摘要:

The nephrotic syndrome is characterized by the increased urinary excretion of albumin and of other serum proteins of intermediate molecular weight accompanied by a decrease in their serum concentration. Albumin synthesis is increased at the level of mRNA synthesis in response to decreased serum oncotic pressure. However, the magnitude of these responses is dependent upon dietary protein and is insufficient to normalize serum albumin. The absolute rate of albumin catabolism is decreased, serving to normalize serum albumin stores, but in contrast to what occurs in other hypoalbuminemic states, the fractional rate of albumin catabolism is increased. This observation is consistent with a hypothesis that increased renal catabolism contributes to total albumin catabolism in nephrosis. Like albumin, IgG is lost in the urine, its serum concentration is decreased, and the fractional rate of its catabolism is increased, suggesting that the kidney contributes to IgG catabolism in the presence of proteinuria. IgG synthesis responds in a variable fashion in the nephrotic syndrome, and may be decreased, thus contributing to its reduced serum concentration. In contrast, the serum concentration of the high-molecular-weight immunoglobulin IgM is increased, as is the serum concentration of a variety of high-molecular-weight liver-derived proteins. It is unknown by what mechanism serum IgM concentration is increased, but this response serves to defend serum protein concentration and oncotic pressure.

ISSN:0250-8095    

DOI:10.1159/000168192

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

In a patient with persistent diarrhea, renal acid excretion was examined because fecal alkali loss was insufficient to account for chronic metabolic acidosis. Bicarbonate wasting did not occur at physiologic serum concentrations, and the patient’s ability to lower urine pH after an acid load was within normal limits. Glomerular filtration rate and the maximal rate of distal hydrogen ion secretion were unequivocally reduced, however, and ammonium excretion was consequently inadequate. Unanticipated hypophosphaturia limited urinary titratable acidity. This case demonstrates that renal dysfunction may contribute significantly to acidosis associated with diarrhea and shows that defects in renal acid excretion may be superficially inapparen

ISSN:0250-8095    

DOI:10.1159/000168051

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

A variety of tubular marker proteins, as compared to healthy controls, are excreted at an increased rate in the urine of patients with renal damage. Beside cytoplasmic glutathione-S-transferase and lysosomal β-N-acetyl-glucosaminidase (β-NAG) the majority of kidney-related urine proteins derives from membrane surface components of the most vulnerable proximal tubule epithelia, among them ala-(leu-gly)-aminopeptidase, γ-glutamyl transpeptidase (GGT), the tubular portion of angiotensinase A, the major brush border glycoprotein ‘SGP-240’ and adenosine-deaminase-binding protein. Urinary tissue proteins, e.g. brush border (BB) microvilli, are immunologically identical with those antigens prepared from cell membranes of the human kidney itself. BB antigens are shed into the urine of patients with glomerulonephritis, interstitial nephritis, systemic diseases, e.g. systemic lupus erythematosus (SLE), diabetes mellitus and multiple myeloma, arterial hypertension, infectious diseases (malaria, AIDS) and after operations, renal grafting and administration of X-ray contrast media, aminoglycosides or certain cytostatics (cz’s-platinum). Tissue proteinuria of tubular proteins is determined by enzyme-kinetic or quantitative immunological assays applying either poly- or monoclonal antikidney antibodies. Clinical, ultrastructural and histochemical studies support the idea that both ‘soluble’ and high-molecular-weight membrane particles (vacuolar blebs, > 106 dalton) as well as microfilamental components of the epithelial cytoskeleton contribute to tubular ‘histuria’ which appears as a sensitive parameter in monitoring tubular damage under clinical conditions at a

ISSN:0250-8095    

DOI:10.1159/000168193

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The role of aldosterone in the abnormal sodium retention in patients with nephrotic syndrome has been debated. In fact, studies using a converting enzyme inhibitor to lower plasma aldosterone have rejected such a role. We therefore studied 5 nephrotic patients and 6 control subjects by using the more specific aldosterone antagonist, spironolactone. After withdrawal of diuretics 5 days prior to the study, the nephrotic patients and control subjects were placed on a high-sodium diet (285 ± 6 mEq/day) for 8 days. After 4 days, spironolactone 200 mg p.o., b.i.d., was given for the remaining 4 days. Plasma renin activity and plasma aldosterone levels were similar in both nephrotic patients and control subjects before the study, after sodium loading and after spironolactone had been given. After 4 days of high sodium intake control subjects were in sodium balance, but the nephrotic patients were in a positive sodium balance (approx. 80 mEq/day; p < 0.01). On days 3 and 4 of spironolactone, the nephrotic patients exhibited an increase in urinary sodium excretion (205 ± 20 vs. 312 ± 13 mEq/day; p < 0.005) but not the control subjects (279 ± 16 vs. 286 ± 13 mEq/day; NS). It is therefore concluded that aldosterone is a significant contributor to the sodium retention in patients with nephrotic synd

ISSN:0250-8095    

DOI:10.1159/000168052

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Hepatic dysfunction was observed in 34 patients with nontraumatic rhabdomyolysis. The serum levels of lactic dehydrogenase were markedly elevated in all patients. The peak values occurred within 72 h of hospitalization. There was no significant difference among patients with (9,044 ± 1,154 U/l) and without acute renal failure (ARF; 9,125 ± 3,067 U/l). Similarly, marked elevation in both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed within 72 h after admission to the hospital. They were significantly higher in patients with ARF (ALT: 4,718 ± 785 vs. 2,496 ± 927 U/l, p < 0.01; AST: 3,635 ± 820 vs. 1,352 ± 624 U/l, p < 0.01). Hyperbilirubinemia was noted in 13 of 22 (60%) patients with ARF and in 5 of the 12 (41 %) of those without ARF. Serum levels of bilirubin ranged from 2.6 to 14.3 mg/dl. Prothrombin time was prolonged in 4 of 12 (33%) without ARF and in 14 of 22 (63 %) of patients with ARF. This abnormality lasted from 1 to 13 days. The magnitude and duration of hyperbilirubinemia and abnormal prothrombin time were similar in patients with and without ARF. Hepatic dysfunction appears to occur in about 25% of patients with rhabdomyolysis. The pathogenesis of these abnormalities is not well defined and may be multifactorial. Hyperpyrexia, hypotension and proteases released from injured muscle may each or all be contributory. These hepatic derangements are rever

ISSN:0250-8095    

DOI:10.1159/000168053

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The mechanisms by which low-molecular-weight proteins filtered at the glomerulus might damage the kidney are reviewed. Despite a strong association between Bence-Jones proteinuria and impairment of renal function, many patients excrete light chains in large amounts and for long periods without evidence of renal abnormality. This critical paradox has still not been resolved despite suggestions, and investigations to explore them, that physicochemical properties of individual proteins might determine toxicity. The data suggest contributions, not mutually exclusive, from toxicity to proximal tubular cells via lysosomal uptake and from tubular obstruction by casts containing light chain and Tamm-Horsfall protein. The mechanisms, if any, of nephrotoxicity of haem proteins are equally uncertain.

ISSN:0250-8095    

DOI:10.1159/000168194

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Complement activation occurs during hemodialysis, and its intensity depends on the type of dialyzer and whether it is new or reused. Neutrophil degranulation also occurs during hemodialysis with release of lactoferrin, myeloperoxidase and elastase. However, it is unclear whether this event is induced by complement activation and whether it is attenuated by reuse. We examined complement activation and neutrophil degranulation during 10 consecutive hemodialyses using the same cuprophane dialyzer. Also the effect of rinsing the latter with 25% human albumin was studied. The rise in plasma C3a and C5a was markedly higher (p < 0.01) during the first than the second use. Plasma levels of lactoferrin and myeloperoxidase increased significantly (p < 0.01) during the first use, and levels were not affected by reuse. In contrast, plasma elastase increased with the first use and decreased with each subsequent use. Treatment of the dialyzer with albumin did not affect the magnitude of rise in plasma levels of C3a or lactoferrin but was associated with a significant reduction in plasma elastase. The data show that neutrophil degranulation is not dependent on complement activation and that the two processes could be dissociated.

ISSN:0250-8095    

DOI:10.1159/000168054

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

We have assessed the peripheral distribution of T cells, using the monoclonal antibodies OKT3, OKT4, OKT8 and LEU7 and the proliferative response to phytohaemagglutinin (PHA), in 10 renal transplant recipients. In each patient, the immunological pattern was evaluated twice, both before and after 1 month of calcium antagonist (calcium channel blockers, CaA) treatment. During treatment with CaA, we have observed both a significant decrease in the mitogenic response to PHA and a significant increase in OKT8 cells. Our data support the hypothesis that CaAs per se may have an immunomodulatory effect on T cell distribution independently of changes in ciclosporin (CS) blood levels. These results could also provide a cellular basis for synergism between CS and CaA.

ISSN:0250-8095    

DOI:10.1159/000168055

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The erythrocytes from 19 chronic hemodialysis patients were examined for Heinz bodies and their sensitivity to oxidant stress. Heinz bodies were found in 63% of patients and an elevated level of oxidized hemoglobin in 36%. When exposed to acetylphenhydrazine oxidant stress, 84% had a normal response and 95% had stable reduced glutathione levels. Ascorbic-acid-induced oxidant stress was tolerated by 84%. The activities of enyzmes associated with the hexose monophosphate shunt were examined and found to be intact. This study demonstrates an increased number of Heinz bodies in hemodialysis patients. However, this is not due to an increased sensitivity to oxidant stress. Other mechanisms must be sought to explain the presence of Heinz bodies in these patients.

ISSN:0250-8095    

DOI:10.1159/000168056

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Nephrotic syndrome (NS) is associated with several disorders of hemostasis: thrombocytosis and platelet hyperaggregability; increased plasma levels of factors V and VIII, and of fibrinogen with blood hyperviscosity; decreased plasma levels of natural anticoagulants: free protein S, and antithrombin III compensated by increased levels of α2-macroglobulin; lowered fibrinolytic activity. Intensity of hypercoagulability is related to the degree of hypoalbuminemia; however, the role of hypercoagulability in the increased incidence of thromboembolic events, including renal vein thrombosis, is not proved. Clotting disorders are due to urinary losses of anticoagulants or to increased liver synthesis of procoagulants stimulated by hypoalbuminemia. Moreover, changes in clotting factors levels may be due to intravascular thrombin formation (marked by increased plasma levels of fibrinopeptide A). During active phases of glomerulonephritides (GN) with NS, thrombin formation might in fact arise in glomeruli, following activation of the glomerular hemostasis system. Isolated glomeruli from human crescentic GN, rabbit nephrotoxic GN and rat HgCl2 autoimmune GN produce excessive amounts of procoagulant (tissue factor) activity (PCA). Sequential studies of the self-limited HgCl2 GN showed that glomerular PCA, proteinuria and glomerular fibrin deposits peaked concomitantly at the acme of the disease, suggesting that immunologically mediated glomerular damage had triggered the extrinsic coagulation pathway

ISSN:0250-8095    

DOI:10.1159/000168196

出版商:S. Karger AG    

年代:1990

数据来源: Karger