The immunoregulatory effect of 1αOHD₃, a precursor form of active vitamin D₃ (1, 25 (OH)₂D₃), was examined in hemodialyzed patients. Four weeks of oral administration of 0.5μg/day of 1αOHD₃ markedly enhanced the lymphoproliferative responses to mitogens, without influencing lymphocyte counts or the ratios of lymphocyte subpopulations. In fact, these responses were nearly normal after 1αOHD₃ treatment. Furthermore, immunoglobulin (IgG, IgM) levels were significantly increased after the same treatment. These results suggest that deficiency of 1, 25 (OH)₂D₃ may play a role in the impairment of immunity in hemodialyzed patients, and that administration of 1αOHD₃ may have therapeutic immunologic benefits.

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Therapeutic blood purification can now be recommended for outpatients with end-stage renal disease (ESRD). Biochemical examination values, mental effects and degree of social rehabilitation were compared in two groups of patients with ESRD. 13 outpatients (8 males and 5 females, mean age 45±12.1 years-Out-G) underwent therapeutic blood purification in our hospital during the 5 years from 1980 to 1984. In 13 inpatients (8 males and 5 females, mean age 43±10.3 years-In-G), age, sex and other factors were simila to Out-G. Measurement of blood pressure and body weight and biochemical examination were performed before and 4 and 12 weeks after initiation of the therapy. No significant differences were observed between the two groups. Mental effects and degree of social rehabilitation were examined via questionnaire. Of mental effects, pain at puncture of blood access and anxiety concerning extracorporeal circulation were the most frequent complaints among the In-G. This seemed to come from erroneous information concerning the therapy provided by other inpatients. Anxieties over the possible need of dialysis therapy for the rest of their lives, dietary restrictions and length of survival were noted in a high 75% of each group. Of the Out-G, 64% were completely rehabilitated, while only 26% of the In-G was. As for duration until social rehabilitation, the Out-G returned to their jobs within shorter terms, and continued their work. It is concluded that initiation of therapeutic blood purification in outpatients with ESRD is more advantageous for social rehabilitation.

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Three hundred five long-term hemodialysis patients surviving more than 10 years were clinically analyzed, and general aspects of their complications were determined. Moderate and severe anemia and renal osteodystrophy (ROD) were most frequently noted.
About 73% of these 305 patients began hemodialysis at the age of 40 or less, and about 84% of the underlying diseases were chronic glomerulonephritis.
Hematocrit (Hct) was 27.5±6.2% (mean±S. D., n=305) and 33 cases (10.8%) had a Hct of less than 20%. Anemia in these cases was generally persistent and did not respond well to various routine supplemental therapies. Among 61 of our own cases, four have continued to show a Hct of less than 20%. The renal size of the four cases calculated from renal CT scans was far below that of average in dialysis patients surviving more than 10 years; multicystic transformation of the diseased kidneys was also less demonstrable and plasma erythropoietin level was relatively low.
It is likely that these were determinant factors in the severe anemia of these cases.
ROD was mainly evaluated from the fluctuation of c-PTH in peripheral blood (65-84h PTH, INC; 46-84h PTH, Eiken).
When the duration of dialysis was divided into four groups- (1) less than 1 year, (2) 1-5 years, (3) 5-10 years, (4) over 10 years- c-PTH level in peripheral blood increased gradually, and the difference was statistically significant.
Serum c-PTH of seven out of 61 cases (11.5%) in our series was more than 10ng/ml, and if six parathyroidectomized cases are excluded, c-PTH in seven out of 55 cases (12.7%) was more than 10ng/ml.
Though subjective manifestations of these seven cases with high circulating c-PTH levels were variable, almost all showed enlarged parathyroid glands in imaging diagnostic aids such as CT, echo and scintigrams (Tc and Tl).
Consequently, they were considered to be candidates for surgical treatment of secondary hyperparathyroidism (2° HPT). It is tentatively proposed that 2° HPT might be diagnosed chiefly from the PTH level when c-PTH is over 10ng/ml, N-PTH over 150pg/ml, and intact PTH over 300pg/ml.
c-PTH showed a highly positive correlation with N-PTH (1-34h PTH, Nichols) and intact PTH (1-84h PTH, INC), but dissociation between the three PTHs was sometimes observed. This remains as a future problem.

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Several immunological parameters, including T-lymphocyte subsets, were studied in 144 patients on maintenance hemodialysis due to chronic glomerulonephritis.
All patients were divided into three groups according to duration of dialysis: stage I, 2-4 months; stage II, 12-36 months; and stage III, more than 48 months. Serum levels of three classes of immunoglobulins, IgG, IgA and IgM, were well maintained within the normal range in a majority of patients at the early phase of hemodialysis, i.e., in stage I. However, with increased duration of hemodialysis, they were gradually lowered in about half of the cases in later phase, i.e. stages II and III. B-lymphocyte count was well maintained in a majority of patients in stage I (358±87/mm³), but showed some increase in stages II and III (552±199/mm³, 611±291/mm³, respectively). In contrast, T-lymphocyte count was markedly reduced in all patients in stage I (855±220/mm³), but progressively recovered in stages II and III (1, 319±440/mm³, 1, 427±323/mm³, respectively). Analysis of T-lymphocyte subsets (helper/suppressor) by Leu-3a positive/Leu-2a positive cells showed a somewhat reduced value in stage I (1.22±0.27) and a significantly recovered value in stages II (1.32±0.34) and III (1.53±0.60).
It is interesting that the variations found in the serum level of immunoglobulins and peripheral lymphocytes were quite different.

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The immune response is known to decrease in chronic renal failure patients. In this study, we estimated the productivity of interleukin-1 (IL-1), which is produced from the accessory cells of the immune system, and studied the dynamics of the immune system in long-term dialysis patients. Since a Limulus-positive substance has been eluted from the cuprophan membrane dialyzer, the effects of various dialyzers and blood purification methods on IL-1 productivity were compared, including hemodialysis using the polymethylmetacrylate (PMMA) membrane dialyzer and continuous ambulatory peritoneal dialysis (CAPD). Forty-one long-term hemodialysis patients, 5 CAPD patients and 43 healthy subjects were selected for the study. The monocyte cell suspension was prepared from the peripheral blood of these patients. Lipopolysaccharide (LPS) was added, and this was cultured for 48 hours. The culture supernatant was separated and added to thymocytes prepared from C3H/HeJ mice. This was then cultured for 72 hours, and 24 hours before cell harvest, [³H]-thymidine was added. IL-1 productivity of the monocytes was estimated by the incorporation of [³H]-thymidine into the acidinsoluble fraction. As a result, IL-1 productivity was significantly high in the longterm hemodialysis patients on the cuprophan membrane dialyzer When the dialyzer wash solution from the cuprophan membrane dialyzer, which was Limulus-positive, was addec to the monocytes, IL-1 productivity increased. However, when the wash solution from the PMMA membrane dialyzer was added, it did not increase. When inactivated serum from healthy subjects and serum from long-term hemodialysis patients were added to the peripheral blood monocytes from healthy subjects, IL-1 productivity of the former was significantly higher than that of the latter.
The IL-1 productivity of the monocytes has been suggested to decrease in chronic renal failure patients, but we found that it increases in long-term hemodialysis patients on the cuprophan membrane dialyzer. This may be due to the Limulus-positive substance eluted from the cuprophan membrane dialyzer.

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A long-term hemodialysis patient with a giant intracranial vascular channel, which has been called giant serpentine aneurysm, is presented. A 50-year-old man was admitted because of headache, nausea and double vision, in January 1986. The patient had an eight-year history of hemodialysis. The diagnosis of chronic glomerulonephritis and hypertension was made in 1978. Six months before admission, he felt headache and nausea during hemodialysis, and computed tomographic scans revealed an abnormal intracranial shadow. One month before admission, he felt increasing headache and nausea and complained of double vision. On admission, blood pressure was 166/106mmHg and a Grade 2 systolic functional murmur was heard along the lower left sternal border. He had an arteriovenous fistula on his left forearm for hemodialysis. Laboratory findings were as follows: RBC 224×10⁴, Hct 21.6%, BUN 79mg/dl, creatinine 17.9mg/dl. Left vertebral arteriography showed that the distal portion of the left vertebral artery was dilated to 17mm in diameter. The basilar artery showed a large tortuous vascular channel and globular aneurysms over 25mm in diameter.
Giant serpentine aneurysm is a rare disease, and to our knowledge, only fourteen cases have been reported. It has not been previously reported as a complication in hemodialysis patients. In general, the etiology of giant serpentine aneurysm is not known. In our case, continued hypertension, hyperlipidemia, hypercalcemia, atherosclerosis and abnormal vascular flow induced from hemodialysis might be suspected of playing a part in its formation.

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The clinical picture of 72 diabetic patients on dialysis treatment (46 cases of HD and 26 of CAPD) was studied.
Uremic symptoms were the major manifestation in the period just after the initiation of dialysis. However, these symptoms were relieved within several weeks to a level similar to non-diabetic patients, by dialysis and water, sodium and potasisum restriction.
The survival and clinical picture of diabetic patients on maintenance dialysis were strongly influenced by the severity of micro-and macro-angiopathy, neuropathy and malnutrition. Mild cases of retinopathy, peripheral neuropathy, muscle weakness and wasting, orthostatic dysregulation and foot gangrene were rehabilitated to the same level of non-diabetic patients. On the other hand, in severe cases of angiopathy, neuropathy and malnutrition, daily activity and survival rate were significantly low.

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Mepitiostane was administered to 33 hemodialysis patients with intractable anemia. Patients were divided into two groups, the effective group (EF, n=21) and the non-effective group (non-EF, n=12), according to the level of hemotocrit (Ht) after 4 months' treatment. When posttreatment hematocrit increased beyond 4 S. D. of the value calculated from 24 measurements during the 6-month pretreatment period, the case was evaluated to be effective.
(1) The EF group showed a significant rise in Ht at one month, followed by a further increase by 4.6% at the end of the study. Other parameters such as RBC, Hb and reticulocytes also increased significantly in this group. Increase of serum creatinine and decrease of BUN were more prominent in the EF than in the non-EF group, probably due to an anabolic effect of mepitiostane. (2) The EF group showed a significant decrease in serum iron level, indicating iron consumption induced by an erythropoietic effect of mepitiostane. (3) Increased PTH in the non-EF group was thought to suppress the effect of mepitiostane.

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