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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2021  |  Volume : 32  |  Issue : 6  |  Page : 1800-1803
Anti-phospholipase A2 Receptor Antibody-Positive Membranous Glomerulopathy due to Anti-Koch’s Therapy in a Tuberculosis Patient

1 Department of Nephrology, Jawaharlal Nehru Medical College, Sawangi, Wardha; Department of Nephrology, Saraswati Kidney Care Center, Nagpur, Maharashtra, India
2 Department of Nephrology, All India Institute of Medical Sciences, Nagpur, Maharashtra, India
3 Department of Medicine, Jawaharlal Nehru Medical College, Sawangi, Wardha; Department of Medicine, Saraswati Kidney Care Center, Nagpur, Maharashtra, India

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Date of Web Publication27-Jul-2022


Tuberculosis (TB)-associated glomerulonephritis is difficult to diagnose that usually presents with hematuria, proteinuria, edema, hypertension, or renal insufficiency, which is similar to symptoms of primary glomerulonephritis. Membranous nephropathy (MN) is uncommonly seen in TB patients. We report a case of a 30-year-old female with Koch’s chest who developed anti-phospholipase A2 receptor antibody-positive MN after initiation of anti-Koch’s therapy and resolved after completion of anti-Koch’s therapy.

How to cite this article:
Balwani MR, Pasari AS, Bhawane A, Tolani P. Anti-phospholipase A2 Receptor Antibody-Positive Membranous Glomerulopathy due to Anti-Koch’s Therapy in a Tuberculosis Patient. Saudi J Kidney Dis Transpl 2021;32:1800-3

How to cite this URL:
Balwani MR, Pasari AS, Bhawane A, Tolani P. Anti-phospholipase A2 Receptor Antibody-Positive Membranous Glomerulopathy due to Anti-Koch’s Therapy in a Tuberculosis Patient. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Sep 25];32:1800-3. Available from: https://www.sjkdt.org/text.asp?2021/32/6/1800/352444

   Introduction Top

Tubercular infections, both pulmonary and extrapulmonary, are very common in developing countries like India. Urogenital tuberculosis (TB) commonly involves the urinary collecting system (including renal pelvis, calyces, ureters, and bladder) and less commonly renal parenchyma (interstitial nephritis and glomerulonephritis).[1]

Membranous nephropathy (MN) either due to TB or anti-Koch’s therapy is not commonly seen or reported. Here, we present a novel case of anti-phospholipase A2 receptor (PLA2R) antibody-positive MN after initiation of anti-Koch’s therapy in a patient of TB. Association of anti-PLA2R antibody-positive MN in a TB patient due to anti-Koch’s therapy has never been reported earlier to the best of our knowledge.

   Case Report Top

A 30-year-old female presented with gradually progressive swelling of lower limbs for 15 days. This was not associated with abdominal or facial swelling. Her urine output was adequate. She had normal appetite with no significant weight loss. There was no history of mouth ulcers, hair loss, joint pain, rash, pain in the abdomen, eye or ear problem, headache, analgesic abuse, alternative medicine intake, or allergy. Past history revealed a history ofproductive cough one month back, for which she was investigated and was diagnosed as sputum-positive pulmonary TB. At that time, she was started on anti-Koch’s therapy of intensive regimen comprising isoniazid, ethambutol, rifampicin, and pyrazinamide.

At the time of nephrology consultation, her systemic examination revealed pitting pedal edema and normal blood pressure. The rest of the systemic examination was unremarkable. Routine investigations revealed mild microcytic hypochromic anemia (hemoglobin - 11.9 g/dL). Serum urea, creatinine values, and electrolyte levels were normal, and liver function test showed hypoalbuminemia (albumin - 2.65 g/dL and globulin - 2.75 g/dL). Urine examination was unremarkable except for 3+ proteinuria. 2D echocardiography study was normal. At this stage, a provisional diagnosis of pedal edema of renal origin was made and was investigated on lines of nephrotic syndrome (NS). The 24-h urinary protein was 5.31 g. Ultrasonography of the abdomen was normal. Serum cholesterol was high (348 mg/dL). Serum antinuclear antibody (ANA) by enzyme-linked immunosorbent assay method came to be negative. Thus, a diagnosis of NS was made in a TB patient who is on anti-Koch’s therapy. Renal biopsy revealed features of membranous glomerulopathy [Figure 1]. On light microscopy, the kidney specimen contained 13 glomeruli. Glomeruli revealed diffuse thickening of capillaries with intramembranous mottling on silver methenamine staining. There was no evidence of segmental sclerosis, tuft necrosis, sub-endothelial/Congo deposits, endocapillary cellularity, intracapillary thrombi, or crescent formation. There was no granuloma in the renal tissue sample. Arterioles were unremarkable. Immunofluorescence staining was positive for immunoglobulin (Ig) G along the glomerular capillary walls, and there was no light chain restriction. The glomeruli were negative for C3, IgA, IgM, and C1q. Immunohistochemical for anti-PLA2R showed diffuse granular positivity along glomerular capillary walls. Thus, histopathological diagnosis of anti-PLA2R-positive antibody MN was made. Due to cost constraints, electron microscopy examination was not performed.
Figure 1. Anti-phospholipase A2 receptor antibody-positive membranous glomerulopathy.

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We followed up this report with a battery of tests for the evaluation of secondary causes of MN, including serology for hepatitis B and C and ANA. All tests were negative. She was started on telmisartan 40 mg once a day. She was followed up closely at monthly intervals.

Sputum examination at the end of two months of intensive regimen was negative for acid-fast bacilli. After completion of intensive phase, she was shifted to maintenance regimen of isoniazid, rifampicin, and ethambutol. She was compliant to anti-Koch’s medicines. Monthly spot urine protein-creatinine ratio was performed which was always above 4 and <8. After four months of maintenance regimen, anti-Koch’s therapy was stopped. After seven days of completion of anti-Koch’s therapy, she noticed that froth in urine has disappeared. 24-h urine protein and urine albumin examination tests were performed which came out to be normal. Thus, a provisional diagnosis of anti-PLA2R antibodypositive MN in a TB patient due to anti-Koch’s therapy (isoniazid, rifampicin, or ethambutol) was made.

The authors obtained all appropriate consent forms from the patient for the publication of this case report.

   Discussion Top

MN is one of the common causes of NS in adults, with a potential to progress to end-stage renal disease in 40%-50% of untreated patients in 10-15 years.[2],[3] Common secondary causes of MN are infections, drugs, toxins, autoimmune diseases, and malignancy. It is important to distinguish between primary MN and secondary MN as the treatment approach differs in both. For secondary MN, therapy is focused on treatment of underlying cause, but primary MN is treated with immunosuppressant drugs if not responded to conservative and supportive management. Beck et al demonstrated autoantibodies against M-type PLA2R (a membrane glycoprotein located on the podocytes) in 60%-80% of primary MN patients.[4],[5] Anti-PLA2R antibody positivity supports the diagnosis of primary MN. It is a common assumption that after ruling out secondary causes of MN and if anti-PLA2R antibody is positive, one can treat the patient as primary MN.

However, in a study by Qin et al serum anti-PLA2R antibodies were found to be positive in six of 46 patients with apparent secondary causes, namely systemic lupus erythematosus, hepatitis B infection, and malignancy.[6] As in our case of MN, anti-PLA2R antibody stain was positive though it was secondary to anti-Koch’s drugs. The authors are of the opinion that even if anti-PLA2R antibody is positive, one should look for secondary causes of MN and focus more on drug and allergic history to pick causes not mentioned in the literature.

In a review by Glassock on MN, 6.6% of patients represented drug-induced disease.[7]

The pathogenesis of drug-induced MN (DIMN) likely involves an immune response to a therapeutic agent or its byproduct. The most plausible mechanism is that the cationic drug-derived antigens traverse the glomerular basement membrane (GBM). They are planted at the subepithelial aspect of the GBM. The in situ antigen bound to circulating antibodies are directed against these antigens resulting in renal damage. This is similar to mechanism which underlies the early-childhood MN that occurs in response to cationic BSA present in cow’s milk.[8]

With gold salts, penicillamine, and bucillamine, proteinuria is frequently seen and urine monitoring is required. Proteinuria develops in 3%-7% of patients with gold-based treatment.[9],[10]

In DIMN, renal biopsy most commonly reveals stage 1 or 2 MN, indicating early detection because of screening. Treatment of DIMN begins with withdrawal of the culprit drug. After withdrawal, proteinuria resolves in most patients.[9],[11]

In our patient, NS developed after initiation of anti-Koch’s therapy and it persisted till the patient was taking these medicines (isoniazid, ethambutol, and rifampicin). Renal biopsy in our patient showed anti-PLA2R-positive antibody stage 1 MN. All other causes of MN were excluded and a rapid remission of the NS was achieved following stoppage of anti-Koch’s therapy. This case report highlights that anti-PLA2R-positive antibody MN can be seen with DIMN. Here, the authors could not find the exact drug (among isoniazid, ethambutol, and rifampicin), due to which MN may have developed as retrospectively only the diagnosis of DIMN was made.

   Conclusions Top

As withdrawal of the offending drug may result in prompt and complete recovery of normal renal function, a drug history should be sought in patients with MN. In our patient, anti-PLA2R-positive antibody MN was seen with anti-Koch’s therapy, which could be the first reported case to the best of our knowledge.

   References Top

Chapagain A, Dobbie H, Sheaff M, Yaqoob MM. Presentation, diagnosis, and treatment outcome of tuberculous-mediated tubulointerstitial nephritis. Kidney Int 2011 ;79:671-7.  Back to cited text no. 1
Jha V, Ganguli A, Saha TK, et al. A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy. J Am Soc Nephrol 2007;18: 1899-904.  Back to cited text no. 2
Torres A, Dominguez-Gil B, Carreño A, et al. Conservative versus immunosuppressive treatment of patients with idiopathic membranous nephropathy. Kidney Int 2002;61:219-27.  Back to cited text no. 3
Beck LH Jr., Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009;361:11-21.  Back to cited text no. 4
Ronco P, Debiec H. Antigen identification in membranous nephropathy moves toward targeted monitoring and new therapy. J Am Soc Nephrol 2010;21:564-9.  Back to cited text no. 5
Qin W, Beck LH Jr., Zeng C, et al. Antiphospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 2011;22:1137-43.  Back to cited text no. 6
Glassock RJ. Secondary membranous glomerulonephritis. Nephrol Dial Transplant 1992;7 Suppl 1:64-71.  Back to cited text no. 7
Debiec H, Lefeu F, Kemper MJ, et al. Early-childhood membranous nephropathy due to cationic bovine serum albumin. N Engl J Med 2011;364:2101-10.  Back to cited text no. 8
Katz WA, Blodgett RC Jr., Pietrusko RG. Proteinuria in gold-treated rheumatoid arthritis. Ann Intern Med 1984;101:176-9.  Back to cited text no. 9
Silverberg DS, Kidd EG, Shnitka TK, Ulan RA. Gold nephropathy. A clinical and pathologic study. Arthritis Rheum 1970;13:812-25.  Back to cited text no. 10
Hall CL, Fothergill NJ, Blackwell MM, Harrison PR, MacKenzie JC, MacIver AG. The natural course of gold nephropathy: Long term study of 21 patients. Br Med J (Clin Res Ed) 1987;295:745-8.  Back to cited text no. 11

Correspondence Address:
Manish R. Balwani
Department of Nephrology, Jawaharlal Nehru Medical College, Sawangi, Wardha, Maharashtra, India.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.352444

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