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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2016  |  Volume : 27  |  Issue : 2  |  Page : 391-394
Cerebral venous thrombosis and secondary polycythemia in a case of nephrotic syndrome

1 Department of Nephrology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
2 Department of Radiology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India

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Date of Web Publication11-Mar-2016


Cerebral venous thrombosis (CVT) and polycythemia are considered as rare and life threatening complications of nephrotic syndrome. We report an unusual combination of both these complications in a case of nephrotic syndrome due to minimal change disease that was treated successfully. There was prompt and complete remission of nephrotic syndrome with steroid therapy, concurrent with complete resolution of polycythemia and CVT.

How to cite this article:
Nagaraju SP, Bairy M, Attur RP, Sambhaji CJ. Cerebral venous thrombosis and secondary polycythemia in a case of nephrotic syndrome. Saudi J Kidney Dis Transpl 2016;27:391-4

How to cite this URL:
Nagaraju SP, Bairy M, Attur RP, Sambhaji CJ. Cerebral venous thrombosis and secondary polycythemia in a case of nephrotic syndrome. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Nov 29];27:391-4. Available from: https://www.sjkdt.org/text.asp?2016/27/2/391/178575

   Introduction Top

Patients with nephrotic syndrome are at increased risk of thromboembolic complications. Multiple factors contribute to the hypercoagulable state. [1],[2] Cerebral venous thrombosis (CVT) is a very rare and serious complication with a few isolated reports in the medical literature. [2],[3],[4],[5] Secondary polycythemia in nephrotic syndrome is also unusual and has been described with minimal change disease and membranous nephropathy. [6],[7],[8]

We report an unusual combination of both of these complications occurring in a patient with minimal change disease who recovered completely with early detection and prompt treatment.

   Case Report Top

A 27-year-old young man with no significant past medical history presented with four days history of facial puffiness, decreased urine output, vomiting, headache, and photophobia. On physical examination, he was afebrile, his blood pressure was 200/110 mm Hg, his eyes were congested, and his face was puffy. Ocular fundus examination showed papilledema. There was no pedal edema and the rest of the systemic examination was unremarkable.

On initial laboratory investigation, hemoglobin was 22.8 g/dL; packed cell volume was 68.5%; serum albumin was low (1.8 g/L); urinalysis showed 3+ proteinuria without hematuria; blood urea was 46 mg/dL; serum creatinine was 2.0 mg/L; complement levels (C3, C4) were within normal limits; anti-nuclear antibodies were negative; 24-h urine proteinuria was 8.3 g; arterial blood gas analysis was normal.

Ultrasound abdomen showed bulky kidneys with normal size. Renal vein and arterial Doppler were normal. Accordingly, a clinical diagnosis of nephrotic syndrome with acute kidney injury, polycythemia, and severe hypertension was made, and the patient was started on three antihypertensive medications and intravenous nitroglycerin drip. He was also subjected to phlebotomy in view of polycythemia. Once the blood pressure was controlled, he was subjected to a kidney biopsy and was empirically started on prednisolone 60 mg/day. He also underwent a bone marrow aspiration and biopsy. JAK 2 mutation analysis and erythropoietin levels were obtained as further work-up for polycythemia. His serum erythropoietin levels were normal. JAK 2 mutation was not detected and there was no evidence of a myeloproliferative disorder in the bone marrow biopsy.

Since his headache and photophobia were persistent despite good control of blood pressure, a magnetic resonance imaging (MRI) of brain was done to detect any intracranial event. MRI showed thrombosis of the superior sagittal, right transverse sinus, and right sigmoid sinus [Figure 1] and a small area of venous infarct in the right precentral gyrus [Figure 2].
Figure 1: Magnetic resonance imaging brain showing loss of flow void with high signal intensity opacity in the superior sagittal, right sigmoid and right transverse sinus.

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Figure 2: Magnetic resonance imaging brain showing area of diffusion restriction in the right precentral gyrus suggestive of venous infarct.

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His kidney biopsy showed nine glomeruli which were essentially normal with minimal increase in mesangial matrix in two glomeruli. Immunofluorescence was negative for IgG, IgM, IgA, and C3. The diagnosis of nephrotic syndrome was minimal change disease.

Secondary polycythemia and cortical venous thrombosis were added to the list of the medical complications of the nephrotic syndrome of the patient. During the hospital stay, he was continued on the antihypertensive agents, steroids (60 mg/day), and phlebotomy. Intravenous heparin was given for cortical venous thrombosis for a week and was switched to warfarin to target an INR of 2-3. Within three days of control of hypertension and initiation of steroids, serum creatinine was normalized to 1.0 mg/dL.

On follow-up, the patient's proteinuria disappeared in two weeks. His hemoglobin decreased to 14 g/dL and was normalized by the end of four weeks. Steroids were tapered and stopped. His antihypertensive medications were gradually decreased and discontinued in two months. He was continued on oral anticoagulation for six months. Presently, the patient is asymptomatic and is not on any medications and doing well.

   Discussion Top

The association of nephrotic syndrome and thromboembolic phenomena is well known. In adults with nephrotic syndrome, common sites of thrombosis include the deep veins of the lower limbs and the renal veins. [9] Several mechanisms are responsible for the development of a hypercoagulable state in nephrotic syndrome including the urinary loss of antithrombin III, protein C, and protein S coupled with increased production of fibrinogen and coagulation factors, besides alteration in platelet function, hemoconcentration, hypoalbuminemia, hyperlipidemia, increased blood viscosity, thrombocytosis, dehydration, and use of diuretics and steroids. [1],[2],[9],[10]

Involvement of cerebral vessels has been rarely reported in nephrotic syndrome. It is probably less recognized or remains underreported. [10],[11] Clinical presentation of CVT is extremely variable and nonspecific. It may just present with headache, vomiting with or without signs of raised intracranial pressure, as presented in our case, or it may present with severe symptoms such as focal or generalized seizures, decreased level of consciousness, and/or focal neurological deficits including hemiparesis and cranial nerve palsies. The diagnosis can be difficult without appropriate imaging. [2],[3],[12] MRI with magnetic resonance venography is the preferred modality over computerized tomography scan for diagnosis and follow-up of cerebral venous thrombosis because of its high sensitivity. [13]

The most commonly used treatment is unfractionated heparin or low-molecular-weight heparin to arrest the thrombotic process for the initial few days with an overlap of oral anticoagulants in the last two days of parental heparin. [14] The optimal duration of oral anticoagulant treatment after the acute phase is unknown in this particular situation, but in the absence of recurrent thrombosis it is to be continued at least for 6 months with targeted INR range of 2.0-3.0. [15] If not recognized early and treated promptly, CVT may cause significant morbidity or mortality. Our patient was treated with steroids, unfractionated heparin followed by oral anticoagulant for six months. He showed a complete recovery of CVT.

In addition to CVT, our patient also had secondary polycythemia, which also could have contributed for the hypercoagulable state. Secondary polycythemia is occasionally associated with renal diseases such as renal cysts, tumors, renal artery stenosis, and postrenal transplantation. [16] It is rare with the nephrotic syndrome, [6],[8] and pathogenesis of secondary polycythemia associated with the nephrotic syndrome is not clear. Heavy proteinuria and hypoalbuminemia can result in renal interstitial edema, ischemia and hypoxia. Increased production of erythropoietin due to renal ischemia and hypoxia or increased sensitivity to erythropoietin, abnormal feedback regulation of erythrocytosis, and extra renal erythropoietic substance were suggested as the mechanisms of secondary erythrocytosis in the nephrotic syndrome [6],[7],[16] besides the increased activity of renin-angiotensin system. [17] In our case, the erythropoietin levels were normal, bone marrow and JAK 2 mutation analysis was negative for primary polycythemia, and there was complete resolution of the polycythemia on the remission of the nephrotic syndrome. We did not use any angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for the control of polycythemia in our case.

We conclude that CVT and secondary polycythemia are rare but serious complications of the nephrotic syndrome. Our case is the first case report of this unusual combination in a case of minimal change disease. Early recognition and diagnosis of these allow the clinicians to commence appropriate treatment early and thereby reduce the associated morbidity.

Conflict of interest: None declared.

   References Top

Rabelink TJ, Zwaginga JJ, Koomans HA, Sixma JJ. Thrombosis and hemostasis in renal disease. Kidney Int 1994;46:287-96.  Back to cited text no. 1
Fluss J, Geary D, deVeber G. Cerebral sinovenous thrombosis and idiopathic nephrotic syndrome in childhood: Report of four new cases and review of the literature. Eur J Pediatr 2006;165:709-16.  Back to cited text no. 2
Rodrigues MM, Zardini LR, de Andrade MC, Mangia CM, Carvalhaes JT, Vilanova LC. Cerebral sinovenous thrombosis in a nephrotic child. Arq Neuropsiquiatr 2003;61:1026-9.  Back to cited text no. 3
Urch C, Pusey CD. Sagittal sinus thrombosis in adult minimal change nephrotic syndrome. Clin Nephrol 1996;45:131-2.  Back to cited text no. 4
Burns A, Wilson E, Harber M, Brunton C, Sweny P. Cerebral venous sinus thrombosis in minimal change nephrotic syndrome. Nephrol Dial Transplant 1995;10:30-4.  Back to cited text no. 5
Emanuel DA, Wenzel FJ. Erythrocytosis associated with the nephrotic syndrome. JAMA 1962;181:788-90.  Back to cited text no. 6
Singh G, Singh H, Singh N. Polycythaemia due to nephrotic syndrome. J Indian Med Assoc 1978;70:183-4.  Back to cited text no. 7
Sonneborn R, Perez GO, Epstein M, Martelo O, Pardo V. Erythrocytosis associated with the nephrotic syndrome. Arch Intern Med 1977; 137:1068-72.  Back to cited text no. 8
Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 1985;28:429-39.  Back to cited text no. 9
Divekar AA, Ali US, Ronghe MD, Singh AR, Dalvi RB. Superior sagittal sinus thrombosis in a child with nephrotic syndrome. Pediatr Nephrol 1996;10:206-7.  Back to cited text no. 10
Sébire G, Tabarki B, Saunders DE, et al. Cerebral venous sinus thrombosis in children: Risk factors, presentation, diagnosis and outcome. Brain 2005;128(Pt 3):477-89.  Back to cited text no. 11
Raizer JJ, DeAngelis LM. Cerebral sinus thrombosis diagnosed by MRI and MR venography in cancer patients. Neurology 2000;54: 1222-6.  Back to cited text no. 12
Rizzo L, Crasto SG, Rudà R, et al. Cerebral venous thrombosis: Role of CT, MRI and MRA in the emergency setting. Radiol Med 2010;115:313-25.  Back to cited text no. 13
Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2005;352:1791-8.  Back to cited text no. 14
Monagle P, Chan A, Massicotte P, Chalmers E, Michelson AD. Antithrombotic therapy in children: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126 3 Suppl:645S-87S.  Back to cited text no. 15
Basu TK, Stein RM. Erythrocytosis associated with chronic renal disease. Arch Intern Med 1974;133:442-7.  Back to cited text no. 16
Danovitch GM, Jamgotchian NJ, Eggena PH, et al. Angiotensin-converting enzyme inhibition in the treatment of renal transplant erythrocytosis. Clinical experience and observation of mechanism. Transplantation 1995;60:132-7.  Back to cited text no. 17

Correspondence Address:
Shankar Prasad Nagaraju
Department of Nephrology, Kasturba Medical College, Manipal University, Manipal - 576 104, Karnataka, India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.178575

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