Search

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.

In an attempt to reveal a correlation between the degree of glomerular hypertrophy, interstitial damage, and hemodynamic parameters in chronic nephritis, the glomerular area (GA) and proportion of interstitial area (IA%) were determined quantitatively with an image analyzer, and the effective renal plasma flow (ERPF) and filtration fraction (FF) were determined simultaneously. The subjects were 12 patients with focal glomerulosclerosis (FGS) and 12 patients with IgA nephropathy (IgAN), all of whom had a similar glomerular filtration rate (GFR). The GFR was 58.6 +/- 11.4 ml/min/1.48 m2 in the FGS group and 53.9 +/- 13.1 ml/min/1.48 m2 in the IgAN group, and the difference between the two groups was not significant. On the other hand, ERPF was significantly lower and FF was significantly higher in the FGS group than in the IgAN group. GA was significantly higher in the FGS group than in the control group (10 kidney donors), and GA in the IgAN group was equivalent to that in the control group. IA% was almost equal in the FGS and IgAN groups, and significantly higher in both groups than in the control group. Although GA was not correlated with GFR in the two groups, it tended to be positively correlated with FF in the FGS group, and the correlation between GA and FF reached statistical significance when the IgAN group was combined with the FGS group. The above findings suggest that the pattern of progression of the glomeruli and interstitial lesions and of the intrarenal hemodynamics involved in them may differ in the FGS and IgAN groups. However, since ERPF significantly decreased in the FGS group, even though IA% was the same in both groups, the possibility that ERPF was functionally decreased in the FGS group cannot be ruled out.

A 40-year-old woman suffered from toxemia of pregnancy in 1977 and was admitted to hospital. Thereafter, she developed nephrotic syndrome, underwent a renal biopsy, and a diagnosis of membranoproliferative glomerulonephritis (MPGN) was made. She received steroid therapy, immunosuppressive drug and anticoagulant therapy, and recovered sufficiently to be discharged from hospital in April, 1979. During subsequent ambulatory treatment at our outpatient department, her renal function deteriorated gradually, and maintenance hemodialysis was started from June, 1990. In July, 1991, she was admitted to our hospital with pleurisy and pericarditis. There was no improvement despite antibiotic treatments. Laboratory data revealed leukopenia and lymphopenia. Under suspicion of systemic lupus erythematosus (SLE), relevant tests were carried out. Immunological abnormalities such as positive LE cells and the presence of various autoantibodies, together with clinical signs of hypersensitivity to sunlight, stomatitis and serositis, satisfied the diagnostic criteria of the ARA and a diagnosis of SLE was made. This case did not exhibit any clinical or serological abnormalities except for the renal disorder for a 10-year period after the histological diagnosis of MPGN, but was eventually diagnosed as SLE as a result of the manifestation of SLE symptoms for the first time after one year of maintenance hemodialysis. Immunological abnormalities and SLE during maintenance hemodialysis are discussed in relation to other reports.

We investigated the early changes of tubules and effect of the oral adsorbent, AST-120, on the early changes of tubules in rats with chronic renal failure. Sprague-Dawley rats were divided into two groups with and without AST-120, after 3/4 nephrectomy. Although there were no significant differences in levels of blood urea nitrogen, serum creatinine, creatinine clearance, inulin clearance, para-aminohippuric acid clearance and urinary N-acetyl-beta-D-glucosaminidase at week 8 between the two groups, the amount of 24-hour urinary protein excretion and the direct systolic blood pressure at week 8 were significantly decreased in the group with AST-120. Examinations by light microscopy at week 8 revealed that proteinaceous casts in the tubules, tubular dilatation and infiltration of monocytes into the interstitium in the group with AST-120 were less prominent than those in the group without AST-120. A significant difference in numbers of proteinaceous casts was noted at week 8 between the two groups. In rats with chronic renal failure at the early stage, it is concluded that the formation of proteinaceous casts, resulting in tubular damage, is increased and that AST-120 delays the occurrence of proteinaceous casts by delaying the increase in urinary protein excretion.

Endogenous creatinine clearance (Ccr) has been much more commonly used to estimate renal function in clinical medicine, in comparison with inulin clearance (Cin) which is more accurate measure of glomerular filtration rate (GFR). There is, however, increasing difference between Ccr and Cin as renal function deteriorates. Since this difference is considered to be resulting from the tubular secretion of creatinine, Cin and Ccr were simultaneously measured in 81 patients with chronic renal disease, as well as 12 control subjects in this study. As Cin decreased, the Ccr/Cin ratio increased and the ratio varied widely even in patients with similar degree of renal impairment. The subjects were classified into 3 groups, group I (Cin greater than 80 ml/min), group II (80 ml/min greater than or equal to Cin greater than or equal to 40 ml/min) and group III (Cin less than 40 ml/min). The mean values of tubular creatinine secretion (Tcr) were 0.07 +/- 0.173 mg/min (+/- SD) in group I, 0.205 +/- 0.136 mg/min in group II and 0.333 +/- 0.139 mg/min in group III, respectively. Therefore, Tcr in the group of the severe impairment was the highest. In addition, Ccr and Cin were measured in 15 patients with chronic nephritis before and after an intravenous bolus injection of cimetidine (5 mg/kg BW). Following the injection Ccr/Cin ratio was reduced from an initial value of 1.51 +/- 0.23 to 1.18 +/- 0.13 in group II and from 2.00 +/- 0.44 to 1.55 +/- 0.25 in group III, respectively. Tubular secretion of creatinine appeared to be inhibited by cimetidine even in the patients with severe renal dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Urea kinetic modeling (UKM) was carried out to evaluate the water control in patients undergoing long-term hemodialysis. In 21 patients on chronic dialysis, the results of two different determinations of the total body water, i.e. by the deuterium oxide (D2O) method and by UKM, were compared. A correlation was observed with Y = 0.98X + 5.9 (P less than 0.01, r = 0.91) for males and Y = 0.97X + 6.2 (P less than 0.01, r = 0.90) for females, indicating that UKM is useful for determining the total body water. In addition, the 21 patients were classified into two groups based on their ECG findings, and UKM was performed in the two groups for comparison. The values of the total body water were 68.5 +/- 4.0% and 68.6 +/- 6.2% of body weight, respectively, with no significant difference between them. However, the CTR was 50.2 +/- 2.8% and 46.2 +/- 4.4%, respectively. Thus, not only X-ray examinations but also UKM should be carried out to determine the standard weight (SW-DW) in the presence of cardiac dysfunction. Instructions for water control were given when the total body water exceeded 73% during the UKM measurements over 5 years, which allowed an optimal total body water to be maintained thereafter. The possible influence of erythropoietin (EPO) was also examined by performing UKM in 8 cases receiving EPO and 7 cases without EPO. No noticeable difference was observed between the two groups. 17 patients using a polyacrylonitrile (PAN) membrane were further divided into those with and those without EPO to evaluate the possible influence of the PAN membrane-EPO combination. As a result, no significant difference was demonstrated, suggesting that UKM can be satisfactorily performed under such conditions. In 11 patients on chronic dialysis, the levels of alpha-human atrial natriuretic peptide (alpha-hANP) were measured pre- and post-dialysis to examine the relationship between the change in alpha-hANP and rate of weight loss (%). A significant correlation was observed with Y = 12.8X + 5.1 (P less than 0.05, r = 0.68). In conclusion, UKM was found to be useful for evaluating the water control and for assessing the optimal dialysis in patients receiving long-term hemodialysis.

We present here a case of young adult-onset primary systemic amyloidosis with AA protein. A 29-year-old male presenting with macrohematuria was transferred to our hospital because of aggravation of renal function. Amyloid protein was detected in the bladder, stomach and thyroid. The amyloid protein proved to be AA type by potassium permanganate histochemical analysis. Since secondary amyloidosis was excluded by the laboratory data and there was no family history of amyloidosis, a diagnosis of primary systemic amyloidosis with AA protein was reached. Although the patient was prescribed dimethyl sulphoxide, his renal function worsened with gastrocolic symptoms and a bleeding tendency. Hemodialysis (HD) was then initiated. After starting the HD, the patient's general condition recovered and subsequently the patient on treatment with maintenance HD was discharged.

The pharmacokinetics and optimum dose for maintenance of disopyramide (DP) which is effective against arrhythmia were studied in patients with chronic renal failure (CRF, n = 10), who had a creatinine clearance (Ccr) less than 30 ml/min. The plasma concentrations (PC) of DP and mono-isopropyl-disopyramide (MDP) an active metabolite of DP, were measured by high performance liquid chromatography. Samples from patients and controls were obtained at 0, 1, 2, 3, 4, 6, 8, 12, 24, 33, and 48 hr after oral administration (OA) of 100 mg DP. The pharmacokinetic parameters were calculated using a two-compartment model. In CRF, the plasma half life (T 1/2) of DP was 5.25 to 22.42 hr (average is 12.45 hr) and that of MDP was 5.09 to 131.66 hr (average is 16.9 hr). In normal controls, the T 1/2 of DP was 6.05 hr, but that of MDP could not be determined the available sensitivity of measurement. T max was 3.11 hr at the total PC of DP and MDP, and C max was 2.48 g/ml on average. In conclusion, the present study revealed that: (1) the PC of a mixture of DP and MDP should rise following OA of DP every 8 or 12 hr in CRF; (2) it is necessary therefore to monitor the accumulation of MDP after rolling OA of DP; and (3) OA of DP every 24 hr can maintain an effective PC.

Studies were performed on the platelet aggregation (PA) in patients with chronic renal failure (CRF) and normal subjects (NS). The PA was investigated in the whole blood by the electrical impedance method. The concentrations of plasma (P-) and erythrocyte (E-) guanidinosuccinic acid (GSA) and methylguanidine (MG) in uremic patients with CRF were determined by high performance liquid chromatography. GSA and MG are guanidino compounds (GC) and have been widely shown to act as uremic toxins. The effects of GSA and/or MG on the PA of NS were also investigated. The results showed that the PA of conservative therapy patients with CRF was significantly lower than that of NS, while the PA of hemodialysis (HD) patients was improved. The PA of continuous ambulatory peritoneal dialysis (CAPD) patients was rather high and the possibility of sugar and lipid metabolic disorders was suggested as the cause. The concentrations of P- and E-GSA and MG in uremic patients with CRF were increased. But there were no significant correlations between the PA and the concentrations of GSA and MG. In vitro, GSA and/or MG at a high concentration exerted a significant inhibitory effect, while at a low concentration they showed a lesser inhibitory effect on the PA. In conclusion, based on their inhibition of the PA in patients with CRF, the dialyzable materials, GSA and MG, are considered to represent active uremic toxins.

To produce a compatible model of early renal failure easily, we prepared three-quarters nephrectomized animal. 20 Sprague-Dawley rats were divided into the following two groups: 10 rats which received three-quarters nephrectomy (Nx group), assuming the weight of both kidneys to be equal, and another 10 rats which underwent sham operations (S group). The levels of creatinine clearance in Nx group and S group were 286.5 +/- 33.5 vs. 431.1 +/- 55.9 microliters/min/100 g BW (P less than 0.001) on week 2, and 233.0 +/- 16.7 vs. 562.3 +/- 62.9 microliters/min/100 g BW (P less than 0.001) on week 10, respectively. The indirect and direct systolic blood pressure (SBP) values of Nx group and S group at the 10th week were 154.5 +/- 5.5 vs. 131.1 +/- 3.6 mmHg (P less than 0.01), and 148.2 +/- 4.8 vs. 130.7 +/- 6.6 mmHg (P less than 0.01), respectively. Significant changes in the levels of urinary protein excretion, urinary sodium output, urinary epinephrine, urinary norepinephrine and plasma renin activity between both groups were recognized on the 10th week. The planar area of Nx group was significantly increased as compared to that of S group (11.0 +/- 0.3 vs. 7.2 +/- 0.1 x 10(-3) mm2, P less than 0.001). It is concluded that this model resembles early renal failure in humans because slow progression of renal dysfunction occurred with mild elevation of SBP, and that it is adequate for evaluating the influence of glomerular hypertrophy, resulting in glomerulosclerosis.

The effects of CaCO3 with vitamin D metabolite and without vitamin D metabolite on secondary hyperparathyroidism were investigated in 18 patients undergoing maintenance hemodialysis. 9 patients (Group 1) were treated with 1 microgram/day 1 alpha (OH)D3 and 2 g/day Al(OH)3, and the other 9 patients (Group 2) received 2 g/day Al(OH)3 without vitamin D metabolite. CaCO3 at amounts of 3 g/day was subsequently administered to all patients instead of Al(OH)3. The levels of mid portion-parathyroid hormone (M-PTH) in Group 2 and of 1,25-dihydroxyvitamin D3 in Group 1 during the baseline period were significantly increased as compared to those in the other group, respectively. In Group 1 only, the level of serum ionized calcium was appreciably elevated at the 4th and 12th weeks as compared to the baseline value, and the level of M-PTH was significantly decreased at the 4th and 12th weeks as compared to the baseline value. The levels of serum phosphate, calcitonin, magnesium and bicarbonate in both groups at the 4th and 12th weeks were not appreciably different from the baseline values. The level of serum aluminum in all patients of both groups were reduced at the 12th week as compared to the baseline values. A close correlation was recognized between M-PTH and the level of intact parathyroid hormone. It is concluded that prescription of 3g/day CaCO3, together with adequate doses of vitamin D metabolite, can ameliorate mild secondary hyperparathyroidism.

C3 nephritic factor (C3 NeF) has been found mainly in the sera of patients with membranoproliferative glomerulonephritis (MPGN) and partial lipodystrophy (PLD). We examined whether peripheral blood mononuclear cells (PBMC) from patients with PLD and MPGN could produce C3 NeF. We investigated the in vitro immunoglobulin synthesis of PBMC with mitogen. We further studied whether or not C3 NeF was included in the IgG of the culture supernatants by the C3bBb stabilizing activity and agglutination assay. The IgG of PLD patient was able to agglutinate only EAC4bBb cells and none of the other intermediate cells. We thus demonstrated that C3 NeF could be produced in vitro by PBMC derived from the patient with PLD. However, as regard case of C3 NeF weakly positive and C3 NeF negative patients, C3 NeF couldn't be produced in vitro by PBMC derived from the patients.

A 59-year-old woman was admitted to the hospital with a complaint of right visual disturbance. At admission, she had proteinuria and microscopic hematuria. The pulmonary X-ray showed bilateral hilar lymphadenopathy (BHL) but tuberculin test were negative. Also, bronchoalveolar lavage (BAL) and renal biopsy were performed. Bronchoalveolar lavage fluid (BALF) contained a high percentage of OKT 4 positive cells. In renal biopsy, light microscopic study showed thickening glomerular basement membrane (GBM) with tubulo-interstitial legion. Immuno-fluorescent study revealed granular deposits of IgG along glomerular capillary wall. Electron microscopic study showed subepithelial electron dense deposits of GBM, which are characteristic for membranous nephropathy (MN). It is well known that both sarcoidosis and MN are associated with immunological abnormality. This case might be significant for the study of pathogenesis of sarcoidosis.

Incubation of normal human serum with hemodialysis membranes in vitro resulted in conversion of C3 which was detected by crossed immunoelectrophoresis. In addition, formation of C3d was also observed, as was detected by double-decker rocket immunoelectrophoresis. Furthermore, breakdown products of complement (iC3b, C4d & Bb) in plasma samples were measured by ELISA. The microassay plates were coated with monoclonal antibodies which bind specifically to human iC3b, C4d and Bb, respectively, while the plasma samples were drawn from five polycystic kidney patients during initial hemodialysis. As a result, the iC3b and Bb levels in plasma were seen to increase during hemodialysis but the C4d levels revealed no significant changes. It was also observed that the Bb levels in patients undergoing hemodialysis were significantly higher than those in various renal and collagen diseases. Terminal complement complex (TCC) was not present in detectable amounts in normal human serum when measured by ELISA. However, incubation of normal human serum with hemodialysis membranes in vitro resulted in detection of TCC. TCC was present in the same plasma samples drawned from the five polycystic kidney patients during initial hemodialysis. It is suggestive that activation of complement by hemodialysis membrane is predominantly mediated through the alternative pathway and products such as TCC and anaphylatoxin are formed by this activation.

The effects of CaCO3 were investigated in 7 patients undergoing maintenance hemodialysis who had been treated with 1 microgram/day 1 alpha (OH)D3 and 2 g/day Al(OH)3. CaCO3 (3 g/day) was administered instead of Al(OH)3. The levels of serum total calcium and ionized calcium were significantly increased, the level of C-terminal parathyroid hormone was appreciably decreased and the levels of serum aluminum in all patients were reduced. There were no significant changes in the levels of serum phosphate, calcium x phosphate product, alkaline phosphatase, calcitonin, magnesium and bicarbonate. It is concluded that 3 g/day CaCO3 is equivalent to 2 g/day Al(OH)3 in terms of its phosphate-binding effect, and the prescription of CaCO3 together with 1 alpha (OH)D3 ameliorates secondary hyperparathyroidism.

The influence of a small amount of 1 alpha (OH)D3 on patients with chronic renal failure at the predialytic stage (CRFPS patients) receiving CaCO3 was investigated. 7 patients given CaCO3 (3 g/day) were administered 1 alpha (OH)D3 (0.25 micrograms/day) over a period of 12 weeks. 2 patients were eliminated from the study because of obvious deterioration of renal function. The others revealed no significant changes in levels of serum creatinine, adjusted calcium, phosphate, calcium x phosphate product, alkaline phosphatase, C-terminal parathyroid hormone, pH and bicarbonate. Our results indicated that even 0.25 micrograms/day 1 alpha (OH)D3 should not be prescribed to CRFPS patients given 3 g/day CaCO3. We recommend a little sole use of CaCO3 in CRFPS patients, paying attention to any exacerbation of renal function due to a rise in serum calcium concentration, when therapy for secondary hyperparathyroidism is required.

In this study we examined the role of the complement system in acute glomerulonephritis (AGN). Breakdown products of complements (iC3b, C4d and Bb) and Terminal complement complex (TCC, SC5b-9 complex) in plasma samples were measured by ELISA. The microassay plates were coated with monoclonal antibodies which bind specifically to human iC3b, C4d, Bb and SC5b-9 complex. This assay accurately quantitates small amounts of in vivo complement activation. The plasma samples were drawn from patients with AGN and other glomerulonephritis. There were some patients with various glomerulonephritis whose plasma iC3b, C4d and Bb concentrations were higher than those in normal human. However specificity was not found. The ratios iC3b/C3 and C4d/C4 were increased in the early stages of AGN, but plasma Bb concentrations revealed no significant changes. Plasma SC5b-9 complex concentrations were increased in the early stages of AGN. C3c, C3d, C4d and SC5b-9 were found to be localised in the glomeruli of those AGN patients. It is suggestive that in these cases of AGN (especially case 2) complement activation is predominantly mediated through the classical pathway and TCC is formed by this activation. This complement activation in the blood and the renal tissue is presumed to be involved in the initiation and progression of AGN.