Outcomes of hemodiafiltration based on Japanese dialysis patient registry.

Effectiveness of various therapeutic modalities was analyzed among 1,196 patients entered in the registry of the Japanese Society for Dialysis Therapy who were on hemopurification therapy as of the end of 1998 and developed dialysis-related amyloidosis during 1999. In the investigation, the effectiveness of various hemopurification modalities on the dialysis-related amyloidosis was ranked as exacerbation, unchanged, or alleviation, so as to analyze the possible relationship between the hemopurification modality and its effectiveness. The analysis was performed using a logistic regression approach, and the results were shown as "the risk of a worse therapeutic ranking" among the hemopurification modalities. The smaller "the risk of a worse therapeutic effect" was, the more effective the treatment modality. When the risk of a worse therapeutic effect for the hemodialysis patients treated by a regular membrane was put at 1.0, the risk for hemodialysis patients using high-flux membrane was 0.489, the off-line hemodiafiltration risk was 0.117, the on-line hemodiafiltration risk was 0.013, and the risk of push/pull hemodiafiltration was 0.017. For hemodialysis with a beta(2)-microglobulin adsorption column, a low risk of 0.054 was found. The results indicated that hemodiafiltration therapy and simultaneous hemodialysis with beta(2)-microglobulin adsorption therapy were more effective treatment for dialysis-related amyloidosis.

Renal and hemodynamic effects of endothelin in anesthetized dogs.

The effects of endothelin on systemic hemodynamics and renal functions were investigated in anesthetized dogs. Infusion of endothelin at a dose of 1 ng/kg/min decreased renal blood flow and increased renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg/min significantly decreased cardiac output, glomerular filtration rate, renal plasma flow, urine volume, and urinary sodium excretion. Mean arterial pressure showed a transient decrease at doses higher than 50 ng/kg/min. These results showed that endothelin in systemic administration has effects on renal functions as well as on systemic hemodynamics.

Effects of endothelin on renal regional blood flow in dogs.

The effects of intrarenal infusion of endothelin on renal blood flow were investigated in anesthetized dogs. Endothelin produced a biphasic change in the renal blood flow (RBF): an initial, transient increase followed by a marked, long-lasting decrease. The changes in the RBF were parallel to those in the renal cortical blood flow, whereas the changes in the medullary blood flow were less prominent. These results suggest that endothelin affects RBF, preferentially in the renal cortex.

Clinical profile of Japanese dialysis patients with diabetic nephropathy, diagnosed as having diabetes before the age of thirty.

Diabetic nephropathy is the leading cause of death in young diabetic patients. There are a large number of patients with non-insulin-dependent diabetes mellitus (NIDDM) who are diagnosed before the age of 30 in Japan. We investigated 36 patients with young-onset diabetes who started dialysis between 1978 and 1987 in our hospital. Of the 36 patients, 12 (33.3%) were classified as having insulin-dependent diabetes mellitus (IDDM), 22 (61.1%) had NIDDM, and 2 (5.6%) could not be classified clinically. The percentages of the different types of diabetes in our series of dialysis patients were almost identical with those in Nagai's series of 551 diabetic patients diagnosed before the age of 30 at the Diabetes Center of Tokyo Women's Medical College from 1976 to 1981. The present study showed the young-onset NIDDM in Japan was associated with almost the same incidence of end-stage diabetic nephropathy as was IDDM. However, the number of NIDDM patients diagnosed under 30 years of age was almost double that of IDDM patients. Thus, we have to pay greater attention to the development of diabetic nephropathy in young-onset NIDDM patients than has been thought necessary in the past.

Effects of endothelin on renal hemodynamics and excretory functions in anesthetized dogs.

The effects of endothelin on renal hemodynamics and excretory functions were investigated in anesthetized dogs. Infusion of endothelin at a rate of 1 ng/kg.min resulted in a slight but significant decrease in renal blood flow and an increase in renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg.min significantly decreased cardiac output, glomerular filtration rate, urine volume, and urinary sodium and potassium excretion, whereas it increased systemic vascular resistance. Mean arterial pressure and heart rate showed a transient decrease and increase, respectively, at doses higher than 50 ng/kg.min. Plasma renin activity and plasma aldosterone concentrations were increased only at the dose of 100 ng/kg.min. These effects lasted for more than 60 min. These results suggest that endothelin may have an important role in the modulation of renal functions as well as in the modulation of systemic hemodynamics.

Two antiprothrombin antibodies against prothrombin and prothrombin-phosphatidyl serine show partial but not total identity.

Recently, an enzyme-linked immunosorbent assay (ELISA) using prothrombin (PT) as the antigen has become a widely used test. Two ELISA methods for the detection of antiprothrombin antibody have been used extensively: one method employs PT as an antigen (aPT), and the other employs PT and phosphatidyl serine (aPT/PS) as antigens along with Ca. However, the results obtained by the two methods are not necessarily consistent with each other even using the same samples, suggesting the possibility that aPT and aPT/PS are different antibodies. We conducted an investigation to determine whether aPT and aPT/PS are identical or different antibodies. Five patients who were positive for both tests become negative to aPT after absorption with an aPT-ELISA plate or fluid-phase PT; however, they retained reactivity to aPT/PS after the same absorption procedure. These results suggest that aPT and aPT/PS are partially identical, yet still different antibodies. However, further examination employing more samples may be needed to verify our hypothesis including clarification of the clinicopathological significance of these antibodies in the future.

Accumulation of phosphatydilcholine-hydroperoxide in dialysis patients with diabetic nephropathy.

Plasma lipid peroxidation in noninsulin dependent diabetes mellitus (DM) patients were evaluated in DM patients undergoing hemodialysis (HD) by means of a chemiluminescence-HPLC for the specific determination of phosphatidylcholine hydroperoxide (PCOOH). Thirty-three uremic patients with DM nephropathy, undergoing 12 hours HD a week using polymethylmethacrylate membrane, were studied. Of them 22 DM patients on HD were divided into 2 age and sex matched groups treated and conventional group in order to clarify therapeutic effect of 500 mg alfa-tocopherol and 600 mg probucol daily. Fifty DM patients without end-stage renal disease (ESRD) who were age-, period of diabetes-, and sex-matched, were selected as positive control of the subjects. Plasma PCOOH levels were significantly elevated in both DM patients, while the plasma PCOOH in normal controls were 227.0 +/- 68.7 pmol/ml. Plasma PCOOH levels of DM patients undergoing HD were significantly higher than that of patients without ESRD (1,330.8 +/- 642.7 pmol/ml vs. 756.6 +/- 431.9 pmol/ml, p < 0.025). Partial correlation coefficient of plasma PCOOH level demonstrated PCOOH and period of HD in DM patients were highly significantly positively correlated (p < 0.01), although single session of HD was not found to produce significantly increased lipid-peroxidation. Plasma PCOOH roughly remained within similar levels as base lines by medication with anti-oxidant compared to that of conventional group. From these results we conclude that HD intensifies lipid peroxidation and such accumulation of hydroperoxide could account for accelerated progress of atherosclerosis in DM patients with renal insufficiency. It is worthwhile to try an administration of free radical scavenger in order to reduce PCOOH and slow down the progression of atherosclerotic vascular disease.

Hereditary serum cholinesterase deficiency associated with severe lipid deposition in the kidney.

A 47-year-old woman who was homozygous for a silent cholinesterase gene (hereditary serum cholinesterase deficiency) presented with nephrotic syndrome and hyperlipidemia. Renal biopsy performed in 1986 demonstrated mesangial proliferative glomerulonephritis. Four years later, a second biopsy revealed progression with mesangial interpositions and severe lipid deposition in the glomeruli, tubules and interstitium. This is the first case of hereditary serum cholinesterase deficiency accompanied by renal disease. Serum cholinesterase deficiency may be related to hyperlipidemia and abnormal lipid deposition in the kidney, which promotes the progression of renal disease.

Continuous monitoring of blood volume in double filtration plasmapheresis.

A continuous hematocrit (HCT) monitor, Crit-Line, was introduced to examine the change in patients' blood volume (BV) due to albumin loss during double filtration plasmapheresis (DFPP) treatments. Nine patients with autoimmune diseases or ABO incompatible renal transplantation received 15 DFPP treatments under Crit-Line monitoring. In these patients, plasma albumin concentration (C(P)) changed from 3.7 +/- 0.6 g/dl to 3.5 +/- 0.5 g/dl and HCT from 28.7% +/- 3.3% to 31.3% +/- 4.3% (change ratio [CR] of BV = -8.1%) during treatment with albumin concentrations (C(S)) of 9.5 +/- 1.0 g/dl and 500 ml volumes (V(S)) of supplementation fluid. Although the apparent CR value of C(P) was -5.3%, on average, the CR of albumin in the patients' plasma (M(P)) was -16.1%, which means a corrected CR value of C(P) by the HCT value to eliminate the influence of the patient's blood volume contraction during treatment. Albumin loss usually occurred in DFPP treatments. The decrease in BV was induced by an oncotic pressure drop due to albumin loss, and often resulted in a blood pressure drop. The amount of albumin loss during DFPP treatments strongly depends on sieving coefficients of the plasma separator (SC(PS)) and the plasma fractionator (SC(PF)), the filtration fraction of the plasma fractionator (FF(PF)), pretreatment C(P) value, and C(S) and V(S) values of the supplementation fluid. To determine the optimum C(S) and V(S) values for each patient, the authors introduced a variable blood volume model for albumin transport in DFPP. In this model, changes in C(P), HCT, and BV values could be estimated during treatment. For example, a patient with an HCT of 31.2%, body weight of 61.1 kg, and pretreatment C(P) of 4.4 g/dl received a DFPP treatment using a plasma separator, OP-05 (SC(PS) of 0.99), and a plasma fractionator, Evaflux 2A (SC(PF) of 0.40), under FF(PF) of 0.8 with a V(S) of 500 ml. A value for C(S) of about 10 g/dl is required for the patient to maintain a normal C(P) level during treatment by an estimation from the model. As a result of the treatment with a C(S) of 10 g/dl, the patient had no adverse reactions, such as a blood pressure decrease, during treatment under these conditions.

Microscopic observation of leukocyte kinesis in the vascular bed during hemodialysis using the rabbit ear chamber technique.

Leukocyte kinesis in the capillary vascular bed during hemodialysis (HD) was investigated to elucidate the mechanism of transient leukopenia. Leukocyte movement was observed microscopically during HD using the rabbit ear chamber (REC) technique, which permits visualization of the movement of blood corpuscles in capillaries. Blood was drawn from the femoral artery and returned into the auricular and/or carotid artery so that the blood passing through the hollow fiber artificial kidney (HFAK) flowed into capillaries in the REC. Leukocyte counts of blood samples taken from the afferent and efferent limbs of the HD circuit, the right jugular vein and the right atrium were determined consecutively during HD. The difference in the leukocyte count was observed between the afferent and efferent limbs for the first 15 minutes and thereafter between the efferent limb and the jugular vein. The "transpulmonary" difference in the leukocyte count was not noticed throughout HD. Between 15 and 90 minutes after the start of HD, scarcely any circulating leukocytes were found in capillaries in the REC and some leukocytes were attached to the endothelial surface. Thereafter circulating leukocytes were seen again and detachment of leukocytes from the endothelial surface was observed. No leukocyte aggregation or embolization of aggregating leukocytes was noticed. This evidence suggests that leukopenia may be attributed to the transient shift of leukocytes to the marginal pool of the vessel lumen and this process may not be specific for the pulmonary vasculature, but may occur in the first capillary bed into which the blood passing through the HFAK flows.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of glucose on the proliferation of peritoneal fibroblasts.

The purpose of this study was to clarify the pathophysiological role of glucose and glucose transporters (GLUTs) in the proliferation and production of extracellular matrix (ECM) in peritoneal fibroblasts. Peritoneal fibroblasts from rat omentum were cultured in medium M199 with 5% fetal bovine serum (FBS) with (Group B) and without (Group A) 4% glucose. The rate of cell growth at the M stage of the cell cycle in Group B was higher than that in Group A at 12 and 24 hours after culture. However, cell numbers in Group B were less than in Group A at 24, 72, and 120 hours after culture. The GLUT inhibitor suppressed the proliferation of cells 72 and 120 hours after culture. The procollagen III peptide (PIIIP) contents in the supernatant of cells cultured in a high glucose medium were higher than those of control cells at 24, 72, and 120 hours after culture. PIIIP levels of cells cultured with the GLUT inhibitor were also higher than those of cells without the GLUT inhibitor. These results suggest that initially glucose stimulates cell proliferation and thereafter inhibits its proliferation. GLUTs may accelerate the proliferation of peritoneal fibroblasts. We suggest that glucose stimulates the ECM component PIIIP, and GLUT may have an inhibitory effect on the production of the ECM component PIIIP.

[Improvement of malnutrition indices in adult patients with end stage renal disease by recombinant human growth hormone].

Recombinant human growth hormone (r-hGH), 1 U/kg body weight/week, was administered subcutaneously for 2-4 weeks to two end stage renal disease patients with severe malnutrition. Following r-hGH, there were significant increase in hematocrit level and serum concentration of albumin, IGF-1 and GH, and decrease of urea nitrogen. It was concluded that r-hGH exerts a therapeutic effect to nutritional status in renal failure patients by improving severe hypoalbuminemia, susceptibility to infectious disease, intractable ascites and so on.

Renal and hemodynamic effects of synthetic atrial natriuretic peptide in dogs with chronic renal failure.

The present experiments were performed to clarify the renal and hemodynamic effects of atrial natriuretic peptide (ANP) in dogs with chronic renal failure (CRF; produced by 5/6 nephrectomy 3-4 weeks before study). Synthetic alpha-hANP was administered intravenously (0.1 micrograms/kg body weight for 30 min) with a priming bolus injection (1.0 micrograms/kg body weight) to anesthetized controls (n = 8) and CRF-dogs (n = 10). The effects of ANP on renal function, cardiac function, lithium clearance, and plasma ANP levels during clearance studies were determined. Effects of ANP on the hemodynamics were observed to the same degree in both groups. An increase in inulin clearance (CIn) was noted only in the CRF-dogs (7.5 +/- 2.1 to 9.6 +/- 2.9 ml/min; p less than 0.01). The infusion of ANP increased the urine volume, absolute sodium excretion, and osmolar clearance in the control and CRF groups. The fractional excretion of lithium (FELi), a marker of the proximal reabsorption of sodium, was higher at baseline in the CRF group (control group, 24.4 +/- 6.7 vs. CRF group, 41.5 +/- 13.2%; p less than 0.001). Following ANP infusion, FELi increased in both groups. The plasma ANP levels were monitored during the clearance study, and those of the CRF group were higher throughout the experiments. Thus, extrinsic ANP induced diuresis and natriuresis in CRF-dogs, produced by nephron mass reduction. Discrepancies in the pattern of response and plasma ANP levels were observed between the controls and CRF-dogs, suggesting that the action and metabolic clearance rate of ANP were altered in the CRF state.

Analysis of the expression of cell surface antigens and intercellular adhesion molecules on lymphocytes in CAPD patients.

The aim of the present study was to assess immunological aspects in patients on continuous ambulatory peritoneal dialysis (CAPD). The CAPD patients were divided into two groups. Group A consisted of patients in which high-somolar dialysate was used infrequently, and group B consisted of patients in which high-osmolar dialysate was used frequently. We characterized cell populations in the peritoneal effluent (PE) of CAPD patients. Analysis of the nucleated cell composition revealed that one-third of the PE cells were lymphocytes. Flow cytometric analysis of the surface antigen expression on lymphocytes revealed that the proportion of helper/inducer T-cells was lower in PE than in peripheral blood (PB). By contrast, the rates of DR antigen expression on T-cells and CD45RO antigen expression on helper/inducer T-cells (memory T-cells) were higher in PE than in PB. However, there were no statistically significant differences between the rates of expression of any lymphocyte surface antigens in the two groups. Expression of intercellular adhesion molecules, such as ICAM-1 and LFA-1, was higher in PE than in PB. It is of interest that the expression of ICAM-1 and LFA-1 on T-cells in PB was significantly higher in group B than in group A. In summary, there is an increase in memory T-cells in the PE and up-regulation of intercellular adhesion molecules of PE lymphocytes of CAPD patients. The up-regulation of intercellular adhesion molecules is also observed in PB lymphocytes in whom high-osmolar dialysate is used frequently.

Mechanism of elevated local oxidant stress in early anti-glomerular basement membrane nephritis: an evaluation of oxidant production and superoxide dismutase expression.

The present study was designed to identify the mechanism of increased oxidant stress in the rat model of anti-glomerular basement membrane nephritis. Sixty-three Sprague-Dawley rats were injected with nephrotoxic serum and evaluated 1 to 24 hours later. In these rats, CeCl3 deposition, an index of hydrogen peroxide production, was observed on the surfaces of glomerular endothelial cells and polymorphonuclear leukocytes, whereas no such depositions were observed in controls. Renal cortical level of lipid peroxidation products (phosphatidylcholine hydroperoxide) was significantly (p < 0.05) elevated at one hour after the injection and remained elevated at least for 24 hours. Protein levels of glomerular Mn-superoxide dismutase (SOD) decreased from 1.55 +/- 0.38 microgram/mg protein to 0.67 +/- 0.18 microgram/mg protein at one hour and normalized by 12 hours after the injection. The activity of the enzyme showed a similar trend. In contrast, Mn-SOD mRNA increased 3.4-fold at 3 hours after the injection. In situ hybridization showed increased Mn-SOD mRNA expression in glomeruli. Cu/Zn-SOD mRNA expression was transiently suppressed. These results indicated that both increase in local production of reactive oxygen species (ROS) and reduction in antioxidant enzyme activities are responsible for the enhanced oxidant stress in the heterologous phase of anti-glomerular basement membrane nephritis. The paradoxical increase in Mn-SOD mRNA expression indicates that the posttranscriptional down regulation of Mn-SOD (i.e., reduction in protein and activity) and the increased ROS may activate transcription of the gene.

[The effects of ACE inhibitor treatment and ACE gene polymorphism on erythropoiesis in chronic hemodialysis patients].

Aggravation of anemia in chronic renal failure patients by angiotensin-converting enzyme inhibitors (ACEIs) has been attributed to the inhibition of angiotensin II which facilitates erythropoietin(Epo) production. This study was aimed at evaluating whether ACEIs aggravate anemia in maintenance hemodialysis patients and to investigate the influence of ACE gene polymorphism on erythropoiesis in these patients. Ninety-one hemodialysis patients were divided into 2 groups, based on whether or not they were administered ACEIs, into the ACEI group(n = 24) and the non-ACEI group(n = 67), and comparisons were made of the doses of recombinant human Epo(rHuEpo) administered, the hematocrit(Hct) and the plasma Epo concentrations. Among the patients in the non-ACEI group, only 17 did not receive rHuEpo, while all of the patients in the ACEI group received rHuEpo. The average dose of rHuEpo was 102.7 +/- 45.4 IU/kg/week in the ACEI group and 57.8 +/- 55 IU/kg/week in the non-ACEI group and the difference between the two groups was statistically significant. A statistically significant difference in the Hct was also observed between the two groups: the mean Hct in the ACEI group was 28.7 +/- 2.9% while that in the non-ACEI group was 31.1 +/- 3.7%. The plasma Epo concentrations were significantly lower in the ACEI group than in the non-ACEI group. No significant differences in the rHuEpo dose and Hct were observed between the three ACE genotype classes in either the ACEI or the non-ACEI group, however, there was a significant difference among the three genotypes in the non-ACEI group in regard to the plasma Epo concentrations; patients with the DD genotype had higher concentrations than those with the DI or II genotypes. These data suggest that anemia in maintenance hemodialysis patients is worsened by ACEIs as a result of the suppression of Epo production. Although it has been suggested that the endogenous Epo concentrations in maintenance hemodialysis patients are associated with ACE gene polymorphism, no significant influence of the ACE genotype on the rHuEpo dose or Hct was evident. Therefore, it is possible that exacerbation of anemia by ACEIs in the patients receiving rHuEpo is a result of an inhibited bone marrow response to Epo.