Dialysis-related hypotension as a cause of progressive frontal lobe atrophy in chronic hemodialysis patients: a 3-year prospective study.

BACKGROUND/AIM: Brain atrophy is known to develop more rapidly in hemodialysis (HD) patients than other individuals. The present study was designed to examine the role of HD-related hypotension in brain atrophy in patients on chronic HD. METHODS: By using magnetic resonance imaging, whole brain atrophy was assessed by the ventricular-brain ratio (VBR; ventricular area/whole brain area). Frontal brain atrophy was assessed by the frontal atrophy index (FAI; frontal brain area/intracranial frontal space). The number of lacunae was also counted. We studied 32 HD patients without symptomatic neurological abnormalities or diabetes mellitus: male/female ratio 19/13; mean age +/- SD 53 +/- 10 (range 28-77) years; mean HD duration +/- SD 11 +/- 6 (range 1-22) years. Magnetic resonance imagings were taken in 1995 and 1998. All dialysis-related hypotension episodes during the same period were identified from the medical records and counted. RESULTS: The VBR ranged from 8.8 to 18.7% in 1995 (12.8 +/- 2.2%) and was not different in 1998 (13.1 +/- 2.7%). However, the VBR increased by more than 5% in 14 patients, and their HD duration of 13 +/- 6 years was significantly longer than that of 18 patients with stable VBR (p < 0.05). The FAI in 1995 was 62.2 +/- 4.2% (range 55.8-71.3%) and decreased significantly to 59.7 +/- 4.7% (range 50.2-70.9%) in 1998 (p < 0.05). The change in FAI correlated significantly with both the total number of dialysis-related hypotension episodes (r = 0.45, p < 0.05) and the increase in number of lacunae (r = 0.42, p < 0.05). CONCLUSION: Our results suggest that dialysis-related hypotension plays a role in progressive frontal lobe atrophy in HD patients.

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.

Myeloperoxidase-antineutrophil cytoplasmic antibody-associated glomerulonephritis superimposed on biopsy-proven diabetic nephrosclerosis.

We present a case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis with diabetic nephrosclerosis, diagnosed by serial renal biopsies within a short period. A 78-year-old man with renal insufficiency, who had been diagnosed with diabetic nephrosclerosis by renal biopsy 9 months earlier, was admitted to the hospital for dyspnea and rapid deterioration of renal function. The titer of serum MPO-ANCA was high, and the second renal biopsy confirmed the presence of necrotizing glomerulonephritis with crescents. Methylprednisolone pulse therapy followed by oral administration of prednisolone led to resolution of respiratory symptoms and reversal of MPO-ANCA. Renal function did not improve, however, necessitating hemodialysis. A review of the literature showed several cases of necrotizing glomerulonephritis superimposed on diabetic nephropathy but only a few reported cases of MPO-ANCA glomerulonephritis associated with diabetic nephrosclerosis. Diabetic patients who show rapid deterioration of renal function should undergo renal biopsy to determine the concomitant presence, if any, of other glomerular diseases and to prevent life-threatening systemic involvement.

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.