Lymphocyte function in patients with chronic glomerulonephritis

Lymphocyte suppressive activity after stimulation with Con A and lymphocyte function as the effectors in the ADCC test had been examined in 68 patients with chronic glomerulonephritis (GN) and in 20 healthy controls. Lymphocyte suppressive activity was lower in patients with chronic GN than in the healthy individuals. In regard to chronic proliferative GN and mesangial GN the difference was statistically significant. The lymphocyte efficiency in the ADCC test was generally adequate in patients with chronic GN and none of the morphological types showed significant deviation from the control group. In the general analysis of patients with chronic proliferative, mesangial, membrano-proliferative and membranous GN a decrease of lymphocyte suppressive activity below the lower standard limit has been detected (45% of cases). A similar defect in lymphocyte function in the ADCC test has been found in 18.6%. A statistically significant relationship between the lymphocyte function disorders and the high clinical dynamism of GN has been noticed, although in some cases there was a deviation from this tendency. It is supposed that circulating immune complexes, detected in some patients with chronic GN are not the only decisive factors responsible for defects in lymphocyte function.     

Plasma lipids in patients with chronic glomerulonephritis

The author examined 78 patients with chronic glomerulonephritis and verified their diagnosis on the basis of the kidney biopsy data. With regard to the severity of the tubular interstitial component the patients were enrolled in three groups. It was stated that with the increasing changes developed in the tubular interstitial component, the levels of total cholesterol, cholesterol of high density lipoproteins, low density lipoproteins and triglyceride elevated. In the group of the patients with minimal changes in the tubular interstitial component, the number of those in whom plasma lipid levels were below the upper normal limits was higher than in two other groups. A direct proportional relationship between the levels of plasma lipids and severity of the tubular interstitial component indicated the immediate role of the renal tissue in the pathogenesis of lipid turnover disorders in patients with chronic glomerulonephritis.     

Renal functional reserve in experimental chronic glomerulonephritis

Loss of renal functional reserve, that is, absence of the glomerularvasodilatory response to amino-acid infusion, has been interpretedas equivalent to glomerular hyperperfusion/hypertension, andthere fore proposed as a marker of high risk for progressiveglomerular sclerosis. To substantiate the validity of this hypothesiswe evaluated the renal response to glycine and the extent ofglomerular damage 10–12 weeks after induction of anti-glomerularbasement membrane glomerulonephritis with or without superimposedclip hypertension. Untreated rats and rats chronically treatedwith quinapril, a converting-enzyme inhibitor, were studied.In untreated groups, loss of renal functional reserve was demonstratedsince GFR, single-nephron GFR (SNGFR) and plasma flow (SNPF)did not increase during glycine infusion. The absence of renalreserve was associated with glomerular hyperfusion/hypertension,and development of proteinuria and glomerulosclerosis. Quinaprilreduced proteinuria and diffuse sclerosis in anti-glomerularbasement membrane GN, and decreased blood pressure and segmentalglomeruloscierosis in anti glomerular basement membrane GN withsuperimposed clip hypertension. Both treated groups demonstrateda restoration of renal functional reserve, as depicted by increasesin GFR, SNGFR, and SNPF after glycine, despite persistence ofglomerular hyperperfusion/hypertension. These data demonstrthat renal functional reserve testing, although it does notdetect glomerular hyperperfusion/hypertension, can provide informationon the progression of glomerular damage.     

Uric acid metabolism in patients with chronic glomerulonephritis

Serum uric acid (SUA), creatinine clearance (Ccr), urinary excretion of uric acid (UUAV) and uric acid clearance (CUA) were determined in 357 patients with IgA nephritis (IgAN) and 81 patients with membranous nephropathy (MGN) in an attempt to clarify uric acid metabolism in patients with chronic glomerulonephritis, and UUAV/Ccr and CUA/Ccr levels were measured to investigate their correlations. As a result, hyperuricemia that could hardly be explained with a decline of Ccr alone was recognized in many cases, since the patients with hyperuricemia exceeding 7.0 mg/100 ml of SUA registered even as high as 25.5% in IgAN and 33.3% in MGN, whereas those with the Ccr levels higher than 80 ml/min registered 22.3% in IgAN and 38.0% in MGN. Although the SUA level increased and the UUAV and CUA levels decreased along with a decline of Ccr in IgAN, no similar trends were recognized in MGN. When the distribution of UUAV was studied in the patients with the Ccr levels higher than 80 ml/min, the patients whose UUAV levels higher than 800 mg/24 hrs that suggested excessive uric acid production were markedly as low as 3.9% in IgAN and 3.7% in MGN. Thus, the cause of hyperuricemia could not be attributed to an amount in the uric acid production. On the other hand, the patients whose CUA levels lower than 6.0 ml/min in the distribution of CUA that suggested a decrease of uric acid excretion registered 47.4% in IgAN and 63.0% in MGN, respectively, which equally appeared to be a type of lowered excretion in a majority of patients whose hyperuricemia was recognized in IgAN and MGN. The mechanism of the lowered excretion of uric acids from the kidney despite the normal level of Ccr has yet to be clarified.     

Activity of circulating monocytes in patients with chronic glomerulonephritis

Monocytes of 95 patients with chronic glomerulonephritis (ch.g.) testedin vitro demonstrated characteristics of activation in proliferative, and of functional suppression in mesangiocapillary glomerulopathy. Fc and C₃ receptor function studied by rosette assay and metabolic potential measured by the NBT reduction test constituted result patterns. Receptor tests were supplemented with their counterparts after monocyte triggering with heat-inactivated sera and in case of NBT assay — stimulation with zymosan. Membranous, minimal change, mesangial and focal glomerulonephritis monocytes presented less specific configurations of data than those of proliferative and mesangiocapillary, with a uniform increase of trypsin-resistant Fc receptor activity. There was no appreciable correlation between the presence of circulating immune complexes (c.i.c.) in patient sera and parameters tested. The mesangiocapillary suppression pattern suggests mononuclear phagocyte defect in this glomerulopathy.     

The acute effect of atorvastatin on proteinuria in patients with chronic glomerulonephritis

BACKGROUND: Hyperlipidemia may develop early in the course of renal disease, and statin treatment to lower lipid levels in these patients is effective. In addition, it has been suggested that proteinuria may decrease after prolonged periods of statin treatment. In the present study, we set out to evaluate the short-term effect of atorvastatin after only six weeks of therapy. MATERIAL AND METHODS: Plasma albumin, creatinine, creatinine clearance, proteinuria and lipid profiles were assessed in 31 consecutive patients with glomerulonephritis and proteinuria > 0.3 g/24 h. All patients were treated with ACE inhibition for more than three months. Twenty patients consented to receive additional treatment with atorvastatin 10 mg daily in conjunction with a cholesterol-reducing diet, while 11 patients received standard care. Analyses were performed at baseline and after six weeks. RESULTS: After six weeks of treatment with atorvastatin urinary protein excretion was reduced from 1.80 g/24 h to 1.42 g/24 h (22%, p = 0.005), while no change was observed in this parameter in the untreated patients over the same period. Plasma albumin did not change in treated or in untreated patients. Lipid and lipoprotein parameters improved in all treated patients (all p < 0.001). No correlation was observed between the percentual changes in lipids and proteinuria. Plasma creatinine and creatinine clearance did not change (p > 0.05). CONCLUSIONS: Six weeks of therapy with low-dose atorvastatin, added to ACE inhibition, resulted in a 22% decrease of proteinuria compared to untreated patients.     

Effect of hemodialysis on the content of fatty acids in monolayers of erythrocyte membranes in patients with chronic renal failure

Lipid metabolism disorders are found in patients with chronic renal failure (CRF). Changes in the content of fatty acids of the phospholipid fraction of erythrocyte membranes can lead to changes in the rheological properties. The objective of our study was to assess the effect of hemodialysis on the composition of fatty acids in two fractions of phospholipids: sphingomyelin (SPH, representative of the external monolayer) and phosphatidylethanolamine (PE, representative of the internal monolayer). Venous blood was drawn from patient with CRF before and after the HD procedure. Lipids from the erythrocyte stroma were extracted using the Rose and Oklander method and then were separated into phospholipid fractions using thin-layer chromatography (TLC). PE and SPH fractions were extracted, and the fatty acid profile was determined using gas chromatography (Perkin Elmer 8400; RTx 2330 column; length: 105 m). In the phospholipid fractions tested, a high content of saturated FA with a medium carbon chain (C 16:0 to C 18:2) and a long carbon chain such as C 24:0, C 24:1; C 22:6; and C 26:0 was found. The HD procedure affected the FA profile in the fractions tested. The proportion of saturated and unsaturated long-chain FA (above 18 C) increased in PE. However, the content of medium-chain FA C 16:0 to C 18:1 decreased. A significant decrease in the content of the majority of long-chain FA could be noted in SPH. The ratio of unsaturated (U) to saturated (S) fatty acids in the SPH fraction increased. Hemodialysis has a significant effect on the content of fatty acids in the PE and SPH fractions of erythrocyte membranes in patients with CRF.     

Urinary prostaglandins and thromboxane in patients with chronic glomerulonephritis

To evaluate the potential contribution of prostaglandins (PGs) and thromboxane (TX) to the development of chronic glomerulonephritis, we measured the urinary excretion of PGE, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 by radioimmunoassay in 36 patients with chronic glomerulonephritis. In patients with nephrotic syndrome, urinary excretion of PGE and TXB2 was highly increased, whereas that of PGF2 alpha and 6-keto-PGF1 alpha remained normal. In patients with non-nephrotic chronic glomerulonephritis, urinary excretion of TXB2 was significantly increased, whereas that of PGE and 6-keto-PGF1 alpha remained normal and that of PGF2 alpha was significantly decreased. In patients with chronic renal failure, the urinary excretion of all PGS and TX was markedly decreased presumably due to a decrease in the number of cells which can metabolize arachidonic acid. These results suggest that TXA2 plays an important role as an exaggerating factor in the development of chronic glomerulonephritis, particularly that accompanying nephrotic syndrome, and that renal synthesis of PGE is compensatorily increased to maintain renal function in nephrotic syndrome.     

Subpopulations of peripheral blood T-lymphocytes in patients with chronic glomerulonephritis

Patients with membranous proliferative glomerulonephritis in the presence of nephrotic syndrome of without it were investigated for subpopulation composition of T lymphocytes and their functional activity in pHA blast transformation test. Though no difference was revealed in E+- and Fc+-receptor occurrence, both spontaneous and PHA-induced malformation of autoreactive T cells were observed. The results justified the previous data on the deficiency in lymphopoiesis of undifferentiated cells with end deoxynucleotidyltransferase as a marker. In patients with nephrotic syndrome PHA-induced blast transformation test revealed a decrease in lymphocyte function.     

慢性肾小球肾炎患者血清新蝶呤的水平及其意义

本研究通过检测血清新蝶呤(NP)、白介素10(IL-10)及转化生长因子β(TGF-β1)的水平,探讨细胞免疫在慢性肾小球肾炎(CGN)发病中的意义.     

Clinical effects of trandolapril in chronic glomerulonephritis patients with renal insufficiency

Trandolapril is a newly developed angiotensin converting enzyme inhibitor (ACEI) whose characteristic is that it undergoes hepatic excretion. ACEI appears to have a specific reno-protective and antiproteinuric role in patients with chronic glomerulonephritis(CGN). Although renally excreted ACEI tend to accumulate and cause side-effects in patients with renal dysfunction, the pharmacokinetics of trandolapril were not affected by renal dysfunction. We compared the effect of other renally excreted ACEI with those of trandolapril on serum creatinine (s-Cr), creatinine clearance(Ccr), proteinuria and total protein(TP) in CGN patients who switched from another ACEI to trandolapril. Twelve hypertensive patients with chronic renal failure(nine males and three females, ranging from 30 to 72 years of age) who were treated by other renally excreted ACEIs for long periods(2 to 8 years) with some effects on proteinuria and renal function, were enrolled in the present study. After ACEI therapy, s-Cr had decreased(2.09 to 1.80 mg/dl, p < 0.01) as well as proteinuria(1.65 to 0.71 g/day, p < 0.01). A single daily oral dose of 1 mg of trandolapril was administered to these patients regardless of their blood pressure status and renal functions. After change to trandolapril therapy, s-Cr(2.25 to 2.06 mg/dl, p < 0.01) and urinary protein(1.82 to 1.34 g/day, p < 0.05) significantly decreased. On the contrary, both Ccr and TP significantly increased at the level of 39.4 to 44.4 ml/min(p < 0.05) and 6.80 to 7.02 g/dl (p < 0.01), respectively. No apparent side effects, such as hyperkalemia, hyponatremia, anemia or worsening of the existing renal dysfunction except for coughing, were observed in these patients. Furthermore, none of the 12 patients treated with trandolapril required discontinuation of the compound. In conclusion, it was shown from this study that trandolapril is effective for the treatment of hypertensive patients with renal insufficiency irrespective of the original diseases. Thus, it can be envisaged that trandolapril is one of the most appropriate agents compared to other renally excreted ACEI for these patients with renal insufficiency. We recommend the change from other ACEIs to trandolapril, when renal dysfunction might be due to ACEI accumulation.     

Activation of platelets in patients with chronic proliferative glomerulonephritis and the nephrotic syndrome

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 functional properties of thrombocytes in patients with suppurative peritonitis

An examination of 49 patients with local and diffuse purulent peritonitis at different stages of surgical treatment has shown that the pyodestructive process in the abdominal cavity develops against the background of thrombocytosis, thrombocyte destruction, their decreased energy resources and tendency to retarded and irreversible aggregation. To correct the disturbed aggregation properties of thrombocytes the HBO and intraaortal infusions of antiaggregants and vasoactive drugs may be used.     

Clinicopathological study of membranous glomerulonephritis in patients with rheumatoid arthritis]

Of 103 patients with membranous glomerulonephritis proved by renal biopsy, 11 (10.7%) had rheumatoid arthritis. Nine of these 11 patients received systemic treatment with anti-rheumatic remedies including gold, D-penicillamine and bucillamine. Two others were administered only token of nonsteroidal antiinflammatory drugs. Renal function of the patients was well maintained and within normal limits. Four patients showed nephrotic syndrome, while mild to moderate proteinuria was found in the other 7. Hematuria was minimal to mild, and it was not a major symptom. Six patients resolved proteinuria completely and 2 patients incompletely after discontinuation of chrysotherapy. Nine cases of the membranous lesion in patients with rheumatoid arthritis were stage 1. Thus it was often difficult to identify the glomerular change only by light microscopy. IgA nephropathy and AA amyloidosis were associated in one patient respectively. Our data lead us to conclude that chrysotherapy would cause membranous lesions, but rheumatoid arthritis itself also induce membranous glomerulonephritis.     

Analysis of nitric oxide in the exhaled air of patients with chronic glomerulonephritis.

BACKGROUND: Nitric oxide (NO) plays an important role in renal hemodynamics and function. Although production of NO in the glomeruli has been found to be increased in animal models of glomerulonephritis, it remains unclear whether its endogenous production is enhanced in patients with chronic glomerulonephritis (CGN). SUBJECTS AND METHODS: We measured NO output in exhaled air as an indicator of its local production in the lungs and plasma and urinary nitrite plus nitrate (NO2-/NO3-) levels as indicators of its production in the whole body in 21 patients with CGN in 31 healthy controls. RESULTS: The patients exhaled higher concentrations of NO (29.5 +/- 1.4 vs. 18.7 +/- 1.0 parts per billion (ppb), mean +/- SEM, p < 0.0001) and exhaled NO output was also higher than in controls (166.6 +/- 6.8 vs. 95.5 +/- 5.6 nl/min/m2, p < 0.0001). Plasma NO2-/NO3- concentrations were also significantly greater in the patients than in the controls (81.6 +/- 7.2 vs. 41.1 +/- 4.3 micromol/l, p < 0.001). In patients with CGN, exhaled NO output correlated negatively with creatinine clearance (r = -0.62, p < 0.05). Oral administration of prednisolone (60 mg/day) for two weeks did not significantly affect the exhaled NO output in the patients (160 +/- 7 vs. 200 +/- 30 nl/min/m2, p = NS) despite a decrease in urinary protein excretion (12.0 +/- 2.9 vs. 1.4 +/- 0.6 g/day, p < 0.01). CONCLUSION: These findings suggested that endogenous NO production is increased in patients with CGN. Increased endogenous NO production may play some pathophysiological role in these patients.