A 29-year-old woman with SLE nephropathy who was under hemodialysis developed a bleeding tendency after cefazolin (CEZ) administration. Since the excretion of this drug is considerably lowered in patients on hemodialysis, the drug is considered to be closely related to hemorrhagic diathesis.
Several studies were made to elucidate the causal relationship of this drug to the hemorrhagic diathesis, and the following results were obtained:
1) No circulating anticoagulant was detected in the patient's plasma,
2) Among the blood-coagulating factors, only vitamin K dependent factors (II, IX and X factor) were decreased.
3) In patient's plasma, so-called protein-by-vitamin-K-absence (PIVKA) was detected, suggesting marked vitamin K deficiency.
4) Administration of vitamin K ameliorated the hemorrhagic diathesis in association with the disappearance of PIVKA from the circulation.
5) The plasma level of CEZ in this patient rose to 280μg/ml, an unexpectedly high level in individuals with nomal renal function.
These findings suggest a causal relationship between CEZ and the vitamin K deficiency which is directly related to the hemorrhagic tendency. It is concluded that altered intestinal flora induced by the accumulation of CEZ played an etiologic role in the vitamin K deficiency.

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Fairly large ectopic calcification in four chronic hemodialysis patients was reported. Control of serum inorganic phosphate was poor in every case and consequently the calcium-phophate product was over 50. Definite intake of phosphate binding agent was mandatory and a low-phosphate diet was tried with success. Cimetidine and calcitonin might prove effective in cases with ectopic calcification.
In two cases, calcified masses were surgically extirpated: Cloudy fluid and block-or powder-like material were contained in a fairly thick capsule, and chemical analyses revealed calcium phosphate.
Ectopic calcification is one of the results following disturbances of calcium-phosphate metabolism, which must be contolled on a daily basis.

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For patients on maintenance hemodialysis, sexual life is a matter of great importance. In Japan, however, little recognition has been accorded to this concern. We believe it is important to record penile tumescence objectively in the diagnosis of impotence.
We investigated the correlation between penile tumescence and pituitary-gonadal function. The patients, aged 25 to 64 years, were male uremic patients who received hemodialysis 3 times per week. These patients, 8 in number, underwent examination for sexual function and pituitary-gonadal function.
The method for testing penile tumescence employed an audiovisual sexual stimulation test. We recorded EEG, blood pressure, pulse, Galvanic skin reflex, respiration wave, and bulbocavernous EMG for the purpouse of recognizing the level of stimulation. As this method is quantitative in the recording of tumescence and the mount of stimulation, no hospital admission is required.
In 2 cases the penile change could be considered normal, 3 cases showed slight reaction, and in 3 cases there was no reaction. The degree of tumescence showed no definite correlation with age or period of dialysis. The penile changes showed no correlation with testosterone, LH, FSH, PRL, serotonin or Zn. It remained unclear whether there was any relationship between Zn insufficiency and sexual function.
For the present, it is still necessary to make an effort to clarify the causes of impotence.

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The purpose of the present study is to investigate electrophysiological properties in patients with chronic renal failure (CRF) and correlate them with changes in blood chemistry.
The study group consisted of 11 patients with CRF (mean age; 49 years, 5 were on hemodialysis). Sinus node recovery time (SNRT), AH and HV were 1, 099±58, 104±5, and 45±1msec (mean±SE), respectively. The AH interval was prolonged in four cases and on the average exceeded the normal range. SNRT and AH were longer in patients on hemodialysis than in non-hemodialysis patients, but the difference was not significant (1, 361±162 vs 881±21, 158±14 vs 129±6, respectively). No significant correlation was observed between electrophysiological measurements and serum creatinine, BUN and electrolytes.
In four of these 11 patients, new conduction disturbances were noted during hospitalization (AV block in two and sinus arrest in two). Predisposing factors seemed to be elevation of serum creatinine, potassium and calcium and vagotony.
In conclusion, in 40% of the patients with CRF, the AH interval was prolonged and new conduction disturbances frequently appeared. Therefore, close observation on electrocardiograms is required in patients with CRF.

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We sent out questionnaires on diabetic retinopathy and visual disturbance observed just prior to the time when the first dialysis was started in the five years from February 1979 to February 1984 to 534 institutions out of those performing artificial kidney treatment in all parts of Japan. We examined 1, 434 cases, 919 men and 515 women, from the 211 institutions that replied.
At the time when the first dialysis was started, the ages of the male patients ranged from 13 to 95, 55.6±10.8 on the average, and from 23 to 78 (54.6±12.1) for the women. The average age regardless of sex was 55.2±11.3, At the time when the first dialysis was started, the diabetic retinopathy cases consisted of nonproliferative retinopathy (44.2%), proliferative retinopathy (27.1%) and vitreous hemorrhage (28.7%). As for visual disturbance, it was slight to medium in degree in 49.3% of the cases, a one-side high-grade disturbance in 13.8% and bilateral high-grade disturbance in 36.9%. The younger the patient when diabetes mellitus was discovered or the longer the period of morbidity, the greater the number of cases of serious retinopathy, such as proliferative retinopathy and vitreous hemorrhage.
Significantly high percentages of hyperlipidemia and hypertension cases were observed in the proliferative retinopathy and vitreous hemorrhage groups when compared with the nonproliferative retinopathy group. The incidence of serious retinopathy was higher in the patients on insulin than in those who were not taking this drug. Although the patients were prescribed various types of insulin, the group using the long-acting type was the largest. However, differences in the conditions of the patients with retinopathy that might have been caused by various kinds of insulin were not noted.

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This study was planned to evaluate the role of secondary hyperparathyroidism in the mechanism of hypertriglyceridemia seen in chronic renal failure (CRF).
The incidence of hypertriglyceridemia was 48.2% in the patients with CRF, though that of hypercholesterolemia was low. In comparison with the decreasing tendency of cholesterol after the initiation of hemodialysis (HD), hypertriglyceridemia was maintained over the course of HD in 30 patients who did not have previous calcitonin or vitamin D administration. With the same assay in these patients, there was a positive correlation between alkaline phosphatase and serum triglyceride.
In two cases of hypertriglyceridemia out of 5 parathyroidectomized patients, it was shown that hypertriglyceridemia was improved after parathyroidectomy. In an experiment with partially nephrectomized (5/6) uremic rats, parathyroidectomy was effective in reducing the serum level of triglycerides (from 123±37mg/dl to 76±6mg/dl, p<0.05).
These results suggest that secondary hyperparathyroidism plays a role in the mechanism of hypertriglyceridemia seen in CRF.

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In addition to their important role in energy metabolism, the plasma free fatty acids (FFA) may produce pathological effects when present in abnormally high concentrations. A single hemodialysis with heparin (heparin dialysis) produces an unusual increase in plasma FFA because of the agent's action to promote lipolysis in the circulation. Therefore, we investigated the biological effects of the plasma FFA increased with heparin dialysis on the blood components.
The serum obtained from patients at the end of a single heparin dialysis (2, 000 units for priming and 1, 000 units per hour for continuous supplement) increased the membrane fragility of the erythrocytes from healthy subjects, and suppressed the incorporation of radioactive thymidine in phytohemagglutinin-stimulated lymphocytes in vitro. These effects correlated significantly with the concentrations of FFA in the serum. The serum with high FFA levels exhibited abnormal mobility on agarose-gel electrophoresis of the lipoproteins. The critical levels of FFA pathologically affecting the erythrocytes, lymphocytes and lipoproteins were approximately 1.0, 1.2 and 1.7mEq/l, respectively. Of ten patients, four attained the critical level at the fifteen minutes after the start and two at the end of the dialysis. These results confirmed the hazardous effects of increased FFA during heparin dialysis and charged us to consider a countermeasure.
The concentration of FFA correlated positively with the level of the plasma triglycerides (TG) at the end of a single heparin dialysis. The FFA did not reache the critical level when synthetic proteinase inhibitors (MD-850, FUT-175) were used as anticoagulants. The increase of FFA during the dialysis was partially suppressed when the heparin dose was reduced to no priming and 400 units per hour for continuous supplement. Thus, we found that each of the following conditions would contribute to lowering the FFA level during hemodialysis; controlling of plasma TG, using an anticoagulant such as MD-805 or FUT-175, with no promoting effect of lipolysis, and employing a low dose of heparin.

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There are two factors in shortening the period of hemodialysis therapy: (1) the solute removal rate, and (2) the number of times of therapy in a week. The former is accomplished not only with higi-periormance dialyzers, but by using hypertonic dialysate for removing excess fluid from the body water. And for the latter, it is advantageous to remove solutes by increasing the frequency of the therapy during the same total therapeutic time each week.
It was possible to shorten the therapeutic time by using high-performance dialyzers. However, predialysis urea-N and creatinine concentration levels (PDC) gradually increased. And the psuedo solute generation rate of uric acid and phosphate also increased, though the PDC of those solutes was not so obviously changed. Considering the declining tendency of hematocrit, it was a little too difficult to perform the short-time dialysis relying exclusively on high-performance dialyzers.
We have also been able to make sure that the therapeutic schedule was closely related with the capability of the solute removal. That is to say, in patient whose therapeutic schedule was changed from twice a week (7.5hr/Rx) to three times a week (5.0hr/Rx), it was observed that a decreasing tendency was seen in the solute concentration level. We thus concluded that frequent treatment is superior to the conventional schedule and this method is effective for shortening the therapeutic time.

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It is generally held that computed tomography (CT) is useful in diagnosing acquired renal cyst in long-term dialysis patients, as well as renal cancer, which very often follows as a complication. Few cases in which ultrasonography (US) works for that purpose have been reported. But we believe that US is highly useful in diagnosing renal cancer and renal cyst and have been using the technique as the first alternative to conventional X-ray examination.
We performed US on 94 long-term dialysis patients for the screening of renal cancer and renal cyst and compared the results with those from CT. Our findings are as follows.
With US, most kidneys (96.8%; with the exception of very contracted kidneys) were successfully pictured. Renal cysts were better diagnosed by US than by CT. With US and CT together, multiple cysts were diagnosed in 44.2% of all patients and solitary cyst was noted as a complication in 11.6%. The longer dialysis had been performed, the higher the cyst complication rate was: 41.4% when dialysis was performed for less than 2 years; 48.1% for 2-4 years; 66.6% for 4-6 years; 83.4% for 6 years and longer. With US, two cases of renal cancer were diagnosed, but one of them could not be diagnosed with CT. CT provided a better diagnosis of calcification, most of which could not be diagnosed by US. Three cases of intracystic hemorrhage diagnosed by US and US-guided puncture.
Besides renal lesions, US also provided successful diagnosis of 11 cases of cholelithiasis and 4 cases of liver cysts, hepatomegaly and splenomegaly, 2 cases of pleural effusion and 1 case of ascites, some cases of dilatation of the hepatic vein and inferior vena cava.
Considering the above results and the ease, noninvasiveness, economy of US, we believe that US should come first in diagnosing abdominal disease, including renal cyst and cancer in dialysis patients. We also believe that regular abdominal ultrasonography preformed on patients with chronic renal disease even before dialysis is started will be effective in gaining an overall understanding of chronic renal failure.

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Since it is suggested that low hepatic triglyceride lipase (H-TGL) activity may cause serum intermediate density lipoprotein (IDL) retention and could be regulated by low serum triiodethyronine (T₃) concentrations in uremia, thyroid hormone powder or T₃ was administered to 24 hemodialysis patients at a daily dose of 50mg per the powder or 25μg per T₃ for 2 months. Before and after the administration, following chemical analysis were performed, ie, serum levels of lipids and lipoproteins, postheparin lipolytic activity which consists of lipoprotein lipase (LPL) and H-TGL activity and polyacrylamide gel electrophoresis.
Serum total cholesterol and triglyceride levels significantly decreased while high density lipoprotein (HDL)-cholesterol levels remained unchanged. With respect to serum lipoprotein levels, very low density lipoprotein (VLDL) and IDL decreased significantly, while low density lipoprotein (LDL) with normalized chemical composition increased. These changes were confirmed by the partial improvement of uremic electrophoretic profiles which usually have mid-band at a frequency of 50%. Moreover, there was a selective elevation of H-TGL activity but not of LPL activity.
The results in the present study suggest that the supplement of thyriod hormone may have an effect on serum lipid and lipoprotein abnormalities, particularly IDL retention, in chronic hemodialysis patients.

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Of the 288 patients who began hemodialysis treatment between January 1966 and December 1973, 108 died and 64 were transferred to other facilities. One handred and eleven survivors for more than 10 years were reviewed.
The cumulative survival rate was 60.7% for five years, 53.9% for 10 years and 46.1% for more than 10 years.
The main causes of the death were cardiac failure (25%), cerebrovascular disease (15.7%), sepsis (12.0%), pericarditis (11.1%), hepatitis (9.3%) respectively.
Parathyroidectomy (PTX) was performed in 19 cases, representing 12% of the patients surviving more than 10 years. Approximately 15-20% of those patients might need PTX.
Carpal tunnel syndrome (CTS) was recognized in 37 out of 216 patients, and it showed an increasing rate of appearance during long-term dialysis. Eight patients with severe CTS dialyzed for more than 12 years underwent successful surgery. Trigger fingers were frequently associated with CTS. Amyloid deposition was revealed in all eight cases.

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