Epidemiological survey and clinical investigation of pediatric IgA nephropathy.

BACKGROUND: Since school urinalysis screening was introduced in 1974, the number of cases requiring initiation of dialysis due to glomerulonephritis has been steadily decreasing and school urinalysis screening has been praised for contributing to the early detection and treatment of glomerulonephritis. However, the lack of nationwide epidemiological surveys is also a problem. METHODS: We conducted an epidemiological survey focusing on the frequency of occurrence of pediatric IgA nephropathy in Nishinomiya City. Subjects comprised 374,846 children who underwent school urinalysis screening from 2003 to 2012. Renal biopsy findings and clinical findings of these pediatric IgA nephropathy cases were retrospectively investigated. RESULTS: There were 37 (mean 3.7/year) newly diagnosed cases of pediatric IgA nephropathy in Nishinomiya City. The IgA nephropathy onset rate per 100,000 children who underwent school urinalysis screening was 9.9 cases/year. Compared to the histologic low grade group, the histologic high grade group had significantly higher urinary P/C ratio (P < 0.001). In the histologic high grade group, the number of cases of proteinuria remission 3 years after starting treatment was significantly higher in the group treated with steroids (P = 0.045). CONCLUSIONS: Our study found that 9.9 cases of pediatric IgA nephropathy were diagnosed per 100,000 in the pediatric population, which is equivalent to or slightly more than past reports. IgA nephropathy, which poses a high histologic risk, presents with heavy proteinuria; but the proteinuria remission rate following steroid therapy is high 3 years after treatment, which suggests that administration of steroids results in an improved clinical outcome.

[Clinical usefulness of CD68 staining in children with various glomerular diseases].

PURPOSE: Glomerular macrophage accumulation is a common feature of proliferative forms of human glomerulonephritis and kidney injury. Our present study was designed to investigate the role of macrophages in pediatric kidney diseases by using CD68 staining. MATERIAL AND METHODS: Seventy-four patients (39 boys and 35 girls) with pediatric kidney disease yielding 81 specimens were investigated. A monoclonal anti-human CD68 mouse antibody (KP1) was used as a macrophage marker in this study. Paraffin-embedded renal biopsy specimens were stained for immunohistochemical analysis. The average number of macrophages per glomerulus in each patient was calculated as the total number of CD68 (+) cells within all glomeruli divided by the total number of glomeruli in a single section and the average number of observed interstitial macrophages was calculated in 3-5 high power fields. RESULTS: Glomerular macrophage accumulations were increased with crescentic proliferative glomerulonephritis, mesangial proliferative glomerulonephritis, and focal segmental glomerulosclerosis. Glomerular and interstitial macrophage accumulations were correlated with hematuria, proteinuria and renal function (eGFR). In particular, activity and chronicity index, as well as the severity of glomerular IgA, C3, and fibrinogen deposition were correlated with glomerular macrophage accumulation. CONCLUSIONS: Macrophage accumulation observed by CD68 staining was a useful marker in providing a deeper understanding of the clinicopathologic state of children with chronic kidney diseases, and was effective in the selection of treatment.

A case of atypical hemolytic uremic syndrome due to anti-factor H antibody in a patient presenting with a factor XII deficiency identified two novel mutations.

A 9-year-old boy with pallor and macrohematuria showed hemolytic anemia, thrombocytopenia and renal failure. There was no history of diarrhea and the stool culture was negative. A diagnosis of atypical hemolytic uremic syndrome (HUS) was confirmed; however, the cause of the prolonged activated partial thromboplastin time (APTT) was unknown. Plasma exchange and hemodialysis were performed because of progressive hemolytic anemia and renal dysfunction. Fresh frozen plasma was administered frequently to correct the prolonged APTT after hemolysis was controlled and C3 levels had recovered. Factor H (FH) and factor I (IF) levels were normal and we did not detect mutations of FH, IF and membrane cofactor protein. Further investigation revealed the presence of anti-FH antibody in the patient's plasma and a deficiency of coagulation factor XII. Analysis of the patient's coagulation system displayed <3% functional activity of factor XII, whereas levels of other coagulation factors were within the normal range. Two novel mutations (W222G and R447S) were identified upon analysis of the factor XII gene in this patient. Moreover, further investigation revealed that compound heterozygous mutations were present in two of the patient's three siblings, while the third sibling only had a mutation at W222G. The patient was treated for atypical HUS; however, no treatment was required for factor XII deficiency as he did not display a hemorrhagic tendency. We report here a rare case of atypical HUS due to anti-FH antibody presenting with a coagulation factor XII deficiency.

Semiquantitative scoring in children under treatment for atopic dermatitis.

BACKGROUND: Atopic dermatitis is the most frequently seen childhood allergic disease in outpatient clinics. Improvement, exacerbation, and response to treatment are typically assessed subjectively and occasionally inaccurately. METHODS: The authors developed two forms for scoring of dermal manifestations and used them to assess 56 children. The correlation between two pediatricians' scores and correspondence to established categories (mild, moderate, and severe) were determined. RESULT: The two physicians' scores for the children correlated well for both forms of scoring. Correspondence of scores as 'mild' and 'moderate' categories were significant (few children participating were 'severe'). CONCLUSION: Use of well-constructed scoring forms should improve clinical assessment of patient course and treatment response.

Hepatocyte growth factor gene therapy retards the progression of chronic obstructive nephropathy.

BACKGROUND: Unilateral ureteral obstruction (UUO) is characterized by progressive tubular atrophy and interstitial fibrosis. Rupture of the balance between cell proliferation and apoptosis plays a critical role in renal atrophy. Hepatocyte growth factor (HGF) is a cytokine function on cell survival and tissue regeneration. We studied the effects and possible mechanisms of HGF gene therapy on tubular cell survival and anti-fibrosis in chronic obstructed nephropathy. METHODS: An in vivo transfection procedure of repeatedly transducing skeletal muscles with the HGF gene using liposomes containing the hemagglutinating virus of Japan (HVJ liposome) was tested on UUO rats. Expression of HGF and c-Met were examined by in situ hybridization, ELISA, or immunohistochemical staining. Interstitial fibrosis and macrophage infiltration were evaluated by Masson's Trichrome staining, alpha-smooth muscle actin and ED-1 immunostaining. Cell survival indices including proliferating cell nuclear antigen (PCNA), Bcl-2, Bcl-xL and Bax were measured by immunohistochemistry and Western blots. Apoptosis was determined by the TUNEL method. RESULTS: After HVJ-HGF gene transfer, endogenous HGF and c-Met were up-regulated in UUO kidneys. Renal fibrosis, macrophage infiltration and tubular atrophy were suppressed both at day 14 and 28 after UUO (P < 0.05 or 0.01). Tubular cell proliferation was activated while apoptosis was inhibited, especially at the late stage of UUO. Bcl-2 was enhanced in the HGF-transfected UUO rats, while no changes of Bcl-xL and Bax were found. CONCLUSIONS: In vivo HGF gene transfection retards the progression of chronic obstructed nephropathy and protects tubular cell survival in the long-term UUO model. Bcl-2 rather than Bcl-xL or Bax may contribute to the anti-apoptotic function of HGF.