Monoclonal Gammapathy of Renal Significance: Morphological Variants of Lesion
https://doi.org/10.20514/2226-6704-2021-11-5-325-334
Abstract
The article discusses the concept of monoclonal renal gammopathy, which combines various renal diseases caused by the deposition of monoclonal immunoglobulin and / or their components in the glomeruli and tubulointerstitium. This nosological group was identified within the group of monoclonal gammopathies of undetermined significance (in 2012). The data on the study of morphological kidney damage associated with monoclonal renal gammopathy are presented. The spectrum of renal diseases in monoclonal renal gammopathy is diverse, and its classification is based on the localization of renal lesions in the glomeruli, tubules, vascular interstitium and stroma, as well as the peculiarity of the deposition of immunoglobulins (organized and unorganized). Kidney biopsy is required in most cases to locate the lesion, assess its severity, and predict patient survival. Diagnostics requires the integration of morphological changes using light microscopy, immunofluorescence, electron microscopy, and in some cases, staining of monoclonal protein for Ig isotypes is used (staining with hematoxylin / eosin, Schiff stain (PAS reaction), Jones stain, Congo Red stain, Masson’s trichromal stain). Early diagnosis and timely prescription of clone-oriented therapy by a hematologist and / or a hematooncologist can stop the progression of the malignant process and kidney malfunction. A nephrologist should monitor the patient, interacting with the hematologist.
About the Authors
N. V. FominaRussian Federation
Kemerovo
E. V. Utkina
Russian Federation
Ekaterina V. Utkina
Kemerovo
References
1. Kozlovskaya L.V., Rameev V.V., Kogarko I.N., et al. Renal lesions associated with monoclonal gammopathies of undetermined significance : clinical forms, mechanisms of development, approaches to treatment. Klin. med. 2016; 94(12): 892-901. DOI: http://dx.doi. org/10.18821/0023-2149-2016-94-12-892-901 [In Russian]
2. Smirnov A.V., Dobronravov V.A., Khrabrova M.S. et al. An interdisciplinary approach in the practice of general physician: a focus on monoclonal gammopathy of renal significance (shot ver sion of the Consensus of hematologists and nephrologists of Russia on the establishment of nosology, diagnostic approach and rationale for clone specific treatment). Therapy. 2020; 2(36): 22-33. DOI: https://dx.doi. org/10.18565/therapy.2020.2.22-33 [In Russian]
3. Smirnov A.V., Afanasyev B.V., Poddubnaya I.V. et al. Monoclonal Gammopathy of Renal Significance: Consensus of Hematologists and Nephrologists of Russia on the Establishment of Nosology, Diagnostic Approach and Rationale for Clone Specific Treatment. The Russian Archives of Internal Medicine. 2020; 10(2): 102-118. DOI: 10.20514/2226-6704-2020-10-2-102-118 [In Russian]
4. Smirnov A.V., Dobronravov V.A., Khrabrova M.S. et al. Kidney involvement in monoclonal gammopathies: multidisciplinary approach in oncohematology and nephrology. Onkogematologiya. 2020; 15(2): 49–60. DOI: 10.17650/1818-8346-2020-15-2-49-60 [In Russian]
5. Khrabrova M.S, Dobronravov V.A, Smirnov A.V. Kidney disease associated with monoclonal gammopathies: single-center study. Nephrology (Saint-Petersburg). 2018; 22(6): 38–46. DOI: 10.24884/1561- 6274-2018-22-6-38-46 [In Russian]
6. Amaador K, Peeters H, Minnema MC, et al. Monoclonal gammopathy of renal significance (MGRS) histopathologic classification, diagnostic workup, and therapeutic options. Neth J Med. 2019; 77(7): 243-254.
7. Leung N, Bridoux F, Batuman V., et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group [published correction appears in Nat Rev Nephrol. 2019 Feb; 15(2): 121]. Nat Rev Nephrol. 2019; 15(1):45-59. DOI:10.1038/s41581-018- 0077-4
8. Fermand JP, Bridoux F, Dispenzieri A., et al. Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications. Blood. 2018; 132(14): 1478–1485. DOI: 10.1182/ blood-2018-04-839480
9. Leung N, Bridoux F, Hutchison CA., et al. Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant. Blood. 2012; 120(22): 4292–4295. DOI: 10.1182/ blood-2012-07-445304
10. Kyle RA, Therneau TM, Rajkumar SV., et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006; 354(13): 1362-1369. DOI:10.1056/NEJMoa054494
11. Delanaye P, Glassock RJ, Pottel H., et al. An Age-Calibrated Definition of Chronic Kidney Disease: Rationale and Benefits. Clin Biochem Rev. 2016; 37(1): 17-26.
12. Swaminathan S, Leung N, Lager DJ., et al. Changing incidence of glomerular disease in Olmsted County, Minnesota: a 30-year renal biopsy study. Clin J Am Soc Nephrol. 2006; 1(3): 483-487. DOI:10.2215/CJN.00710805
13. Bridoux F, Leung N, Hutchison CA., et al. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 2015; 87(4): 698–711. DOI: 10.1038/ki.2014.408
14. Fermand JP, Bridoux F, Kyle RA., et al. How I treat monoclonal gammopathy of renal significance (MGRS). Blood. 2013; 122(22):3583- 3590. DOI:10.1182/blood-2013-05-495929
15. Nasr SH, Valeri AM, Cornell LD., et al. Fibrillary glomerulonephritis: a report of 66 cases from a single institution. Clin J Am Soc Nephrol. 2011; 6(4): 775-784. DOI:10.2215/CJN.08300910
16. Nasr SH, Valeri AM, Cornell LD., et al. Fibrillary glomerulonephritis: a report of 66 cases from a single institution. Clin J Am Soc Nephrol. 2011; 6(4): 775-784. DOI:10.2215/CJN.08300910
17. Nasr SH, Markowitz GS, Stokes MB., et al. Proliferative glomerulonephritis with monoclonal IgG deposits: a distinct entity mimicking immune-complex glomerulonephritis. Kidney Int. 2004; 65(1): 85-96. DOI:10.1111/j.1523-1755.2004.00365.x
18. Nasr SH, Vrana JA, Dasari S., et al. DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis. Kidney Int Rep 2017; 3(1): 56–64. DOI: 10.1016/j.ekir.2017.07.017
19. Said SM, Sethi S, Valeri AM., et al. Renal amyloidosis: origin and clinicopathologic correlations of 474 recent cases. Clin J Am Soc Nephrol. 2013; 8(9): 1515-1523. DOI:10.2215/CJN.10491012
20. Gibier JB, Gnemmi V, Glowacki F., et al. Intratubular amyloid in light chain cast nephropathy is a risk factor for systemic light chain amyloidosis. Mod Pathol. 2018; 31(3): 452-462. DOI:10.1038/ modpathol.2017.124
21. Bridoux F, Javaugue V, Bender S., et al. Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management. Kidney Int. 2017; 91(2): 423-434. DOI:10.1016/j.kint.2016.09.004
22. Nasr SH, Valeri AM, Cornell LD., et al. Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from a single institution. Clin J Am Soc Nephrol. 2012; 7(2): 231-239. DOI:10.2215/ CJN.08640811
23. Alexander MP, Dasari S, Vrana JA., et al. Congophilic Fibrillary Glomerulonephritis: A Case Series. Am J Kidney Dis. 2018; 72(3): 325-336. DOI:10.1053/j.ajkd.2018.03.017
24. Dasari S, Alexander MP, Vrana JA., et al. DnaJ Heat Shock Protein Family B Member 9 Is a Novel Biomarker for Fibrillary GN. J Am Soc Nephrol. 2018; 29(1): 51-56. DOI:10.1681/ASN.2017030306
25. Ojemakinde K, Turbat-Herrera EA, Zeng X., et al. The many faces of cryoglobulinemic nephropathy: a clinico-pathologic study of 47 cases with emphasis on the value of electron microscopy. Ultrastruct Pathol. 2014; 38(6): 367-376. DOI:10.3109/01913123.2014.952803
26. Heher EC, Rennke HG, Laubach JP., et al. Kidney disease and multiple myeloma. Clin J Am Soc Nephrol. 2013; 8(11): 2007-2017. DOI:10.2215/CJN.12231212
27. Karras A, Noël LH, Droz D., et al. Renal involvement in monoclonal (type I) cryoglobulinemia: two cases associated with IgG3 kappa cryoglobulin. Am J Kidney Dis. 2002; 40(5): 1091-1096. DOI:10.1053/ ajkd.2002.36350
28. Kapur U, Barton K, Fresco R., et al. Expanding the pathologic spectrum of immunoglobulin light chain proximal tubulopathy [published correction appears in Arch Pathol Lab Med. 2008 Jan; 132(1): 13. Leehy, David J [corrected to Leehey, David J]]. Arch Pathol Lab Med. 2007; 131(9): 1368-1372. DOI:10.1043/1543-2165(2007)131[1368:ET PSOI]2.0.CO;2
29. Stokes MB, Valeri AM, Herlitz L., et al. Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era. J Am Soc Nephrol. 2016; 27(5): 1555-1565. DOI:10.1681/ ASN.2015020185
30. Herrera GA. Proximal tubulopathies associated with monoclonal light chains: the spectrum of clinicopathologic manifestations and molecular pathogenesis. Arch Pathol Lab Med. 2014; 138(10): 1365-1380. DOI:10.5858/arpa.2013-0493-OA
31. Larsen CP, Messias NC, Walker PD., et al. Membranoproliferative glomerulonephritis with masked monotypic immunoglobulin deposits. Kidney Int. 2015; 88(4): 867-873. DOI:10.1038/ki.2015.195
32. Leung N, Buadi FK, Song KW., et al. A case of bilateral renal arterial thrombosis associated with cryocrystalglobulinaemia. NDT Plus. 2010; 3(1): 74-77. DOI:10.1093/ndtplus/sfp140
33. Larsen CP, Bell JM, Harris AA., et al. The morphologic spectrum and clinical significance of light chain proximal tubulopathy with and without crystal formation. Mod Pathol. 2011; 24(11): 1462-1469. DOI:10.1038/modpathol.2011.104
34. de Alba Campomanes AG, Rutar T, Crawford JB., et al. Crystal-storing histiocytosis and crystalline keratopathy caused by monoclonal gammopathy of undetermined significance. Cornea. 2009; 28(9): 1081- 1084. DOI:10.1097/ICO.0b013e318199f73b
35. Dogan S, Barnes L, Cruz-Vetrano WP. Crystal-storing histiocytosis: report of a case, review of the literature (80 cases) and a proposed classification. Head Neck Pathol. 2012; 6(1): 111-120. doi:10.1007/s12105- 011-0326-3
36. El Hamel C, Thierry A, Trouillas P., et al. Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome. Nephrol Dial Transplant. 2010; 25(9): 2982-2990. DOI:10.1093/ndt/gfq129
37. Kanagal-Shamanna R, Xu-Monette ZY, Miranda RN., et al. Crystalstoring histiocytosis: a clinicopathological study of 13 cases. Histopathology. 2016; 68(4): 482-491. DOI:10.1111/his.12768
38. Koo H, Oh DH, Chun YS., et al. A case of crystalline keratopathy in monoclonal gammopathy of undetermined significance (MGUS). Korean J Ophthalmol. 2011; 25(3): 202-205. DOI:10.3341/kjo.2011.25.3.202
39. Gupta V, El Ters M, Kashani K., et al. Crystalglobulin-induced nephropathy. J Am Soc Nephrol. 2015; 26(3): 525-529. DOI:10.1681/ ASN.2014050509
40. Leung N, Barnidge DR, Hutchison CA. Laboratory testing in monoclonal gammopathy of renal significance (MGRS). Clin Chem Lab Med. 2016 Jun 1; 54(6): 929-37. DOI: 10.1515/cclm-2015-0994.
41. Bhutani G, Nasr SH, Said SM., et al. Hematologic characteristics of proliferative glomerulonephritides with nonorganized monoclonal immunoglobulin deposits. Mayo Clin Proc. 2015; 90(5): 587-596. DOI:10.1016/j.mayocp.2015.01.024
42. Vignon M, Cohen C, Faguer S., et al. The clinicopathologic characteristics of kidney diseases related to monotypic IgA deposits. Kidney Int. 2017; 91(3): 720-728. DOI:10.1016/j.kint.2016.10.026
43. Sethi S, Rajkumar SV. Monoclonal gammopathy-associated proliferative glomerulonephritis. Mayo Clin Proc. 2013; 88(11): 1284-1293. DOI:10.1016/j.mayocp.2013.08.002
44. Czarnecki PG, Lager DJ, Leung N., et al. Long-term outcome of kidney transplantation in patients with fibrillary glomerulonephritis or monoclonal gammopathy with fibrillary deposits. Kidney Int. 2009; 75(4): 420-427. DOI:10.1038/ki.2008.577
45. Zand L, Kattah A, Fervenza FC., et al. C3 glomerulonephritis associated with monoclonal gammopathy: a case series. Am J Kidney Dis. 2013; 62(3): 506-514. DOI:10.1053/j.ajkd.2013.02.370
46. Lloyd IE, Khalighi MA. Glomerulonephritis with Masked Monotypic Immunoglobulin Deposits and Concurrent Lymphomatous Infiltration. Am J Kidney Dis. 2016; 68(4): 640-644. DOI:10.1053/j.ajkd.2016.05.012
47. Vos JM, Gustine J, Rennke HG., et al. Renal disease related to Waldenström macroglobulinaemia: incidence, pathology and clinical outcomes. Br J Haematol. 2016; 175(4): 623-630. doi:10.1111/bjh.14279
48. Ravindran A, Go RS, Fervenza FC., et al. Thrombotic microangiopathy associated with monoclonal gammopathy. Kidney Int. 2017; 91(3): 691-698. DOI:10.1016/j.kint.2016.09.045
49. Blanc C, Togarsimalemath SK, Chauvet S., et al. Anti-factor H autoantibodies in C3 glomerulopathies and in atypical hemolytic uremic syndrome: one target, two diseases. J Immunol. 2015; 194(11): 5129- 5138. DOI:10.4049/jimmunol.1402770
50. Mahmood U, Isbel N, Mollee P., et al. Monoclonal gammopathy of renal significance triggering atypical haemolytic uraemic syndrome. Nephrology (Carlton). 2017; 22 Suppl 1: 15-17. DOI:10.1111/nep.12934
Review
For citations:
Fomina N.V., Utkina E.V. Monoclonal Gammapathy of Renal Significance: Morphological Variants of Lesion. The Russian Archives of Internal Medicine. 2021;11(5):325-334. https://doi.org/10.20514/2226-6704-2021-11-5-325-334