Takane Ito

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.

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.

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.

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.

Mesalazine allergy in a boy with ulcerative colitis: clinical usefulness of mucosal biopsy criteria

Abstract5-Aminosalicylic acid preparations have been used as first-line drugs for treatment of ulcerative colitis (UC). However, some patients with UC present with exacerbation of symptoms because of allergy to mesalazine. Diagnosis of mesalazine allergy in active UC may be challenging because its symptoms mimic those of UC. Here we describe a 13-year-old boy with mesalazine allergy who achieved remission when his medication was changed from mesalazine to salazosulfapyridine. During his clinical course mesalazine was prescribed twice, and on each occasion exacerbation of the symptoms occurred. We considered a diagnosis of mesalazine allergy, and this was confirmed by a drug lymphocyte stimulation test; the result for salazosulfapyridine was negative. On the basis of criteria involving simple mucosal biopsy combined with endoscopy for predicting patients with UC who would ultimately require surgery, we considered that the UC in this case might be susceptible to steroid treatment, and we therefore treated the patient with salazosulfapyridine and prednisolone. Shortly afterwards, remission was achieved and the patient has remained in good condition on salazosulfapyridine alone. When treating patients with mesalazine, the possibility of allergy should always be borne in mind, especially when the clinical course is inconsistent with the results of biopsy.

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.

Elevated serum interleukin-7 level in idiopathic steroid-sensitive nephrotic syndrome.

Background:  Several cytokines have a pathological association with idiopathic steroid‐sensitive nephrotic syndrome (ISSNS) in inducing proteinuria or regulating T cells. Because interleukin (IL)‐7 plays important roles in regulating T‐cell proliferation and sustaining naïve or memory T cells, IL‐7 is one of the candidate cytokines in the pathogenesis of ISSNS. Very little is known, however, about the association of IL‐7 with ISSNS. To clarify the IL‐7 dynamics in children with ISSNS, serum IL‐7 level was investigated, from the nephrotic phase before steroid treatment (STx; group A1) to the remission phase with STx (group A2) and without STx (group A3).

Non‐enhanced magnetic resonance imaging versus renal scintigraphy in acute pyelonephritis

The utility of non‐enhanced magnetic resonance imaging (MRI) has not been examined extensively for diagnosing acute pyelonephritis (APN) in children. The aims of this study were to compare non‐enhanced MRI with technetium‐99 m dimercaptosuccinic acid (99mTc‐DMSA) renal scintigraphy in detecting APN. Six boys and one girl with temperature ≥38°C and positive urine culture received both non‐enhanced MRI with whole body diffusion‐weighted imaging (DWI) and 99mTc‐DMSA scintigraphy ≤7 days from the fever onset. The sensitivity and specificity of MRI in detecting APN lesions diagnosed on 99mTc‐DMSA scintigraphy were 80% and 100%, respectively. Non‐enhanced MRI in children with suspected APN ≤7 days from fever onset might be a suitable replacement for 99mTc‐DMSA scintigraphy for the detection of APN.

Top-down approach is possible strategy for predicting breakthrough fUTIs and renal scars in infants

Acute‐phase technetium‐99 m dimercaptosuccinic acid (DMSA) scintigraphy is recommended for initial imaging in children with febrile urinary tract infection (fUTI). Recently, the importance of identifying patients at risk of recurrent fUTI (r‐fUTI) has been emphasized. To clarify the effectiveness of DMSA scintigraphy for predicting r‐fUTI in infants, we investigated the relationship between defects on DMSA scintigraphy and r‐fUTI.

Renal-limited necrotizing granulomatous vasculitis in a pediatric patient.

A 10‐year‐old girl presented with mild proteinuria and hypertension. Laboratory data indicated slightly elevated serum creatinine (0.67 mg/dL) and elevated serum IgG (2111 mg/dL). On renal arteriography mild stenosis over the entire length of the right renal artery and irregular stenosis of the interlobar arteries in the right kidney were seen. She was diagnosed with renovascular hypertension, and received conventional anti‐hypertensive therapy, but did not respond to them. The right kidney had atrophy and dysfunction on technetium‐99m‐labeled dimercaptosuccinic acid renal scintigraphy, and was therefore resected. Histopathology of the kidney indicated severe necrotizing granulomatous vasculitis affecting the arteries from the renal hilus to the interlobar area. After nephrectomy plus steroid pulse therapy, blood pressure and urinary protein returned to normal. To our knowledge, this is the first report of necrotizing granulomatous vasculitis limited to the medium‐sized renal arteries.