Clinical and morphological presentation of lupus nephritis: a single-center study of 157 cases

THE AIM: Analysis of clinical and morphological manifestations of lupus nephritis (LN) and their correlations. PATIENTS AND METHODS. A retrospective cross-sectional study included 157 patients (pts) with clinical signs of LN (females 87 %, age 39±13 years). The diagnosis was confirmed morphologically in 133 cases. Clinical (including SELENA-SLEDAI score), immunological and histological parameters were analyzed at the time of kidney biopsy. Clinical factors associated with the development of proliferative and necrotizing LN phenotype were determined in multivariate logistic regression models. RESULTS. Forty eight percents of patients with LN had the estimated glomerular filtration rate (eGFR) ≤59 ml/min/1.73 m². Acute kidney injury (AKI) was found in 14 % of cases. Nephrotic syndrome was detected in 33 % of cases, while immunological activity of systemic lupus erythematosus (SLE) was obvious in 87 %. Dominant morphological class of LN was IV (31.1 %) and 68.2 % of all LN cases were represented by proliferative LN classes. Lupus podocytopathy was diagnosed in three patients (2,3 %). eGFR was mainly associated with the severity of acute and chronic changes in tubulointerstitium and vessels and, to a lesser degree, with glomerular alterations. Proteinuria and hematuria, immunological activity of SLE correlated with active glomerular inflammatory injuries. Proliferative classes LN were able to be identified in patients who did not have significant proteinuria at the time of kidney biopsy. In logistic regression analysis the risk of developing proliferative LN was associated with the level of antibodies to double-stranded DNA (anti-dsDNA) >130 IU/ml (hazard ratio (HR) 3.36 95 % confidence interval (CI) 1.18-9.59) and systolic blood pressure (BP) (НR 1.28 95 % CI 1.01-1.55 (for every +10 mm Hg). Focal necrotizing glomerular lesions with cellular crescents formation was detected in 27 % of LN (71 % of them were classes III or IV). These cases had significantly more pronounced clinical and histological manifestations (glomerular and tubulointerstitial inflammation). Independent clinical factors associated with necrotizing LN were the presence of AKI at the time of kidney biopsy (HR 6.10 95 % CI 1.57-23.75) and a combination of abnormal anti-dsDNA with the decrease of serum complement (C3 and/or C4) (НR 9.99 95 % CI 2.10-47.25). CONCLUSION. Glomerular injury mediated by immune complexes and local activation of complement in SLE is heterogeneous being represented by proliferative, non-proliferative classes of LN or their combinations, as well as special variants of glomerular damage – lupus podocytopathy and necrotizing LN. A precise clinicomorphological diagnosis of LN and associated vascular and tubulointerstitial alterations should be the basis for assessing the disease severity and prognosis and for a choice of personalized therapy.

systemic lupus erythematosus, lupus nephritis, lupus podocytopathy, glomerulonephritis, clinical manifestation, morphological diagnostics, immunomorphology, morphology, clinical and morphological correlations, necrotizing lupus nephritis, crescents

1. Hanly JG, O'Keeffe AG, Su L et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology (Oxford) 2016;55(2):252-262. doi: 10.1093/rheumatology/kev311

2. Wang H, Ren Y-L, Chang J et al. A systematic review and meta-analysis of prevalence of biopsy-proven lupus nephritis. Arch Rheumatol 2018;33(1):17-25. doi: 10.5606/archrheumatol.2017.6127

3. Mahajan A, Amelio J, Gairy K et al. Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression. Lupus 2020;29(9):1011-1020. doi: 10.1177/0961203320932219

4. Yu F, Haas M, Glassock R, Zhao M-H. Redefining lupus nephritis: clinical implications of pathophysiologic subtypes. Nat Rev Nephrol 2017;13(8):483-495. doi: 10.1038/nrneph.2017.85

5. Tektonidou MG, Dasgupta A, Ward MM. Risk of endstage renal disease in patients with lupus nephritis, 1971–2015: a systematic review and Bayesian meta-analysis. Arthritis Rheum 2016;68:1432-1441. doi: 10.1002/art.39594

6. Weening JJ, D'Agati VD, Schwartz MM et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 2004;65(2):521-530. doi: 10.1111/j.15231755.2004.00443.x

7. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Inter 2012;2:139-274

8. Association of rheumatologists of Russia. Clinical practice guidelines for the diagnosis and treatment of systemic lupus erythematosus. https://rheumatolog.ru/experts/klinicheskierekomendacii (In Russ.)

9. Fanouriakis A, Kostopoulou M, Cheema K et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ ERA–EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 2020;79:713-723. doi: 10.1136/annrheumdis-2020-216924

10. Tareeva IE. Variants of the lupous nephritis course. Clinical Nephrology 2011;2:5-8

11. Mikhailova NA, Zakharova EV, Ipatieva EI et al. Systemic Lupus Erythematosus with renal involvement: clinical features and experience of treatment in the Division of Nephrology of Botkin City hospital (1991-2001). Nephrology and dialysis 2002;4(3):186-191

12. Zakharova EV. Lupus glomerulonephritis: clinical features, morphology and prognosis. Nephrology and dialysis 2003;5(2):116-122

13. Zakharova EV, Ipatjeva EI, Tareeva EI et al. Clinical course and predictors of death and esrd in patients with systemic lupus erythematosus and systemic vasculitis with kidney involvement. Nephrology and dialysis 2006;8(2):128-140

14. Arzimanova NA, Marasaev VV, Abissova TO. Immuno-morphological features of glomerular and tubulointerstitial kidney damage in patients with systemic lupus erythematosus. Rheumatology Science and Practice 2009;47(2):17-22. (In Russ.) doi: 10.14412/1995-4484-2009-454

15. Torgashina AV, Solovyev SK, Aleksandrova EN et al. Use of rituximab in patients with lupus nephritis. Rheumatology Science and Practice 2010;48(4):14-26. (In Russ.) doi: 10.14412/19954484-2010-1161

16. Kozlovskaya NL, Shilov EM, Metelev NA et al. Clinical and morphological characteristics of lupus nephritis in systemic lupus erythematosus with antiphospholipid syndrome. Terapevticheskiy arkhiv 2006;78(5):21-31

17. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725. doi: 10.1002/art.1780400928

18. Bombardier C, Gladman DD, Urowitz MB et al. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthr Rheum 1992;35:630-640. doi: 10.1002/art.1780350606

19. Christopher-Stine L, Siedner M, Lin J et al. Renal biopsy in lupus patients with low levels of proteinuria. J Rheumatol 2007;34:332-335

20. Wakasugi D, Gono T, Kawaguchi Y et al. Frequency of class III and IV nephritis in systemic lupus erythematosus without clinical renal involvement: an analysis of predictive measures. J Rheumatol 2012;39:79-85. doi: 10.3899/jrheum.110532

21. De Rosa M, Rocha AS, Graciela De Rosa G and al. Low-Grade Proteinuria Does Not Exclude Significant Kidney Injury in Lupus Nephritis. Kidney Int Rep 2020;13;5(7):1066-1068. doi: 10.1016/j.ekir.2020.04.005

22. Feng Yu F, Tan Y, Gang Liu G et al. Clinicopathological characteristics and outcomes of patients with crescentic lupus nephritis. Kidney Int 2009;76(3):307-317. doi: 10.1038/ki.2009.136

23. Alsuwaida A, Husain S, Ghonaim MAl et al. Glomerular necrotic lesions and long-term outcomes among patients with proliferative lupus nephritis. Int J Clin Exp Pathol 2015;8(5):57875792

24. Zhang W, Yuan M, Hong L et al. Clinical outcomes of lupus nephritis patients with different proportions of crescents. Lupus 2016;25(14):1532-1541. doi: 10.1177/0961203316642312

25. Tao J, Wang H, Wang S-X et al. The predictive value of crescents in the disease progression of lupus nephritis based on the 2018 International Society of Nephrology/Renal Pathology Society Revision System: a large cohort study from China. Renal Failure 2020;42(1):166-172. doi: 10.1080/0886022X.2020.1726385

26. Bajema IM, Wilhelmus S, Alpers CE et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int 2018;93(4):789-796. doi: 10.1016/j.kint.2017.11.023

27. Bomback AS, Markowitz GS. Lupus Podocytopathy: A Distinct Entity. Clin J Am Soc Nephrol 2016;11(4):547-548. doi: 10.2215/CJN.01880216

28. Sakhi H, Moktefi A, Bouachi K et al. Podocyte Injury in Lupus Nephritis. J Clin Med 2019;8(9):1340. doi: 10.3390/jcm8091340

29. Hu W, Chen Y, Wang Sh et al. Clinical-Morphological Features and Outcomes of Lupus Podocytopathy. Clin J Am Soc Nephrol 2016 Apr 7;11(4):585-592. doi: 10.2215/CJN.06720615

30. Tektonidou MG, Sotsiou F, Nakopoulou L et al. Antiphospholipid syndrome nephropathy in patients with systemic lupus erythematosus and antiphospholipid antibodies: prevalence, clinical associations, and long-term outcome. Arthritis Rheum 2004;50(8):2569-2579. doi: 10.1002/art.20433