Amyloidosis in a renal transplant recipient: A diagnostic challenge - A case report

Sahil Bagai; Dinesh Khullar; Vipra Malik; Bhavna Bansal

doi:10.4103/ijot.ijot_36_21

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CASE REPORT

Year : 2021 | Volume : 15 | Issue : 4 | Page : 371-373

Amyloidosis in a renal transplant recipient: A diagnostic challenge - A case report

Sahil Bagai¹, Dinesh Khullar¹, Vipra Malik², Bhavna Bansal³
¹ Department of Nephrology and Renal Transplant Medicine, Max Super Specialty Hospital, Delhi, India
² Department of Pathology, SGT University, Gurgaon, Haryana, India
³ Department of Pathology, Max Super Specialty Hospital, Delhi, India

Date of Submission	22-Apr-2021
Date of Decision	10-May-2021
Date of Acceptance	19-Jul-2021
Date of Web Publication	30-Dec-2021

Correspondence Address:
Dr. Dinesh Khullar
Department of Nephrology and Renal Transplant Medicine, Max Super Specialty Hospital, Press Enclave Road, 1 and 2, Saket, Delhi - 110 017
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_36_21

Abstract

Amyloidosis is an infiltrative disease where amyloid fibrils get deposited in the extracellular space. Inflammatory arthritis, chronic infections, and malignancies are some known etiologies. Liver is commonly involved in amyloidosis, more common in primary (AL) than secondary (AA) amyloidosis. It is a perplexing diagnosis as it usually presents with nonspecific symptoms and minimal laboratory derangements. In this study, the patient had ankylosing spondylitis as an existing risk factor, but renal cell carcinoma detected in the native kidneys after transplantation accelerated the liver decompensation. This case highlights the importance of excluding liver amyloidosis in patients of systemic amyloidosis as liver amyloidosis can be clinically silent pretransplantation.

Keywords: Amyloidosis, hepatic amyloidosis, renal cell carcinoma, renal transplantation

How to cite this article:
Bagai S, Khullar D, Malik V, Bansal B. Amyloidosis in a renal transplant recipient: A diagnostic challenge - A case report. Indian J Transplant 2021;15:371-3

How to cite this URL:
Bagai S, Khullar D, Malik V, Bansal B. Amyloidosis in a renal transplant recipient: A diagnostic challenge - A case report. Indian J Transplant [serial online] 2021 [cited 2022 Jan 26];15:371-3. Available from: https://www.ijtonline.in/text.asp?2021/15/4/371/334429

Introduction

Secondary amyloidosis is a common form of amyloidosis. Kidney, liver, and spleen are the common sites affected. Liver per se is the second most common site of involvement in systemic amyloidosis and is more commonly involved in primary amyloidosis. Here, we report an interesting case of liver amyloidosis post renal transplantation.

Case Report

Mr. RM, a middle-aged businessman, a diagnosed case of ankylosing spondylitis since 1995, presented with generalized anasarca and frothuria in 2005. On evaluation, he had urine protein 4+, serum albumin 2.5 g/dL, serum creatinine 0.9 mg/dL, and 24 h urinary protein of 5 g/day. He underwent a kidney biopsy, and a diagnosis of serum amyloid A (SAA)-positive renal amyloidosis was confirmed. He was managed with disease-modifying anti-rheumatic drugs and injection etanercept besides angiotensin receptor blockers. He reached end-stage kidney disease status in December 2016 and was initiated on hemodialysis. He underwent a live renal allograft transplantation in June 2017 with his brother-in-law as the donor. He received antithymocyte globulin as induction therapy and triple immunosuppression as tacrolimus, mycophenolate mofetil, and steroids. His liver function tests (LFT) and ultrasound abdomen were normal pre transplantation. Immediate post transplantation period was uneventful, and the patient had serum creatinine between 0.8 and 1 mg/dL. In July 2018, he complained of fatigue, anorexia, and intense intractable pruritus. On evaluation, he had isolated rise in alkaline phosphatase (ALP) of 197 U/L. Fibroscan revealed stage 2 fibrosis with liver stiffness measurement (LSM) of 11.4 kPa and controlled attenuated parameter of 238 dB/m. A clinical diagnosis of compensated cirrhosis was made, and he was worked up extensively for cholestasis [Table 1]. A percutaneous liver biopsy was performed which showed preserved lobular architecture but had pink eosinophilic acellular material in the walls of the arteries within three portal tracts. These deposits were periodic acid-Schiff and thioflavin T positive, were congophilic, and showed apple green birefringence on polarizing microscope, confirming liver amyloidosis [Figure 1a and b]. He had elevated inflammatory markers [Table 2]. Magnetic resonance imaging (MRI) spine showed the presence of Anderson lesion L3–L4 level with no soft-tissue collection, indicating no active lesions attributable to ankylosing spondylitis. Incidentally, an exophytic T2/T1 isointense lesion was noted in the anterior cortex of the mid pole of the left kidney, showing diffusion restriction. Positron emission tomography-computed tomography confirmed metabolically active exophytic lesion arising from the anterolateral cortex of the native kidney (interpolar region), consistent with the MRI findings [Figure 2]a and [Figure 2]b. He underwent left native nephrectomy. Intraoperatively, a 2.4 cm × 2-cm size tumor was excised from the lower pole of the left kidney, which on histopathology was consistent with papillary renal cell carcinoma (RCC) [Figure 3].

Table 1: Cholestasis work up done in the patient

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Table 2: Inflammatory markers done in for evaluation of liver amyloidosis

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Figure 1: (a) Periodic acid-Schiff stain showing amyloid deposition in the portal tract. (b) Thioflavin T showing amyloid deposition in the portal tract

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Figure 2: (a) Magnetic resonance imaging kidney, ureter, and bladder showing a mass in the upper part of the left native kidney. (b) Positron emission tomography scan confirming it to be a metabolically active lesion.

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Figure 3: (a and b) Periodic acid-Schiff stain × 10 and × 40, respectively, showing papillae or tubulopapillary architecture with fibrovascular core with foamy macrophages

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Follow-up a month later revealed LSM of 9 kPa, and ALP was on a declining trend.

Discussion

Amyloidosis is characterized by deposition of nonbranching fibrils composed of various serum proteins in the extracellular tissues in a β-pleated confirmation. Amyloid is diagnosed as an extracellular substance which: (1) stains positively with Congo red, (2) exhibits apple green birefringence on polarization microscopy, (3) shows aggregations of approximately 10-nm-wide fibrils on electron microscopy, (4) exhibits a β-pleated sheet configuration, and (5) shows resistance to proteases other than pronase.^[1] It occurs secondary to inflammatory arthritis such as rheumatoid arthritis, ankylosing spondylitis, chronic infections such as tuberculosis and osteomyelitis, and neoplasms such as non-Hodgkin's lymphoma and RCC.^[2]

Hepatic involvement is common in amyloidosis. Almost 90% of patients with primary and 60% of patients with secondary amyloidosis have liver involvement. The median time for liver involvement is variable and was about a decade in our case. This case highlights the importance of performing a liver biopsy or liver scintigraphy pre transplantation in patients with amyloidosis to ascertain end-organ damage with certainty. In this study, we showcase that RCC acted as a second trigger accelerating the hepatic decompensation.

Hepatic amyloidosis is a challenging clinical diagnosis as majority present with mild symptoms such as fatigue and anorexia although patients presenting with portal hypertension or hepatic failure have also been reported.^[3] No single or group of tests can reliably differentiate between patients with and without hepatic amyloid. Furthermore, there exists no correlation between amyloid deposition and abnormal LFTs.^[4] Elevated ALP might be the only clue in patients, and this was also seen in our case.^[5] Proteinuria (88%), abnormal serum protein electrophoresis (64%), hyposplenism on the peripheral blood smear (62%), and hepatomegaly (81%) disproportional to the liver enzyme abnormalities are other reported findings in hepatic amyloidosis, but fortunately our case had none.^[3] The gold standard for diagnosis is liver biopsy. In previously described cases of hepatic amyloidosis, amyloid deposition was seen in the parenchyma, along the sinusoids within the space of Disse, or in blood vessel walls, but interestingly, in our patient, amyloid deposits were limited to portal tracts, sparing the liver parenchyma and sinusoids.

The etiology for liver amyloidosis seems bi-factorial in this patient. We believe that ankylosing spondylitis would have led to the initial insult but was probably unidentified during pretransplant workup as we failed to perform a liver biopsy or scintigraphy pre transplant. RCC probably added as fuel in the fire. He had raised inflammatory markers (tumor necrosis factor, SAA, and interleukin-6 [IL-6]) but radiologically on the MRI, ankylosing spondylitis appeared quiescent. Incidentally, papillary RCC of left native kidney was identified. RCC is a well-established risk factor for SAA amyloidosis and is associated with high IL-6 levels, which can result in high CRP and SAA levels. This is a possible explanation of raised inflammatory markers seen in our case.^[6] Our patient was immediately subjected to nephrectomy, with margins being free and frozen section confirming no nodal spread. Post nephrectomy, repeat fibroscan revealed LSM of 9 kPa, and his ALP showed a declining trend. He currently complains only of pruritus and graft function is normal.

Learning points

Liver involvement should always be ruled out in a case of systemic amyloidosis
Pre transplantation, liver amyloid can be definitely excluded by liver biopsy/scintigraphy as no single or group of tests can help differentiate patients with silent amyloidosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Kim SH, Han JK, Lee KH, Won HJ, Kim KW, Kim JS, et al. Abdominal amyloidosis: Spectrum of radiological findings. Clin Radiol 2003;58:610-20.
2.	Ogawa S, Murakami T, Inoshima Y, Ishiguro N. Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis. Amyloid 2015;22:236-43.
3.	Shin YM. Hepatic amyloidosis. Korean J Hepatol 2011;17:80-3.
4.	Levine RA. Amyloid disease of the liver. Correlation of clinical, functional and morphologic features in forty-seven patients. Am J Med 1962;33:349-57.
5.	Park MA, Mueller PS, Kyle RA, Larson DR, Plevak MF, Gertz MA. Primary (AL) hepatic amyloidosis: Clinical features and natural history in 98 patients. Medicine (Baltimore) 2003;82:291-8.
6.	Miki S, Iwano M, Miki Y, Yamamoto M, Tang B, Yokokawa K, et al. Interleukin-6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinomas. FEBS Lett 1989;250:607-10.