Hemagglutination inhibition technique using anti-antibody (AA method) was used to measure the circulating immune complexes (GIG) in various primary renal diseases and lupus nephritis to evaluate its availability for clinical use; especially as an indicator to estimate activity of primary renal diseases. Type O, Rh (+) red blood cells sensitized with anti-D human antibody were used as indicator cells for hemagglutination inhibition technique. Serum containing anti-antibody used in this study was obtained from a 54 year old female with a mild mesangial proliferative glomerulonephritis after screening more than 1700 sera. Results obtained from this study were as follows. 1) AA method revealed a higher incidence of positive GIG compared to binding assay or solid phase assay using Clq or conglutinin. GIG levels measured by AA method reflected accurately clinical activity of primary renal diseases even if in minimal-change nephrotic syndrome or membrano -proliferative glomerulonephritis as well as lupus nephritis. 2) Rheumatoid factor added to GIG positive serum specimens agglutinated the sensitized red blood cells but did not interfere with the end-point of hemagglutination inhibition . However, when agglutination titer of rheumatoid factor was higher than aggultination inhibition titer of CIC, the AA method gave a negative result. 3) Anti-antibody added to GIG positive specimens lowered the end-point. 4) Thus, serum specimens should be checked routinely for anti globulin antibody when measuring GIG by AA method. 5) In conclusion, AA method is useful and reliable for estimation of activity in renal diseases.

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In the sera of three patients with partial lipodystropyh (PLD), CH₅₀ and C3 hemolytic activity were markedly reduced, while the other complement components activities, especially C5 activity, were within normal limits. These sera showed high C3 nephritic factor (NeF) activities. The purpose of this paper is to clarify the effect of NeF on the complemet system focusing the attention to the stabilizing effect of NeF on C3 convertase (C3bBb) activity. NeF was partially purified from three PLD sera and each was active as a stabilizer for the alternative pathway C3 convertase (C3bBb), but not active for the classical pathway C3 convertase (C42). Though NeF was equally active as a stabilizer of C3bBb on EA as properdin (P), P stabilized C3bBb was easily decayed by the action of 131H globulin (β₁H), while NeF stabilized C3bBb was resistant to β₁HH action. Moreover, C3- and C5-cleaving activities on ZX formed in the serum with NeF was stable, while those activities on ZX formed in the serum without NeF decayed rapidly. NeF could stabilize C3 convertase in the fluid phase phase as well as on solid phase. The reaction mixture of purified proteins, P, B, D, C3b-INA, β₁H, C3, C5 and NeF, caused remarkable reduction of C3 activity, but C5 activity was not redused presumably due to the inefficient formation of C5 convertase (C3bnBb) in the fluid phase. This may be the cause of reduced C3 and normal C5 activities in the PLD serum.

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Circulating immune complexes containing IgA (IgA-IC) were measured in sera from patients with various renal diseases using conglutinin solid phase assay (K-SP), which detects a fixed fragment of C₃ on IC. Patients included in this study were 4 cases of AGN, 55 cases of mesangial proliferative glomerulonepgritis (PGN) including 33 cases of IgA nephropathy, 11 cases of membranoprolif erative glomerulonephritis (MPGN), 13 cases of membranous nephropathy (MN), 15 cases of lupus nephritis (LN) and 2 'cases of purpura nephritis. Twenty healthy adults were also included as a control group. K-SP was followed the description of Casali et al and levels of IgA-IC were expressed by radioactivities. The results obtained from this study were as follows. 1) Raised levels of IgA-IC were found in about 30% of PGN and IgA nephropathy, and in more than 40 % of AGN, MPGN and LN. There was a significant correlation between levels of IgA-IC and IgG-IC in PGN, MN and LN. 2) However, circulating IgA-IC were not correlated to the glomerular IgA deposition or serum IgA levels. 3) Serial measurements of IgA-IC for two weeks to 12 months in 31 cases of various renal diseases showed that IgA-IC changed in parallel with disease activity in AGN and one case of LN, but not in PGN and MPGN. These results suggest that IgA-IC might be implicated in pathogenesis of IgA nephropathy and other glomerulonephritides and serial measurements of IgA-IC can be clinically useful to estimate disease activity in AGN and LN.

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The response of heart function to angiotensin II (AT) was studied in 22 patients on chronic hemo dialysis. The mean age was 33 years and they were dialyzed for 55 months in the average. The patients were divided into two groups according to the duration of hemodialysis; Group-I with the duration less than 3 years, and Group-II over 3 years. AT was infused from large vein to elevate the left ventricle systolic pressure by 40mmHg. Before and after the rise of blood pressure, M-mode echocardiography of and cartoid pulse with electro- and phonocardiography was recorded. The response to AT was then analyzed and compared with those from normal control subjects (N=7). Following a rise of blood pressure, a significant fall in heart rate was observed only in the control group; Group-III. Stroke index, cardiac index, or left ventricular dimension index obtained by echocardiography showed no significant difference in three groups. No significant change was found in these parameters after AT. A high output state (cardiac index over 3.9 L/min/m2) was odserved in 48 % of the patients. Ejection fraction was slightly but significantly depressed in Group-II in comparison with Group-III (p<0.05). After AT, ejection fraction reduced from 0.77 ±0.07 to 0.64 ±0.16 in Group-I(p<0. 01) and from 0.72±0.13 to 0.64±0.09 in Group-II (p<0.01). While in Group-III, it remained above 0.60 after AT. A similar change was suggested from the systolic time analysis. These results suggest that the heart function of the patients on chronic hemodialysis may be subclinically depressed and it becomes abnormal upon acute pressure loading even though it may be normal at rest.

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Hypoglycemic attacks were experienced in 3 non-diabetic dialysed patients (2 males and 1 female) who received with .A-blooking drugs for the past 7 years. Their age ranged from 39 to 51 years old (mean, 44, 3), and their underlying disease was chronic glomerulonephritise Their durations of dialysis ranged from 12 to 93 months (mean, 44). Hypoglycemic attacks in 3 patients were recognized in the periods between 1 and 24 months (mean, 14.3) after the medication of β-blookers (propranolol 30 mg/day and pindolol 15 mg/day) and appeared during an omission of foods intake, because of losing appetite. At that time, their blood glucose levels ranged from 13 to 50 mg/100 ml (mean, 26). Intravenous glucose tolerance test (iv-GTT) was normal. The plasma immunoreactive insulin, growth hormone, and cortisol at hypoglycemic attacks were not abnormal except one patients, but insulinoma was ruled out in all cases. From these results, following conclusions were obtained. In non-diabetic dialysed patients, they had an abnormal glucose-insulin metabolism, characterized by decreased glycogen storage, delayed glym cogenolysis and elongation of insulin half-life before the medication of β-blockers. When the patients showed hypoglycemic attacks during dialysis, they did scarcely eat foods before dialysis, but took .Ablockers. If these patients undergo the dialysis treatment, even though small amounts of glucose (20-30 gm) may accelerate these patients to develope pre-hypoglycemic states. In these situations, β-blockers may play some roles promoting the hypoglycemic tendency in these patients, via inhibition of the glyw cogenolytic action due to catecholamine. A caution must be taken for the hypoglycemic symptoms when the .A-blocking drugs are used in hypertensive patients with chronic dialysis.

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Plasma concentration of amino acids in fasting state of 10 normal individuals and 62 patients with renal disease, classified from A to F according to AHA criteria, has been measured by means of amino acid a utoanalyser. The results are shown as follows: 1) significant decrease in total EAA in class D, E, F, 2) increase in total NREAA in class C, D, E, F, 3) marked decrease in E/N ratio in class C, D, E, F, elevation in Phe/Tyr ratio in 'class D, E, F, decreased Val/Gly and Val/Ala ratios in class D, E, F, and 4) decreased Lys, Val and Tyr in class D, E, F, increased Gly in class C, D, E, F, and increased Pro in class D, E, F. There are high correlation coefficients between Ccreat and total EAA, total N-EAA, E/N ratio, Phe/Tyr ratio, Val/Gly ratio, Val/Ala ratio, plasma Val, 3-M. Hist and Tyr concentrations. By means of pattern similarity analysis, plasma AA concentration pattern in class D, E, F is sig nificantly altered as compared to that of class A0 In addition, there is also significant correlationship between plasma AA concentration pattern and Ccreat. Oral FAA supply increases total FAA and E/N ratio in patients of class D and E. Total FAA, E/N ratio, Val/Gly and Val Ala ratios tended to be improved after one month treatment with HD w There is no correlation between duration of HD and improvement in plasma AA pattern.

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Uremic ultrafiltrate obtained during hemodialysis using the extracorporeal ultrafiltration method was analyzed by an open tubular glass capillary column gas chromatography-mass spectrometry. Six previously undescribed polyphenols, catechol, resorcinol, hydroquinone, 2-methoxyresorcinol, 3-methoxycatechol and methoxyhydroquinone were identified in the ultrafiltrate. The concentrations of conjugated and unconjugated phenol, p-cresol, benzyl alcohol, catechol, hydroquinone, homocatechol and 2-methoxyresorcinol in uremic serum were determined using a mass fragmentographic method. The concentrations of all phenols in uremic serum were higher than those in normal serum. Particularly the concentrations of phenol and p-cresol were highly elevated in uremic serum. Conjugated phenols existed mainly as sulfate esters. Concentrations of unconjugated phenol, conjugated and unconjugated hydroquinone significantly correlated with those of urea and creatinine, but not with the hematocrit value. In uremic patients with the cerebral disorder, coma or lethargy, and the hemorrhagic tendency the concentrations of phenol and hydroquinone were highly elevated as compared with the patients without the symptoms.

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A case of renovascular hypertension was treated with percutaneous transluminal angioplasty. A 45-yearRold man was found to have hypertension 7 years prior to admission and since that time was given several antihypertensive drugs. He was referred to our hospital because adequate control of blood pressure was not achieved. At admission, blood pressure was 190/134 mmHg and optic fundi, Keith-Wagener IIa. Renal functions including creatinine clearance were normal. Isotopic renogram demonstrated a decreased uptake and a delayed excretion of 1311 labelled Hippuran from the right kidney. Renogram showed a delayed accumulation phase and a retentive terminal phase of the right kidney. Abdominal aortography showed a 90% stenosis at the midportion of the right renal artery. Plasma renin activity (PRA) of peripheral blood was as high as 9.8 ng/ml/hr in the supine position under 10 g of daily salt intake and PRA ratio (affected/unaffected renal vein) was 2.0. A diagnosis of renovascular hypertension was made and percutaneous transluminal angioplasty (P.T.A) was performed for the right renal artery stenosis. Repeat abdominal artography demonstrated patency of angioplasty site after P. T. A. Blood pressure was 148/110 mmHg at 30 min, after P. T. A., and gradually decreased to 126/96 mmHg at 24 days after P. T. A. Responses of blood pressure and PRA to angiotensin II analogue (1-sar, 8-ile, angiotension II; 600 ng/kg/min) infusion and a single oral administration of angiotensin converting enzyme inhibitor (SQ 14, 225; 25 mg) were compared before and 2 weeks after P.T.A. Mean blood pressure (MBP) was unchanged to angiotensin II analogue infusion before P. T. A., whereas pressure reponse (15% increment in MBP from the control level) was observed after P. T. A. Ten %reduction in MBP and reactive hyperreninemia (9.8&rarr105 ng/ml/hr) were observed at 1 hr after the single administration of SQ 14, 225 before P.T.A., whereas both changes were not observed after P. T. A. These findings suggest that activity of the renin-angiotensin system was ameliorated after P. T. A.

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We describe a 39-year-old woman who was admitted to our hospital because of bullous pemphigoidd associated with membranous glomerulonephritis. An immunofluorescent staining of the skin biopsy specimen showed linear deposition of IgG, C3 and fibrinogen along the basement membrane zone. Patient's serum contained anti-basement membrane zone antibody and showed positive staining up to 1:1024 inn dilution as revealed by indirect immunofluorescent technique. Six months later, she manifested nephrotic syndrome. Renal biopsy specimen showed membranous glomerulonephritis (Stage I, Churg J.) with fine granular deposition of IgG and C3 along glomerular capillary loops. Anti-complementary activity of the serum was negative and Clq binding activity was within normal limits. FITC-labeled patient's 1-globulin failed to stain normal and patient's renal spe cimens and acid-eluted patient's renal specimens, demonstrating that patient's serum did not containn anti-glomerular basement membrane antibody and skin basement membrane zone antigens did not deposit in the glomeruli. Membranous glomerulonephritis is considered as immune complex disease andd bullous pemphigoid also as autoimmune disease. Both diseases may be mediated by the same fundamental immunological mechanism. However, immunological relationship of both diseases could not be proved in our patient, although this association is very interesting to speculate the pathogenesis of the immunological disorders.

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Cerberovascular accidents in patients with chronic renal failure undergoing hemodialysis can have serious clinical consequences. We describe a 24-year-old male with tuberous sclerosis who had been on hemodialysis for 14 months and was admitted to our hospital because of suspected subdural hematoma. He underwent surgical removal of the hematoma. Post operative course was without sequelae by the use of peritoneal dialysis as well as hemodialysis with a reduced heparin dosage. Renal angiography revealed hypervascular tumors and polycystic kidney, He had multiple adenoma sebaceum in his face and periungual f ibromas were noticed on toenails. Ophthalmoscopic examination revealed a phacoma in both eyes, As no tumors nor vascular abnormalities were found around the hematoma at the time of surgery, the possibility of underlying tuberous sclerosis as being the etiologic factor of the subdural hematoma appeared remote. Hemorrhagic tendency associated either with renal insufficiency or anticoagulant used with hemodialysis or head trauma were considered as possibly contributing to the cerebral lesion.

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The etiology and pathogenesis of lipoid nephrosis (LN) is not fully understood but a disorder of cell-mediated immunity (CMI) is thought to be involved . CMI was studied in 76 patients with primary renal disease and 24 healthy controls by evaluating delayed hypersensitivity skin test responses to purified protein derivative (PPD) and candida, circulating lymphocytes, T lymphocytes, T cell with receptors for Ig M (T.E) or Ig G (T.A) and concanavalin A (Con A)-induced suppressor cell activity (SCA)r The LN patients in relapse had less mean induration of skin reactivity and smaller proportion reacting to both antigens as compared with control subjects . It was also found that the LN patients in relapse had a significant T lymphocytopenia as well as a significant decrease in absolute numbers of Tp and Tr cells, whereas the patients with chronic glomerulonephritis (CGN) did not differ signi ficantly from the control population. The LN patients had high levels of suppression index (SI) particul arly in the begining of acute exacerbation, In contrast, the mean suppresion values from LN patients with or without nephrotic syndrome were similar to those of the control subjects . Moreover, when individual patients were followed through their clinical illness, the LN patients had high levels of SI paticularly in the begining of actue exacerbations, then the SI levels decreased sharply in latter phase of relapse, and again increased to relatively normal levels with the onset of clinical remission. Thus, the majority of LN patients in relapse demonstrated an altered response in delayed hyperd sensitivity skin test reactions, surface receptor characteristics of lymphocytes and Con A -induced SCA. This alteration may document an abnormality, in LN, possibly of CMI, which may be relevant to its pathogenesis.

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In order to clarify a possible role of plasma aldosterone in maintaining potassium balance in uremic patients, five normal subjects and six normokalemic patients with advanced chronic renal failure (GFR6.0-12.0 ml/min) and secondary hyperaldosteronism were chosen and the balance studies as to potassium and sodium were examined. In uremic patients both fractional excretion rate of potassium (FERK) and sodium (FERNa) in the residual functioning kidney were exceedingly high in spite of slight reduction in daily urinary potassium excretion. By administration of spironolactone, FERK was lowered and FERNa was raised significantly, indicating that aldosterone has an important role both as kaliuretic effect and sodium retainig effect even in the deteriorated kidney of uremic patients. Daily fecal potassium excretion was apparently increased in uremic patients and this change was normalized by administration of spironolaction indicating that the increased plasma aldosterone concentration in uremic patients would also accelerate the fecal potassium excretion. In order to identificate the intestinal sites participating in potassium excretion, in vivo isolated intestine perfusion study was conducted in experimental adrenalectomized rat (Adx rat). In response to intravenous administration of aldosterone to Adx rat, there was a significant increase in potassium equilibrium concentration of stationary perfusate only in colon, but not in jejunum and ileum. These results suggest that colon would be main site precipitating the fecal potassium excretion in the state of renal failure with hyperaldosteronism. In conclusion, it is greatly suggested that in uremic patients with secondary hyperaldosteronism acts an important role in maintaining potassium homeostasis in uremic patients by potassium excretion not only in the residual functioning nephrons but also in colon.

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