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BACKGROUND AND OBJECTIVES: The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score. RESULTS: The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P

Purpose To assess changes in left ventricular function and tissue composition by using MRI after chemotherapy-radiation therapy in participants with esophageal cancer. Materials and Methods Between January 2013 and April 2015, this prospective study enrolled 24 participants (42% women; mean age, 63 years; range, 49-73 years) scheduled for chemotherapy-radiation therapy. 3.0-T MRI examinations were performed before, at 0.5 year, and at 1.5 years after chemotherapy-radiation therapy. Myocardial native T1, postcontrast T1, and extracellular volume were measured in basal septum (as irradiated areas) and apical lateral wall (as nonirradiated areas). Left ventricular function, prevalence of late gadolinium enhancement, and T1 and extracellular volume values were compared over the follow-up period by using Friedman or Cochran Q tests, followed by Dunn test. Results In 14 participants who were followed up for 1.5 years, native T1 and extracellular volume in the septum were elevated at 0.5 year compared with baseline (1183 msec ± 46 [standard deviation] vs 1257 msec ± 35; 26% ± 3 vs 32% ± 3; adjusted P.01 for both), but not in the lateral wall. Left ventricular stroke volume index and late gadolinium enhancement changed at 1.5 years compared with baseline (41 mL/m

Fabry disease is a rare X-linked hereditary disorder (Xq22) caused by a deficiency in alpha-galactosidase (α-GAL) activity. This enzyme deficit results in the systemic accumulation of glycophospholipids, leading to multi-organ failure including the heart, kidneys, and brain. Enzyme replacement therapy (ERT) improves the prognosis of patients with Fabry disease. We describe a case showing progressive renal failure despite ERT. An 18-year-old obese male patient (body mass index (BMI) 29.9 kg/m2) was admitted for detailed examination of mild degree hypertension (150/65 mmHg) and proteinuria occurring for 2 years prior to admittance. Laboratory tests revealed mostly normal kidney function (serum creatinine 0.5 mg/dL, estimated glomerular filtration rate 181 mL/min/m2) with low α-GAL activity, a significant level of proteinuria (0.5–1.0 g/day), and the presence of mulberry cells in the urinary sediment. Renal biopsy demonstrated marked glomerulomegaly with diffuse vacuolization of the glomerular epithelial cells and focal segmental glomerulosclerosis. Electron microscopy revealed typical zebra bodies in the glomerular epithelial cells and effacement of foot processes of the epithelium. We could not find any cause of glomerulomegaly except for obesity. α-GAL gene analysis revealed a missense mutation in R301Q. Although ERT with agalsidase α was initiated, his renal function declined, and hemodialysis was initiated at 22 years of age. We present a case of rapid progression of Fabry nephropathy despite ERT. As with other renal diseases, obesity may aggravate the progression of Fabry nephropathy.

The course of rapidly progressive glomerulonephritis (RPGN) caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is often life-threatening, especially in the elderly when pulmonary involvement and/or severely impaired renal function are present. Corticosteroids and cyclophosphamide are the first-line treatment, but ironically infection, not vascular events such as hemorrhage, caused by the vasculitis itself, is the most common cause of death of RPGN patients. Several new treatment strategies, such as leukocytapheresis (LCAP) and intravenous immunoglobulin (IVIg), have become available during the past decade and these treatments have made it possible to treat high-risk RPGN patients without inducing serious immunosuppressive states. In the present paper we review recent clinical trials of LCAP and IVIg therapy in patients with pauci-immune/ANCA-associated RPGN, and show improved clinical outcomes after using these new treatment strategies in our institution.

Sulfated portions of glycosaminoglycan (GAG) side chains in heparan sulfate proteoglycan (HSPG) are thought to play an important role in charge-dependent selectivity of glomerular filtration against plasma proteins. Heparan sulfate N-acetylglucosamine N-deacetylase/adenosine 3'-phosphate 5'-phosphosulfate: unsubstituted glucosamine N-sulfotransferase (NDST) is the key enzyme regulating sulfation of GAG chains. In this study we investigated transcriptional expression of NDST-1, 1 of 4 isozymes of NDST, in glomeruli of rats with puromycin aminonucleoside (PAN) nephrosis. Nephrosis was induced in rats with a single intraperitoneal injection of 150 mg/kg PAN. On days 10 and 35, expression of NDST-1 messenger RNA (mRNA) in glomeruli was analyzed with the use of Northern-blot analysis. Immunohistochemical studies were also performed with the use of monoclonal antibodies that react specifically with the N-sulfated portion of the GAG chain of HSPG and agrin, a major core protein of HSPG in glomerular basement membrane (GBM). In addition, we studied the expression of NDST-1 mRNA in cultured glomerular epithelial cells (GECs) and glomerular mesangial cells in the presence of PAN. On day 10, when significant proteinuria developed, the ratios of glomerular expression of NDST-1 mRNA against glyceraldehyde-phosphate dehydrogenase mRNA in PAN-treated rats were decreased to 48% +/- 6% of those in controls (P