Icodextrin-based continuous ambulatory peritoneal dialysis therapy effectively reduces left ventricular mass index and protects cardiac function in patients with end-stage renal disease.

Increased left ventricular mass index (LVMI) is commonly observed in patients undergoing peritoneal dialysis (PD). The present study aimed to determine the effect of icodextrin (Ico) on LVMI in PD patients with maintained residual renal function (RRF). This retrospective study included 18 patients (12 men, 6 women; average age: 62 +/- 10 years) diagnosed with indications for PD therapy and divided into two groups: those treated with Ico (Ico group) and without Ico (non-Ico group). Echocardiography was performed at the beginning of continuous ambulatory PD and after 6 and 12 months. A significant reduction in LVMI (p < 0.01) and an increase in ultrafiltration (p < 0.01) were observed after 6 months of lco treatment and were maintained for 12 months. Ejection fraction was significantly lower in the non-Ico group after 12 months (p < 0.01), but was not altered in the Ico group. Blood pressure, cardiothoracic ratio, urine volume, and N-terminal prohormone of brain natriuretic peptide were unaffected by PD treatment up to 12 months. The year-averaged ultrafiltration and the reduction in LVMI were significantly correlated (p < 0.05). Ico effectively improved LVMI and maintained ejection fraction in end-stage renal disease patients within 1 year from PD initiation. Notably, treatment with Ico resulted in a reduction of LVMI (associated with increased ultrafiltration), with no significant reduction in RRF.

The new method to make diagnosis and identify the location of leakage of pleuroperitoneal communication in peritoneal dialysis patients.

Pleuroperitoneal communication is a severe complication in peritoneal dialysis, and about half of the patients forced to discontinue peritoneal dialysis. The method of coloring dialysis solution by indocyanine green or CT peritoneography have been reported to make diagnosis of pleuroperitoneal communication, however sensitivity of these tests is not a satisfactory level. By repairing the pleural hole with thoracoscopic surgery, it is possible to resume peritoneal dialysis. However, the recurrence rate is very high unless precisely detecting the location of the pleural hole during surgery. We report three cases of pleuroperitoneal communication in peritoneal dialysis patients, in which we found the combination of contrast-enhanced ultrasonography and the indocyanine green fluorescence system are reliable method to make diagnosis and identify the location of leakage of pleuroperitoneal communication. By making definite diagnosis and precisely identifying the localization, we were able to close diaphragm holes by video-assisted thoracoscopic surgery.

IL-15, a survival factor for kidney epithelial cells, counteracts apoptosis and inflammation during nephritis.

IL-15, a T cell growth factor, has been linked to exacerbating autoimmune diseases and allograft rejection. To test the hypothesis that IL-15-deficient (IL-15-/-) mice would be protected from T cell-dependent nephritis, we induced nephrotoxic serum nephritis (NSN) in IL-15-/- and wild-type (IL-15+/+) C57BL/6 mice. Contrary to our expectations, IL-15 protects the kidney during this T cell-dependent immunologic insult. Tubular, interstitial, and glomerular pathology and renal function are worse in IL-15-/- mice during NSN. We detected a substantial increase in tubular apoptosis in IL-15-/- kidneys. Moreover, macrophages and CD4 T cells are more abundant in the interstitia and glomeruli in IL-15-/- mice. This led us to identify several mechanisms responsible for heightened renal injury in the absence of IL-15. We now report that IL-15 and the IL-15 receptor (alpha, beta, gamma chains) are constitutively expressed in normal tubular epithelial cells (TECs). IL-15 is an autocrine survival factor for TECs. TEC apoptosis induced with anti-Fas or actinomycin D is substantially greater in IL-15-/- than in wild-type TECs. Moreover, IL-15 decreases the induction of a nephritogenic chemokine, MCP-1, that attracts leukocytes into the kidney during NSN. Taken together, we suggest that IL-15 is a therapeutic for tubulointerstitial and glomerular kidney diseases.

Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney.

During ischemia-reperfusion (I/R) injury in the rat kidney, apoptosis was observed in the distal tubules of the cortico-medullary region and outer medulla (OM) while severe necrosis was seen in the proximal straight tubules of the OM. The majority of these changes disappeared within 2 weeks. We examined the contents of 8-oxo-2'-deoxyguanosine (8-oxo-dG), which is a major type of oxidative damage in DNA, in the rat kidney during I/R injury, and also investigated the expression level of the OGG1 gene encoding the 8-oxoguanine DNA glycosylase. High-performance liquid chromatography with an MS/MS analysis of the nuclear DNA revealed an immediate accumulation of 8-oxo-dG in the nuclear DNA prepared from the cortex and OM of the kidney 1h after I/R, and an immunohistochemical analysis demonstrated the immediate accumulation of 8-oxo-dG in the nuclei of renal tubular cells both in the cortex and OM. A delayed increase of cytoplasmic staining with anti-8-oxo-dG was observed only in the cortico-medulla and OM, where the cytoplasmic staining in the proximal tubular cells is higher than in the distal tubular cells. The level of cytoplasmic staining representing 8-oxo-dG in mitochondrial DNA, peaked at 6h after I/R and preceded the necrosis of proximal tubular cells in the OM. An RNase protection assay showed a high level of OGG1 mRNA in the normal kidney, and the level decreased within 3h only in the OM, and increased thereafter 1-7 days of I/R both in the cortex and OM. In situ hybridization showed higher levels of OGG1 mRNA expression in the renal tubules in the OM than in the cortex of the normal kidney, which decreased rapidly within 3h of I/R. Thus, the accumulation of 8-oxo-dG in the mitochondrial DNA rather than in nuclear DNA is likely to be involved in the pathogenic responses such as necrosis of renal tubular cells during I/R injury of the kidney, together with an altered level of OGG1 expression.

MCP-1 and RANTES are expressed in renal cortex of rats chronically treated with nitric oxide synthase inhibitor. Involvement in macrophage and monocyte recruitment.

Long-term inhibition of nitric oxide synthase (NOS) in rats is known to cause systemic hypertension and renal parenchymal injury. We have previously reported that activation of intra-renal renin-angiotensin system was a major contributing factor for renal injury in chronically NOS-inhibited rats. Massive interstitial infiltration of monocytes/macrophages (M/M) was characteristically seen in this model. The present study was performed to elucidate the role of chemokines, RANTES and MCP-1, in promoting M/M recruitment into the renal cortex. The number of infiltrating ED-1-positive cells was examined in association with the level of expression of RANTES and MCP1 mRNAs in the renal cortex of rats treated orally for 12 weeks with L-NAME. Compared to controls rats, the number of infiltrating ED-1-positive cells was significantly higher in L-NAME-treated rats. The mRNA expressions of both RANTES and MCP-1 were significantly higher in L-NAME-treated rats than the control. In L-NAME-treated rats, the high number of ED-1-positive cells and increased expression of both RANTES and MCP-1 were suppressed by ACE inhibitor, but not by hydralazine. In contrast, neither ED-1 counts nor RANTES mRNA expression were affected by angiotensin (Ang) II type 1 receptor antagonist. These results suggest the likely involvement of RANTES and MCP-1 in the recruitment of M/M into the renal cortex of rats with chronic NOS inhibition. Furthermore, it is also indicated that Ang II stimulates MCP-1 expression via Ang II type 1 receptor, whereas RANTES expression is mediated via Ang II type 2 receptor.

Locally activated renin-angiotensin system associated with TGF-beta1 as a major factor for renal injury induced by chronic inhibition of nitric oxide synthase in rats.

Chronic inhibition of nitric oxide synthase (NOS) is known to cause renal parenchymal injury with systemic hypertension. To elucidate the pathogenetic mechanism in renal damage induced by NOS inhibition, N(omega)-nitro-L-arginine methyl ester (L-NAME) was given orally for 12 wk in Wistar rats, and the roles of tissue renin-angiotensin system and transforming growth factor-beta1 (TGF-beta1) were investigated. BP and urinary protein excretion increased significantly in L-NAME rats compared with control rats, and glomerulosclerosis and interstitial fibrosis developed. In L-NAME rats, the cortical tissue levels of angiotensin-converting enzyme activity and angiotensin II were significantly higher than those in control rats. The cortical mRNA expressions of both TGF-beta1 and fibronectin were significantly elevated in L-NAME rats. Immunohistochemically, increased expressions of both fibronectin and alpha-smooth muscle actin were also revealed in L-NAME rats. In L-NAME rats, these histologic injuries and the increased expression of TGF-beta1 were equally ameliorated by either angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist, but not by hydralazine. In conclusion, the locally activated renin-angiotensin system in connection with the increased TGF-beta1 expression is a major pathogenetic feature of renal injury in chronically NOS-inhibited rats.