[Urokinase as a blood and urine plasminogen activator in chronic glomerulonephritis and amyloidosis]. / Urokinaza kak aktivator plazminogena krovi i mochi pri khronicheskom glomerulonefrite i amiloidoze.

To estimate the individual role of the plasminogen activators (PA) urokinase (u-PA) and tissue (t-PA) in the development of two renal diseases (the nephrotic forms of chronic glomerulonephritis (CGN) and amyloidosis, the baseline plasma and urine levels of u-PA and t-PA antigens, their functional activity (FPAA), and changes in these parameters were determined after protein loading test (0.7 g/kg). In healthy individuals and patients with amyloidosis, the baseline FPAA changes from 0 to the maximum were caused only by the alterations of u-PA levels, in those with CGN, they were induced by the changes in the content of u-PA and t-AP antigens. The functional loading test revealed PA reserves solely in patients having a high baseline FPAA for both nephropathies: u-PA in amyloidosis and t-PA in CGN. In all the patients, the urine levels of u-PA antigens were 20-40 times more than those of t-PA antigens and 5-6 times less than those plasma u-PA. The findings suggest that urokinase may be regarded as the major plasminogen activator involved in CGN and amyloidosis.

[Clinical morphological characteristics of intravascular coagulation in glomerulonephritis]. / Kliniko-morfologicheskaia kharakteristika vnutrisosudistoi koaguliatsii pri glomerulonefrite.

Clinical and morphologic signs of intravascular coagulation have been studied in 63 patients with primary glomerulonephritis (GN) and in 19 patients with nephritis associated with systemic lupus erythematosus. A relationship between the frequency of fibrin deposition in the kidneys and severity of clinical signs and marked morphologic changes in GN has been revealed. Signs of local hypercoagulation are of prognostic significance. A more favourable prognosis is characteristic for patients who show nor fibrin deposition in the renal tissue and whose fibrinolytic system provides an adequate reaction.

[Trypsin inhibitor in the urine of patients with glomerulonephritis]. / Ingibitor tripsina mochi u bol'nykh glomerulonefritom.

Concentrations of urinary trypsin inhibitor (UTI) and acid stable antitryptic activity (AS-ATA) were estimated in morning urine of 50 patients with chronic glomerulonephritis and of 13 healthy persons in order to detect interrelationship between severity of kidney impairment and the content of the inhibitor in urine. In healthy persons concentrations of UTI and AS-ATA were equal to 1.05 +/- 0.15 micrograms/ml and 0.12 +/- 0.04 IU/ml, respectively. Similar values of the substances were detected in patients with latent form of glomerulonephritis and normal kidney function. Statistically distinct (P less than 0.01) increase of both these inhibitors was found in urine of patients with latent form of glomerulonephritis and impaired kidney function (4.77 +/- 1.24 micrograms/ml and 0.39 +/- 0.15 IU/ml, respectively) as well as with nephrotic form (26.17 +/- 7.55 micrograms/ml and 1.37 +/- 0.35 IU/ml, respectively) of glomerulonephritis of both primary type and caused by accompanying systemic diseases. Further increase in concentration of UTI up to 31.74 +/- 7.38 micrograms/ml and activation of AS-ATA in urine was observed in the patients with nephrotic form of glomerulonephritis at the step of chronic kidney insufficiency. The increase in UTI concentration observed did not correlate with the level of leukocyturia. Proteinases of monocytes, mast cells, fibroblasts, involved in inflammation and formation of connective tissue in kidney, but not of enzymes from polymorphonuclear leukocytes, appear to be responsible for formation of UTI out of its precursor inter-alpha-trypsin inhibitor in glomerulonephritis.

[Concentration of acid-stable inhibitors--metabolites of plasma inter-alpha trypsin inhibitor--in the urine of healthy people and in patients with nephrotic syndrome]. / Kontsentratsiia kislotostabil'nykh ingibitorov--proizvodnykh inter-al'fa-ingibitora tripsina plazmy krovi--v moche zdorovykh liudei i bol'nykh s nefroticheskim sindromom.

Concentration of acid stable inhibitors (ASI)--metabolites of plasma inter-alpha-trypsin inhibitor--was measured in urine samples of healthy persons and of 6 patients with nephrotic syndrome by means of modified cross immunoelectrophoresis. There was obtained 2-25 mg of ASI (Mr 22,000 and 32,000) in diurnal urine samples of patients with nephrotic syndrome, which were 10-20 times higher as compared with these inhibitors level in the urine of healthy persons. The reverse correlation was established for the value of glomerular filtration and the lever of ASI (Mr 32,000) in the urine of patients with nephrotic syndrome.

[The venous occlusion test in assessing the fibrinolytic activity of the vascular endothelium in lupus nephritis patients]. / Test venoznoi okkliuzii v otsenke fibrinoliticheskoi aktivnosti sosudistogo éndoteliia u bol'nykh volchanochnym nefritom.

A venous occlusion test was used to evaluate the reserves of the kidneys and that of vascular endothelium fibrinolytic activity (VEFA) in patients with lupus nephritis (LN). Prior to and following venous occlusion functional activity of plasminogen activators in plasma and urine (PAPU), plasma activity of antiactivator (PAAA), urokinase urine activity (UUA) were measured by fibrin plate lysis test in 24 patients with active LN, 6 SLE patients with intact kidneys, 10 healthy subjects. Venous occlusion test revealed normal reserve of plasma activator activity in mild LN and depletion of this reserve in LN patients with nephrotic syndrome and rapidly progressive LN. In the latter patients PAPU and PAAA were suppressed. PAPU reserve existed in all the patients, but those with rapidly progressive LN. UUA in LN was close to normal and did not change significantly after venous occlusion. The data obtained suggest that patients with severe LN had reduced reserves of VEFA, while in those with progressive LN there were also diminished reserves of renal fibrinolytic activity reflecting the severity of endothelial lesion.

[Disorders of purine metabolism as an etiological factor in renal pathology]. / Narushenie purinovogo obmena kak étiologicheskii faktor porazheniia pochek.

Of 3200 patients admitted to the nephrology department within several years, hyperuricemia was detected in 696. Excluding from this number persons with signs of chronic renal insufficiency (146 persons) and patients who were treated by diuretics (89), the frequency of hyperuricemia was 16.2% which exceeded almost 2-fold (9.2%) the value determined during the examination of 594 healthy persons. The authors discussed a possibility of early development of renal pathology in purine metabolic derangement with hyperuricosuric and hyperuricemic stages characterized by certain clinical peculiarities, including a possibility of development of immune complex nephritis.

[Clinical value of the study of hemostasis in nephrology]. / Klinicheskoe znachenie issledovaniia gemostaza v nefrologii.

The results of many-year studies on the humoral and platelet links of hemostasis in chronic glomerulonephritis (CGN) and amyloidosis were analyzed with relation to a stage of disease and prognosis of its course. Activation of the blood coagulation system (BCS), platelet hyperaggregation and suppression of the fibrinolytic system were revealed in CGN. Hypercoagulation was most noticeable in patients with active and prognostically unfavorable GGN types correlating with the frequency of local (in the kidney) intravascular coagulation, the frequency of peripheral thromboses and DIC-syndrome. In amyloidosis hypercoagulation shifts of BCS were combined with the activation of fibrinolysis and thrombocytopenia. Pathogenetic, adaptive and compensatory significance of changes of system of hemostasis revealed in CGN and amyloidosis was discussed.

[Immune complex hyperuricemic nephritis: aspects of its morphology and pathogenesis]. / Immunokompleksnyi giperurikemicheskii nefrit: nekotorye aspekty morfologii i patogeneza.

The authors described the results of an immunohistochemical, electron microscopic and morphometric study of the kidney bioptates of 45 patients with latent glomerulonephritis with hyperuricemia, 8 patients with primary gout and 12 patients with latent glomerulonephritis without hyperuricemia. Two possible variants of the involvement of the renal glomerula were revealed against a background of purine metabolism: typical immunocomplex glomerulonephritis and the so called "reactive" mesangial changes. The expression of interstitial changes (by the results of histometric investigation) was maximum in gout, slightly less in latent nephritis with hyperuricemia and minimum in nephritis without hyperuricemia. The authors emphasized the possibility of immunocomplex nephritis as one of the variants of renal lesion in gout and hyperuricemia and the necessity of specifying therapeutic modalities to be used in this condition including general nephrological approaches to the treatment of latent nephropathies.

[The effect of a protein loading test on the fibrinolytic system in patients with chronic glomerulonephritis and amyloidosis]. / Vliianie belkovoi nagruzochnoi proby na fibrinoliticheskuiu sistemu u bol'nykh khronicheskim glomerulonefritom i amiloidozom.

Investigation of the reserves of the fibrinolytic system with the aid of protein stimulation was carried out in 10 patients with chronic glomerulonephritis and in 10 patients suffering from amyloidosis. All the patients manifested proteinuria exceeding 3.5 g/day and other symptoms of nephrotic syndrome of varying intensity. Renal function was preserved in all the patients. The reserves of the fibrinolytic system were measured by analyzing blood plasma and urine before and after beef protein stimulation. The data revealed reciprocal responses of activator activity in blood plasma and urine in patients suffering from chronic glomerulonephritis and amyloidosis. In patients with amyloidosis, the test revealed complete depletion of activator activity in urine while its considerable reserves were preserved in blood plasma of the systemic channel.

[Antistreptococcal antibodies in the blood serum of glomerulonephritis patients]. / Protivostreptokokkovye antitela v syvorotke krovi u bol'nkyh glomerulonefritom.

To study humoral antistreptococcal immunity, 29 patients with acute glomerulonephritis (AGN), 211 patients with chronic glomerulonephritis (CGN) and 30 healthy donors were examined. According to EIA, blood sera of the indicated groups demonstrated antibodies (AB) to structural components of Streptococcus--A-polysaccharide (A-ps) and hyaluronic acid (HA) and to its extracellular products--streptokinase (SK) and streptolysin-O (ASLO). It has been shown that in the blood of AGN patients, the levels of AB to A-ps, SK and ASLO were high. The highest level of AB and SK was detected in 55% of the patients with the disease standing of up to half a year. In patients of all the clinical groups of CGN, the levels of AB to A-ps, SK and HA were elevated. The degree of the rise of the levels of all AB depended on the disease activity. Of prognostic importance in the chronicity of AGN and progression of CGN are high titers of AB and SK. The etiological role of streptococcus in glomerulonephritis and its importance in CGN exacerbation and prognosis are under discussion.

[The clinical importance of determining the von Willebrand factor in patients with lupus nephritis]. / Klinicheskoe znachenie opredeleniia faktora Villebranda u bol'nykh volchanochnym nefritom.

Venous occlusion test has found out the reserve of vascular and renal endothelium in excretion of Willebrand factor in patients with inactive lupus nephritis and those with active lupus nephritis with urinary syndrome. In severe active lupus nephritis (lupus nephritis with nephrotic syndrome and rapidly progressive lupus nephritis) it was not recorded. This fact evidences intensity of immune inflammation and coagulation in the kidneys in the above forms of lupus nephritis.

[Use of chromogenic substrates for estimation of indicators of kallikrein-kinin and blood coagulation systems in blood plasma of patients with nephrotic syndrome]. / Otsenka s pomoshch'iu khromogennykh substratov pokazatelei kallikrein-kininovoi i svertyvaiushchei sistem v plazme krovi bol'nykh s nefroticheskim sindromom.

A distinct increase of kallikrein content in blood plasma of patients with nephrotic syndrome as well as activation of thrombin simultaneously with a decrease in the prothrombin level were recorded in samples with synthetic chromogenic substrates S-2160 (Bz-Phe-Val-Arg-pNa), S-2238 (D-Phe-Pip-Arg-pNA) and S-2302 (D-Pro-Phe-Arg-pNA). Limited proteolysis of prothrombin by blood plasma kallikrein appears to be among the possible reasons of thrombin activation in the patients with nephrotic syndrome. Activity of plasmin, measured with S-2251 (D-Val-Leu-Lys-pNA) as a chromogenic substrate, was practically unlatered in blood plasma of these patients.

[The functional activity of plasminogen activators in the blood plasma and urine of patients with lupus nephritis]. / Funktsional'naia aktivnost' aktivatorov plazminogena v plazme krovi i v moche bol'nykh volchanochnym nefritom.

A fibrin plate technique was employed to study functional activity of plasminogen activators in plasma and urine (FAAP, FAAU), activity of antiactivator in plasma (AAAP), urokinase urine activity (UUA) in 35 lupus nephritis (LN) patients. The latter comprise 3 groups by the disease severity: 22 patients with active LN attended by urinary syndrome (group 1), 7 patients with LN associated with nephrotic syndrome (group 2), 6 patients with rapidly progressing LN (group 3). Control groups included 5 SLE patients with unaffected kidneys and 25 healthy subjects. FAAP proved heterogeneous both in SLE and healthy subjects. SLE patients with progressive LN had diminishing FAAP which was accompanied by growing AAAP. The latter reached maximal values in groups 2 and 3. UUA declined with LN aggravation. The relation of low FAAP in LN patients to affection of vascular endothelium and binding of plasminogen activators with the inhibitors to form inactive complexes is considered.

[Fibrinolytic activity of the urine during chronic glomerulonephritis and amyloidosis]. / Fibrinoliticheskaia aktivnost' mochi pri khronicheskom glomerulonefrite i amiloidoze.

Correlative interconnections between plasminogen activator (PA) activity (fibrin plate method) and level of urokinase antigen (Ag UAP) and tissue PA antigen (Ag TAP) in urine and blood (ELISA) were studied in 60 patients with chronic glomerulonephritis (CGN) and 38 patients with amyloidosis. The high degree of positive correlation between blood and urine initial PA activity and Ag UAP content was found. This suggests the possible leading role of UAP in formation of the basal fluctuations of fibrinolytic activity in blood and urine. High degree of correlation--r = +0.84 and p < 0.001--was found between blood Ag UAP and urine Ag TAP in amyloidosis only. The functional protein loading probe revealed great importance of high urine and blood AP activity in realizing of ultrafiltration renal process--in CGN and amyloidosis.

[State of the kinin system and level of serum proteinase inhibitors in latent nephritis and the nephrotic syndrome of different etiology]. / Sostoianie kininovoi sistemy i uroven' ingibitorov proteinaz syvorotki krovi pri latentnom nefrite i nefroticheskom sindrome razlichnoi étiologii.

Main components of kinin system, the arginine-esterase activity and proteinase inhibitors were estimated in blood serum of patients with nephrotic syndrome of various etiology (glomerulonephritis, amyloidosis, systemic lupus erythematous) and also in patients with latent nephritis and in healthy donors. Content of all the kinin system components (kallikreinogen, kininogen and kininase 1) proved to be increased in all the forms of nephropathy studied. Free kallikrein was found in blood serum of patients with nephrotic syndrome as distinct from healthy persons and patients with latent nephritis. The arginine-esterase activity, which shows the level of trypsin-like proteinases, was altered dissimilarly, depending on the nephrotic syndrome etiology: it was maximally increased in nephrotic syndrome of amyloid genesis and decreased in patient with systemic lupus erythematosus. High content of kallikrein and kininase I with simultaneous decrease in kininogen was typical for patients with severe form of nephrotic syndrome. Impairment of kidney in nephrotic syndrome was also characterized by an increase in alpha1-antitrypsin and in the total antitryptic activity, which reached the maximal value in nephrotic syndrome of the I degree and decreased at the II degree of the disease. In nephrotic syndrome content of alpha2-macroglobulin was maximally increased at the II degree of nephrotic syndrome and decreased in severe form of the disease. The primary alteration in content of proteinase inhibitors and high level of kinin system components were assumed to determine the conditions for activation of kinin system in blood serum and to impair the nephrotic syndrome pathogenesis, which was complicated by systemic manifestations. High content of kinin system components was apparently determined by the increased synthesis in liver tissue in response to inflammation and massive proteinuria; kininase I and alpha2-macrolgobulin, as proteins with high molecular weight, were likely to be selectively retained in blood circulation when the capillary penetration was increased.

[Components of kallikrein-kinin system in the urine of patients with glomerulonephritis]. / Komponenty kallikrein-kininovoi sistemy v moche bol'nykh glomerulonefritom.

Activities of main components of the kallikrein-kinin system: tissue (renal) and blood plasma kallikreins, kininases I and II, bradykinin-activating activity as well as free kinins, were estimated in urine of patients with latent and nephrotic forms of glomerulonephritis as compared with those parameters in urine of healthy persons. Content of tissue kallikrein was decreased in urine of patients with nephrotic form of glomerulonephritis as distinct from the disease latent form and healthy persons. At the same time, urine of these patients with nephrotic form contained elevated amount of blood plasma kallikrein and other proteinases of blood plasma origin. Bradykinin-inactivating activity as well as activities of kininase I and II were increased in urine of patients with the disease latent form 2-, 7- and 2.5-fold, respectively, and in urine of patients with nephrotic form--40-, 45- and 40-fold, respectively as compared with normal state. Daily excretion of free kinins with urine of healthy persons constituted 6.6 +/- 0.9 micrograms-eqv of bradykinin (BK), in patients with latent and nephrotic forms of glomerulonephritis--1.7 +/- 0.3 and 2.8 +/- microgram-eqv BK, respectively. Three kinins were found in all the examined persons when urine was collected in acid medium: BK, lysyl-BK and Met-Lys-BK; content of BK was minimal in urine of healthy persons and maximal--in urine of patients with nephrotic form of the disease. Clinical importance of the patterns studied and their role in correction of treatment course of patients with nephrotic form of glomerulonephritis are discussed.

[Activators and inhibitors of fibrinolysis in chronic glomerulonephritis and amyloidosis]. / Aktivatory i ingibitory fibrinoliza pri khonicheskom glomerulonefrite i amiloidoze.

Functional activities of plasminogen activators (FPAA) and their inhibitors and plasminogen activators's (PA), antigen level were determined in 31 patients with chronic glomerulonephritis, 23 patients with amyloidosis and 15 healthy persons. High FPAA correlated with favourable prognosis of diseases, elevated PA antigen level and diminished alpha 1-antitrypsin, alpha 2-macroglobulin and antiactivator activities. There were decreased PA antigen level and increased inhibitor's activities in group with zero FPAA. Protein loaded functional probe demonstrated the presence of PA reserves in high FPAA patients and "pathological proteolysis" in zero FPAA patients. The last phenomenon was likely connected to nonspecific proteases differed from PA.

[The clinico-morphological characteristics of psoriatic nephropathy]. / Kliniko-morfologicheskie osobennosti psoriaticheskoi nefropatii.

Based on studying the data obtained during examination of patients with psoriasis combined with the urinary syndrome possible varieties of psoriatic nephropathy, namely chronic glomerulonephritis (CGN) and amyloidosis were distinguished. CGN combined with psoriasis was mainly represented by latent glomerulonephritis (GN) and morphologically, it was mostly represented by the mesangio-proliferative variant, with IgA and C3 being fixed on the basal membrane of the capillaries and in the mesangium. The clinicomorphological feature of that form of psoriatic GN is combination of the signs of both associated CGN and hyperuricemia and IgA-nephritis. Special emphasis is laid on the diagnosis of rapid-progressing GN which is of paramount importance for institution of early etiopathogenetic therapy. Amyloidosis associated with psoriasis is characterized by the signs of acquired disease (AA-amyloidosis) and does not differ in its course from amyloidosis coupled with other diseases.

[Assessment of the protein quota in the ration of patients with the nephrotic syndrome according to balance studies]. / K otsenke kvoty belka v ratsione bol'nykh s nefroticheskim sindromom po dannym balansovykh issledovannii

From data derived from equilibrium investigations in patients with the nephrotic syndrome a negative nitrous balance which indicates the presence of a chronic protein deficiency developing in the organism of these patients was revealed. Observations showed that an increased quota of protein in the ration of patients with the nephrotic syndrome is quite justifiable. The quantity of protein comprising 1.5--2 g per kg of the patient's body weight per day, of which 3/4 is protein of animal origin, is optimal for this category of patients. Possible improvement of the protein supply in patients with the nephrotic syndrome is largely determined also by the qualitative composition of the protein in the ration.