Takahiro Kanai

Foot Process Effacement Is an Early Marker of Nephropathy in Young Classic Fabry Patients without Albuminuria

In Fabry disease, globotriaocylceramid (GL3) starts to accumulate in kidney cells in utero, and continues to accumulate throughout childhood and adulthood with progressive tissue damage, which may lead to renal failure. Material and Methods: Eight children with classical Fabry disease, median age 12 (range 4-16 years) had a renal biopsy performed before the initiation of enzyme replacement therapy (ERT). All patients were normalbuminuric and had normal GFR. Three patients were re-biopsied after three or five years. Results: In all patients, significant GL3-accumulation was found in several types of kidney cells with high amounts of GL3 in the podocytes. Segmental podocyte foot process effacement was shown in all but two patients; no effacement was seen neither in the youngest male patient at 4 years of age nor in a male aged 12. A 12-year-old female patient had normal podocyte foot processes before the start of ERT, but de novo foot process flattening and unchanged high score of podocyte GL3 accumulation were seen in the re-biopsy after three years of ERT (agalsidase alpha 0.2 mg/kg/every other week). Two boys showed worsening of podocyte effacement in kidney biopsy after five years of agalsidase alpha 0.2 mg/kg/eow. Conclusions: Podocyte foot process effacement was found in the majority of eight young classical Fabry patients of both genders after the age of 11 years, without clinical signs of Fabry nephropathy. Kidney biopsies are essential in the early diagnosis of nephropathy and in the evaluation of the response to enzyme replacement therapy of early Fabry nephropathy.

Macrophage inflammatory protein-1β and interleukin-8 associated with idiopathic steroid-sensitive nephrotic syndrome

Background:  The cytokines associated with idiopathic steroid‐sensitive nephrotic syndrome (ISSNS) have not been identified definitively, because previous studies had variable sampling and population heterogeneity. To clarify the cytokines involved, serum cytokine levels were measured using uniform sampling in a homogeneous population.

Utility of non-enhanced magnetic resonance imaging to detect acute pyelonephritis

It has been established that enhanced computed tomography (CT) and 99mTc‐dimercaptosuccinic acid renal scintigraphy (99mTc‐DMSA scintigraphy) used in conjunction with single‐photon emission CT is a useful tool for the diagnosis of acute pyelonephritis (APN). The utility of non‐enhanced magnetic resonance imaging (MRI), however, has not been investigated extensively for the diagnosis of APN or renal abscess in children. We describe the case of a 23‐month‐old boy with suspected APN who received non‐enhanced MRI. Whole body diffusion‐weighted imaging (DWI) was used, and a background body‐signal suppression sequence was applied. High‐intensity focal lesions were identified on DWI and low‐intensity lesions on the apparent diffusion coefficient map in the acute phase. This case suggested that non‐enhanced MRI could be a useful tool for the diagnosis of APN in children, because it can avoid the risks of not only radiation exposure but also nephrogenic systemic fibrosis associated with gadolinium‐based contrast agents, especially in infants.

Anomalous segmentation of Diphyllobothrium nihonkaiense.

An anomalous tapeworm with abnormal segmentation was obtained from a 6-year-old boy in Japan. The tapeworm consisted of proglottids with slanted anterior and posterior margins of proglottids and 4-6 sets of reproductive organs arranged between the margins. The morphology of the tapeworm did not correspond to any of the described cestodes. However, molecular identification based on nuclear and mitochondrial genes clearly showed the tapeworm was Diphyllobothrium nihonkaiense.

Plasma Exchange and Tacrolimus Therapy for Focal Segmental Glomerulosclerosis Collapsing Variant and the Cytokine Dynamics: A Case Report

To the Editor, Focal segmental glomerulosclerosis (FSGS) is the common form of steroid-resistant nephrotic syndrome (SR-NS). Steroid-resistant FSGS (SR-FSGS) is frequently a progressive condition resulting in endstage renal disease, especially the collapsing variant (1), but an effective treatment has not yet been established. Although the pathogenesis of this disease has not been clearly elucidated, accumulating evidence suggests the involvement of several cytokines in this disease (2). We present the case of a patient with the collapsing variant of SR-FSGS who was resistant to cyclosporine A (CsA), mizoribine (MZ), and combination therapy with low-density lipoprotein apheresis (LDL-A) (3), CsA and methylprednisolone (mPSL) pulse therapy (Tx1); however, his nephrotic condition improved with combination therapy that included plasma exchange (PE) (4), tacrolimus (TAC) (5), and mPSL pulse therapy (Tx2). To our knowledge, this is the first report showing differences in serum cytokine dynamics between Tx1 and Tx2.

Norovirus‐associated renal acute renal failure with nephrotic syndrome

Norovirus (NV) is one of the most common causes of acute enterocolitis throughout the world. NV infection occasionally develops into pre-renal acute renal failure (ARF) as a result of the dehydration caused by severe diarrhea and vomiting. A young boy developed a renal ARF associated with nephrotic syndrome (NS), without presenting with dehydration, during the course of an NV enterocolitis. This is the first report of NV-associated renal ARF with NS in a previously healthy individual.

Apolipoprotein AII levels are associated with the UP/UCr levels in idiopathic steroid-sensitive nephrotic syndrome.

AbstractBackground Various humoral factors have been proposed as causal agents of idiopathic steroid-sensitive nephrotic syndrome (ISSNS), resulting in varying data. We used mass spectrometry (MS) to analyze serum proteins in a search for proteins that might be involved in ISSNS pathophysiology.MethodsSerial serum samples were obtained from 33 children with ISSNS. Samples were collected during Phase A1 [the acute phase prior to steroid treatment (STx)], Phase A2 (remission with STx), and Phase A3 (remission without any medication). We also included age- and sex-matched two control groups comprising children with normal urinalysis (Group B) and children with a nephrotic syndrome other than ISSNS (Group C). The urinary protein/urinary creatinine (UP/UCr) ratios were not statistically different between Phase A1 and Group C. Samples were analyzed using surface-enhanced laser desorption/ionization time of flight MS.ResultsA total of 207 peptide ion peaks were detected in the range of m/z 2000–10000. Four peptide ions (m/z 6444, 6626, 8695, and 8915) were detected at significant elevation during Phase A1 compared with Phase A2, Phase A3, and Group C. The intensities of m/z 6444 and 8695 were higher in Phase A3 than in Group B. There were significant correlations between the intensities of m/z 6626, 8695, and 8915 and UP/UCr levels. The m/z 8695 was identified as apolipoprotein AII.ConclusionsApolipoprotein AII was detected as a protein associated with the UP/UCr levels in pediatric ISSNS. Our findings present an interesting starting point for further investigation into the pathophysiology of ISSNS.

Seasonal variation in first episode of childhood idiopathic steroid-sensitive nephrotic syndrome and adult minimal change nephrotic syndrome.

To the Editor Epidemiological and clinical features differ between childhood minimal change nephrotic syndrome (MCNS) and adult MCNS [1, 2]. MCNS accounts for 80–90 % of childhood idiopathic nephrotic syndrome, and [90 % children with MCNS have steroid-sensitive nephrotic syndrome. The purpose of this study was to compare the seasonal variation in the first onset of childhood idiopathic steroid-sensitive nephrotic syndrome (ISSNS) with that of adult idiopathic MCNS and consider the differences in pathophysiology between childhood MCNS and adult MCNS. This retrospective study was approved by the Ethics Committee of Jichi Medical University (approval number Epidemiology 09-24). Idiopathic nephrotic syndrome (INS) was defined based on the criteria of the International Study of Kidney Disease in Children. ISSNS was defined as INS with complete remission within 4 weeks of full-dose steroid therapy (prednisone 2 mg/kg/day). The definition of adult nephrotic syndrome was based on the diagnostic criteria of the Research Project Team for Progressive Renal Lesions in the Ministry of Health, Labor and Welfare, Japan. Adult MCNS was defined as nephrotic syndrome with minor glomerular abnormalities detected in a renal biopsy specimen. Data were collected from the medical records of 52 children fulfilling these criteria for ISSNS (16 girls and 36 boys, median age 5 years) who were treated in 4 hospitals in Tochigi, including our center, between January 2005 and December 2011. Data of adult patients with MCNS were collected from the medical records of 80 patients (39 women and 41 men, median age 35 years) who were treated in the Jichi Medical University Hospital between January 2000 and December 2009. Chi square tests were used to evaluate the circannual variation between childhood ISSNS and adult MCNS. Bonferroni correction was used to compare the incidence between different seasons in each group. The seasonal incidence of the initial episode of childhood ISSNS was 15 (28.8 %) in spring (March–May), 10 (19.2 %) in summer (June–August), 21 (40.4 %) in autumn (September–November), and 6 (11.6 %) in winter (December–February) (P \ 0.05); the incidence was higher in autumn than in winter (P \ 0.008). The seasonal incidence of the first episode of adult MCNS was 19 (23.8 %) in spring, 16 (20 %) in summer, 21 (26.2 %) in autumn, and 24 (30 %) in winter (P = 0.637). The seasonal variation in the incidence of the initial episode was significantly different between childhood ISSNS and adult MCNS (P \ 0.05) (Fig. 1). There was no difference in the frequencies of allergic complications (bronchial asthma, allergic rhinitis, allergic conjunctivitis, or atopic dermatitis) between 2 groups (46.2 vs 47.1 %). Previous report regarding the circannual variation in the onset of childhood ISSNS has indicated that the incidence J. Odaka (&) T. Kanai T. Yamagata Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e-mail: mrjo@jichi.ac.jp

Apolipoprotein C-I Levels Are Associated with the Urinary Protein/Urinary Creatinine Ratio in Pediatric Idiopathic Steroid-Sensitive Nephrotic Syndrome: A Case Control Study

Humoral factors may cause idiopathic steroid-sensitive nephrotic syndrome (ISSNS). In the present study, we analyzed serum proteins using mass spectrometry (MS) to identify proteins associated with the pathophysiology of pediatric ISSNS. We collected serial serum samples from 33 children during each ISSNS phase; Phase A1 is the acute phase prior to steroid treatment (STx), Phase A2 represents the remission period with STx, and Phase A3 represents the remission period after completion of STx. Children with normal urinalyses (Group B) and children with a nephrotic syndrome other than ISSNS (Group C) served as controls. No significant differences in urinary protein/urinary creatinine (UP/UCr) ratios were observed between the children with phase A1 ISSNS and Group C. We used surface-enhanced laser desorption/ionization time of flight MS for sample analysis. Four ion peaks with a mass-to-charge ratio (m/z) of 6,444, 6,626, 8,695, and 8,915 were significantly elevated during ISSNS Phase A1 compared to Phase A2, Phase A3, and Group C. The intensity of an m/z of 6,626 significantly correlated with the UP/UCr ratio and an m/z of 6,626 was identified as apolipoprotein C-I (Apo C-I). Apo C-I levels correlate with the UP/UCr ratio in pediatric ISSNS. Our findings provide new insights into the pathophysiology of ISSNS.

A case of post-pneumococcal acute glomerulonephritis with glomerular depositions of nephritis-associated plasmin receptor

We report the case of a 12-year-old girl who was referred to our hospital with anuria associated with pneumonia. On admission, the patient’s blood test results revealed severe renal failure, hypoproteinemia, and hypocomplementemia. Her urinalysis results revealed hematuria, proteinuria, and a positive titer for Streptococcus pneumoniae. S. pneumoniae was also detected in her sputum and blood cultures. The patient was diagnosed with post-pneumococcal acute glomerulonephritis (AGN) with acute renal failure. A renal biopsy demonstrated the infiltration of neutrophils and mononuclear cells into capillary loops. Immunofluorescence studies showed dominant-positive deposition of C3c along the capillary loops and nephritis-associated plasmin receptor (NAPlr) depositions in the mesangial area and capillary loops. Electron microscopy revealed dense deposits in the glomerular basement membrane without a hump in the subepithelial area. These findings were consistent with endocapillary proliferative glomerulonephritis. AGN associated with pneumococcal infection is very rare. This case suggests that NAPlr is the causative antigen not only of post-streptococcal AGN, but also of post-pneumococcal AGN. To our knowledge, this is the first report that shows a relationship between post-pneumococcal AGN and NAPlr depositions in the glomeruli.