistical analysis. We also evaluated the relationship between the therapeutic effects and serum concentration of MZR two hours after the administration. RESULTS: The low dose and high-dose groups were well matched in terms of baseline characteristics. After the initiation of MZR, beneficial therapeutic effects ensued in the high-dose group (incidence of relapse: 3.61 vs. 1.59 times/year before and after the therapy, p < 0.05), daily dosages of PSL (0.65 vs. 0.29 mg/kg/day before and after therapy, p<0.001), but did not occur in the low-dose group(3.97 vs. 2.84 times/year; 0.84 vs. 0.53 mg/kg/day, n. s.). All patients with a serum MZR concentration of over 3 microg/ml had relapses less than three times a year. One patient in the high-dose group and the other in the low-dose group showed hyperuricemia, and responded well to medical treatment. No other adverse effect was observed. CONCLUSIONS: High-dose MZR therapy in the management for FRNS may provide more beneficial effects without significant adverse effects.
Adolescent↗
Membranoproliferative glomerulonephritis in a patient with X-linked agammaglobulinemia.
Immune complex and complement systems play an important role in membranoproliferative glomerulonephritis (MPGN). X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by severe hypogammaglobulinemia. We report the case of an XLA patient who developed MPGN during an intravenous immunoglobulin (IVIG) treatment. In this patient, the serum IgG level was maintained at more than 400 mg/dl of regular IVIG administration (2.5 g/dose/month). The patient presented with microscopic hematuria, proteinuria (U-pro/Cr: 4.0-4.2) and low serum complement levels (C3: 57.8 mg/dl) 3 years after IVIG treatment and was diagnosed histopathologically as having MPGN type III. Both hematuria and proteinuria significantly improved, and the serum complement level returned to a normal level following methylprednisolone pulse therapy. To our knowledge, this is the first case report of MPGN associated with XLA. Although it is unclear how MPGN occurred in this XLA patient, we suggest that residual humoral immunity in the patient could be associated with the development of MPGN.
Agammaglobulinemia↗
Cyclosporin A absorption profiles in children with nephrotic syndrome.
A single blood concentration measurement of Neoral 2 h after administration (C2) is a new concept in therapeutic drug monitoring (TDM). In most adult patients, the concentration of cyclosporin A (CyA) peaks within 2 h after Neoral administration. Therefore, monitoring the area under the concentration-time curve over the first 4 h post-dose (AUC0-4) is considered to be the most reliable strategy for Neoral TDM. In addition, C2 is considered to be the most accurate predictor of AUC0-4, with which C2 correlates best. Thus, in adult patients, C2 monitoring is recommended as the best single-point TDM method for Neoral. However, in paediatric patients, the effectiveness of C2 monitoring is still unclear. We examined the trough concentration (C0), C1, C2, C3, and C4 of CyA in 60 patients (1 to 20 years old, mean age 7.42+/-0.67 years) who had nephrotic syndrome treated with Neoral. The peak concentration of C0-C4 was C1 or C2 in 38 patients (early peak group) and C3 or C4 in 22 patients (late peak group). C2 in the late peak group was significantly lower than that in the early peak group (422+/-50.1 vs. 665 +/-53.8 ng/ml, P =0.0008), although the administered doses of Neoral and C0 were similar between these groups. Therefore, TDM by C2 using the same standard as in the early peak group might result in an overdose of CyA in the late peak group. As the concentration peaked at 3 h or more after Neoral administration in the late peak group, AUC0-4 does not necessarily reflect the Neoral absorption profile. As more than 33% of the paediatric patients were in the late peak group, TDM by AUC0-4 or C2 should be used carefully in paediatric patients treated with Neoral.
Absorption↗
A prospective trial of steroid withdrawal after renal transplantation treated with cyclosporine and mizoribine in children: results obtained between 1990 and 2003.
A prospective trial of adrenocorticostertoid (steroid) withdrawal after pediatric renal transplantation was begun in 1990. Ninety-four pediatric renal transplant recipients were enrolled in our multicenter study. Immunosuppressive therapy with cyclosporine (CyA), methylprednisolone (MPL), and mizoribine (MZ) was started after transplantation. MPL was reduced to administration on alternate days in 69 patients (73.4%) and was withdrawn in 27 patients (28.7%). Rejection episodes occurred in nine patients (33.3%) after withdrawal of MPL. It occurred within 3 months after withdrawal of MPL in two patients and more than 6 months in the others. Among them, two patients lost the grafts. Thirteen-year patient survival rate and graft survival rate were 94.6 and 83.1%, respectively. Forty-four of the 94 patients reached their final height. Mean final height was 155.0 cm in males and 146.3 cm in females and their height standard deviation score was -2.6 s.d., the same as that at the time of transplantation. Management of growth retardation before transplantation and further reduction in the steroid dose after transplantation will increase the final height of children with chronic renal failure.
Adolescent↗
Analysis of NPHS1, NPHS2, ACTN4, and WT1 in Japanese patients with congenital nephrotic syndrome.
BACKGROUND: Congenital nephrotic syndrome (CNS) causes significant renal failure, and is classified into two types: (1) Finnish type; and (2) other, including diffuse mesangial sclerosis. Mutations of NPHS1 and NPHS2, which encode the slit diaphragm components nephrin and podocin, cause CNS and autosomal-recessive familial steroid-resistant nephrotic syndrome, respectively. Most patients with Finnish-type CNS in Europe and the United States have NPHS1 mutations. However, NPHS2 mutations have been detected in some cases. Mutations in ACTN4, encoding alpha-actinin-4, cause an autosomal-dominant focal segmental glomerulosclerosis. alpha-actinin-4 stabilizes the podocyte cytoskeleton structure, connecting with actin filaments. WT1 mutations, causing Wilm's tumor, have been demonstrated in some CNS patients with diffuse mesangial sclerosis. Systematic investigation of genes for CNS in Japan has never been performed. METHODS: To clarify the role of mutations in these four genes, we used polymerase chain reaction (PCR) and direct sequencing to investigate all exons and exon-intron boundaries for these genes in 13 unrelated CNS patients from regional pediatric kidney disease centers in Japan. RESULTS: A novel homozygous nonsense mutation of NPHS1, E246X in exon 7, and a novel homozygous deletion mutation of NPHS1, 2156_2163del in exon 16 were detected in one patient each. A novel homozygous nonsense mutation of NPHS2, R196X in exon 5, was found in one patient, and the same heterozygous nonsense mutation was detected in another. No ACTN4 or WT1 mutations were detected. CONCLUSION: These studies demonstrate that mutation of NPHS1 is not a major cause of CNS in Japanese patients, and that mutation of NPHS2 can be responsible for CNS in this population.
Actinin↗
[Changes in the clinical features of MPGN type-I in childhood over three decades].
UNLABELLED: This retrospective study was conducted to evaluate changes in the clinical features of MPGN type I in childhood during a 30-year period from 1970 through 1999. Renal biopsies were performed on 2,260 children with glomerulonephritides, among whom were 71 patients with MPGN type-I. Changes in the mode of onset were investigated in patients separated according to the period of onset into two groups by 1974 in which school urinary screening had been widespread. The difference in symptoms after onset was examined between patients with the onset in the 1980s and 1990s under the same circumstances of school urinary screening and of our steroid regimen. Finally, the incidences of this disease in each of the three decades were analyzed. Chance proteinuria and/or hematuria increased (p=0.0107) and acute nephritic syndrome decreased (p=0.0237) in the ratio of the initial symptom on and after 1974. Regarding the clinical presentation after onset, non-nephrotic range proteinuria increased (p=0.0415) and nephrotic syndrome decreased (p=0.0415) in the 1990s, in comparison with the respective rates in the 1980s. The incidence of this disease decreased (p<0.01) in chronological order. CONCLUSION: The clinical features of this disease definitely changed over three decades suggesting that the clinical presentation has ameliorated in recent years, regardless of effective palliation of severe symptoms afforded by our steroid regimen.
Child↗
[Treatment guidelines for the idiopathic nephrotic syndrome in children].
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Child↗
Efficacy of methylprednisolone pulse therapy in steroid-resistant nephrotic syndrome.
Steroid-resistant nephrotic syndrome (SRNS) in children is intractable, and the optimal treatment regimen is not known. We investigated the efficacy of methylprednisolone pulse therapy (MPT) in SRNS patients. Using only MPT plus heparin, we have treated ten pediatric SRNS patients that were resistant to cyclophosphamide (CPM) or cyclosporin A (CsA) and predicted to have a very poor prognosis. Administration of 30 mg/kg per day methylprednisolone with heparin for 3 days was taken as one course, and this was given 14 times over 2 years. One patient discontinued MPT because of peritonitis. Of the remaining nine patients, complete remission was achieved by four patients, persistent mild proteinuria remained in three patients, and no effect was observed in two patients. All patients that had been diagnosed with minimal change (MC) pathology ( n=3) at the initial renal biopsy achieved complete remission. Observed adverse events were peritonitis in one patient and a transient decrease in pulse rate only during MPT in one patient. These results demonstrate that MPT with heparin can induce remission in children with SRNS, even when the patient is resistant to CPM and CsA.
Adolescent↗
Evaluation of the inferior vena cava in potential pediatric renal transplant recipients.
Vascular anomalies due to occlusion or thrombosis of the inferior vena cava (IVC) may be hazardous to renal transplantation, and preoperative vascular evaluation is important for safe and successful surgery. The purpose of this study was to assess the utility and accuracy of two-dimensional time-of-flight (2D-TOF) magnetic resonance venography (MRV) as an alternative to conventional angiography for evaluating the IVC and iliac vein in potential pediatric renal transplant recipients. Four children with chronic renal failure were evaluated with 2D-TOF MRV by superior presaturation pulse and target maximum intensity projection. The whole MRV examination and filming required less than 30 min. All four patients had a normal IVC and iliac vein. Two of the patients underwent renal transplantation, and the MRV findings were in total agreement with the final anatomy revealed intraoperatively. MRV is accurate for evaluating the condition of the IVC and iliac vein. It is a reliable, noninvasive and rapid technique that can be considered as an alternative to invasive angiography for evaluation of children scheduled for transplantation. We recommend the use of this noninvasive procedure to ascertain the patency of the IVC in all infants and children with a history of indwelling catheters in the IVC or those with a propensity to thrombosis, i.e., all recipients with nephrotic syndrome. The insertion of catheters in the femoral vein in children who may become candidates for renal transplantation should be discouraged.
Adolescent↗
Hemolytic uremic syndrome induced by lipopolysaccharide and Shiga-like toxin.
Induction of experimental hemolytic uremic syndrome (HUS) by simply administering Shiga-like toxin (Stx) to rodents has not yet been successful. Attention has been paid to the role of lipopolysaccharide (LPS) in the pathogenesis of HUS. In this study, we showed successful induction of an experimental HUS in LPS responder mice by administering Stx together with LPS. Intraperitoneal administration of 200 ng of Stx 2 for 2 days, followed by 250 microg of LPS on the 2nd day of Stx administration, caused a significant decrease of thrombocytes and deterioration of renal function, with proteinuria and hematuria. Electron microscopy revealed alterations of glomerular endothelial cells. Administration of Stx alone or LPS alone caused neither hematological nor histopathological changes, as were observed with Stx and LPS co-administration. Interestingly, when LPS was administered before Stx, no hematological and histological changes were observed. The results showed that LPS was essential for the induction of HUS, but LPS pretreatment might protect against Stx toxicity. The order of LPS and Stx administration is important for the induction of experimental HUS.
Animals↗
Merit of the cuff-shaving procedure in children with chronic infection.
Catheter replacement and cuff-shaving are per-formed as a surgical treatment against tunnel infection(TI) in patients on chronic peritoneal dialysis. The efficacy of catheter replacement is well established, but that of cuff-shaving is not. For the purpose of evaluating the efficacy of cuff-shaving, we compared the time interval between each procedure and subsequent TI. In order to perform this comparison, we reviewed data from 32 cuff-shaving procedures and 29 catheter replacement procedures at Tokyo Metropolitan Kiyose Children's Hospital in the period from 1 March 1991 to 1 May 2001, retrospectively. There was no significant difference in the time interval between each procedure and subsequent TI(P=0.284). The incidence of recurrence was no more than 12.5% for the cuff-shaving procedures. The incidence of peritonitis due to post-surgery TI with the cuff-shaving procedures was 9.3% and 6.8% with the replacement procedure (P=0.725). There was no significant variation in time interval to post-cuff-shaving TI according to the reason for the cuff-shaving procedure. In conclusion,cuff-shaving may be worth considering for TI in adequately selected patients.
Adolescent↗
Typical MPGN with few urinary abnormalities.
We describe the concurrent appearance of membranoproliferative glomerulonephritis (MPGN) in renal biopsy samples and normal urinary sediment without hematuria, proteinuria, or renal dysfunction in 1 child and asymptomatic microscopic hematuria without significant proteinuria or renal dysfunction in 2 children who were subsequently followed up for many years. The only other abnormality detected was hypocomplementemia. This is the first report of biopsy-proven typical MPGN in patients with few urinary abnormalities. A renal biopsy should be considered in children with hypocomplementemia, regardless of urinalysis findings, to exclude MPGN.
Biopsy↗
[Clinical significance of the terminal complement complex in children with type I membranoproliferative glomerulonephritis].
We measured the concentrations of terminal complement complex (TCC) in plasma (n =25) and urine (n=13) using an enzyme-linked immunosorbent assay in pediatric patients with type I membranoproliferative glomerulonephritis(MPGN). Frozen tissue from 18 renal biopsies was evaluated for the presence of TCC by direct immunoperoxidase staining. In the acute phase of the disease, TCC concentrations in plasma were elevated above 0.5 AU/ml in 14 of 25 patients (High TCC group), while the remaining 11 patients showed less than 0.5 AU/ml (Low TCC group). In the High TCC group, TCC was deposited more diffusely and intensely in the glomerulus, compared to that in the Low TCC group (p= 0.034). Furthermore, urinary TCC concentrations in the High TCC group were higher than those in the Low TCC group (p=0.0001). The High TCC group showed not only a poorer response to steroid treatment, but also a poorer prognosis than the Low TCC group. These results suggest that, in pediatric patients with type I MPGN, TCC in circulation may play a certain role in TCC formation in the glomerulus and in urine. The TCC concentration in plasma could be used as a marker of responsiveness to steroid treatment and long-term prognosis.
Adolescent↗