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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR  
Year : 2022  |  Volume : 33  |  Issue : 1  |  Page : 221-224
Anticoagulation-related Nephropathy: An Uncommon Enemy!


1 Department of Pathology and Department of Nephrology, Kolkata, West Bengal, India., India
2 Department of Nephrology, Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India., India

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Date of Web Publication16-Jan-2023
 

   Abstract 


How to cite this article:
Sengupta M, Basu K, Dasgupta S, Chaudhury AR. Anticoagulation-related Nephropathy: An Uncommon Enemy!. Saudi J Kidney Dis Transpl 2022;33:221-4

How to cite this URL:
Sengupta M, Basu K, Dasgupta S, Chaudhury AR. Anticoagulation-related Nephropathy: An Uncommon Enemy!. Saudi J Kidney Dis Transpl [serial online] 2022 [cited 2023 Jan 29];33:221-4. Available from: https://www.sjkdt.org/text.asp?2022/33/1/221/367821


To the Editor,

Anticoagulation-related nephropathy (ARN) is a crucial but underappreciated consequence of anticoagulation therapy. The presence of gross hematuria and acute kidney injury (AKI) in a background of over-anticoagulation [international normalized ratio (INR) >3] raises the clinical suspicion.[1] However definitive diagnosis relies on the demonstration of excessive erythrocyte cast in distal tubules with acute tubular epithelial injury and demonstrable ferric iron or hemosiderin pigments in Perl’s stain in absence of active/acute glomerulonephritis. We present a case of a 17-year-old boy suffering from congenital cyanotic heart disease and developed biopsy-proven ARN following Warfarin therapy.

A 17-year-old boy, born out of non-consanguineous marriage presented to us with a history of oliguria, body swelling, and severe shortness of breath of one-week duration, preceded two weeks before by an episode of fever and upper respiratory tract infection. In the past history, parents told that child used to have cyanotic spells since his childhood and he undertook open heart surgery one year back, and after that, he was on regular blood thinning medication. Details of nature of the cardiac disease, nature of operation, drug list and doses were not known to them, nor could they show any previous records. No history of rash, arthralgia, photosensitivity, pain abdomen, epistaxis etc. No history of similar illness in past. Parents and one sibling were in good health.

General physical examination showed pallor with appreciable edema. Neck veins were engorged but no cyanosis was noticed. His pulse rate was 110 beats/min, blood pressure of 140/90 mm Hg and respiratory rate of 28 breaths/min. Systemic examination revealed bilateral pleural effusion with dull lung bases. On auscultation, s1 and s2 were audible with loud p2. A soft holosystolic murmur at the left parasternal area was detected. No organomegaly or any neurologic abnormality was noted. Fundus was normal on opthalmoscopic examination. Laboratory workup revealed abnormal renal function with baseline creatinine of 6 mg/dL and serum was blood urea nitrogen 91 mg/dL. Urine examination revealed 3+ proteinuria, plenty red blood cells, and albumin:creatinine ratio of 1.3. His serum albumin was 2.00 g/dL. Ultrasound examination revealed a bilateral normal-sized kidney with normal cortical echo texture and corticomedullary differentiation. Hemogram showed a hemoglobin of 9.5 g/dL, total leukocyte count of 12 × 10[9]/L with a normal differential count, and platelets of 1.65 × 10[9]/L. Fasting and post-prandial blood sugars were within normal limits. Liver function tests showed mildly raised transaminase level (aspartate transaminase/alanine transaminase 48/50). Coagulation workup revealed elevated INR of 2.2. Lipid profile showed normal triglyceride level. Serum complement levels were normal. His antinuclear antibodies, myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA) and PR3-ANCA were negative. Human immunodeficiency virus, hepatitis B surface antigen and anti-hepatitis C virus antibodies were negative.

A renal biopsy was performed under ultrasound guidance. Two cores received were processed and examined. A total of six glomeruli were identified and all were enlarged with diffuse and global mesangial matrix expansion with focal hypercellularity along inflated capillary loops. There was no evidence of any endocapillary or extracapillary proliferation. The glomerular basement membrane is stout without any appreciable spikes or double contouring in silver methanaminestained section. The tubules showed patchy minimal atrophy but acute tubular injury with extensive erythrocyte casts was identified. The interstitium showed minimal patchy fibrosis with extravasated erythrocytes in nonscarred interstitium. Vessels were unremarkable. Interstitial fibrosis with tubular atrophy was minimal (5%). Perl’s Prussian blue stained section revealed intracytoplasmic hemosiderin deposits in tubular epithelial cells [Figure 1] and [Figure 2]. Immunofluorescence findings of glomerular compartment revealed trace granular mesangial deposition of all immunoglobulin (Ig) heavy chains (IgG, IgA, and IgM); complements (C3c and C1q) and Ig light chains (kappa and lambda). No extraglomerular deposition was noted. Overall features were suggestive of mesangioproliferative glomerulonephritis with minimal tubulointerstitial chronicity. Considering the presence of acute tubular injury and extensive erythrocyte casts, anticoagulant-associated nephropathy was the final diagnosis.
Figure 1: Kidney biopsy finding (a) shows enlarged glomerulus and presence of red blood cell cast in distal tubule. (PAS, ×100), (b) shows global mesangial hypercellularity (PAS, ×200), (c) shows open and congested capillary loops without any appreciable spikes or double contouring along glomerular basement membrane (Jones Methanamine Silver, ×200).

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Figure 2: Kidney biopsy findings (a) shows excessive erythrocyte casts in distal tubules (Masson Trichrome, ×100), (b) shows extravasations of erythrocytes in interstitium (Masson Trichrome, ×200), (2) shows excessive erythrocyte casts in distal tubules (H and E, ×400), (d) intracytoplasmic hemosiderin deposits in tubular epithelial cells (Perl’s Prussian blue, ×200)

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In the hospital, he became anuric on day 2 with severe shortness of breath, urgent hemodialysis (HD) started with left femoral D/L catheter, but despite two successive sessions of HD, he remained dyspneic, so to rule out any late surgical complication of heart surgery, urgent ECHO done, that showed ventricular septal rupture, urgent cardiothoracic vascular surgery opinion sought, but patient collapsed on day 5 of in hospital course before surgical repair of rent could have been performed.

ARN is a freshly described pathological change characterized by unexplained AKI in a background of supratherapeutic anticoagulation. Initially, this entity was described as Warfarin-associated nephropathy, but later its association with other vitamin k antagonists such as dabigatran, apixaban, and rivaroxaban contributed to the shift to present terminology.[2]

Several confounding factors such as old age, diabetes, cardiovascular disease, and background chronic kidney disease pose difficulty in initial diagnosis and modify its clinical outcome.[3] In our case, background history of cyanotic heart disease creates a diagnostic dilemma and a renal biopsy was performed. The absence of endocapillary or extracapillary proliferation and significant immune complex deposition rules out acute or active glomerulonephritis which supports the clinical presumption of ARN. Glomerular changes such as enlargement, thick and dilated capillary channels, and mesangial matrix expansion may be attributed to cyanotic heart disease.[4] Although supportive care is the mainstay of management, high mortality was documented according to various literatures.[5]

ARN should be kept in mind while evaluating patients with unexplained AKI with oral anticoagulant therapy. A high index of suspicion, clinical finding, and native renal biopsy will help in reducing the number of under-diagnosed cases.

Conflict of interest: None declared.



 
   References Top

1.
Glassock RJ. Anticoagulant-related nephropathy: It's the real McCoy. Clin J Am Soc Nephrol 2019;14:935-7.  Back to cited text no. 1
    
2.
Ryan M, Ware K, Qamri Z, et al. Warfarin-related nephropathy is the tip of the iceberg: Direct thrombin inhibitor dabigatran induces glomerular hemorrhage with acute kidney injury in rats. Nephrol Dial Transplant 2014; 29:2228-34.  Back to cited text no. 2
    
3.
Brodsky S, Eikelboom J, Hebert LA. Anticoagulant-related nephropathy. J Am Soc Nephrol 2018;29:2787-93.  Back to cited text no. 3
    
4.
Gupte PA, Vaideeswar P, Kandalkar BM. Cyanotic nephropathy – A morphometric analysis. Congenit Heart Dis 2014;9:280-5.  Back to cited text no. 4
    
5.
Kalaitzidis RG, Duni A, Liapis G, et al. Anticoagulant-related nephropathy: A case report and review of the literature of an increasingly recognized entity. Int Urol Nephrol 2017;49:1401-7.  Back to cited text no. 5
    

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Correspondence Address:
Dr. Moumita Sengupta
Department of Pathology and Department of Nephrology, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.367821

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