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During development, glomerular visceral epithelial cells, or podocytes, undergo extensive morphologic changes necessary for the creation of the glomerular filter. These changes include formation of interdigitating foot processes, replacement of tight junctions with slit diaphragms, and the concomitant opening of filtration slits. It was postulated previously and confirmed recently that podocalyxin, a sialomucin, plays a major role in keeping the urinary space open by virtue of the physicochemical properties of its highly negatively charged ectodomain. By a cell aggregation assay, the expression level of podocalyxin correlated closely with the anti-adhesion effect. Treatment of the cells with sialidase reversed the inhibitory effect of podocalyxin, indicating that sialic acid residue is required for inhibition of cell adhesion. In addition to its ectodomain, the highly conserved cytoplasmic tail of podocalyxin may contribute to the unique organization of podocytes. By immunocytochemistry, it was shown that two cytosolic adaptor proteins, Na+/H+-exchanger regulatory factor 2 (NHERF2) and ezrin, colocalize with podocalyxin along the apical plasma membrane of podocytes, where they form a co-immunoprecipitable complex. Moreover, the podocalyxin/NHERF2 /ezrin complex interacts with the actin cytoskeleton, and this interaction is disrupted in pathologic conditions associated with changes in the foot processes, indicating its importance in maintaining the unique organization of this epithelium. Further studies will be needed to identify the signaling molecules responsible for the regulation of this complex in podocyte damage. [ABSTRACT FROM AUTHOR]

A 62-year-old-Japanese man had a history of probable granulomatosis with polyangiitis (GPA) from 7 years previously, showing kidney and vasculitis symptoms with PR3-ANCA (864 EU) without renal biopsy. Remission with normalization of renal function and urinary findings was induced by corticosteroid therapy. Prednisolone (PSL) was tapered to 5 mg/day and maintained for 6.5 years with a low positive titer of PR3-ANCA. After 7 years of remission, he was referred to our hospital because of arthralgia, fever, general fatigue and appetite loss with apparent urinary abnormality, increased serum Cr (1.8 mg/dL) and C reactive protein (CRP : 30.1 mg/dL). On admission, he showed a high titer of PR3-ANCA (> 300 U/mL). Renal biopsy demonstrated the existence of the pauci-immune type of severe crescentic necrotizing glomerulonephritis, tubulo-interstitial damage and perivascular granuloma. He was diagnosed as relapse of GPA (kidney-localized type) without upper respiratory tract (E) and lung (L) symptoms. Accordingly, he received steroid pulse therapy leading to improvement of these symptoms and renal function. Oral PSL at the dosage of 40 mg/day was administered after steroid pulse therapy, and then tapered to 20 mg/day. Cyclophosphamide was added within 8 weeks. He was discharged 8 weeks after treatment with a decreased level of Cr (1.5 mg/dL) and PR3-ANCA (244 U/mL). After discharge, PSL was tapered to 10 mg/day during the course of stability resulting in a further improved level of Cr (1.2 mg/dL), PR3-ANCA 40 U/mL in the outpatient clinic. In Japan, PR3-ANCA-positive GPA has a lower incidence than MPO-ANCA-positive microscopic vasculitis. In GPA, the kidney-localized (K) type without upper respiratory tract (E, L) symptoms is rare. Histologically, not only necrotizing crescentic glomerulonephritis but also perivascular granuloma in the kidney are very rare and interesting.

Chronic kidney disease (CKD) is increasingly recognized not only as a cause of end-stage renal disease but also as a cause of cardiovascular disease. Importantly, it is intimately associated with non-healthy lifestyles such as obesity, metabolic syndrome, hypertension, diabetes mellitus, smoking, and heavy drinking. To define CKD direct measurement of GFR or estimation of GFR (eGFR) is required. Japan Society of Nephrology is asking nationwide project to create "original" equation without using ethnic factor to obtain eGFR. Early detection and early treatment are vital to prevent not only CKD progression but also cardiovascular events. A comprehensive health education campaign and screening of the general populace are needed in order to detect CKD early. The control of hypertension, dyslipidemia, proteinuria, obesity, are intervention strategies that retard or prevent progression of CKD. Blockade of the renin-angiotensin system can be beneficial, especially if proteinuria is present.