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 Table of Contents  
Year : 2022  |  Volume : 9  |  Issue : 2  |  Page : 238-241

Unusual presentation of membranous nephropathy

Department of Nephrology, MGM Medical College and Hospital, Aurangabad, Maharashtra, India

Date of Submission12-Aug-2021
Date of Acceptance04-May-2022
Date of Web Publication17-Jun-2022

Correspondence Address:
Dr. Sudhir Gajanan Kulkarni
Department of Nephrology, MGM Medical College and Hospital, N-6, CIDCO, Aurangabad 431003, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mgmj.mgmj_60_21

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Stroke is one of the most severe complications of nephrotic syndrome (NS) which causes severe mortality and morbidity and patient initially presenting with stroke is rare. Here, we describe a case in which an 18-year-old female presented with ischemic stroke as an initial complication of membranous nephropathy (MN). Renal biopsy showed features of MN. This case illustrates that it is important to diagnose MN and anticoagulated this high-risk group of patients before they develop severe complications. There are only a few cases in the literature where the initial presentation of MN is ischemic stroke and it occurs in a young female patient with no risk factors apart from NS.

Keywords: Membranous nephropathy, stroke, young female

How to cite this article:
Data A, Gadekar KG, Mogal VR, Ayyagari S, Kulkarni SG. Unusual presentation of membranous nephropathy. MGM J Med Sci 2022;9:238-41

How to cite this URL:
Data A, Gadekar KG, Mogal VR, Ayyagari S, Kulkarni SG. Unusual presentation of membranous nephropathy. MGM J Med Sci [serial online] 2022 [cited 2022 Jul 6];9:238-41. Available from: http://www.mgmjms.com/text.asp?2022/9/2/238/347699

  Introduction Top

Thromboembolism (TE)is one of the most severe complications of nephrotic syndrome (NS). The incidence of Venous Thromboembolism (VTE) reported in the literature varies from 3.4%[1] to as high as 35%.[2] Literature on the epidemiology of Arterial Thromboembolism (ATE) is scarce with one study showing the annual incidence of ATE to be 1.5%.[3] The varied incidence of TE is mainly due to different risk factors associated with it which include male sex, proteinuria, low serum albumin (SA), and histological diagnosis.[1] Among different histological diagnoses, membranous nephropathy (MN) seems to be most commonly associated with TE.[1],[2],[3] Risk of VTE in MN has been reported as 37% in one review[4] and 19.2% in another[3] with just one patient out of 78 having ATE in form of Stroke. Ischemic stroke is a devastating phenomenon and has been reported sporadically with MN sometimes as the first presentation of the disease[4] and sometimes in already diagnosed cases.[5]

We here present a case of a young female who presented with ischemic stroke as an initial manifestation of MN with no additional risk factor.

  Case report Top

Eighteen-year-old female presented with acute onset of left upper and lower limb weakness and slurring of speech. She gave a history of deviation of the angle of the mouth towards the right. There was no bowel and bladder involvement. There was no history of loss of consciousness, seizures, headache, or fever.

She had a history of bilateral pedal edema 3 months before this illness. She had no history of rheumatic heart disease, syncope, tuberculosis, hypertension, diabetes, or peripheral vascular disease. She had no history of any drug or substance abuse, no history of any prior hospital admissions, surgeries, or allergies. She had normal menstrual cycles. There was no significant family history.

On examination, the patient had normal blood pressure and other vital signs were normal. There was bilateral pitting pedal edema. She was conscious and oriented in time, place, and person. Her speech was slurred with normal comprehension. Her intelligence and memory were intact. Cranial nerve examination was normal apart from upper motor neuron type of left facial nerve palsy. Motor system examination suggestive of left-sided upper motor neuron type of left hemiparesis with grade 3 power. Her fundus examination was normal. Examination of other systems was normal.

Her magnetic resonance imaging (MRI)brain showed an area of restricted diffusion with corresponding low apparent diffusion coefficient values noted in the right Centrumsemi ovale and bilateral frontoparietal lobe appearing hyperintense on coronal fluid-attenuated inversion recovery (FLAIR)images suggestive of acute external water-shed infarcts likely embolic. Her MR angiography of the brain and major vessels did not show any abnormality. Other lab reports revealed that she had nephrotic range proteinuria with decreasedSAand dyslipidemia[Table 1]. Ultrasonography of the abdomen had bulky kidneys with bilateral pleural effusion. 2D-Echo did not reveal any abnormality. No arrhythmia was found during Holter monitoring. She was started on Aspirin 150 mg with Atorvastatin 20 mg once daily and Enoxaparin 0.6cc subcutaneously twice daily. Anti-Nuclear antibody, Anti-neutrophil cytoplasmic antibody (ANCA), and Anti-phospholipid antibody were negative. Considering her NS kidney biopsy was done which showed a core of renal cortex with 6 glomeruli and 1 artery. The glomeruli showed a mild, diffuse thickening and rigidity of the basement membrane with subepithelial pinholes and no increase in cellularity. The tubules were closely packed with no significant atrophy, interstitium and blood vessels were unremarkable. The immunofluorescence showed 4 glomeruli with significant peripheral fine granular deposits of IgG. Features were suggestive of MN. Electron microscopy and Anti phospholipase A2 receptor (PLA2R) antibody staining of the sample could not be done, however, her serum Anti PLA2R IgG was negative. Protein C and S could not be done.
Table 1: Laboratory investigations

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She was then advised to start Tab Tacrolimus 0.1 mg /kg body weight in two divided doses and prednisolone 10 mg per day. After 3 days she was started on tablet Warfarin 4 mg once daily. She showed neurological recovery after 15 days with the power of grade 5 but still complained of weakness in the fine distal movements of the left hand.

  Discussion Top

We describe here a case of an 18-year-old female who presented with ischemic stroke of possible embolic etiology with NS later diagnosed as MN. Our patient had severe hypoalbuminemia and 24-hour urinary protein excretion of 6.5 grams which has also been implicated as a risk factor for TE. Gyamlani et al. and Barbour et al. concluded that VTE was directly proportional to the severity of proteinuria and inversely related to the albumin level.[1],[6] Another study on Idiopathic MN compared patients who did not have an event, those who had a TE had significantly greater 24-hour proteinuria (10.7gm v/s 7.1gm), and lower SA (1.9 v/s 2.4), and higher serum cholesterol (414 v/s 317).[3] Zou et al. implicated hypoalbuminemia as the dominant independent risk factor for VTE but did not find hypoalbuminemia to be a risk factor for ATE. Risk factors for ATE were severe proteinuria, aging, smoking, hypertension, and prior ATE with aging was demonstrated as the independent risk factor for ATE.[7] A single-center retrospective study also reported that neither the degree of proteinuria nor the level of SA predicted ATE rather male sex, age, hypertension, diabetes, smoking, prior ATE, and estimated glomerular filtration rate were significantly associated with ATE.[8] MN has male predominance with a median age of presentation being 40 years in the Indian population.[9] The risk of TE is found to be maximum within the initial 6 months. A study published in 2008 showed that annual incidences of VTE and ATE were 1.02% and 1.48% respectively but over the first 6 months, these rates were 9.85% and 5.52% respectively.[8] Two more studies done on idiopathic MN patients concluded that most of the events occurred within the first 6 months of the disease.[3],[7]

Pallavi et al. reported a case who presented with stroke and right middle cerebral artery (MCA)infarcts, patient was a 34-year-old female with SA of 1.7 g/dL, nephrotic range proteinuria, and normal renal function, without any other risk factor.[4] This patient was similar to our patient apart from being an indifferent age group. Another case associated ischemic stroke of embolic etiology with MN. A 43-year-old female, smoker, presented with hypoalbuminemia, proteinuria, and myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA)slightly elevated. Her CT angiography showed evidence of TE.[5] A case of renal artery thrombosis with renal infarction in a 42-year-old male patient diagnosed to have MN 7 years before this event was found to have increased creatinine with hypoalbuminemia and proteinuria.[10] Gigantic et al. reported a case of a 71-year-old male of MN with hypertension and auto-immune hemolytic anemia (AIHA), who presented with ATE[11] [Table 2].
Table 2: Summary of published case on ATE in NS

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  Conclusion Top

Complications are an important cause of morbidity so, risk stratification should be done for all cases with MNand anticoagulation should be considered in patients’ high-risk profiles. Although many cases are reported of ATE, our case is peculiar as our patient is a young female of 18 years without any risk factors.NS should be ruled out in all cases of young stroke as it is a rare but potential cause for stroke.

Ethical consideration

Approval/clearance has been obtained from the Institutional Ethics Committee of MGM Medical College and Hospital, Aurangabad, Maharashtra, India vide letter no.MGM-ECRHS/2021/58dated08/07/2021 for undertaking the proposed study on unusual presentation of Membranous Nephropathy. Also informed written consent has been taken from the patient and her parents.

Financial support and sponsorship

Not applicable.

Conflicts of interest

There are no conflicts of interest.

  References Top

Barbour SJ, Greenwald A, Djurdjev O, Levin A, Hladunewich MA, Nachman PH, et al. Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int 2012;81:190-5.  Back to cited text no. 1
Zhang LJ, Zhang Z, Li SJ, Meinel FG, Nance JW Jr, Zhou CS, et al. Pulmonary embolism and renal vein thrombosis in patients with nephrotic syndrome: Prospective evaluation of prevalence and risk factors with CT. Radiology 2014;273:897-906.  Back to cited text no. 2
Kumar S, Chapagain A, Nitsch D, Yaqoob MM Proteinuria and hypoalbuminemia are risk factors for thromboembolic events in patients with idiopathic membranous nephropathy: An observational study. BMC Nephrol 2012;13:107.  Back to cited text no. 3
Pallavi R, Sunggeun L, Baumstein D, Mendoza RC, Chaudhari A Stroke in a young woman as a presenting manifestation of membranous nephropathy. Am J Ther 2016;23:e950-4.  Back to cited text no. 4
Roy C, Deschaintre Y, Sabbagh R, Roy D, Cardinal H, Bollée G Ischemic stroke of possible embolic etiology associated with nephrotic syndrome. Kidney Int Rep 2017;2:988-94.  Back to cited text no. 5
Gyamlani G, Molnar MZ, Lu JL, Sumida K, Kalantar-Zadeh K, Kovesdy CP Association of serum albumin level and venous thromboembolic events in a large cohort of patients with nephrotic syndrome. Nephrol Dial Transplant 2017;32:157-64.  Back to cited text no. 6
Zou PM, Li H, Cai JF, Chen ZJ, Li C, Xu P, et al. A cohort study of incidences and risk factors for thromboembolic events in patients with idiopathic membranous nephropathy. Chin Med Sci J 2018;33:91-9.  Back to cited text no. 7
Mahmoodi BK, ten Kate MK, Waanders F, Veeger NJ, Brouwer JL, Vogt L, et al. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: Results from a large retrospective cohort study. Circulation 2008;117: 224-30.  Back to cited text no. 8
Das U, Dakshinamurty KV, Prayaga A Pattern of biopsy-proven renal disease in a single center of South India: 19 years experience. Indian J Nephrol 2011;21:250-7.  Back to cited text no. 9
Nandwani A, Pathania D, Jha PK, Kher V Renal artery thrombosis with renal infarction: A rare cause of acute abdomen. Indian J Nephrol 2017;27:313-5.  Back to cited text no. 10
Gigante A, Barbano B, Liberatori M, Sardo L, Gasperini ML, Rosato E, et al. Nephrotic syndrome and stroke. Int J Immunopathol Pharmacol 2013;26:769-72.  Back to cited text no. 11


  [Table 1], [Table 2]


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