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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 1994  |  Volume : 5  |  Issue : 1  |  Page : 28-32
Arterial Thrombosis in Nephrotic Syndrome due to Minimal Change Glomerulonephritis

1 Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait
2 Ameri Renal Center, Ministry of Health, Kuwait

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We describe our experience with spontaneous arterial thrombosis (AT) in two men with nephrotic syndrome secondary to minimal change glomerulonephritis. Arterial thrombosis developed shortly after a nephrotic crisis in each case. Serum antithrombin III, protein C and protein S levels were normal in both patients. The two cases emphasize the role of defective hemodynamic circulation in the pathogenesis of AT in patients with nephrotic syndrome. Despite their atastrophic presentation, the patients ultimately responded to multiple thrombectomies, volume expanders, anticoagulants and steroid therapy.

Keywords: Arterial thrombosis, Minimal change glomerulonephritis, Anticoagulation, Nephrotic syndrome.

How to cite this article:
El-Reshaid K, Kapoor M, Hakim A. Arterial Thrombosis in Nephrotic Syndrome due to Minimal Change Glomerulonephritis. Saudi J Kidney Dis Transpl 1994;5:28-32

How to cite this URL:
El-Reshaid K, Kapoor M, Hakim A. Arterial Thrombosis in Nephrotic Syndrome due to Minimal Change Glomerulonephritis. Saudi J Kidney Dis Transpl [serial online] 1994 [cited 2022 Jul 6];5:28-32. Available from: https://www.sjkdt.org/text.asp?1994/5/1/28/41358

   Introduction Top

Nephrotic syndrome (NS) is associated with an increased risk for spontaneous thrombosis. Deficiency of antithrombin III, protein C and protein S are considered major predisposing factors since low levels of these natural anticoagulants are prevalent in, and their urinary losses correlate with, the severity of the NS [1] . Thrombosis, when it occurs, usually affects the venous side of circulation and arterial thrombosis (AT) is rare [2] . We report two patients in whom AT developed shortly after the relapse of NS while their antithrombin III, protein C and protein S levels were normal. The role of defective hemodynamic circulation during nephrotic crisis and that of microscopic atherosclerosis in chronic cases will be discussed.

Case I

A 45 year old Pakistani male developed the NS in 1975. At that time, a kidney biopsy showed minimal change glomerulonephritis. Since then, he had four relapses treated each time with steroids achieving prompt response. The last relapse was about two years ago. One week prior to the current admission he had a relapse and presented with anasarca. He refused admission initially and was given prednisone 1 mg/kg daily along With spironolactone 25 mg orally, three times daily.

The patient was subsequently hospitalized with a one day's history of severe pain and swelling of the right leg. His blood pressure was 90/60 mm Hg and central venous pressure was 0 cm water. Hemoglobin was 19 gm/dl and platelet count was 300 x 109/L. Blood urea and serum creatinine levels were normal. Serum albumin was 9 gm/L and 24 hours urinary protein excretion was 11 gm. He was managed with infusions of human albumin to maintain a central venous pressure of at least 5 cm water.

At the time of presentation the patient's antithrombin III, protein C and protein S levels were normal (47%, 90% and 105% respectively by functional assay). The hemoglobin level during the attack of 19 gm/dl was secondary to intravascular volume contraction since he had normal red cell mass and leukocytic alkaline phosphatase. Initially, serum cholesterol was 7.2 mmol/L which decreased to 3.5 mmol/L after two months. The heart was examined as a possible source of emboli using echocardiogram. The test was normal.

An aorto-femoral angiogram revealed a "saddle" thrombus obstructing both common iliac arteries, the right more than the left, with a normal appearance of the vessel wall [Figure 1]. Thrombectomy was done, as well as fasciotomy of the right leg to relieve a compartmental syndrome which had resulted in ischemic rhabdomyolysis. The thrombus was 2 x 5 cm of fibrin meshwork containing erythrocytes and a few neutrophils.

He received heparin to keep the activated thromboplastin time at twice the normal control level. Heparin was given in a dose of 10,000 IU initially followed by a maintenance dose of 1,000 IU per hour. The patient rethrombosed twice during the first 48 hours of admission and thrombectomies were performed each time. He also received prednisone 1 mg/kg daily, which was tapered gradually over two months. The patient's NS responded promptly to corticosteroid administration, after one week, his serum albumin had increased to 30 g/L and after one month of therapy the urinary protein excretion decreased to 200 mg/day.

He left the hospital one month later with a right foot drop secondary to nerve compression (confirmed by EMG) which occurred despite the fasciotomy. He was continued on warfarin 5 mg daily for 6 months in addition to aspirin 100 mg daily.

Case No. 2

A 50 year old Kuwaiti male was admitted for evaluation of anasarca of two weeks duration. He had used furosemide 40 mg daily for one week prior to his admission. His systolic blood pressure was 100 mm Hg lying down and fell to 70 mm Hg on standing. Serum albumin was 8 gm/L and urinary protein excretion was 20 gm/day. The left foot was cold to touch and the popliteal pulsations were absent. Digital substraction angiography showed complete obstruction of the left femoral artery with normal appearance of the blood vessels [Figure 2]. He underwent thrombectomy and the pathological examination of the thrombus showed a recent, benign, large blood clot. He was managed with anticoagulation (usual loading and maintenance dosing of heparin) and after one week, heparin was replaced by warfarin. He received 40 gram of human albumin intravenously twice daily.

Furosemide (80 mg) was given after stabilization of his intravascular volume and only when he was symptomatic of his anasarca. Serological tests for secondary causes of nephrotic syndrome were negative. Renal biopsy was performed after two weeks and showed minimal change glomerulonephritis. He received prednisone 1 mg/kg daily and after two weeks of therapy, the edema subsided and the peripheral circulation was intact. Clinical examination and investigations showed no evidence of myeloproliferative disease or malignancy. Echocardiogram was normal. Upon admission antithrombin III, protein C and protein S levels were normal (80%, 90% and 120% respectively by functional assay). Serum cholesterol was 8 mmol/L and decreased after two months of therapy to 4 mmol/1. Warfarin therapy was continued for six months.

   Discussion Top

Arterial thrombosis in patients with NS was first reported in 1935 [3] . The condition is rare compared to venous thrombosis and to our knowledge only 62 cases have been reported to date [4],[5],[6],[7],[8],[9],[10],[11] . In these patients, lack of significant radiological evidence of atherosclerosis associated with spontaneous thrombosis suggested that NS is a "prothrombotic state." Recent clinical observations describe thrombosis as a reflection of "defective interaction between vascular endothelium, platelet and coagulation systems" [12] . Normally, protein C binds to thrombomodulin on endothelial surface of blood vessels aided by its co-factor, protein S. Activated protein C binds to thrombin and inhibits coagulation through its proteolytic destruction of factors Va and Villa. Antithrombin III inactivates free thrombin and transports it to the liver for degradation [13] . The two cases described in this report had normal levels of these natural anticoagulants which indicated that other pathogenic factors were responsible for AT in them. Earlier reports [4],[5],[6],[7],[8],[9],[10],[11] have shown that AT in NS was not limited to any specific age group, sex, site or glomerular pathology [Table 1]. The duration between the onset of AT and NS varied considerably between patients. The onset of AT was short (days) in severe and acute forms e.g. most cases of minimal change disease, while moderate and chronic cases such as proliferative and membranous glomerulonephritis developed AT after a much longer latent period (months or years). This observation indicates that different mechanisms might contribute to thrombosis in different patients i.e. defective hemodynamic circulation in those who present with acute and severe NS, and "microscopic atherosclerosis" in those who have prolonged and indolent course.

Both our patients had acute decrease in oncotic pressure (nephrotic crisis) and their intravascular volume was probably further compromised by diuretic use.

Clinical and experimental studies have shown that acute and severe forms of NS have low intravascular volume [14] , while those with chronic and moderate forms are protected through "wash out of proteins in tissue fluids" that ultimately balances the oncotic pressure between the intravascular and interstitial fluid compartments [15] . On the other hand, microscopic atherosclerosis is common in patients with chronic NS due to persistent hypercholesterolemia and/or long-term steroid therapy [4] . Traditionally, macroscopic atherosclerosis is acknowledged as fixed lesions (plaques) limiting directly the blood flow and causing AT. However, recent reports have shown that atherosclerosis even at the microscopic level impairs the endothelial function and promotes thrombosis [12] . Normally, aggregated platelets release vasoactive substances and initiate the coagulation cascade through thrombin formation. Intact endothelium serves as a diffusion barrier to prevent such vasoactive substances from reaching smooth muscle layers of media thereby causing contraction [12] . Furthermore, the endothelium degrades some of these substances and prevents platelet aggregation through production of Prostacyclin (PGI2) and Endothelium - Dependent Relaxing Factor (EDRF), which are vasodilators [12] . The production of PGI2 and EDRF diminish as a consequence of atherosclerosis [12] . Ultimately, patients with chronic NS and microscopic atherosclerosis become "thrombotic prone."

Review of the literature [3],[4],[5],[6],[7],[8],[9],[10],[11] showed a high morbidity and mortality associated with AT in patients with NS. Most of these cases ended with death, loss of organs or amputations. It should be emphasized that surgery, anticoagulation and treatment of the primary disease are the corner stones of therapy. These measures should be combined with early support of the hemodynamic state and measures to limit atherosclerosis in order to avoid failure of therapy and/or rethrombosis. Our two cases show that such therapy could be successful if instituted promptly.

   Acknowledgement Top

We thank Augustilia G. Pinto for her secretarial assistance.

   References Top

1.Kauffmann RH, Veltkamp JJ, Van Tilburg NH, Van Es LA. Acquired antithrombin III deficiency and thrombosis in the nephrotic syndrome. Am J Med 1978;65:607-13.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Cameron JS, Ogg CS, Wass VJ. Complications of the nephrotic syndrome. In: Cameron JS, Glassock RJ. (eds). The nephroticsyndrome New York, Marcel Dekker, 1988;849-920.  Back to cited text no. 2    
3.Schwartz H, Kohn JL. Lipoid nephrosis: a clinical and pathological study. Am J Dis Child 1935;49: 579-93.  Back to cited text no. 3    
4.Patel R, Mandal AK. Arterial thrombosisassociated with the nephrotic syndrome. J Cardiovasc Surg 1978;19:129-34.  Back to cited text no. 4    
5.Sullivan MJ 3d, Hough DR, Agodoa Y. Peripheral arterial thrombosis due to the nephrotic syndrome: the clinical spectrum.South Med J 1983;76: 1011-6.   Back to cited text no. 5    
6.Malinverni R, Mahler F, Steurer J, Kuhlmann U. Arterial thrombosis in the nephrotic syndrome. Schweiz Med Wochenschr 1983; 113: 1576-80.  Back to cited text no. 6  [PUBMED]  
7.Nitatori T, Niitu K, Kudoh S, Satoh Y, Abe K. Femoral arterial thrombosis in nephritic syndrome. Steroid and long term heparin therapy. J Cardiovasc Surg 1987;28:189-92.  Back to cited text no. 7    
8.Liote H, Baglin A, Feret J, et al. Acute ischemia of the lower limbs in nephrotic syndrome in a young woman. Sem Hop Paris1983;59:2831-3.  Back to cited text no. 8    
9.Menon A, Wang F. Arterial thrombosis in nephrotic syndrome. Singapore Med J 1977; 18; 196-200.  Back to cited text no. 9    
10.Temes Montes XL, Almaraz Jimenez MA, Lorenzo Aguiar MD, et al. Renal artery thrombosis occuring in an adult with theidiopathic nephrotic syndrome, results of local treatment with streptokinase. Clin Nephrology 1979; 12:90-2.  Back to cited text no. 10    
11.Parag KB, Somers SR, Seedat YK, Byrnes S, Da Cruz CM, Kenoyer G. Arterial thrombosis in nephrotic syndrome. Am JKidney Dis 1990; 15: 176-7.  Back to cited text no. 11    
12.Hoak JC, ed. The endothelium, platelet and coronary spasm, In: Advances in Intern Med 1989 (vol 34), Year Book Med Publishers,353-75.  Back to cited text no. 12    
13.Nossel HL. In: Petersdorf RG, Adams RD, Braunwald E, Isselbacher KJ, Martin JB, Wilson JD. (eds). Principles of InternalMedicine, New York, McGraw-Hill 10 th edition 1985.  Back to cited text no. 13    
14.Meltzer JI, Keim HJ, Laragh JH, et al. Nephrotic syndrome: vasoconstriction and hypervolymic types indicated by renin-sodiumprofiling. Ann Intern Med 1979;91:688-96.  Back to cited text no. 14  [PUBMED]  
15.Koomans HA, Geers AB, Dorhout Mees EJ, Kortlandt W. Lowered tissue-fluid oncotic pressure protects the blood volume in thenephritic syndrome. Nephron 1986;42:317-22.  Back to cited text no. 15  [PUBMED]  

Correspondence Address:
K El-Reshaid
Department of Medicine, Faculty of Medicine, Kuwait University
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Source of Support: None, Conflict of Interest: None

PMID: 18583759

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