Acquired Deficiency and Urinary Excretion of Antithrombin III in Nephrotic Syndrome

Vaziri, Nosratola D.; Paule, Petra; Toohey, Julianne; Hung, Eleanor; Alikhani, Shahriar; Darwish, Riad; Pahl, M. V.

doi:10.1001/archinte.1984.00350210124021

Cited by 83 publications

(20 citation statements)

References 10 publications

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“…Thus a sole and direct casual relationship cannot be ascribed. Plasma AT III levels correlate well with serum albumin levels and the degree of proteinuria [3,12,14,17]. This relationship is explained by the molecular weight and charge of AT III that are quite similar to those of albumin.…”

Section: Discussionmentioning

confidence: 72%

Hemostatic problems and thromboembolic complications in nephrotic children

Çıtak

Emre

Sâirin

et al. 2000

Pediatric Nephrology

124

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A hypercoagulable state and the risk of thromboembolism in both arterial and venous circulation is a relatively frequent and serious feature of nephrotic syndrome (NS) in children and adults. The aim of this study was to evaluate the coagulation states of children with NS before and after corticosteroid (CS) therapy and to compare the results with a healthy control group. The first group consisted of 49 nephrotic children (30 boys and 19 girls) with a mean age of 6. 5+/-4.9 years (range 1-16 years). The control group included 17 healthy children (9 boys and 8 girls). At the time of admission, all patients were evaluated for the presence of clinical thromboembolism, hematological and biochemical indicators of a hypercoagulative state, and renal disease. This was repeated after CS treatment. Deep vein thrombosis was observed in 2 nephrotic patients who had very low plasma antithrombin III (AT III) levels and fibrinogen levels above 750 mg/dl. Thus, the prevalence of thromboembolism was 4% in our pediatric nephrotic population. The mean AT III level of the study group was 68.2+/-23.4% at the onset of the disease, which was significantly lower than the level of the control group (84.0+/-7. 6%). Plasma AT III levels increased to 74.4+/-15.3% after CS treatment, which correlated with the serum albumin levels. However, there was no correlation with urinary protein excretion. Protein C levels were higher than controls during all stages of the disease in both steroid-responsive and -unresponsive patients. The mean protein S level was similar in both groups. Plasma fibrinogen and cholesterol levels were significantly higher in the study group but decreased to within normal limits with remission. Our study suggests that thromboembolic complications are not infrequent in children with NS, and may be related to low plasma AT III and albumin and high fibrinogen and cholesterol levels.

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Section: Discussionmentioning

confidence: 72%

Hemostatic problems and thromboembolic complications in nephrotic children

Çıtak

Emre

Sâirin

et al. 2000

Pediatric Nephrology

124

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“…Low levels of antithrombin III have been shown to occur in as many as 80% of patients with nephrosis. 1 Various other conditions associated with nephrotic syndrome, including plasma lipid abnormalities, hypovolemia with hypoalbuminemia, hypertension, circulating immune complexes, and susceptibility to infection, are also considered to be factors contributing to the hypercoagulable state in nephrotic syndrome. Recently, a deficiency in free protein S has also been implicated as a contributing factor in thrombotic diathesis.…”

Section: Discussionmentioning

confidence: 99%

Acute arterial thrombosis with antithrombin III deficiency in nephrotic syndrome: Report of a case

et al. 2000

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Nephrotic syndrome frequently causes venous thromboembolic complications. Arterial thrombosis has rarely been reported and is mainly observed in children. Only six cases of lower extremity arterial thrombosis in adults have been reported in the literature. The outcome in these cases was unsatisfactory because of the high rates of limb loss and recurrence of thrombosis. We report successful treatment of a 39-year-old man who suffered from right lower extremity arterial thrombosis associated with decreased levels of serum antithrombin III. He was admitted to our hospital with severe pain in his right foot. No pulse was palpable in his right dorsalis pedis or posterior tibial arteries. His right foot was cold and mottled, with a reduced sensation and motor activity. The laboratory data revealed a serum total protein concentration of 3.9g/dl and an albumin concentration of 1.5 g/dl. The coagulation profile showed a fibrinogen level of 879 mg/dl and antithrombin III value of 9.5%. Right lower extremity arteriography showed a complete occlusion of the right deep femoral artery and popliteal artery, and a filling defect in the common femoral artery. An emergency thrombectomy was performed under general anesthesia. The patient was treated successfully, and surgical treatment was followed by anticoagulant therapy with 1,000 units of antithrombin III. A renal biopsy revealed histologic evidence of minimal change of glomerulonephritis. He was discharged 3 months later, and no recurrence of thrombosis has yet been observed.

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“…Although the fate of intraepithelial antithrombin in proximal tubules is not known, the physiological importance of tubule antithrombin is supported by significant reductions in plasma antithrombin concentrations in patients with end-stage renal disease (Vaziri et al 1994) and by low serum antithrombin concentrations in patients with nephrotic syndrome (Vaziri et al 1984;Farkas et al 1993) and in animal models of induced nephrotic syndrome (Cruz et al 1994). Indeed, the relatively short antithrombin half-life of 1.86 days (Hatton et al 1997) suggests that the kidneys may help to conserve high plasma antithrombin concentrations.…”

Section: Discussionmentioning

confidence: 99%

Localization and Characterization of Antithrombin in Human Kidneys

Torry

Labarrere

Nelson

et al. 1999

J Histochem Cytochem.

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Antithrombin is a serine protease inhibitor that is critical in maintaining a thromboresistant vasculature. The association between low serum antithrombin concentration and renal disease suggests that the kidney plays a role in the conservation of plasma antithrombin. We used immunohistochemical techniques to determine the spatial distribution, heparin binding characteristics, and intracellular and intercellular localization of antithrombin in biopsy specimens (n = 53) of human donor kidneys obtained at the time of transplantation. In the renal cortex, double antibody techniques demonstrated the presence of intracellular antithrombin in proximal tubule epithelial cells. The reactivity was granular and was co-localized with vesicle-like structures. Distal and collecting tubules did not demonstrate intraepithelial antithrombin reactivity. No tubule structures in the medullary region demonstrated intracellular antithrombin, but all these structures showed intense basement membrane antithrombin reactivity. Double antibody techniques also demonstrated that the heparin binding domain of intraepithelial antithrombin was occupied. Semiquantitative scores for intraepithelial antithrombin were significantly decreased in renal biopsy specimens obtained 30 min after anastomosis compared with biopsies from the same organ obtained before anastomosis. These findings suggest that antithrombin, probably in association with heparin or heparan sulfate, is internalized by renal proximal epithelial cells. Although the ultimate fate of intraepithelial antithrombin is not known, this may represent a mechanism by which the kidney helps to maintain plasma antithrombin concentrations.

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Acquired Deficiency and Urinary Excretion of Antithrombin III in Nephrotic Syndrome

Cited by 83 publications

References 10 publications

Hemostatic problems and thromboembolic complications in nephrotic children

Hemostatic problems and thromboembolic complications in nephrotic children

Acute arterial thrombosis with antithrombin III deficiency in nephrotic syndrome: Report of a case

Localization and Characterization of Antithrombin in Human Kidneys

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