The changes of urinary sodium excretion by furosemide was studied in 6 normal subjects, 10 patients with low renin essential hypertension, 6 normal responders and 6 hyperresponders. All patients were hospitalized and allowed to take ordinary diet containing 250-350 mEq of sodium per day. Every antihypertensive drug had been discontinued at least 2 weeks before the study. Sampling of control urine and plasma was done in recumbent posture for one hour in the morning. To evaluate changes of urinary sodium excretion, an iv injection of furosemide (60 mg) and taking 2 hours' upright posture were loaded. Thereafter, urine and plasma were obtained. Plasma renin activity was measured by radioimmunoassay of angiotensin I. Urinary sodium excretion rates during control period were 16.3±0.9 mEq/hr in 6 normal subjects and 16.9±1.6 in 22 essential hypertension. No significant difference between both groups was found. In normal persons, however, greatly increased output of urinary sodium by furosemide was observed compared with those in essential hypertension. The values were 158.2±8.9 mEq/2 hrs in the former and 112.4±8.7 mEq/ 2 hrs in the latter. An obvious correlationship between urinary sodium excretion of control period (UNaVI) and after furosemide injection (U_NaV₂) were found in normal subjects (U_NaV₂=9.6 U_NaV₁+1.9), in low renin group (U_NaV₂ =1.46 U_NaV₁+ 93.4) and in normal renin group (U_NaV₂ =11.78 U_NaV₁-117.7). In hyperresponder, however, there was no relationship between them. From these results, it seems that this difference is attributed not only to difference of tubular sodium reabsorption but also to the changes of glomerular filtration rates by furosemide injection or other factors.

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The rational use of steroids for the treatment of idiopathic nephrotic syndrome depends on a method of selecting those who will respond and those who will not. At the present time, the renal biopsy and the selectivity index of urinary proteins are most widely used methods of predicting the response to steroid treatment. The selectivity index θ and the transR-IgG (Joachim & Cameron) have been valuable in clinical use but may not always correctly reflect the GBM sieving effect on plasma protein and thus may not correctly predict the response to steroids. We undertook to clarify this point and to develop an accurate method of selecting patients for steroid therapy. The method included a precise analysis of urinary protein using molecular subdivision by Amikon-Filter and single radial immunodiffusion. We applied this technique to 25 nephrotic patients with the following results. 1. Fragments of IgG molecules (M-IgG : M. W. 5-10×10⁴, S-IgG: M. W.1- 5×10⁴) were present in the urine in addition to normal IgG (L-IgG). These fragments were immunologically identical with the intact IgG molecule and therefor, could falsely portray the permeability of the GBM. 2. The data strongly suggest that the fragment S-IgG found in the nephrotic urine is IgG-Fc fragment present in increased amounts in such urine. 3. The ratio of L-IgG to S-IgG shows a positive correlation with θ and transR-IgG and can be used as a new and better selectivity index of GBM permeability. This, in turn, may provide a more accurate means of predicting the response to steroid therapy. For example, in our analysed cases, the transR-IgG and θ were incorrect in 32.0% and 20.0% respectively, whereas our new method was incorrect in only 12.0%.

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The studies of cell-mediated immunity have been undertaken in vitro by the migration inhibition test (MIT) to KPS (Glycoprotein substance purified from human placenta) and WHP (Trypsinized soluble human placenta) antigens in 39 patients with various forms of toxemia of pregnancy, 10 patients with normal pregnant women and 10 unmarriaged control females. We also have studied the renal biopsied specimens from 8 pre-eclamptic patients by immunofluorescent method.Our results are as follows: 1) Using KPS preparations at 200 μg/ml tissue culture fluid, 43.2% of patients with various forms of toxemia of pregnancy showed inhibition of migration. Among them, positive results to KPS antigen were more frequent in patients with recurrent toxemia of pregnancy and in patients with developed proteinuria with or without hypertension after delivery. 2) Using WHP preparations at 200μg/ml tissue culture fluid, 36.8% of patients with various forms of toxemia of pregnancy showed inhibition of migration. Positive results to WHP antigen were more frequently seen in patients who developed proteinuria with or without hypertension after delivery and pre-eclamptic patients. 3) Normal pregnant women were all negative to both KPS and WHP antigens. 4) The pregnant patients who had chronic nephritis or essential hypertension were almost negative to both antigens. 5) There was seen some relationship between results of MIT and the newborn weight in toxemia of pregnancy 6) The immunofluorescent study showed that glomeruli from the preeclamptic patients were fixed with fluoresceinlabelled immunoglobulines (IgG, IgA, IgM), β₁C, fibrinogen in many instances. The staining pattern was almost granular but sometimes linear. Half of the cases, complement (β₁C) was found in renal arterioles. It is therefore suggested that cell-mediated immunity and humoral immunity may play some part in the pathogenesis or the development in human toxemia of pregnancy.

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A modified macrophage migration test (MIT) using calf thymus n-DNA (n-DNA), collagenase Soluble Human Glomerular Basement Membrane (coll. SH. GBM) for antigen, were carried out on 51 patients with systemic lupus erythematosus (SLE) and 14 control subjects. In the same time, two antibody titers, n-DNA antibody and coll. SH. GBM antibocy, were measured using a passive hemaggultination test in SLE and control subjects. The results were obtained as follows, i The positive rate of MIT, using n-DNA at 100 mg/ml in tissue culture fluid was approximately 51% of patients with SLE, and 18% of SLE was positive rate that using coll. SH. GBM at 100 mg/ml. At that time, significant influence was seen using n-DNA, but no significant showed using coll. SH. GBM. ii 79.5% of SLE have had a n-DNA antibody, a coll. SH. GBM antibody was seen at 41.1% of SLE. MIT and antibody titers a tendency that to be positive in the active phase. iii MIT to both antigens was seen significant migration inhibition between nephrotic group and nonnephrotic group in SLE. iv A significant migration inhibition showed as compared with normal group and decreased group of renal function using coll. SH. GBM for antigen, but coll. SH. GBM antibody was seen in group of SLE with nephritis, but was not seen iu group of SLE with non-nephritis. v In histology of renal biopsy, gromerulitis type showed significant migration inhibition as comparied with actve glomerulonephritis and membranous glomerulonephritis using n-DNA for antigen, no significant influence using coll. SH. GBM. vi A average % Mig. to both antigens was droped with granular pattern +, linear pattern, granular pattern ++ and +++.

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