To clarify the role of sodium and potassium in borderline hypertension, hemodynamic and endocrine studies were performed in 23 patients with borderline hypertension and 21 normotensives. Eleven of 23 patients with borderline hypertension, and nine of 21 normo-tensives received NaCI load (180 mEq/day) in combination with KC1 supplement (96 mEq /day) for 7 days after treatment with diuretics (Mefruside 25 mg/day for 7 days), whereas the other 1 of patients with borderline hypertension and 12 of normotensives had NaCI load without KCl supplement for 7 days after diuretics. The results were as follows. (1) The young borderline hypertensives had significantly higher cardiac output, heart rate and mean velocity of circumferential fiber shortening (hyperkinetic circulatory state) as compared to age-matched normotensives. Moreover, the former had higher plasma renin activity, plasma norepinephrine concentration and plasma epinephrine concentration than the latter, It is suggested that an increased adreno-sympathetic activity may contribute to the hyperkinetic circulatory state in young adults with borderline hypertension. (2) Whereas blood pressure remained unchanged with diuretics and salt loading in normotensives, blood pressure and cardiac output significantly decreased with diuretics in borderline hypertensives, and both parameters significantly increased by salt loading. It is suggested that the changes in blood pressure with diuretics and salt loading in border-line hypertensives are associated with those in cardiac output. (3) In the young borderline hypertensives, the elevation of blood pressure due to salt loading was inhibited by KCl supplement, possibly because of suppression of increased cardiac output. Although the mechanisms of the pressor action of sodium and the depressor action of potassium are still unknown, the evidences presented suggest that adreno-sympathetic nervous system may participate partially in the changes in blood pressure due to alterations of sodium and potassium balance in borderline hypertension.

View full abstract

GBM antigen prepared from four models of experimental GN [Masugi nephritis (rabbit anti-rat GBM antibody induced GN), passive Heymann nephritis, autologous immune complex nephritis, chronic serum sickness (BSA) nephritis] and normal rats were used in this study. The rats were immunized with the GBM antigen isolated from kidneys of various expe-rimental GN rats and complete Freund's adjuvant once a week for five times. All rats were sacrificed 35 to 60 days after first immunization. All of the experimental rats which were immunized with GBM antigen derived from Masugi nephritis demonstrated proliferative GN associated with crescent formation in 40% and tubulointerstitial nephritis in 30%. By immunofluorescence (IF), the kidney showed li-near deposits of rat IgG along the GBM in 100% and the tubular basement membrane (TBM) in 30%, whereas staining for rabbit IgG was consistently negative. By indirect IF, linear staining for rat IgG in the eluate from kidney of the same group was seen along GBM and TBM in the kidney of normal Wistar rats, mice, rabbits, but only along GBM in the kidney of human and guinea pigs. And the antibody was found to have no reactivity of BM of other organs such as liver, lung and spleen. In the experiments of passive transfer by means of the injection with the eluate obtai-ned from the kidney of the same group, continuous linear deposits of rat IgG were seen along GBM in recepient rats. The kidney sections of rats immunized with GBM from the other experimental GN rats ?and from normal rats demonstrated no abnormalities by light microscopy and IF. These results suggested that the immunization with GBM antigens derived from the kidney of Masugi nephritis elicited autoantibody against GBM and induced autoimmune anti-GBM antibody mediated GN. Moreover, we could demonstrate that the anti-GBM autoantibody seemed to have a nature of kidney specificity and a reactivity with both GBM and TBM in rats, mice and rabbits and only with GBM in human and guinea pigs.

View full abstract

To clarify the connection between the humoral immunity and cellular immunity, we measured serum immune complex by Clq binding test solid phase assay and lymphocyte subpopulations by rosette formations (in 53 patients of chronic glomerulonephritis)a Biopsy renal tissues from these patients were also examined by light immunofluorescent and elect ron-microscopy. The cases with elevated serum immune complex levels showed low percentage of T cells and Tγ cells and high percentage of Tμ cells. The cases with negative serum immune complex showed no significant changes in T cell sub-populations and T cell subsets, as in controls. No correlation between T cell alterations and the degree of renal histology were observed. From these we assumed that in chronic glomerulonephritis, supression of Tγ cells might lead to immune complex formation which might maintain the activity of the nephritis.

View full abstract

In order to clarify the role of cell mediated immunity in primary renal diseases, we investigated concanavalin A induced suppressor T cell (Con A-Ts) function and autologous mixed lymphocyte reaction (AMLR). We modified the Shou's method to study Con A-Ts function and evaluated AMLR in the following three pairs, T and non T cells, Ty and non T cells, and non Ty and non T cells. The patients studied included 23 cases of IgA nephropathy (IgA-GN), 19 of minimal change lesions (MCL), 20 of membranous glomerulonephritis (MGN) based on renal biopsy findings and 20 of healthy volunteers as control group. Con A-Ts function in patients with IgA-GN was significantly decreased as compared to that in the control group. However, Con A-Ts function tended to be higher at nehr-otic stage than at non-nephrotic stage in MCL, and showed no remarkable change in MGN. AMLR between Tγ and non T cells in patients with IgA-GN was significantly lower than that of control group. Moreover the responding Tγ cells from MCL was again increased at nephrotic stage. On the contrary, there was no significant change in AMLR between Tγ and non T cells among patients with MGN. There was a correlation between Con ATs function and AMLR of Ti cells in IgA-GN. These observations suggest that MGN is less related to cell mediated immunity than IgA-GN and MCL, and changes of Con ATs function and AMLR in IgA-GN result from Tγ cells dysfunction.

View full abstract

Serum and urinary β₂-microglobulin (BMG) were measured by radioimmunoassay in 53 patients with primary glomerulonephritis. And at the same time various renal function tests were also done. Studied patients were 11 cases of membranoprolif erative glomerulonephritis, 21 cases of IgA glomerulonephritis, 10 cases of non IgA mesangial proliferative glomerulonephritis, 3 cases of membranous glomerulonephritis and 8 cases of minimal change glomerulonephritis. All cases were diagnosed by open renal biopsy.The results were as follows.1) There was a significant correlation between serum BMG and Ccr on double-logar-ithmic graph (r=-0.62).2) Serum BMG was a sensitive marker for the detection of slight reduction of GFR compared with serum creatinine.3) Urine BMG was not reliable marker for diagnosis of focal tubulointerstitial changes in primary glomerulonephritis.4) Serum and urinary BMG were not correlated to the glomerular histopathological specificity, and serum BMG was most significantly related with serum creatinine levels.

View full abstract

We have reported that the HbAi level is high in patients with renal failure and sugg-ested that some substance which is produced in renal failure bound to Hb resulting in the formation of HbAi. Then, we investigated on the mechanism of HbAI formation and its clinical application of HbAI in the treatment of renal failure. On the experimental studies, it was suggested that HbAI formed in renal failure may be related with urea, i. e. cyanate undergoes carbamylation with Hb to be increased HbAi levels. On the clinical analyses, we studied the correlation between HbAi and BUN levels over a period of several weeks prior to blood collection in non-hemodialysis patients. In uremic state, HbAi was best correlation with BUN of 1 to 2 weeks before. Thus, it is indicated that HbAi might be used as an indicator of BUN control of 1 to 2 weeks before in renal failure.

View full abstract

Comparative studies between the variations in blood and urine loading with intravenous arginine and renal function were made with special reference to their levels of statistical significance. The obtained results suggested the availability of such variations in β₂m levels due to arginine loading for early detection of mild tubular disturbances. No remarkable difference was observed among blood β₂m levels with variation of arginine loading. In the normal and mildly reduced renal function groups, a statistically significant arginine -dose- dependent increase in urinary excretion of β₂m was observed. Then, in the experiment made to find a method for the detection of mild tubular f unctional disturbance, variations in blood and urine β₂m levels in the patients with various renal diseases, loaded with intravenous arginine, were examined. The results obtained were comp ared with those of clinical renal function tests. Ratios of β₂m excretion in urine and clearances (Cβ₂m) before and after arginine loading (post-loadin values/pre-loading values) were determined, with relation to each group of disease. The result obtained revealed the tendency for reduction in renal tubular function together with decrease in the ratio, and this was remarkable especially in the groups of patients with ATN, RTA, etce when the examination was confined to those 58 cases with Ccr of 80l/day or more, there were slight differences in blood, urine β₂m and Cβ₂m levels before loading between a part of the groups and the normal control group, while a significant difference in the ratio was observed between almost all the groups and the normal control group, and this was obvious particularly in the CGN group (type II) with interstitial changes and in the ATN group. A good correlation of urine β₂m (or Cβ₂m) with the results of several renal function tests such as 15' value of PSP test and Fishberg concentration test which reflect renal tubular or interstitial disturbances. This fact also suggested the availability of this experiment for the diagnosis of tubular disturbance.

View full abstract

To ascertain whether renal prostaglangin (PG) E synthesis is decreased in patients with essential hypertension (EH), urinary PGE excretion (UPGEV) was measured in 47 normal females and 62 female patients with ER And UPGEV was also measured in female patients with various hypertensive diseases [renovascular hypertension(RVH), primary aldosteronism (PA) and idiopathic hyperaldosteronism (IHA) ]. Only females were selected in order to avoid contaminations of urine by seminal fluids. UPGEV in patients with EH (226.9±13.7 ng/day, p<0.001) was lower than that in normal females (317.3±22.1 ng/day). From 15 to 39 years, UPGEV in EH was significantly lower than that in normal females. After 40 years, there was no significant difference in UPGEV between patients with EH and normals There were no significant differences in UPGEV among patients with low renin EH, normal renin EH, RVH, PA and IHA. UPGEV in female patients with EH was not correlated to the level of creatinine clearance and Keith-Wagener fundoscopic grades. Urinary sodium and potassium excretions were significantly related to UPGEV in normal females, but not in patients with EH. We reconfirmed a decrement in renal PGE synthesis in patients with EH as compared normal subjects. These results also suggest that renal PGE synthesis is not influenced by the renin-angiotensin system in these hypertensive diseases.

View full abstract

In uremics, middle moleculer substance (M. M.) which are supposed to cause various metabolic abnormalities has been reported. In this study, the effect of M. M. which was isolated from ultraf filtrate obtained during hemodialysis on carbohydrate and lipid metabolism were investigated in vitro and in vivo. M. M. markedly supperssed the insulin effect on glucose utilization of rat diaphragm in vitro. Effect of M. M. on LPL activity was not shown in vitro, but slight supperssive effect was shown in vivo by using rat plasma at 30 minutes after dextran sulfate adminis tration. This suppressed LPL activity by M. M. was not improved by insulin administration. FFA release from adipose tissue by epinephrin increased in the medium without M. MM but was significantly suppressed in the medium after incubation with M. M. in vitro. FurU hermore we determined CAMP formation in situ. CAMP in adipose tissue was significantly lowered with addition of M. M. compared to non M. M. added control. From this evidence, we can speculate that M. M. has some suppressive effect to the hormone sensitive lipase in adipose tissue. From our results, it was considered that suppressive activity of M. M. were responsible for the disturbance of lipid and carbohydrate metabolism in chronic renal failure.

View full abstract

The association of glomerulonephritis with infection of a ventriculoatrial (V-A) shunt was first described by Black, Challacombe, and Ockenden (1965). Since then 27 cases have been described in detail, and another eight have been reported at clinical meeting. We report here two further cases of "Shunt nephritis". Case 1, born in he had a V-A shunt at the age of 9 months, Since he had intermittent fever, persistent gross hematuria, and proteinuria (0.6 gr/day). Creatinine clearance was low (18.6 ml/min), and serum CH50 level was lower than 12 U/ml. Culture of cerebrospinal fluid grew anaerobic gram (+) bacillus. There was not hepato-splenomegaly nor edema. In he had generalized edema and minimal azotemia (BUN level, 44 mg/dl, creatinine level, 1.8 mg/dl). Open biopsy showed membranoproliferative glomerulonephritis. Immunofluorescent microscopy showed presence of immunoglobulin G and Clq on the glomeruli in a nodular pattern. Electron microscopy revealed accummulation of electon-dense at subendotherial space and intramembrane Case 2, horn in she received a V-A shunt at the age of 4 months. Gross hematuria and generalized edema appeared in and continued. Urine protein was negative. She had intermittent fever. Serum complement level was low (C3 level. 32 mg/dl, C4 level, 4 mg/dl, and CH50 level, lower than 12 U/ml). BUN and creatinine level was normal. Culture of cerebrospinal fluid grew gram (+) micrococcus. After her shunt was re-placed, serum CH50 and C3 level was elevated to normal range. Percutaneous renal biopsy revealed focal prolif erative glomerlonephritis. She died suddenly from heart failure. Shunt nephritis is rare, but this nephritis may progress and irreversible renal failure may occur, and mortality is high (41%). Then, we should make efforts to discover "shunt nephritis" in patients with V-A shunt as soon as possible.

View full abstract

We report a 26-year-old male with IgA nephritis accompanied by malignant hypertension.Five months before admission, he was first found to have proteinuria and hypertension of 160/110 mmHg. A month prior to entry, he developed headache and blurred vision for which papilledema and severe hypertension of 260/150 mmHg were observed. On admission pertinent data included proteinuria of around 1 g/day with scanty sediments, BUN 36 mg/dl creatinine 3.3 mg/dl and creatinine clearance 17 ml/min. Plasma renin activity was 0.95ng/ ml/hr. The cause of hypertension other than renal parechymal disease was denied. The renal biopsy revealed the picture of advanced chronic glomerulonephritis along with severe arteriolosclerosis and f ibrinoid necrosis. The remaining glomeruli by immunof luorescence showed a dominant deposition of IgA and C3 in the mesangium in a granular fashion, being consistent with IgA nephritis. IgA and C₃ were also present along a few arterioles. The high blood pressure was promptly normalized by regimens including β-blocker, a-methyldopa and hydralazine, without further decrease in renal function. In the literature, the incidence of malignant hypertension in IgA nephritis seems to be very low, since only 4 cases from Australia and one from Japan have so far been described.

View full abstract