Conditioned media (CM) of PHA-stimulated lymphocytes from chronic uremic patients were tested for colony-stimulating activities, using methylcellulose hematopoietic progenitor cultures with normal bone marrow cells as a target population.
CMs from uremic patients undergoing hemodialysis were shown to lack potential to support the full growth of early erythroid progenitors (BFU-E) due to the presence of suppressive factors or poor production of burst promoting activity (BPA), or both. However, the stimulatory activity for CFU-GM was increased, particularly among patients on hemodialysis. Disappearance of anti-BPA activities preceded the normalization of hemoglobin levels after the termination of hemodialysis by kidney transplantation.
Based upon the results, disturbance of the regulation of erythropoiesis through leukocyte-derived factor (s) may play a part in the development of anemia in chronic uremic patients.

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A 65-year-old woman was admitted to our hospital with complaints of hemosputum and dyspnea. The clinical diagnoses were marked anemia, pulmonary hemorrhage, and renal disturbance. Infusion of methylpredonisolone was not effective and pulmonary hemorrhage induced rapidly progressive pulmonary failure. Abnormal lung shadows on chest X-P, her symptoms and hypoxemia were improved within 24 hours after plasma exchange was performed on the 3rd hospital day. The patient died on the 8th hospital day of sepsis and DIC. Postmortem histological findings revealed partially crescentic formation and widely hyalinized and collapsed change within the glomeruli, proximal and distal tubular degeneration, and massive intra-and extra-alveolar hemorrhages. Immunofluorescence studies revealed granular accumulations of IgG and C₃ within the glomeruli, but no significant finding within the lung. Her serum antiglomerular basement membrane antibody was negative.
We conclude that the final diagnosis was pulmonary hemorrhage of unknown cause complicated with renal failure probably due to acute exacerbation of chronic glomerulonephritis, and that the relationship between pulmonary hemorrhage and glomerulonephritis was obscure.

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Decreased production of erythropoietin is the major cause of anemia in chronic hemodialysis patients. It has been suggested, however, that many other factors influence this anemia. We administered recombinant erythropoietin (rEPO) to chronic hemodialysis patients, and studied its effects and the factors influencing those effects. Bone marrow findings were also examined. The subjects were 12 patients (6 males and 6 females). Anemia was remarkably improved by rEPO. However, the increase in hematocrit (Ht) value was favorable in some patients but not in others. In the former group, the ferritin level before administration was significantly higher than that of the latter group. The amount of blood transfusion during the six months prior to administration tended to be higher in the former group. There were no significant differences between the two groups in age, sex, duration of dialysis, dose of rEPO, Ht value, or other blood biochemical parameters before administration. Marrow tissues were aspirated by bone marrow puncture before and after medication from three patients. No significant changes were observed in M/E ratio, erythroblast classification, sideroblast ratio or state of iron granules in sideroblasts.
These results indicate that rEPO is effective for anemia in hemodialysis patients. However, no definite pattern was found in the improvement of Ht value. It is thought, therefore, that certain factors influence the effect of rEPO. Since the ferritin level was significantly higher in patients showing favorable improvement of anemia than in those without such improvement, it is assumed that rEPO has a more favorable effect on erythropoiesis in patients who have a greater capacity to store iron in bone marrow. It was difficult to evaluate the effect of rEPO from findings of bone marrow alone. We consider the combined examination of erythroid progenitor cells to be required for proper evaluation.

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To evalute the intestinal absorption of zinc, the oral zinc tolerance test orally administering zinc sulphate containing 50mg of elemental zinc was employed in 14 hemodialysis patients and 9 control subjects. The mean baseline plasma zinc level was significantly lower in the hemodialysis patients than in the control subjects (67.5±16.8 and 83.7±12.0μg/dl, respectively). In the zinc tolerance test, the plasma zinc level and increments in plasma zinc through the first to third hour after the ingestion were significantly lower in the hemodialysis patients than in the controls. The integrated area under the plasma zinc absorption curve was also significantly smaller in the hemodialysis patients than in the controls. There was no significant difference in plasma zinc levels between the patients treated with active vitamin D and the controls. The integrated area was significantly larger in the patients treated with active vitamin D than in those without active vitamin D. Our results suggest that the intestinal absorption of zinc in the hemodialysis patient is impaired and active vitamin D remedies the abnormality.

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The present study was undertaken to determine whether the oxalate deposits seen in renal tubules are a causative factor in the development of acquired renal cysts in chronic renal failure. Thirty 5/6 nephrectomized rats had free access to water containing 8mg/ml of vitamin C (oxalate precursor) and 20 5/6 nephrectomized rats were given tap water without vitamin C. Oxalate deposits were found on microscopy in the renal tubules of the vitamin C-treated rats in the 11th and 12th postnephrectomy months; however, acquired renal cysts were noted far in advance of the appearance of oxalate crystals. It has been suggested that the tubular dilatation seen in 5/6 nephrectomized rats is caused by an abrupt decrease in the functioning renal mass, leading to the production of a so-called “renotropic growth factor.” However, oxalate deposits and renal tubular dilatation in oxalate-treated 5/6 nephrectomized rats preceded the renal tubular dilatation of untreated partially nephrectomized rats. In addition, these histological changes in the kidney were also seen in healthy rats which were given oxalate orally and subcutaneously.
The present study suggested that the pathogenesis of acquired renal cysts is multifactorial. Renotropic factor may play an important role in nephron hyperplasia, but oxalate deposits in the renal tubules seem to be an important factor in the formation of these cysts.

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We report an autopsy case of diabetic renal failure that demonstrated the deposition of amyloid containing β₂-microglobulin (β₂-MG) in the islets of Langerhans.
The patient was a 68-year-old diabetic female who had received diet and insulin therapy for 10 years, and was hospitalized because of systemic edema and azotemia 4 months previously. She died of intestinal bleeding after 4 hemodialyses. Histopathological examination showed the deposition of amyloid in the islets of Langerhans. It was confirmed by immunohistochemical examination using the peroxidase-antiperoxidase (PAP) method that the amyloid deposits contained β₂-MG. There was no amyloid deposition in other organs.
There are several reports concerning the visceral involvement of dialysis amyloidosis, having been found after only four hemodialysis treatments. It was confirmed that the amyloid contained β₂-MG as a component of dialysis amyloidosis.

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During 4hr of isovolemic hemodialysis (HD), we employed a cellulose triacetate membrane (CTA membrane, 1.1m²), which is thought to remove β₂-microglobulin (β₂-MG) mainly by diffusion, to estimate the removal of β₂-MG by the diffusion alone, sieving coefficient (SC) of several marker proteins, kinetics of acute phase reactant (APR) and biocompatibility.
The removal rate of β₂-MG by diffusion alone was 39.7% (mean). The SC of several marker proteins were as follows: β₂-MG=0.607, myoglobin=0.476, α₁-antitrypsin=0.005, albumin=0.003.
The biological effect of the CTA membrane, as evaluated by the response of APR including CRP and by indicators of biocompatibility including PaO₂, WBC count and complement, was that APR was not increased during the course of observation but that a mild, transient decrease in WBC count was observed in the early phase of HD therapy.
To assess the most appropriate mode of therapy, we compared the summation effect of convection (3kg, 8kg) and diffusion alone with the removal rate of β₂-MG by diffusion alone.
The removal rate of 3kg convection plus diffusion was 57.5% (mean). There was no statistically significant difference between 3kg and 8kg convection.
Therefore, it may be concluded that the application of the CTA membrane (1.1m²) for regular HD therapy is more useful than that for hemodiafiltration, but further investigation, especially with a larger CTA membrane is required.

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Systemic lupus erythematosus (SLE) is a multi-systemic disease occurring predominantly in young women. The diagnosis of SLE is especially difficult in patients older than 50 years because the characteristic clinical manifestations are lacking. In aged SLE patients, arthritis, pleuropericarditis and muscle weakness are frequently observed, but severe renal lesions rarely exist. We report the case of a 65-year-old man who suffered from rapidly progressive glomerulonephritis which caused renal insufficiency. Renal biopsy specimen showed diffuse glomerulonephritis with active necrotizing lesions (Class IV-b WHO classification).
Circulating immune complexes were elevated, as detected by C1q solid phase ELISA, but the complement levels were normal and anti-DNA antibodies were not observed. He was administrated orally 20mg/day of predonisolone and 50mg/day of azathioprine, and treated by double filtration plasmapheresis (DFPP) once a week. These therapies were effective and he required no more hemodialysis. In this patient, the concentration of circulating immune complexes seemed to correlate with the renal damage. DFPP improved his renal function, probably by eliminating these immune complexes.

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In this study we evaluated 72 emergency operations and 164 elective operations performed on hemodialysis patients in our institutes from September 1966 to June 1989. Death rates within one month after surgery were 22% for ememgency cases and 0.6% for elective cases. The emergency cases had postoperative complications such as sepsis and respiratory failure.
We experienced 3 cases of diabetic nephropathy among the emergency operations. They all had complications both before and after surgery. Complications after surgery were mainly heart failure and infections. Therefore, we stress the importance of managing water balance and preventing cross infection in hospital.
Hemodialysis after surgery was successfully performed without prolongation of coagulation time and bleeding using low molecular heparin. Low molecular heparin and nafamostat mesilate were available for hemodialysis before and after surgery as anticoagulant drugs. An EVA membrane dialyzer was also useful for hemodialysis before and after surgery.

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The serum level of free light chain immunoglobulins was determined in 5 pre-HD chronic renal failure patients (CRF), 45 CRF patients receiving hemodialysis (HD) therapy and 45 healthy volunteers.
The results were as follows; 1. The serum concentration of free light chain (FLc) immunoglobulins was higher in CRF patients on maintenance HD therapy than in non dialyzed patients. 2. The main component of these free light chains was lambda type. 3. These facts indicate that the accumulation of FLc in the tissues is a causative factor for HD amyloidosis as represented by light chain deposit disease and carpal tunnel syndrome, suggesting the importance of removing FLc in the prophylaxis of these pathologic conditions. 4. As is obvious from the above, we think our present study will help elucidate the pathophysiology of other disease in which excess FLc plays an etiologic role.

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