MORPHOLOGICAL CHANGES IN KIDNEYS AND CLINICAL PRESENTATION IN PATIENTS WITH PRIMARY AND SECONDARY MEMBRANOUS NEPHROPATHY
Abstract
Introduction/Aim: Membranous nephropathy (MN) typically presents as nephrotic syndrome and may be idiopathic (primary MN, pMN) or occur secondary to other diseases (secondary MN, sMN). Given the differing therapeutic approaches, this study aimed to compare clinical and pathohistological parameters between patients with pMN and sMN.
Methods: Through a retrospective analysis of kidney biopsy samples diagnosed at the Institute of Pathology, Faculty of Medicine, Belgrade, between 2011 and 2023, 99 patients with membranous nephropathy were identified. These patients were divided into two groups: patients with pMN (n = 44) and patients with sMN (n = 55). Clinical and pathohistological parameters (by optical and immunofluorescence microscopy) were compared among study participants.
Results: While males more frequently suffered from MN, females more frequently had sMN (p = 0.036). Haematuria was more common in subjects with sMN (p = 0.009). Proteinuria values were significantly higher among patients with pMN (p = 0.018), related to a significantly greater decrease in serum total protein values in them (p = 0.011). Endocapillary proliferation was significantly more frequent among those with sMN (p = 0.032). Marked positivity of several immunofluorescent markers was significantly more common in subjects with sMN: IgA, IgM, C1q, κ-chains, and λ-chains (p < 0.050).
Conclusion: Females are more commonly affected by sMN. Characteristics of sMN include presence of haematuria, endocapillary hypercellularity and immunofluorescence positivity for markers not seen in pMN (IgA, IgM, C1q), while characteristics of pMN include significantly higher levels of proteinuria, accompanied by significantly reduced serum protein values.
References
Lai WL, Yeh TH, Chen PM, Chan CK, Chiang WC, Chen YM, et al. Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment. J Formos Med Assoc. 2015 Feb; 114(2):102-11. doi: 10.1016/j.jfma.2014.11.002.
Ronco P, Beck L, Debiec H, Fervenza FC, Hou FF, Jha V, et al. Membranous nephropathy. Nat Rev Dis Primers. 2021 Sep 30; 7(1):69. doi: 10.1038/s41572-021-00303-z.
Menon S, Valentini RP. Membranous nephropathy in children: clinical presentation and therapeutic approach. Pediatr Nephrol. 2010 Aug; 25(8):1419-28. doi: 10.1007/s00467-009-1324-5.
Glassock RJ. Membranous Nephropathy: Classification Redux? Mayo Clin Proc. 2021 Mar; 96(3):523-525. doi: 10.1016/j.mayocp.2021.01.011.
Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009 Jul 2; 361(1):11-21. doi: 10.1056/NEJMoa0810457.
Tomas NM, Beck LH Jr, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014 Dec 11; 371(24):2277-2287. doi: 10.1056/NEJMoa1409354.
Moroni G, Ponticelli C. Secondary Membranous Nephropathy. A Narrative Review. Front Med (Lausanne). 2020 Dec 3; 7:611317. doi: 10.3389/fmed.2020.611317.
Sethi S, Debiec H, Madden B, Charlesworth MC, Morelle J, Gross L, et al. Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy. Kidney Int. 2020 Jan; 97(1):163-174. doi: 10.1016/j.kint.2019.09.014.
McDonnell T, Wu HHL, Sinha S, Chinnadurai R. The Role of PLA2R in Primary Membranous Nephropathy: Do We Still Need a Kidney Biopsy? Genes (Basel). 2023 Jun 26; 14(7):1343. doi: 10.3390/genes14071343.
Fogo AB, Lusco MA, Najafian B, Alpers CE. AJKD Atlas of Renal Pathology: Membranous Nephropathy. Am J Kidney Dis. 2015 Sep; 66(3):e15-7. doi: 10.1053/j.ajkd.2015.07.006.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct; 100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021.
Jeon SJ, Kim JH, Noh HW, Lee GY, Lim JH, Jung HY, et al. Treatment of rituximab in patients with idiopathic membranous nephropathy: a case series and literature review. Korean J Intern Med. 2022 Jul; 37(4):830-840. doi: 10.3904/kjim.2021.155.
Dietzen DJ, Willrich MAV. Amino Acids, Peptides, and Proteins. In: Rifai N, Chiu RWK, Young I, Burnham CAD, Wittwer CT, editors. Tietz Textbook of Laboratory Medicine. Seventh Edition. St. Louis, Missouri, USA: Elsevier; 2023. p.349.e1—349.e42.
Choi JY, Chin HJ, Lee H, Bae EH, Chang TI, Lim JH, et al. Idiopathic membranous nephropathy in older patients: Clinical features and outcomes. PLoS One. 2020 Oct 9; 15(10):e0240566. doi: 10.1371/journal.pone.0240566.
Couser WG. Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 2017 Jun 7; 12(6):983-997. doi: 10.2215/CJN.11761116.
Ortona E, Pierdominici M, Maselli A, Veroni C, Aloisi F, Shoenfeld Y. Sex-based differences in autoimmune diseases. Ann Ist Super Sanita. 2016 Apr-Jun; 52(2):205-12. doi: 10.4415/ANN_16_02_12.
Almaani S, Parikh SV. Membranous Lupus Nephritis: A Clinical Review. Adv Chronic Kidney Dis. 2019 Sep; 26(5):393-403. doi: 10.1053/j.ackd.2019.08.009.
Pons-Estel GJ, Ugarte-Gil MF, Alarcón GS. Epidemiology of systemic lupus erythematosus. Expert Rev Clin Immunol. 2017 Aug; 13(8):799-814. doi: 10.1080/1744666X.2017.1327352.
Rees F, Doherty M, Grainge MJ, Lanyon P, Zhang W. The worldwide incidence and prevalence of systemic lupus erythematosus: a systematic review of epidemiological studies. Rheumatology (Oxford). 2017 Nov 1; 56(11):1945-1961. doi: 10.1093/rheumatology/kex260.
Alsharhan L, Beck LH Jr. Membranous Nephropathy: Core Curriculum 2021. Am J Kidney Dis. 2021 Mar; 77(3):440-453. doi: 10.1053/j.ajkd.2020.10.009.
Polanco N, Gutiérrez E, Rivera F, Castellanos I, Baltar J, Lorenzo D, et al. Spontaneous remission of nephrotic syndrome in membranous nephropathy with chronic renal impairment. Nephrol Dial Transplant. 2012 Jan; 27(1):231-4. doi: 10.1093/ndt/gfr285.
Polanco N, Gutiérrez E, Covarsí A, Ariza F, Carreño A, Vigil A, et al. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol. 2010 Apr; 21(4):697-704. doi: 10.1681/ASN.2009080861.
Basu K, Sengupta M, Mukherjee S, Karmakar S, Roychowdhury A, Bandopadhyay M. Role of light and immunofluorescence microscopy to differentiate primary and secondary membranous nephropathy. Indian J Pathol Microbiol. 2022 Oct-Dec; 65(4):821-827. doi: 10.4103/ijpm.ijpm_22_21.
Dantas M, Silva LBB, Pontes BTM, Dos Reis MA, de Lima PSN, Moysés Neto M. Membranous nephropathy. J Bras Nefrol. 2023 Apr-Jun; 45(2):229-243. doi: 10.1590/2175-8239-JBN-2023-0046en.
Larsen CP, Messias NC, Silva FG, Messias E, Walker PD. Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies. Mod Pathol. 2013 May; 26(5):709-15. doi: 10.1038/modpathol.2012.207.
Lwezaula BF, Ameh OI, Ekrikpo UE, Botha FC, Okpechi-Samuel US, Wearne N, et al. Diagnostic performance of glomerular PLA2R and THSD7A antibodies in biopsy confirmed primary membranous nephropathy in South Africans. BMC Nephrol. 2021 Jan 7; 22(1):15. doi: 10.1186/s12882-020-02216-7.
Sethi S, Madden BJ, Debiec H, Charlesworth MC, Gross L, Ravindran A, et al. Exostosin 1/Exostosin 2-Associated Membranous Nephropathy. J Am Soc Nephrol. 2019 Jun; 30(6):1123-1136. doi: 10.1681/ASN.2018080852.
Caza TN, Hassen SI, Dvanajscak Z, Kuperman M, Edmondson R, Herzog C, et al. NELL1 is a target antigen in malignancy-associated membranous nephropathy. Kidney Int. 2021 Apr; 99(4):967-976. doi: 10.1016/j.kint.2020.07.039.
Cameron JS. Lupus nephritis. J Am Soc Nephrol. 1999 Feb; 10(2):413-24. doi: 10.1681/ASN.V102413.
