Acute chest pain and dyspnoea as clinical presentation of primary membranous nephropathy. A case report and literature review

Main Article Content

Erika Poggiali
Giorgia Borio
Andrea Magnacavallo
Andrea Vercelli
Gianfranco Cervellin

Keywords

membranous nephropathy, proteinuria, PLA2R, THSD7A, renal transplant, acute renal failure, end stage renal disease, dialysis

Abstract

Membranous nephropathy (MN) is the commonest cause of nephrotic syndrome (NS) in adult male patients worldwide. Most of the cases (80%) are idiopathic (primary MN, PMN), whereas about 20% are associated with autoimmune diseases, malignancies or exposures (secondary MN). PMN is a kidney-specific autoimmune glomerular disease mediated by antibodies to the M-type phospholipase A2 receptor (anti-PLA2R) (85%), thrombospondin type 1 domain containing 7A (THSD7A) (3–5%), or by other still unidentified mechanisms (10%). Most of the patients with PMN present with NS (80%). Clinical course of PMN is characterised by spontaneous remissions (40%) and relapses (15-30%). One third develop end-stage renal disease (ESRD) within 5 to 15 years from the onset. Anti-PLA2R/THSD7A antibodies levels correlate with proteinuria, clinical course, and outcomes. The treatment still remains matter of debate. Hypertension, proteinuria, and hyperlipidaemia must be treated in all patients. Immunosuppressive therapy is indicated in patients with elevated anti-PLA2R/THSD7A levels and proteinuria >3.5 g/d at diagnosis. With proper management, only 10% or less will develop ESRD over the subsequent 10 years.


Here we report a case of a 34-year-old male patient with a ten-year history of asymptomatic PMN, treated with ACE-inhibitors, who presented to our emergency room for acute chest pain and exertional dyspnoea due to ESRD that required urgent dialysis. (www.actabiomedica.it)

Abstract 375 | PDF Downloads 290

References

1. Wasserstein AG. Membranous glomerulonephritis. J Am Soc Nephrol 1997;8(4):664-74.
2. Keri KC, Blumenthal S, Kulkarni V, Beck L, Chongkrairatanakul T. Primary membranous nephropathy: comprehensive review and historical perspective. Postgrad Med J 2019;95(1119):23-31.
3. Deegens JK, Wetzels JF. Membranous nephropathy in the older adult: epidemiology, diagnosis and management. Drugs Aging 2007;24(9):717-32.
4. Lai WL, Yeh TH, Chen PM, et al. Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment. J Formos Med Assoc 2015;114(2):102-11.
5. Kumar V, Ramachandran R, Kumar A, et al. Antibodies to m-type phospholipase A2 receptor in children with idiopathic membranous nephropathy. Nephrology (Carlton) 2015;20(8):572-5.
6. Couser WG. Primary Membranous Nephropathy. Clin J Am Soc Nephrol 2017;12(6):983-997. Erratum in: Clin J Am Soc Nephrol 2017;12 (9):1528.
7. Donadio JV Jr, Torres VE, Velosa JA, et al. Idiopathic membranous nephropathy: the natural history of untreated patients. Kidney Int 1988;33(3):708-15.
8. Lai WL, Yeh TH, Chen PM, et al. Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment. J Formos Med Assoc 2015;114(2):102-11.
9. van den Brand JA, van Dijk PR, Hofstra JM, Wetzels JF. Long-term outcomes in idiopathic membranous nephropathy using a restrictive treatment strategy. J Am Soc Nephrol 2014;25(1):150-8.
10. 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(1):11-21.
11. Hofstra JM, Fervenza FC, Wetzels JF. Treatment of idiopathic membranous nephropathy. Nat Rev Nephrol 2013;9(8):443-58.
12. Bell ET. Renal diseases. London: Henry Kimpton, 1946.
13. Salant DJ, Quigg RJ, Cybulsky AV. Heymann nephritis: mechanisms of renal injury. Kidney Int 1989;35(4):976-84.
14. Akiyama S, Imai E, Maruyama S. Immunology of membranous nephropathy. F1000Res 2019;8:F1000 Faculty Rev-734.
15. Beck LH Jr. PLA2R and THSD7A: Disparate Paths to the Same Disease? J Am Soc Nephrol 2017;28(9):2579-2589.
16. Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ. Anti-phospholipase A₂ receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2011;6(6):1286-91.
17. Oh YJ, Yang SH, Kim DK, Kang SW, Kim YS. Autoantibodies against phospholipase A2 receptor in Korean patients with membranous nephropathy. PLoS One 2013;8(4):e62151.
18. Zhang D, Zou J, Zhang C, Zhang W, Lin F, Jiang G. Clinical and Histological Features of Phospholipase A2 Receptor-Associated and Thrombospondin Type-I Domain-containing 7A-Associated Idiopathic Membranous Nephropathy: A Single Center Retrospective Study from China. Med Sci Monit 2018;24:5076-5083.
19. Qin W, Beck LH Jr, Zeng C, Chen Z, Li S, Zuo K, Salant DJ, Liu Z. Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 2011;22(6):1137-43.
20. Doi T, Mayumi M, Kanatsu K, Suehiro F, Hamashima Y. Distribution of IgG subclasses in membranous nephropathy. Clin Exp Immunol 1984;58(1):57-62.
21. Qin HZ, Zhang MC, Le WB, et al. Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous Nephropathy. J Am Soc Nephrol 2016;27(10):3195-3203.
22. Hofstra JM, Debiec H, Short CD, et al. Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol 2012;23(10):1735-43.
23. Kanigicherla D, Gummadova J, McKenzie EA, et al. Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney Int 2013;83(5):940-8.
24. Beck LH Jr, Salant DJ. Membranous nephropathy: recent travels and new roads ahead. Kidney Int 2010;77(9):765-70.
25. Tomas NM, Beck LH Jr, Meyer-Schwesinger C, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 2014;371(24):2277-2287.
26. Akiyama S, Akiyama M, Imai E, Ozaki T, Matsuo S, Maruyama S. Prevalence of anti-phospholipase A2 receptor antibodies in Japanese patients with membranous nephropathy. Clin Exp Nephrol 2015;19(4):653-60.
27. Iwakura T, Ohashi N, Kato A, Baba S, Yasuda H. Prevalence of Enhanced Granular Expression of Thrombospondin Type-1 Domain-Containing 7A in the Glomeruli of Japanese Patients with Idiopathic Membranous Nephropathy. PLoS One 2015;10(9):e0138841.
28. Hihara K, Iyoda M, Tachibana S, et al. Anti-Phospholipase A2 Receptor (PLA2R) Antibody and Glomerular PLA2R Expression in Japanese Patients with Membranous Nephropathy. PLoS One 2016;11(6):e0158154.
29. Stanescu HC, Arcos-Burgos M, Medlar A, et al. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med 2011;364(7):616-26.
30. Cui Z, Xie LJ, Chen FJ, et al. MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy. J Am Soc Nephrol 2017;28(5):1651-1664.
31. Salant DJ. Genetic variants in membranous nephropathy: perhaps a perfect storm rather than a straightforward conformeropathy? J Am Soc Nephrol 2013;24(4):525-8.
32. De Vriese AS, Glassock RJ, Nath KA, Sethi S, Fervenza FC. A Proposal for a Serology-Based Approach to Membranous Nephropathy. J Am Soc Nephrol 2017;28(2):421-430.
33. Sinico RA, Mezzina N, Trezzi B, Ghiggeri GM, Radice A. Immunology of membranous nephropathy: from animal models to humans. Clin Exp Immunol 2016;183(2):157-65.
34. Xu X, Wang G, Chen N, Lu T, et al. Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in China. J Am Soc Nephrol 2016;27(12):3739-3746.
35. Perkinson DT, Baker PJ, Couser WG, Johnson RJ, Adler S. Membrane attack complex deposition in experimental glomerular injury. Am J Pathol 1985;120(1):121-8.
36. Bomback AS, Fervenza FC. Membranous Nephropathy: Approaches to Treatment. Am J Nephrol 2018;47 Suppl 1:30-42.
37. Fervenza FC, Appel GB, Barbour SJ, et al. Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. N Engl J Med 2019;381(1):36-46.
38. Seitz-Polski B, Dahan K, Debiec H, et al. High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy. Clin J Am Soc Nephrol 2019;14(8):1173-1182.
39. Lu W, Gong S, Li J, Luo H, Wang Y. Efficacy and safety of rituximab in the treatment of membranous nephropathy: A systematic review and meta-analysis. Medicine (Baltimore) 2020;99(16):e19804.
40. Cattran DC, Brenchley PE. Membranous nephropathy: integrating basic science into improved clinical management. Kidney Int 2017;91(3):566-574.
41. Cattran D. Management of membranous nephropathy: when and what for treatment. J Am Soc Nephrol 2005;16(5):1188-94.
42. Cattran DC. Idiopathic membranous glomerulonephritis. Kidney Int 2001;59(5):1983-94.
43. Shiiki H, Saito T, Nishitani Y, et al. Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan. Kidney Int 2004;65(4):1400-7.
44. Pei Y, Cattran D, Greenwood C. Predicting chronic renal insufficiency in idiopathic membranous glomerulonephritis. Kidney Int 1992;42(4):960-6
45. Barbour S, Reich H, Cattran D. Short-term complications of membranous nephropathy. Contrib Nephrol 2013;181:143-51.
46. Thompson A, Cattran DC, Blank M, Nachman PH. Complete and Partial Remission as Surrogate End Points in Membranous Nephropathy. J Am Soc Nephrol 2015;26(12):2930-7.
47. Salant DJ, Cattran DC: Membranous nephropathy. Chapter 20. In: Comprehensive Clinical Nephrology, 5th Ed., edited by Floege J, Johnson RJ, Feehally J, St. Louis, MI, Saunders, an imprint of Elsevier Inc., 2015, pp 239–251.
48. Brenchley PE, Coupes B, Short CD, O'Donoghue DJ, Ballardie FW, Mallick NP. Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy. Kidney Int 1992;41(4):933-7.
49. Rankin AJ, McQuarrie EP, Fox JG, Geddes CC, MacKinnon B; Scottish Renal Biopsy Registry. Venous Thromboembolism in Primary Nephrotic Syndrome - Is the Risk High Enough to Justify Prophylactic Anticoagulation? Nephron 2017;135(1):39-45.
50. Li SJ, Guo JZ, Zuo K, et al. Thromboembolic complications in membranous nephropathy patients with nephrotic syndrome-a prospective study. Thromb Res 2012;130(3):501-5.
51. Ponticelli C, Glassock RJ. Glomerular diseases: membranous nephropathy--a modern view. Clin J Am Soc Nephrol 2014;9(3):609-16.
52. Leeaphorn N, Kue-A-Pai P, Thamcharoen N, Ungprasert P, Stokes MB, Knight EL. Prevalence of cancer in membranous nephropathy: a systematic review and meta-analysis of observational studies. Am J Nephrol 2014;40(1):29-35.
53. FARQUHAR MG, VERNIER RL, GOOD RA. An electron microscope study of the glomerulus in nephrosis, glomerulonephritis, and lupus erythematosus. J Exp Med 1957;106(5):649-60.
54. COONS AH, KAPLAN MH. Localization of antigen in tissue cells; improvements in a method for the detection of antigen by means of fluorescent antibody. J Exp Med 1950;91(1):1-13.
55. du Buf-Vereijken PW, Branten AJ, Wetzels JF. Idiopathic membranous nephropathy: outline and rationale of a treatment strategy. Am J Kidney Dis 2005;46(6):1012-29.
56. Lai KN. Membranous nephropathy: when and how to treat. Kidney Int 2007;71(9):841-3.
57. van de Logt AE, Hofstra JM, Wetzels JF. Pharmacological treatment of primary membranous nephropathy in 2016. Expert Rev Clin Pharmacol 2016;9(11):1463-1478.
58. Cybulsky AV, Walsh M, Knoll G, et al. Canadian Society of Nephrology Commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis: management of glomerulonephritis in adults. Am J Kidney Dis 2014;63(3):363-77.
59. https://kdigo.org/
60. Lionaki S, Derebail VK, Hogan SL, et al. Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol 2012;7(1):43-51.
61. Lee T, Biddle AK, Lionaki S, et al. Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy. Kidney Int 2014;85(6):1412-20.
62. Schieppati A, Mosconi L, Perna A, et al. Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med 1993;329(2):85-9.
63. Cattran DC, Pei Y, Greenwood CM, Ponticelli C, Passerini P, Honkanen E. Validation of a predictive model of idiopathic membranous nephropathy: its clinical and research implications. Kidney Int 1997;51(3):901-7.
64. Collaborative Study of the Adult Idiopathic Nephrotic Syndrome. A controlled study of short-term prednisone treatment in adults with membranous nephropathy. N Engl J Med 1979;301(24):1301-6.
65. Ponticelli C, Zucchelli P, Imbasciati E, et al. Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. N Engl J Med 1984;310(15):946-50.
66. Ponticelli C, Altieri P, Scolari F, et al. A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy. J Am Soc Nephrol 1998;9(3):444-50.
67. Chen M, Li H, Li XY, et al. Tacrolimus combined with corticosteroids in treatment of nephrotic idiopathic membranous nephropathy: a multicenter randomized controlled trial. Am J Med Sci 2010;339(3):233-8.
68. Bruns FJ, Adler S, Fraley DS, Segel DP. Sustained remission of membranous glomerulonephritis after cyclophosphamide and prednisone. Ann Intern Med 1991;114(9):725-30.
69. Jindal K, West M, Bear R, Goldstein M. Long-term benefits of therapy with cyclophosphamide and prednisone in patients with membranous glomerulonephritis and impaired renal function. Am J Kidney Dis 1992;19(1):61-7.
70. Cattran DC, Greenwood C, Ritchie S, et al. A controlled trial of cyclosporine in patients with progressive membranous nephropathy. Canadian Glomerulonephritis Study Group. Kidney Int 1995;47(4):1130-5.
71. Barrett C, Willcocks LC, Jones RB, et al. Effect of belimumab on proteinuria and anti-phospholipase A2 receptor autoantibody in primary membranous nephropathy. Nephrol Dial Transplant 2020;35(4):599-606.
72. Reddy YN, Siedlecki AM, Francis JM. Breaking down the complement system: a review and update on novel therapies. Curr Opin Nephrol Hypertens 2017;26(2):123-128.
73. Ponticelli C, Moroni G, Glassock RJ. De novo glomerular diseases after renal transplantation. Clin J Am Soc Nephrol 2014;9(8):1479-87.
74. Filippone EJ, Farber JL. Membranous nephropathy in the kidney allograft. Clin Transplant 2016;30(11):1394-1402.
75. Cosio FG, Cattran DC. Recent advances in our understanding of recurrent primary glomerulonephritis after kidney transplantation. Kidney Int 2017;91(2):304-314.
76. Gupta G, Fattah H, Ayalon R, et al. Pre-transplant phospholipase A2 receptor autoantibody concentration is associated with clinically significant recurrence of membranous nephropathy post-kidney transplantation. Clin Transplant 2016;30(4):461-9.