Renal Biopsy-induced Hematoma and Infection in a Patient with Asymptomatic May-Hegglin Anomaly.

The May-Hegglin anomaly is characterized by inherited thrombocytopenia, giant platelets, and leukocyte cytoplasmic inclusion bodies. The Fechtner, Sebastian, and Epstein syndromes are associated with mutations of the MYH9-coding nonmuscle myosin heavy chain IIA, similar to the May-Hegglin anomaly, and are together classified as MYH9 disorders. MYH9 disorders may include symptoms of Alport syndrome, including nephritis and auditory and ocular disorders. A 6-year-old boy was diagnosed with an MYH9 disorder after incidental discovery of hematuria and proteinuria. Focal segmental glomerulosclerosis was detected on renal biopsy. However, despite no prior bleeding diatheses, he developed a large post-biopsy hematoma despite a preprocedural platelet transfusion calculated to increase the platelet count from 54,000/µL to >150,000/µL. Idiopathic thrombocytopenic purpura is a major cause of pediatric thrombocytopenia following acute infection or vaccination, and patients with MYH9 disorders may be misdiagnosed with idiopathic thrombocytopenic purpura and inappropriately treated with corticosteroids. Careful differential diagnosis is important in thrombocytopenic patients with hematuria and proteinuria for the early detection of thrombocytopenia. Patients with MYH9 disorders require close follow-up and treatment with angiotensin II receptor blockers to prevent the onset of progressive nephritis, which may necessitate hemodialysis or renal transplantation. The need for renal biopsy in patients with MYH9 disorders should be carefully considered because there could be adverse outcomes even after platelet transfusion.

Seroconversion of hepatitis B envelope antigen by entecavir in a child with hepatitis B virus-related membranous nephropathy.

Membranous nephropathy (MN) is caused by subepithelial deposition of immune complexes in the glomerular basement membrane, with secondary MN arising in association with infection. In secondary MN caused by hepatitis B virus (HBV), seroconversion has been known to occur after the onset of MN, particularly in children. In patients with high serum concentrations of HBV DNA, treatment with interferon-α2b or a nucleoside analog has been reported to induce seroconversion and suppress HBV-DNA levels. We treated a 7-year-old boy who presented with proteinuria and liver dysfunction. He had a history of HBV infection since shortly after birth, as his mother was HBV-positive, and he was neither vaccinated nor treated with immunoglobulin at birth. Chronic hepatitis related to HBV was diagnosed following percutaneous needle biopsy of the liver. Percutaneous renal biopsy revealed HBV-related glomerulonephritis with diffuse global subepithelial and focal segmental mesangial and subendothelial deposits. Therefore, HBV-associated MN was diagnosed. Treatment with the nucleoside analog lamivudine was started to reduce serum HBV-DNA levels, but lamivudine was discontinued and treatment with entecavir was started at a dosage of 0.5 mg/day after 6 weeks because of possible adverse effects. Tests for HB envelope antibody were positive in week 16 of treatment, and proteinuria had resolved by week 22. Elevated levels of aspartate aminotransferase and alanine aminotransferase were seen with both treatments but were probably attributable to the developing immune response to HBV. In the present case, HBV levels needed to be reduced to: 1) lower elevated serum HBV-DNA titers, which put the patient at high risk of hepatocellular carcinoma; and 2) remove the immune complexes causing MN. Use of nucleoside analogs to suppress the HBV load may facilitate early remission of MN, and entecavir therapy did not cause any serious adverse reactions in this case. Given the advent of lamivudine-resistant HBV, entecavir appears promising for patients with elevated serum levels of HBV DNA.

A case of juvenile Sjögren's syndrome with interstitial nephritis.

Primary Sjögren's syndrome (SS) is a rare autoimmune disease, especially in children. Juvenile primary SS with interstitial nephritis is rare in Japan. We report on a 12-year-old girl in whom salivary gland swelling had recurred from the age of 5 years, SS was diagnosed at the age of 10 years, and interstitial nephritis developed at the age of 12 years. The patient presented with a chief complaint of swelling of both parotid glands. The patient had a history of recurrent parotitis from 5 years of age, with episodes recurring 5 to 6 times a year and resolving within 3 days each time. However, at the age of 11 years, the patient had continuous mild swelling of the parotid glands. Examination on admission showed bilateral nontender parotid gland swelling; mild swelling of the lower extremities, xerostomia, and xerophthalmia but no exanthem. Laboratory findings were as follows: serum protein, 10.1 g/dL; immunoglobulin (Ig) G, 3,828 mg/dL; antinuclear antibodies, 1,280-fold; anti-Ro/SS-A antibody, 512-fold; anti-Ro/SS-B antibody, 4-fold; creatinine, 0.45 mg/dL; blood ß2-microglobulin, 2.2 mg/L (slightly elevated); and cystatin C, 0.86 mg/L. Urinalysis showed proteinuria and a ß2-microglobulin concentration of 11,265 mg/L. Thus, this patient had low molecular weight proteinuria. Schirmer's test showed decreased tear secretion (5 mm), and fluorescein staining showed marked bilateral superficial punctate keratitis. A lip biopsy showed infiltration by small round cells (mild to moderate), interstitial fibrosis, loss of salivary gland parenchyma, and atrophy, with no obvious epimyoepithelial islands, leading to a diagnosis of SS. Light microscopic examination of the renal biopsy specimens showed expansion of mononuclear cell infiltration in the renal interstitium, inflammatory cell infiltration of interstitial areas with edema and mild fibrosis, and tubulitis and mononuclear cell infiltration that included many lymphocytes and plasma cells. There were no pathological findings of glomerulonephritis. Small arteries showed no obvious abnormalities. Immunofluorescent staining showed slight, nonspecific deposition of IgM, but no deposition of IgG, complement 1q, 3, or 4. On the basis of the renal biopsy showing nonspecific chronic interstitial nephritis, renal tubular atrophy, and interstitial enlargement, tubulointerstitial nephritis associated with SS was diagnosed.

Caspase-3-independent internucleosomal DNA fragmentation in ischemic acute kidney injury.

BACKGROUND/AIMS: Renal tubular cell death in ischemia-reperfusion does not follow the classical apoptosis or necrosis phenotype. We characterized the morphological and biochemical features of injured tubular epithelial cells in ischemic acute kidney injury (AKI). METHODS: Ischemic AKI was induced in rats by 60 min of ischemia followed by 24 h of reperfusion. Light and electron microscopic TUNEL (LM-TUNEL and EM-TUNEL), gel electrophoresis of extracted DNA, and caspase-3 involvement were examined during the development of death. RESULTS: Damaged tubular epithelial cells with condensed and LM-TUNEL-positive (+) nuclei were prominent at 12 and 18 h after reperfusion with DNA 'ladder' pattern on gel electrophoresis. EM-TUNEL+ cells were characterized by nuclei with condensed and clumping chromatin, whereas the cytoplasm showed irreversible necrosis. The protein levels and activity of caspase-3 did not increase in kidneys after reperfusion. In addition, caspase inhibitor (ZVAD-fmk) failed to inhibit DNA fragmentation and prevent tubular epithelial cell death in ischemic AKI. CONCLUSION: Caspase-3-independent internucleosomal DNA fragmentation occurs in injured tubular epithelial cells undergoing irreversible necrosis in ischemic AKI. The manner of this cell death may be identical to the cell death termed apoptotic necrosis, aponecrosis, or necrapoptosis. Ischemia-reperfusion injury activates caspase-3-independent endonuclease, which in turn induces irreversible damage of tubular epithelial cells, and may contribute to the initiation and development of AKI.