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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2015  |  Volume : 26  |  Issue : 2  |  Page : 355-358
An unusual presentation of venous thrombosis in a child with idiopathic membranous nephropathy


1 Department of Nephrology, Gandhi Medical College, Hyderabad, Andhra Pradesh, India
2 Department of Radiology, Gandhi Medical College, Hyderabad, Andhra Pradesh, India

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Date of Web Publication3-Mar-2015
 

   Abstract 

Venous thrombosis is one of the major complications associated with nephrotic syndrome. Among the primary glomerular diseases, membranous nephropathy is associated with a high incidence of thrombotic events. Although this is well described in adults, there is paucity of the literature regarding venous thrombosis in children. Herein, we report such a thrombotic event involving both the lower limb veins and the inferior vena cava in a child with membranous nephropathy.

How to cite this article:
Burri S, Yadla M, Deshpande P, Enaganti R, Chada R, NarasimhaMoorthy NL, Kumar NA. An unusual presentation of venous thrombosis in a child with idiopathic membranous nephropathy. Saudi J Kidney Dis Transpl 2015;26:355-8

How to cite this URL:
Burri S, Yadla M, Deshpande P, Enaganti R, Chada R, NarasimhaMoorthy NL, Kumar NA. An unusual presentation of venous thrombosis in a child with idiopathic membranous nephropathy. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2019 Nov 12];26:355-8. Available from: http://www.sjkdt.org/text.asp?2015/26/2/355/152512

   Introduction Top


Venous thrombosis is a well-known complication associated with nephrotic syndrome. Deep venous thrombosis is the most common site of thrombosis. [1] Among the various causes of nephrotic syndrome in adults, the highest risk was reported to be with membranous nephropathy, followed by membranoproliferative glomerulonephritis and minimal change disease. [2] Whether children with membranous nephropathy are also at high risk for development of venous thrombosis is not known. One of the life-threatening thrombotic events is the thrombosis of the inferior vena cava (IVC). Herein, we report IVC thrombosis in a child with membranous nephropathy


   Case Report Top


A six-year-old girl was admitted for evaluation of edema of one-year duration. On examination, her blood pressure was 160/110 mm Hg. Systemic examination was normal. Papilledema was absent. Urine examination showed 4+ albuminuria and 15-20 RBCs/hpf. Blood urea was 20 mg/dL and serum creatinine was 0.8 mg/dL. The 24-h urine protein was 2.1 g/day, total cholesterol was 320 mg/dL and LDL-cholesterol was 228 mg/dL. Her total serum protein was 5.8 g/dL and serum albumin was 2.6 g/dL. Viral markers for hepatitis B, hepatitis C and retroviruses were negative. Renal biopsy showed 11 glomeruli with thickening of the basement membrane. Tubules, interstitium and vessels were normal. Immunofluorescence showed positive IgG and C3 along the basement membrane. These features were suggestive of membranous nephropathy. Serology evaluation for antinuclear antibody and anti-ds DNA was negative. She was initiated on oral steroids at 1 mg/kg, after which she went into remission.

Four years later, she presented with bilateral painful pedal edema. On examination, she had tenderness in both the calves. Urine examination showed 2+ albumin and the urine sediment was bland. The 24-h urine protein was 1.4 g/day. Blood urea was 28 mg/dL and serum creatinine was 0.7 mg/dL. Serum albumin was 2.1 g/dL. Doppler evaluation of both the lower limbs showed thrombosis in the popliteal and femoral veins bilaterally. The proximal extension of the thrombus was up to the IVC. There was no evidence of thrombus in the renal veins The prothrombin time, activated partial thromboplastin time, bleeding time, clotting time and platelet counts were all normal. Protein C, Protein S and antithromin III (ATIII) could not be assessed. Serology for ANA, anti-ds DNA and anti-Smith were negative. Anti-cardiolipin antibody (ACA) IgG was 15 GPL/mL, IgM was 18 MPL/mL and IgA was 11 APL/mL (normal up to 15 units/mL). She was initiated on low molecular weight heparin along with oral anticoagulants. For proteinuria, she was initiated on alternative regimens.

At the end of eight weeks of follow-up, a contrast-enhanced angiogram revealed partial re-canalization of the thrombus in infra-renal IVC and complete re-canalization in both the femoral and the popliteal veins bilaterally [Figure 1] and [Figure 2]. Her proteinuria at this time was 2 g/day.
Figure 1: Computed angiogram showing nonopacification of the inferior vena cava.

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Figure 2: Axial section of computed angiogram showing partial re-canalization of the inferior vena cava.

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   Discussion Top


One of the important complications of nephrotic syndrome in adults is thromboembolic events. The causes for increased incidence of thromboembolic complications are dehydration, diuretic usage, corticosteroids, coagulation protein abnormalities, impaired fibrino lysis, increased platelet aggregation and activation, increased fibrinogen levels, decrease in protein C, protein S, antithrombin III (ATIII), higher levels of fibrinopeptide A and loss of thrombin-antithrombin complex in urine.

In adults, membranous nephropathy has been reported to be associated with a high risk of development of thrombotic events, with the incidence varying between 7% and 36%. [3],[4] In the study by Lionaki et al, the incidence of venous thrombosis was found to be higher in the first two years of diagnosis. Hypoalbuminemia was thought to be an independent risk factor for venous thromboembolism. [3]

The incidence of thromboembolism in children with nephrotic syndrome compared with adults is reported to be lower (1.8-5%). [4] The lower incidence in children was attributed to an increase in the levels of protein C and alfa2 macroglobulin. Thromboembolism in children is commonly associated with congenital nephrotic syndrome, minimal change disease and focal segmental glomerulosclerosis. [4] In addition, due to the lower incidence of membranous nephropathy in children (<5% of cases), it is possible that only a few case reports exist for the thrombotic complications.

Deep veins of lower extremities are the most common sites of involvement. Renal venous thrombosis is the second common site. Involvement of major veins like the IVC is rare. Spontaneous IVC thrombosis is associated with conditions like surgery, malignancy, peripheral deep venous thrombosis extension and Budd Chiari syndrome. A high index of suspicion is needed for the diagnosis of IVC thrombosis.

The literature search revealed two cases of IVC thrombosis in adults with membranous nephropathy, [6],[7] of which the patient with acute IVC thrombosis could be successfully treated with anticoagulant therapy and the other patient had chronic IVC thrombosis.

Two cases of IVC thrombosis in children with membranous nephropathy were reported in the literature. Louis et al reported a spontaneous thrombotic event in a nine-year-old child with membranous nephropathy who developed thrombus in IVC extending from the hepatic veins till the right atrium. [4] It was proposed that the spontaneous thrombosis was due to activation of platelets, imbalance in the fibrinogen and the circulating anti-plasmins. Suto et al reported a 13-year-old child with thrombosis of the IVC and right renal vein. [5] The predisposing factors in this child were found to be high fibrinogen levels, factor VIII, low AT III and mild elevation of antiphospho lipid antibodies. [2]

Our patient had a spontaneous thrombotic event involving the bilateral lower limb veins and the IVC sparing the bilateral renal veins. At the time of the thrombotic event, she had nephrotic range proteinuria (>50 mg/kg/day). Proteinuria in our case is probably due to relapse of the glomerular disease. Bilateral renal vein thrombosis may be associated with nephrotic range proteinuria, but isolated IVC thrombosis causing nephrotic range proteinuria is not known. In our case, there was involvement of IVC and sparing of both the renal veins. In addition, the proteinuria continued even after the re-canalization of the IVC, for which she was initiated on alternative regimens.

Anticoagulation with heparin and warfarin was the treatment of choice in the past. [5] But, this may be associated with extension of caval thrombosis in 30% and recurrent pulmonary embolism in 20% of cases. Surgical strategies include saline jet aspiration thrombectomy, balloon embolectomy, etc.

In our case, there was thrombus in the popliteal veins and femoral and iliac veins, extending up to the IVC. The evaluation revealed normal coagulation profile and mild elevation of anti-cardiolipin antibodies (ACA). Thrombotic events are more commonly associated with high levels of IgG. But, in our case, the IgG levels were normal. Mild elevation of IgA levels alone may not be considered significant. The levels of protein C, protein S and AT III, lupus anticoagulant and anti-beta 2 glycoprotein antibodies could not be performed. With the anticoagulation therapy, there was complete re-canalization of the lower limb veins and partial re-canalization of the infra-renal IVC. Further extension of the thrombus or fresh thrombotic events was not observed during the six -month follow-up period.

The role of prophylactic anti-coagulation in nephrotic syndrome is still a matter of debate. But, it may be indicated in those with hypoalbuminemia (<2 g/dL), massive proteinuria and past history of thrombotic event.

The point of interest in this case is two fold: (1) occurrence of extensive thrombosis involving the bilateral lower limb veins and IVC in children with membranous nephropathy and (2) early recognition and timely initiation of anti-coagulation therapy are essential in preventing further progression.

 
   References Top

1.
Kayali F, Najjar R, Aswad F, Matta F, Stein PD. Venous thrombo-embolism in patients hospitalized with nephritic syndrome. Am J Med 2008;121:226-30.  Back to cited text no. 1
    
2.
Radhakrishnan J. Renal vein thrombosis and hypercoagulable state in nephrotic syndrome. In: Up to Date, Sheridan AM, Waltham MA, eds, 2011.  Back to cited text no. 2
    
3.
Lionaki S, Derebail VK, Hogan SL, et al. Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol 2012;7:43-51.  Back to cited text no. 3
    
4.
Louis CU, Morgenstern BZ, Butani L. Thrombotic complications in childhood-onset idiopathic membranous nephropathy. Pediatr Nephrol 2003;18:1208-300.  Back to cited text no. 4
    
5.
Suto M, Aviles DH. Treatment of inferior vena cava and renal vein thrombosis with low molecular weight heparin in a child with Idiopathic membranous nephropathy. Clin Pediatr (Phila) 2004;43:851-3.  Back to cited text no. 5
    
6.
Jeremiah P1, Mackenzie P, Fox JG, Mactier RA, Ingram S, Moss J. Acute inferior vena cava thrombosis in a patient with membranous nephropathy treated by rt-PA lysis. Nephrol Dial Transplant 1997;12(1):195-7.  Back to cited text no. 6
    
7.
Prabahar MR1, Jayakumar M, Soundararajan P. Chronic inferior venacava thrombosis in membranous nephropathy. Nephrol Dial Transplant 2008;23(7):2422-3.  Back to cited text no. 7
    

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Correspondence Address:
Dr. Manjusha Yadla
Department of Nephrology, Gandhi Medical College, Hyderabad, Andhra Pradesh - 500 503
India
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DOI: 10.4103/1319-2442.152512

PMID: 25758889

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