Does LDL-apheresis in steroid-resistant nephrotic syndrome affect prognosis?

Low-density lipoprotein apheresis (LDL-A) was performed for nine episodes of steroid-resistant nephrotic syndrome in eight patients. The clinical and immunohistological findings were analysed retrospectively. Six of the patients had focal glomerular sclerosis (FGS), one had minimal-change nephrotic syndrome (MCNS), and one had membranous nephropathy (MN) with FGS. The LDL-A treatment, carried out 2-13 times (mean 7.33 +/- 4.05) for one nephrotic episode, at average intervals of 3-16 days (mean: 8.5 +/- 5.1 days) and combined with steroid pulse therapy and the administration of an antihyperlipidaemic agent in some cases, led to rapid amelioration of hyperlipidaemia. In six nephrotic episodes (5 patients) more than 50% reduction of proteinuria occurred (less than 3.5 g/day) (response-group). A significant elevation of serum albumin (more than 3.0 g/dl) was obtained in five of these episodes. The other three patients were resistant (resistant-group). The number of and intervals between LDL-A treatments in the response group (5 +/- 2.8 times and 5.8 +/- 4.1 days) were significantly less than those in the resistant-group (12.0 +/- 0.8 times and 13.2 +/- 1.8 days) (P < 0.05). After LDL-A, significant reductions were observed in the serum total cholesterol (T-CHO), phospholipid (PL), triglyceride (TG), free-CHO (F-CHO), and beta-lipoprotein (beta-lipo) (P < 0.05). HDL-cholesterol (HDL-C) increased somewhat after LDL-A. Further, Ccr was elevated in all nephrotic episodes, except in one patient who manifested renal failure after 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Two-compartment model of cholesterol kinetics for establishment of treatment strategy of LDL apheresis in nephrotic hypercholesterolemia.

Cholesterol kinetics in the time course after LDL apheresis using a dextran sulfate cellulose column was analyzed by adapting a two-compartment cholesterol kinetic model. Fifteen sets of serial serum cholesterol concentrations after LDL apheresis from 4 patients with drug-resistant nephrotic hypercholesterolemia due to focal glomerulosclerosis (FGS) were analyzed and cholesterol kinetic parameters were estimated with the nonlinear least-squares method. The fractional cholesterol catabolic rates (Kc; 0.171 +/- 0.073/day, mean +/- SD) were markedly decreased as reported in familial hypercholesterolemia (homo: 0.101/day, hetero: 0.280/day). Cholesterol generation rates (G; 68.0 +/- 28.7 mg/dl/day, mean +/- SD) considerably overlapped the normal range (39.2-77.5 mg/dl/day). This result was compatible with an earlier report that Kc was reduced earlier than G in nephrotic hypercholesterolemia. The time average serum cholesterol concentrations (TAC) in the rebound phase after LDL apheresis can be simulated using these kinetic parameters by the Runge-Kutta-Gill method. According to our previous report, TAC must be reduced to under a near-normal level in order to obtain a beneficial effect on nephrotic syndrome due to FGS. In 10 sets out of the 15, once-weekly treatment of LDL apheresis was sufficient to achieve this aim, but in the remaining 5 cases, more frequent LDL apheresis up to twice a week was necessary in the early phase of treatment. In conclusion, the two-compartment cholesterol kinetic model is useful in clarifying the abnormal cholesterol kinetics in nephrotic syndrome and may be helpful in establishing a more rational strategy of LDL apheresis for nephrotic hypercholesterolemia.

[Utility of recombinant human erythropoietin on the anemia of elderly hemodialysis patients].

Recombinant human erythropoietin was administered to 59 patients over 65 years of age receiving maintenance hemodialysis treatment in Kyoto and Shiga district, in order to evaluate its utility on renal anemia. After 6 months of administration, the hematocrit rose from 20.8 +/- 3.5% to 28.0 +/- 3.7% with concomitant improvement of subjective symptoms related to anemia. Twelve patients developed side effects, in 10 of whom elevation of blood pressure was observed. We found no clinically significant abnormalities in the laboratory data. In conclusion, recombinant human erythropoietin is highly useful in the treatment of renal anemia in elderly hemodialysis patients.

[Effect of uremic middle molecules removed during hemofiltration on the enzyme activity in rat liver cytosol].

It is well known that the products of protein catabolism and some of the intermediates including middle molecules (MM) are a biochemical feature of uremic serum and also the activity of serum alanine aminotransferase decreases relatively. To examine the toxicity of MM, we investigate the effect of MM removed by HF on aminotransferases and peptidases in rat liver cytosol. The following enzymes were selected: aminotransferases (GOT, GPT), leucine aminopeptidase (LAP), gamma-glutamyltranspeptidase (gamma GTP). MM samples were as follows: preparation of MM fraction from each 10 l HF fluid at half intervals of former (F-) and latter (L-) for 5 h. HF of two patients (5 weeks) by 1KD ultrafiltration, and group separation into hydrophobic (Mo) and hydrophilic (Mi) by XAD-4 resin (F-Mo, L-Mo, F-Mi, L-Mi). Except for GOT, the effect of MM were found at the activities decreased on LAP (26-30%), on GPT (5-6%), and increased on gamma GTP (4-23%), as compared to control. We found a little difference in the results by the character of MM (Mo, Mi) and by the intervals of HF (F-, L-). These results suggest that MM might play a role in the formation of uremic peptides.

Different appearance and pathogenic roles of serum IgA against autologous IgG Fc and Fab in patients with IgA nephropathy.

The serum levels of IgA class antibodies against autologous IgG Fc and Fab fragments were measured by ELISA in 62 patients with primary IgA nephropathy (IgAN) and 20 normal healthy volunteers. Both antibodies were significantly higher in the patients (P less than 0.01). The total IgA levels were correlated with those of IgA anti-IgG Fc antibodies (IgA anti-Fc) (rs = 0.57, P less than 0.001), but not with those of the IgA anti-IgG Fab antibodies (IgA anti-Fab). A histopathological comparison revealed that the sera of patients with severe glomerulonephritis had significantly higher levels of IgA anti-Fc than those with milder lesions (P less than 0.01). On the other hand, no correlation was observed between the serum levels of IgA anti-Fab and the histopathological severity. A comparison before and after treatment in 12 patients demonstrated a significant decrease of IgA anti-Fc (P less than 0.01) and an increase of IgA anti-Fab (P less than 0.05) after the treatment. Size analysis in serial sera from 3 patients was performed using HPLC under neutral (pH = 7.0) and under acid (pH = 3.5) buffer conditions. A markedly increased ratio of both antibodies with the polymeric form was observed in the active phase. In the remission phase, the amounts of acid-dissociable polymeric form IgA anti-Fc were decreased. In contrast, high levels of polymeric form IgA anti-Fab continued to be observed in 2 patients at this phase. These results suggest that abnormally stimulated production of IgA class autoantibodies especially with the polymeric form against both IgG Fc and Fab fragments, occurs in IgAN, involving separate regulation with differing reactions to treatment and a distinct relationship between IgA anti-Fc and active histopathological lesions.

[A case of renal cell carcinoma in a horseshoe kidney: a case report].

A case of renal call carcinoma associated with horseshoe kidney is reported. The patient was a 59-year-old woman complaining of right flank mass. Radiological examination showed right renal tumor and horseshoe kidney, and right nephrectomy was performed. Histological examination showed it to be clear cell type renal cell carcinoma. Only 17 cases of horseshoe kidney with renal cell carcinoma have been reported in Japan. We report the 18th case with a review of the literature.

Plasma adsorption using bilirubin-adsorbent materials as a treatment for patients with hepatic failure.

In order to achieve a higher degree of improvement in patients with postoperative hepatic failure, the effects of plasma adsorption (PA) using a serial connection of noncoated charcoal (N 350) and a new bilirubin adsorbent material, styrenedivinylbenzene (BR350), were investigated both experimentally and clinically. After in vitro perfusion of high bilirubin containing plasma through these columns for 3 hours, total bilirubin levels were drastically reduced to 21% of the preperfusion level in the serial connection of N 350 and BR 350, while it remained high at over 40% in the single use of each column. Total branched chain and aromatic amino acid levels were also drastically reduced in the serial connection of these columns to 50, 40, and 7%, respectively, while the total amino acid levels remained high at 87% in the single use of BR 350. The combination of these columns enhanced rather than interfered with one another. Patients who received this treatment achieved an initial reduction of plasma total bilirubin and aromatic amino acids of 57 +/- 6 and 84 +/- 7, respectively. Although the long-term prognosis for these patients was negative, improvement of clinical and laboratory findings were actually obtained by this treatment. This PA system could provide a possibility for an improved supportive therapy for hepatic failure, especially for patients with hepatic coma and hyperbilirubinemia.

[Inhibitory effect of uremic fluorescent substances on the cellular energy generation].

The toxicity of uremic fluorescent substances (F-ure) in hemofiltrates of a dialysis patient on the respiration of rat liver mitochondria was studied in comparison with some fluorescent substances (F-cir) in a cirrhosis urine. These substances found in both the body fluid of chronic disease were fractionated by hydrophobic HPLC. And the characteristic of (1) F-ure and (2) F-cir was as follows: the hydrophobicity based on Sasagawa's constant, (1) 1.1 approximately 1.3 & (2) 1.8; lambda max in UV spectrum, (1) 231, 356 nm & (2) 220 approximately 230, 290 nm; Em in fluorescence, (1) 461 nm & (2) 361 or 504 approximately 7 nm. When F-ure was added into mitochondrial respiratory medium, the respiration of succinate (State 4) decreased about a half in the presence of phosphate and succinate/ADP respiration (State 3) was much suppressed. And about a quarter of this suppression was released by an uncoupled (SF-6847), whereas F-cir on the state 3 respiration showed to be stimulative effect in like manner of uncoupler. The toxicity of uremic fluorescent substances on cellular energy generation could be demonstrated by decreased respiration of mitochondria.

Aluminum transport and dialysance during haemodialysis.

Aluminum transfer and dialysance during haemodialysis and plasma aluminum concentrations in haemodialysis patients were examined. Plasma aluminum in 30 volunteer outpatients tended to decrease after 5-hour dialysis (6.35 +/- 3.02 micrograms/dl before haemodialysis; 5.41 +/- 2.60 micrograms/dl after haemodialysis). The decrease was mainly due to diffusion despite haemoconcentration evidenced by a significant increase in the haematocrit and total plasma protein during dialysis. To study the changes resulting from diffusion, we measured aluminum in the arterial blood and in the dialysate at the inflow and outflow sites of the dialyzer. There was a non-significant decrease in the plasma aluminum of arterial blood from 6.20 +/- 2.90 to 5.64 +/- 2.55 micrograms/dl, but a significant increase in the dialysate aluminum from 0.38 +/- 0.18 micrograms/dl to 1.10 +/- 0.66 micrograms/dl. Aluminum diffused across the dialyzer from the blood to the dialysate in 23 cases and into the blood in 7 others. When aluminum dialysance is high, plasma aluminum can be removed to the dialysate during haemodialysis.

[A case of von Recklinghausen's disease localized in the lower abdominal and external genitalia].

A case of von Recklinghausen's disease localized to the lower abdominal and the external genital region is reported. The patient was a 14-year-old male who complained of an abnormality of the external genitalia. There was a subcutaneous mass with the skin pigmentation, which surrounded the penis, so that the foreskin appeared like a cyst. Excision of the subcutaneous mass and plastic operation of the penis were performed. Histological examination showed it to be diffuse neurofibroma. There has been no recurrence two years after the operation. This type of von Recklinghausen's disease has not been reported in Japan.

Serum and corpuscular nickel and zinc in chronic hemodialysis patients.

Serum and corpuscular nickel and zinc concentrations in 30 chronic hemodialysis patients were examined. Serum nickel and zinc levels before dialysis were 0.22 +/- 0.03 microgram/dl (normal value: 0.56 +/- 0.08 microgram/dl) and 70.0 +/- 13.4 micrograms/dl (normal value: 96 +/- 8 micrograms/dl) low, respectively. However, corpuscular nickel and zinc levels before dialysis were high: 1.25 +/- 0.24 microgram/dl (normal value: 0.88 +/- 0.17 microgram/dl) and 1,299 +/- 146 micrograms/dl (normal value: 1,120 +/- 80 micrograms/dl). Serum zinc levels significantly increased after dialysis, but serum nickel concentrations did not significantly increase during dialysis. Corpuscular nickel and zinc concentrations did not significantly change during dialysis.

Relationship between serum nickel concentrations and anaemia in chronic haemodialysis patients.

Thirty chronic haemodialysis patients were examined with respect to the relationship between renal anaemia and serum nickel concentrations. Red blood cell counts, haemoglobin values, haematocrit values, serum iron values, serum ferritin levels and serum nickel concentrations were measured. No significant relationships were found between serum nickel levels and serum iron values or serum ferritin levels. Dialysis anaemia was found to have a significant correlation with serum nickel concentrations in chronic haemodialysis patients.

Zinc transport during hemodialysis.

Zinc transfer during hemodialysis and plasma zinc concentrations in hemodialysis patients were examined. Fifteen volunteer outpatients undergoing hemodialysis showed significant increases in plasma zinc from 74.0 +/- 7.8 to 88.1 +/- 9.7 micrograms/dl after a 5-h dialysis. The increase was mainly the result of hemoconcentration as evidenced by a significant increase in the hematocrit and total serum protein during dialysis, but was also due to diffusion. To study the changes resulting from diffusion, zinc was measured in the arterial blood and in the dialysate at the inflow and outflow sites of the dialyzer. There was a significant (p less than 0.01) increase in the plasma zinc of the arterial blood from 74.7 +/- 8.1 to 80.2 +/- 6.5 micrograms/dl, but a nonsignificant decrease in the dialysate zinc from 10.6 +/- 2.5 to 9.5 +/- 5.9 micrograms/dl. Zinc diffused across the dialyzer from the dialysate to the blood in 12 cases and into the dialysate in three others.

Serum copper concentration changes in chronic hemodialyzed patients.

We studied the behavior of copper during hemodialysis and the relationship between serum copper levels and hematologic parameters such as red blood cell count (RBC), hematocrit (Hct), hemoglobin (Hb), and serum iron in 48 hemodialyzed patients. To study diffusion, we measured copper in the arterial blood and in the dialysate at the inflow and outflow sites of the dialyzer. To study hemoconcentration, the change in hematocrit values and total serum protein values were examined. To study liberation of copper from the dialyzer membrane, copper concentrations in normal saline were measured before and after the saline was used to wash dialyzers of various kinds. We found that changes in serum copper concentration were due mainly to hemoconcentration and liberation, but partly also to diffusion, and that the net result of changes was a significant increase in serum copper. We observed no correlation between serum copper levels and RBC, Hct, Hb, and serum iron levels.

Changes in copper and zinc in chronic haemodialysis patients.

We studied the behaviour of copper (Cu) and zinc (Zn) during haemodialysis (HD) in 65 chronic renal failure patients. Serum Cu, Zn and total protein were measured before and after dialysis. The dialyser membrane contained Cu and Zn. However, when the dialyser was washed with normal saline, Zn was removed, while Cu was liberated from the membrane during HD. We conclude that during HD serum Cu and Zn concentrations increased significantly (p less than 0.01), Cu from 98 to 120 micrograms/dl by haemoconcentration and liberation from the membrane, and Zn from 78 to 91 micrograms/dl by haemoconcentration.