Search

Background/Aim: Investigators have reported that the nonmuscle myosin heavy chain B (SMemb) expression is enhanced in various types of glomerular diseases which develop into nephrosclerosis. In renal transplantation, transplant glomerulitis is often recognized during acute rejection. Therefore, we hypothesized that SMemb plays important roles in acute kidney rejection. To evaluate the role of SMemb in the development of kidney rejection, we examined its expression in rat kidney transplantation models. Methods: We used Lewis rats as recipients and Wistar rats as donors. Group I: controls; group II: isograft model; group III: allograft model; group IV: as group III +10 mg/kg/day of ciclosporin A (CsA), and group V: as group III + CsA administration for 5 days postoperatively. Histopathological and SMemb immunohistochemical studies were completed. Results: Clear enhancement of SMemb expression was found on day 3 in group III. In groups I, II, IV, and V, SMemb was faintly expressed in the glomerular cells. However, after termination of CsA treatment, the SMemb expression increased. The expression of SMemb was higher in the allograft model than in either isograft or CsA-treated models. Conclusions: Immunohistological investigations show that the SMemb expression was significant from an early stage at which histopathological reactions were hardly identifiable. This, therefore, could be useful for an earlier diagnosis of acute rejection.

Hepatocyte growth factor (HGF) facilitates the regeneration of injured kidney in acute renal failure (ARF). Here we investigated the HGF production in glycerol-induced ARF rats. HGF mRNA expression levels were elevated in liver, spleen, and lung 6-24 h after glycerol injection. Tissue HGF protein levels determined by an enzyme-linked immunosorbent assay also increased in liver and spleen, whereas they decreased in the injured kidney 24 h after injection. Immunohistochemical studies showed that the number of HGF-producing cells did not increase in the liver. HGF receptor/c-Met mRNA levels were elevated only in the kidney. These results indicate that HGF supplied in an endocrine manner may play an important role in the regenerating process following ARF.

Hepatocyte growth factor (HGF) facilitates recovery from tissue injuries. We previously reported that serum HGF levels were elevated in chronic renal failure (CRF) patients. In the present study Western blot analysis of CRF patients' sera showed the majority of their serum HGF was a single-chain precursor molecule. In CRF rats developed by 5/6 nephrectomy or high adenine diet, both HGF mRNA expression levels and tissue HGF concentrations were increased in liver and spleen. The results suggest that HGF production increases in CRF, which may be a response to chronic progressive renal injuries in an endocrine manner.

The serum levels of hepatocyte growth factor (HGF) were determined in chronic renal failure (CRF) patients. Nondialysis patients with renal insufficiency had significantly higher serum HGF than normal subjects (0.34 +/- 0.10 ng/ml, n = 21 vs. 0.19 +/- 0.05 ng/ml, n = 15; p0.001), and the elevated serum HGF correlated with their serum creatinine levels. Hemodialysis (HD) patients treated for 5-10 years showed higher serum HGF than those receiving HD for 1 year or less (0.45 +/- 0.14 ng/ml, n = 8 vs. 0.33 +/- 0.11 ng/ml, n = 9; p0.05). Continuous ambulatory peritoneal dialysis patients also showed elevated serum HGF levels comparable to those of HD patients. There was no difference in serum HGF levels in HD patients with or without acquired cystic disease of kidney. Consequently, serum HGF is elevated in CRF, which may be attributed to the increased production of HGF in response to the chronic renal injury, the effect of heparin, or reduced removal of serum HGF in CRF patients.

The long-term effects of neutralized dialysate used in continuous ambulatory peritoneal dialysis (CAPD) were evaluated in 8 well-controlled patients. Twelve milliliters of 8.4% sodium bicarbonate was added to Dianeal PD-1 immediately before every administration. The final pH was 6.8 and the concentration of sodium bicarbonate was 6 mmol/l. The final sodium level was 138 mEq/l. This dialysate was used for 5 months. For 2 months before and 3 months after this period, Dianeal PD-2 was used as the dialysate for comparison. Blood bicarbonate levels significantly improved during the use of the neutralized dialysate. Blood sodium, chloride and magnesium levels and the effluent volume significantly increased. Sodium balance improved during the period when neutralized dialysate was used. Total leukocyte counts in the effluent decreased, and leukocyte viability increased. Abdominal distention, abdominal pain during instillation, nausea and headache improved. No side effects, including peritonitis, occurred during the trial of neutralized dialysate. The results suggest that this dialysate was less irritating to the peritoneal membrane than the control dialysate and that the therapeutic effects were satisfactory.

The effect of ciclosporin (CS) on cardiac output (CO) and regional blood flow was studied using the microsphere method in heminephrectomized rats with and without renal arterial clamping prior to the administration of CS. The effect of a calcium (Ca) channel blocker, verapamil, was also examined on CS-induced nephropathy. CS at a dose of 40 mg/kg per day was given orally using a gastric tube for 7 days. Verapamil was given in the drinking water for 7 days. Significant increases in blood urea nitrogen (BUN) and serum creatinine (sCr) with a significant decrease in renal inulin clearance (CIn) were noted after 7 days of CS administration in both intact and ischemic-kidney groups, indicating the development of CS-induced nephropathy. The ischemic-kidney group showed a significantly severe nephropathy as compared with the intact-kidney group. As for change in CO and regional blood flow, CS caused a significant decrease in CO, renal blood flow (RBF) and brain blood flow, while hepatic arterial blood flow and muscular blood flow significantly increased. The renal outer cortical blood flow decreased markedly while the inner cortical blood flow remained unchanged. Although verapamil slightly but significantly decreased mean arterial blood pressure in CS-treated rats, CO and its distribution did not change. BUN and sCr were not significantly ameliorated in the intact-kidney group. However, in the ischemic-kidney group, verapamil caused a significant improvement in RBF, ameliorating CS-induced elevation of BUN and sCr, and a decrease in CIn.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured urinary N-acetyl-β- D -glucosaminidase (NAG) excretion before and after extracorporeal shock wave lithotripsy (ESWL) with a view to study the underlying factors which aggr

Silkworm larvae plasma (SLP) reagent is activated by peptidoglycan (PG), a fragment of both the gram-positive and gram-negative bacterial cell wall, as well as beta-glucan (BG), a component of fungi. It is possible to measure contamination of gram-positive bacteria quantitatively by combining the conventional limulus amebocyte lysate (LAL) and PG measurement methods. Therefore, a more highly accurate analysis of dialysate can be made using both SLP and LAL methods to detect endotoxin (ET) and/or PG contamination. We studied the effects of contaminated dialysate on human peripheral blood mononuclear cells (PBMC) by producing various cytokines in vitro. Muramyl dipeptide (MDP) was used as the biologically active minimum constituent of PG. A total of 54 dialysate samples were obtained under sterile conditions from 4 sites: (1) reverse osmosis water unit; (2) proportioning unit; (3) multiple dialysate preparation console, and (4) personal dialysate preparation console, at 9 dialysis facilities. To detect bacterial contamination, the samples were measured with LAL(C), LAL(G) and SLP methods. PBMC were collected from 10 healthy controls and from 10 hemodialysis patients and cultured for 24 h with ET, MDP, ET + MDP and contaminated dialysate. IL-1 receptor antagonist (IL-1Ra), IL-1 beta and TNF-alpha in the culture medium supernatants were measured using the ELISA method. PG was not detected in dialysate from sites 1 or 2. However, dialysate from the inlet of the dialyzer at the bedside monitor of the central supply and personal console showed 4.1 +/- 6.1 ng/ml for site 3 (in 7 of 18 samples) and 3.3 +/- 4.6 ng/ml for site 4 (in 3 of 18 samples). Contamination by PG alone and complex contamination by PG and ET were also detected. Furthermore, IL-1Ra, IL-1 beta and TNF-alpha production by PBMC increased in accordance with the concentrations of MDP. Cytokine production was enhanced 5-10 times more where MDP and ET coexisted than where either MDP or ET existed alone, showing the synergic effects of MDP and ET. Based on these results, there is a high possibility that PG may also be a pyrogen in the dialysate prior to this study. ET had been considered the only pyrogen in dialysate. Therefore, it is essential to recognize the existence of both ET and PG in investigating dialysate contamination.

Plasma prostaglandins (PGs; PGE2, PGF2 alpha, 6-keto-PGF 1 alpha and TXB2) and plasma renin activity (PRA) were measured in 94 end-stage renal disease (ESRD) patients including 15 undialyzed, 74 maintenance-hemodialyzed and 5 anephric patients, and in 27 healthy controls. In the healthy controls, 6-keto-PGF 1 alpha inversely correlated with age, while TXB2 and the TXB2/6-keto-PGF 1 alpha ratio correlated with age. In the ESRD patients, 6-keto-PGF 1 alpha showed a tendency to decrease with age, and the TXB2/6-keto-PGF 1 alpha ratio significantly correlated with age. The undialyzed group showed significantly higher blood pressure and TXB2 but significantly lower 6-keto-PGF1 alpha compared to the other groups. In the dialyzed group, PGE2 and 6-keto-PGF1 alpha tended to be lower and TXB2 higher compared to the healthy control group. In the dialyzed group, 6-keto-PGF1 alpha correlated inversely with blood pressure independently from PRA. As for PGF2 alpha, it was higher in the undialyzed, dialyzed and anephric groups than in the healthy control group. These results suggested that PGs were involved in blood pressure abnormalities, and that PGI2 played an important role in controlling blood pressure in ESRD patients as one of the depressor factors.

In order to study the metabolism of acetate transferred from dialysate, the plasma concentrations of organic acids including the tricarboxylic acid cycle (TCA cycle) intermediates were measured during hemodialysis in a comparative study between acetate dialysate and bicarbonate dialysate in 17 patients on maintenance hemodialysis treatment. Continuous measurements of serum concentrations of these organic acids during hemodialysis were performed using the filtrate obtained through an ultrafiltrate sampling device. The organic acids were measured by isotachophoresis. Serum acetate, malate and citrate concentration increased with time in acetate dialysis compared with bicarbonate dialysis. Correlations were found between these organic acids. Isocitrate became detectable when the serum acetate concentration was over 7 mmol/l which was correlated to the acetate concentration, and was accompanied by the development of symptoms. The above results suggest that an acetate overload on the patients during acetate dialysis affects acetate metabolism through the TCA cycle resulting in an accumulation of organic acids in the serum and the development of symptoms.

Trace element concentrations in hair and fingernails and plasma of nondialyzed, hemodialyzed and hemofiltered patients with chronic renal failure and healthy volunteers were measured by atomic and flameless atomic absorption spectrophotometry and neutron activation analysis. Plasma aluminum concentrations in all three groups of patients were higher than in the controls. Aluminum levels in plasma and red blood cells were higher in hemofiltered patients than in dialyzed patients. The aluminum concentrations in the hair of both nondialyzed and dialyzed patients was higher than in the controls, while that in the hemofiltered patients it was not. These elevated aluminum concentrations appear to be mainly caused by the use of aluminum-contaminated dialysate. Calcium concentrations in the hair of nondialyzed and dialyzed patients were higher than in the controls. Plasma zinc concentrations in all the patients were lower than the controls, and the concentrations in hemofiltered patients were lower than in the dialyzed patients.

Cardiac output (CO), renal blood flow (RBF) and hepatic blood flow (HBF) were measured by the microsphere method before (control) and at 4 and 10 h after the induction of acute renal failure by intramuscular injection of glycerol in water-drinking, long-term saline-drinking and long-term captopril (converting enzyme inhibitor)-drinking rats. At 4 h after glycerol injection, CO, RBF and HBF significantly decreased in all three groups. At 10 h after glycerol injection, CO, RBF and HBF recovered to 88% of the respective control levels in only the saline-drinking rats, whereas CO, RBF and HBF further decreased to 53, 38 and 58% of the control levels, respectively in the captopril-drinking rats. At this time, not only acute renal failure but also hepatic disorder developed in the water-drinking and captopril-drinking rats as indicated by elevations of serum creatinine, urea nitrogen, alanine aminotransferase and other blood chemistry levels. The development of acute renal failure was not suppressed by captopril, but by long-term saline load. Thus, we conclude that the decrease in CO is an important variable of the early decrease in renal and hepatic perfusion in glycerol-induced acute renal failure, and that the early recovery of HBF as well as RBF may play an important role in preventing the development of acute renal failure.