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The voltage-gated potassium channel Kvl.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells ([T.sub.EM]) without affecting the function of naive T cells (TN) and central memory T cells ([T.sub.CM]). We found that Kvl.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the [CD4.sup.+] T cells and some of the [CD8.sup.+] T cells had the [T.sub.EM] phenotype ([CD45RC.sup.-][CD62L.sup.-]). Double immunofluorescence staining using mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kvl.3 was expressed on T cells and some macrophages. We therefore investigated whether the Kvl.3 blocker Psora-4 can be used to treat anti-GBM GN. Rats that had been given an injection of rabbit anti-rat GBM antibody were also injected with Psora-4 or the vehicle intraperitoneally. Rats given Psora-4 showed less proteinuria and fewer crescentic glomeruli than rats given the vehicle. These results suggest that [T.sub.EM] and some macrophages expressing Kvl.3 channels play a critical role in the pathogenesis of crescentic GN and that Psora-4 will be useful for the treatment of rapidly progressive glomerulonephritis. WKY rats; crescentic glomerulonephritis; flow cytometric analysis doi: 10.1152/ajprenal.00374.2010

The protective effects of Rho kinase inhibitor fasudil against renal diseases have recently been reported. We compared the therapeutic effects of fasudil on the spontaneously hypercholesterolemic (SHC) rat, a model of chronic kidney disease (CKD) with proteinuria, with those of the angiotensin receptor blocker olmesartan (OL) by paying attention to the proteinuria and the macrophage phenotype. SHC rats were allocated to six treatment groups: a vehicle (Ve) group, a low-dose fasudil (FL) group, a high-dose fasudil (FH) group, an OL group, a combination of low-dose fasudil and OL (CL) group, and a combination of high-dose fasudil and OL (CH) group. Sprague-Dawley rats treated with vehicle served as a control (n 7/each). The rats were treated for 24 wk. Compared with the Ve group, proteinuria was significantly decreased in the FH, OL, and CL groups, and it completely disappeared in the CH group. Glomerular stainings of nephrin and F-actin were focally impaired in the Ve group but were restored in the CH group. Western blotting showed that the CH group had significantly increased renal nephrin expression compared with the Ve group. Interstitial infiltration of macrophages was significantly increased in the Ve group, which was significantly attenuated in all treatment groups. The ratio of CD206 (M2 macrophage marker) to CD68 mRNA was significantly greater in the CH group than in the Ve group. These results indicate that fasudil with OL reduces proteinuria by protecting podocyte integrity and alters the interstitial macrophage density/phenotype, thereby exerting renoprotective effects against CKD. [ABSTRACT FROM AUTHOR]

The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells (TEM) without affecting the function of naïve T cells (TN) and central memory T cells (TCM). We found that Kv1.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the CD4+ T cells and some of the CD8+ T cells had the TEM phenotype (CD45RC-CD62L-). Double immunofluorescence staining using mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kv1.3 was expressed on T cells and some macrophages. We therefore investigated whether the Kv1.3 blocker Psora-4 can be used to treat anti-GBM GN. Rats that had been given an injection of rabbit anti-rat GBM antibody were also injected with Psora-4 or the vehicle intraperitoneally. Rats given Psora-4 showed less proteinuria and fewer crescentic glomeruli than rats given the vehicle. These results suggest that TEM and some macrophages expressing Kv1.3 channels play a critical role in the pathogenesis of crescentic GN and that Psora-4 will be useful for the treatment of rapidly progressive glomerulonephritis. [ABSTRACT FROM AUTHOR]

The aims of treating hypertension in patients with chronic kidney disease including diabetes are to prevent both cardiovascular events and end stage renal failure, and goal of blood pressure is less than 130/80 mmHg. The first choice is angiotensin II receptor blocker (ARB) or angiotensin converting enzyme inhibitor. If the patient is salt-sensitive and hypervolemic, the second choice is diuretic. When the patient has some risk factors for cardiovascular events, the second choice is calcium channel blocker. In treating patient whose serum creatinine more than 2 mg/dL, we should start the ARB with lower dose and examine serum creatinine and potassium every 2 week.