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Eighteen patients with chronic renal failure due to primary glomerular disease undergoing conservative treatment (CRF patients) were studied to evaluate whether coagulation and fibrinolytic activity in plasma are enhanced in the patients. We measured plasma levels of coagulation-fibrinolysis parameters including thrombin-antithrombin III complex (TAT) (an index of thrombin formation), alpha 2-plasmin inhibitor (alpha 2 PI)-plasmin complex (alpha 2 PIC) (an indicator of plasmin production) and cross-linked fibrin degradation products (XL-FDP) (an index of fibrinolysis secondary to coagulation). There was no correlation between plasma levels of TAT, alpha 2PIC and XL-FDP and serum creatinine levels in CRF patients. Both fibrinogen and TAT were found to be significantly higher in CRF patients than in normal controls. TAT was negatively correlated with serum albumin or total protein. Antithrombin III (ATIII) activity was significantly lower in CRF patients than in normal controls. CRF patients showed significantly but slightly higher alpha 2 PIC and XL-FDP when compared to normal controls. These results suggest that TAT, alpha 2PIC and XL-FDP are good indicators of coagulation-fibrinolysis even in patients with decreased renal function. Coagulation activity is significantly increased in CRF patients but fibrinolysis secondary to coagulation is only slightly enhanced.

Thirty-three patients with chronic uremia on regular hemodialysis treatment (RDT) have been studied to determine whether coagulation and fibrinolysis are enhanced or not. We examined predialysis values of coagulation and fibrinolysis parameters including alpha-2-plasmin inhibitor-plasmin complex (alpha 2PIC), a good index of in vivo plasmin production, and cross-linked fibrin degradation products (XL-FDP), an index of fibrinolysis secondary to coagulation. Fibrinogen was significantly higher (p less than 0.001) in RDT patients than in normal controls. ATIII activity was significantly lower in RDT patients than in normal controls (p less than 0.001). Plasminogen activity and alpha-2-plasmin inhibitor (alpha 2PI) activity were significantly lower (p less than 0.001) in RDT patients than in normal controls. Alpha 2PIC and XL-FDP were both significantly higher (p less than 0.001) in RDT patients than in normal controls. XL-FDP was inversely correlated with alpha 2PI (r = -0.486, p less than 0.01) and positively correlated with alpha 2PIC (r = 0.646, p less than 0.001). These results suggest that coagulation and fibrinolysis are enhanced in RDT patients and that the enhanced fibrinolysis is mainly due to fibrinolysis secondary to coagulation.

A sandwich ELISA system for detecting vascular basement membrane associated collagen (BAC) was developed. Serum levels of BAC were determined in patients with liver diseases (N = 53), various cancers (N = 65) and other diseases (399). Serum levels of procollagen type III (PIIIP) amino propeptide, type IV collagen.7s domain (7s domain) and other parameters (TP, ALB, GOT, GPT, CHE, gamma-GTP, ALP, LDH, CHE, TG, GLU) were also determined in those patients. In the whole patients, serum concentrations of BAC showed a weak correlation with GOT, GPT, ALB and CHE but not with gamma-GTP and ALP. There was no correlation between BAC and PIIIP or 7s domain. Although serum levels of BAC were elevated in both liver diseases and cancers, the increase in liver diseases was more marked. Markedly increased serum levels of BAC with low levels of CHE were found only in liver cirrhosis and liver cirrhosis plus hepatocellular carcinoma. Increased BAC may reflect capillarization of the liver sinusoid or remodeling of the vascular basement membrane which is observed in the progression of liver fibrosis. Serum BAC is thought to be a promising new marker, different from PIIIP or 7s domain for diagnosing fibrosis state in the organs, particularly in the liver.

Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are regarded as reflecting the release reaction by vascular endothelial cells and/or endothelial cell injury, and increased levels of thrombomodulin (TM) antigen as reflecting damage to endothelial cells. We investigated changes in plasma vWF:Ag and TM antigen levels during the course of regular hemodialysis treatment (RDT) in 14 patients undergoing RDT in order to evaluate the effect of hemodialysis (HD) on endothelial cells. vWF:Ag and TM were both measured by the sandwich EIA method. Predialysis levels of vWF:Ag and TM in RDT patients were both significantly higher than normal control values. Neither patient age nor blood pressure was not correlated with predialysis vWF:Ag and TM levels. Both vWF:Ag and TM levels significantly increased during a single HD session. There was a positive correlation between predialysis TM levels and duration of HD and an inverse correlation between the amount of vWF:Ag released during HD and duration of HD. It appears that HD procedures induce stimulation and damage of endothelial cells and that long-term, recurrent HD treatment may predispose to vascular disorders.

Unilateral renal agenesis with impaired renal function was found in all 3 siblings of a single family, in association with various metabolic disorders such as diabetes mellitus, hyperuricemia and hyperbilirubinemia with gallstones. The present report suggests that unilateral renal agenesis could occur as a manifestation of a genetic disorder.

Production of and responsiveness to interleukin 2 (IL-2) were evaluated in lymphocytes from 18 patients with nephrotic syndrome. The IL-2 production of T cells, when stimulated with autologous non-T cells separated on a polystyrene resin column, was significantly decreased in patients with minimal-change nephrotic syndrome. No significant difference in the level of IL-2 production was noted between minimal-change nephrotic syndrome patients in the nephrotic stage and those in remission. The IL-2 production was also significantly decreased in lymphocytes from patients with membranous nephropathy. The responsiveness to IL-2 was inconstant among patients with nephrotic syndrome. These results indicate that the immune system of regulating IL-2 production is impaired in patients with nephrotic syndrome.

The distribution curves of urinary red-blood-cell (RBC) size were obtained from automated blood-cell analysis in 146 patients with definite causes of haematuria. In 65 of 67 patients (97%) with haematuria and glomerulonephritis demonstrated by renal biopsy, urinary RBC had an irregular and asymmetrical distribution with RBC size showing a much smaller volume than that of venous RBC. This "glomerular" distribution contrasted with the "non-glomerular" normal distribution when the peak for RBC was at a larger volume than that for peripheral RBC. In 46 of 47 patients with haematuria who had lower urinary tract lesions other than infection, a non-glomerular distribution was obtained; 30 of these cases also showed glomerular distribution, and were classified as "mixed". All 32 patients with urinary tract infection had either a glomerular or mixed distribution, suggesting that they excreted distorted and dysmorphic urinary RBC. After excluding infections, this simple, rapid, reproducible, and non-invasive technique provides reliable information in distinguishing glomerular bleeding from other causes of haematuria.

In order to determine the role of intrarenal vascular coagulation (IVC) in chronic glomerulonephritis, coagulant parameters in renal blood (RVB), urine FDP's and renal histology were examined in 70 patients with chronic glomerulonephritis (CGN). RVB was obtained by Seldinger's technique. A correlation was obtained between an increase of fibrinogen, FDP and soluble fibrin monomer complexes (SFMC) in RVB and the degree of intraglomerular fibrin deposition shown on immunofluorescence. An increase of FDP's, SFMC and a slight decrease of fibrinolytic activity in RVB were observed in patients with CGN with decreased renal function or with the nephrotic syndrome. Daily excretion of FDP in the urine and the extent of intraglomerular fibrin deposition were greater in nephrotics than in non-nephrotics. We conclude that measurement of coagulation parameters in RVB is a reliable and sensitive method of assessing IVC, and that IVC plays an important role in aggravation of chronic glomerulonephritis, particularly when the nephrotic syndrome is present.

Differences in clinical and laboratory findings between different renal histological lesions were examined in 138 patients with primary glomerular diseases, and discriminant analysis was carried out in 72 patients to determine whether each histological type could be distinguished by the linear combination of these findings. The histological types were classified into 7 groups: minimal change nephrotic syndrome (MCNS); focal glomerular sclerosis (FGS); membranous nephropathy (MN); membranoproliferative GN (MPGN); proliferative GN (PGN); PGN with focal crescents (P X fc); and minor glomerular lesions (MGL). Ten variantes were selected from the clinical and laboratory findings in the early stage of the disease: sex, age of onset, acute onset, oliguria, urine protein, RBC in urinary sediment, serum albumin, serum total cholesterol, serum creatinine, and systolic blood pressure. In the discriminant analysis made regarding all these items collectively as continuous variantes, there was a significant difference (p less than 0.001) in the combination patterns of the variantes among histological types. Therefore, further analysis was performed using canonical axes and a multi-stage discriminant method. The canonical score and data obtained by a multi-stage discriminant method demonstrated that MCNS, MN, MPGN, and the group of PGN, P X fc and MGL could be distinguished from each other well, but that the degree of proliferation or the presence of focal lesions could not be predicted. As a result of these studies, we obtained a discriminant formula with which we could predict, with fairly high accuracy, some histological types on the basis of data on the 10 items mentioned.

Tuberculosis associated with dialysis was studied at the Renal Unit of the Tokyo Medical and Dental University and Yokosuka Mutual Aid Hospital Kidney Center, in both of which the treatments of chronic renal failure are the same. There are 12 tuberculosis patients out of 367 patients on maintenance hemodialysis from January 1967 to December 1976, an incidence of 3.3%. This was 6-16 times greater than that in the general population of this country according to yearly statistics. The characteristics of dialysis-associated tuberculosis include a high incidence of miliary tuberculosis, especially in aged patients and difficulty in establishing the diagnosis before death. Clinical features which are helpful in the early diagnosis are intermittent high fever of unknown origin, weight loss, anorexia, abnormalities of the central nervous system, erythrocyte sedimentation rate over 100 mm/h, leukocytosis and high value of the C-reactive protein. With the increasing number of dialysis patients, an increase of dialysis-associated tuberculosis is expected and this will be one of the major problems of dialysis patients in future.

Platelet count, volume and aggregation and plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were measured in 54 patients with chronic glomerulonephritis (CGN). Platelet count and platelet aggregation induced by ADP, adrenaline and collagen were significantly higher in the patients than in normal subjects, and platelet aggregation was markedly increased in the cases with progressive glomerular lesions. Plasma levels of beta-TG and PF-4 were significantly higher in the patients than in the normal subjects. There was a significant inverse correlation between plasma beta-TG and creatinine clearance. Nephrotic patients showed significantly smaller platelet volume and markedly elevated plasma beta-TG levels when compared to the controls. Plasma beta-TG decreased remarkably in 3 out of 4 patients with markedly increased beta-TG levels when they were given antiplatelet drugs. The results suggest that platelet aggregation and the release reaction were increased in patients with CGN. Activated platelets may be an important factor in the genesis of the thrombotic tendency in the nephrotic syndrome.

The purpose of this study was to investigate the accuracy and reproduction of a microelectrode with a glass capillary, and to discuss the correlation between the pH level and the microflora in periodontal pockets or the clinical findings in the various stages of periodontal disease. The upper or lower anterior teeth of 34 patients with mild to severe periodontal disease were examined. Before the measurement, supragingival plaque was removed from each tooth. A special glass capillary was incorporated in the microelectrode to cover its tip, so that it would not touch the pocket walls or tooth surfaces during pH measurement. After the pH in the crevicular fluid was determined, subgingival plaque was collected with paper points from each periodontal pocket. This bacterial plaque was sonicated with saline solution, and examined under a phase contrast microscope with a calibrated eyepiece graticule to count and morphotype groupings of microorganisms as 1) coccoid forms, 2) rods, 3) filaments, 4) motile rods, 5) spirochetes or other cell types. Crevicular fluid flow measurements and clinical findings (pocket depth, and gingival inflammation) were also investigated. The following conclusions were drawn: The electrode with capillary was useful to determine the pH of the crevicular fluid clinically. A reduction in pH level was seen in deep pockets or severe gingival inflammation. A close correlation was seen between salivary and crevicular pH. The pH level was significantly positively related with the proportion of coccoid forms, but was negatively correlated with the proportion of motile organisms that are reported to be related with periodontal disease.

Total platelet adenosine diphosphate (ADP) and adenosine triphosphate (ATP) contents and amounts of ADP and ATP released from platelets by 3 micrograms/ml of collagen were studied in 20 patients with primary glomerular disease (PGD) to examine the metabolism of these platelet substances in the disease. ADP and ATP were measured by Holmsen's firefly luciferase method. The patients had significantly lower total platelet ATP compared with controls and total platelet ATP was significantly lower in nephrotic patients than in patients whose serum albumin levels were normal. Releasable platelet ADP and ATP were both significantly decreased in patients. Releasable ADP: total ADP ratio and releasable ATP: total ATP ratio were both significantly lower in patients' platelets than in normal platelets. There was no significant difference in platelet counts between patients and controls. Platelet aggregation induced by ADP and adrenaline were significantly higher in patients compared with controls. We conclude that total ATP content and the amount of ADP and ATP released by collagen are decreased in PGD patients' platelets.

The intraglomerular location of coagulation-fibrinolysis factors (CFF) and a platelet membrane antigen (glycoprotein IIb-IIIa; GPIIb-IIIa) was determined in 101 patients with various glomerular diseases. Renal biopsy specimens were examined by immunofluorescence microscopy, using antisera against fibrinogen/fibrin reactive antigen (FRA), cross-linked fibrin degradation products (XL-FDP), fibronectin (FN), factor XIII-subunit a (F-XIIIa), plasminogen (Plg), alpha 2-plasmin inhibitor (alpha 2-PI) and GPIIb-IIIa. Intraglomerular deposits of the CFF were found at high rates in patients with IgA glomerulonephritis (GN), membranous nephropathy (MN) and lupus GN. The coexistence of deposits of these factors was ascertained by the double-staining method. The deposition rates of XL-FDP and GPIIb-IIIa were very low in patients with minimal-change nephrotic syndrome and focal glomerulosclerosis. Some cases of diabetic glomerulosclerosis (DGS) showed CFF deposition. FRA deposits associated with F-XIIIa and FN may indicate the presence of the cross-linked fibrin. Furthermore, the presence of Plg deposits together with alpha 2-PI and XL-FDP suggests the deposition of fibrin followed by fibrinolysis, but not of fibrinogen, and the coexistence of GPIIb-IIIa suggests the involvement of platelets in the reactions. These studies provide evidence that stabilized fibrin deposition with subsequent fibrinolysis and platelet activation take place in glomeruli in a fairly large proportion of patients with IgA GN, MN and lupus GN and in some cases of DGS.

Although the etiology and pathogenesis of IgA nephropathy is not fully understood, it has been classified as an immune-complex induced glomerulonephritis caused by an immunological mechanism. Forty-two patients with primary IgA nephropathy underwent tissue typing for HLA-A, B, and DR antigens by the standard method using a microlymphocytotoxicity test. There was no significant correlation between HLA-A and B antigens and this disease. However, the frequency of HLA-DR4 was 57.1% in the patients with normal renal function, 85.7% in those with decreased renal function, 100% in dialysis patients, and 39.2% in the control group. It is statistically significant in the patients with renal dysfunction (corrected P less than 0.05). Our results suggest that the HLA system may play an important role in the occurrence and exacerbation of IgA nephropathy in the Japanese population.

The pathogenetic roles of platelets were studied in unilateral progressive Masugi nephritis in the rabbit. On fourteenth day after the injection of anti-kidney serum, peripheral platelet counts, platelet aggregation and platelet aggregation rate were not changed statistically compared with those before the initial injection. The presence of platelet antigen within the glomeruli of the unclamped nephritic kidney suggests the participation in the pathogenesis of glomerular lesion. No significant difference was observed in the intrarenal uptake of 111Indium-labeled platelets between clamped and unclamped kidneys. This is probably due to the possibility of the participation of the very small amount of platelets or the possible decreased renal blood flow in the nephritic side in this model, or the active uptake of platelet not being found in this progressed stage of this model.

HLA-A, B, DR, and MT antigens were examined in 50 patients with idiopathic membranous nephropathy (IMN) by the standard microlymphocytotoxicity technique. The frequency of HLA-DR2 was significantly increased in the patients in comparison to the controls. Significant decreases in the frequencies were seen for HLA-DR4, DRw8 and DRw9 in the patients. The linkage disequilibrium between HLA-Bw52 and DR2 was noted in the controls, but it was significantly weaker in the patients. The frequency of MT1 was significantly higher, and that of MT3 was significantly lower in the patients as compared with the controls. The findings suggest that an immunological disturbance under the influence of genetic factors may confer a susceptibility to IMN.