Top

Open Access 28-03-2024 | Lupus Nephritis | Observational Research

Clinical and laboratory characteristics of early-onset and delayed-onset lupus nephritis patients: A single-center retrospective study

Authors: Joanna Kosałka-Węgiel, Radosław Dziedzic, Andżelika Siwiec-Koźlik, Magdalena Spałkowska, Mamert Milewski, Joanna Żuk-Kuwik, Lech Zaręba, Stanisława Bazan-Socha, Mariusz Korkosz

Published in: Rheumatology International

Abstract

Background

Lupus nephritis (LN) manifests systemic lupus erythematosus (SLE) and is characterized by various clinical and laboratory features. This study aimed to comprehensively evaluate the characteristics of LN patients according to the time of LN diagnosis: early-onset (LN diagnosed within one year from SLE diagnosis) vs. delayed-onset (LN diagnosed more than one year after SLE diagnosis).

Methods

We conducted a retrospective analysis of medical records from all SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected data on demographic, clinical, and laboratory characteristics, including histological findings, treatment modalities, and disease outcomes. Statistical analyses were performed to identify factors impacting LN development and prognosis.

Results

Among 331 LN patients, early-onset was diagnosed in 207 (62.54%) and delayed-onset was documented in 122 cases (36.86%). In 2 (0.6%) LN cases, the time of first kidney manifestation in the SLE course was unknown. Delayed-onset LN had a higher female-to-male ratio and younger age at SLE diagnosis. This group was associated with more severe clinical manifestations. In turn, studied subgroups did not differ in internist comorbidities, kidney histopathology, and family history regarding autoimmune diseases. Delayed-onset LN exhibited a higher frequency of anti-dsDNA, anti-Smith, anti-Ro, anti-RNP, and anti-cardiolipin IgG autoantibodies. During a 14-year follow-up period, 16 patients died. Mortality rate and causes of death were comparable in both analyzed subgroups.

Conclusions

More severe clinical manifestations in delayed-onset LN prompt strict monitoring of non-LN SLE patients to diagnose and treat kidney involvement early. Also, recognizing the higher frequency of autoantibodies such as anti-dsDNA or anti-Smith in delayed-onset LN underscores the potential value of autoantibody profiling as a diagnostic and prognostic tool.

Lisnevskaia L, Murphy G, Isenberg D (Nov. 2014) Systemic lupus erythematosus. Lancet 384(9957):1878–1888. https://doi.org/10.1016/S0140-6736(14)60128-8

Ballou SP, Khan MA, Kushner I (1982) Clinical features of systemic lupus erythematosus, Arthritis & Rheumatism, vol. 25, no. 1, pp. 55–60, Jan. https://doi.org/10.1002/art.1780250109

Tsai Y-G, Liao P-F, Hsiao K-H, Wu H-M, Lin C-Y, Yang KD (Sep. 2023) Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus. Front Immunol 14:1230264. https://doi.org/10.3389/fimmu.2023.1230264

Kosalka J, Jakiela B, Musial J (2015) Changes of memory B- and T-cell subsets in lupus nephritis patients, Folia Histochem Cytobiol, p. VM/OJS/J/43314, Feb. https://doi.org/10.5603/FHC.a2016.0005

Ruiz-Irastorza G, Khamashta MA, Castellino G, Hughes GR (Mar. 2001) Systemic lupus erythematosus. Lancet 357(9261):1027–1032. https://doi.org/10.1016/S0140-6736(00)04239-2

Renaudineau Y, Brooks W, Belliere J (Sep. 2023) Lupus Nephritis Risk factors and biomarkers: an update. IJMS 24:14526. https://doi.org/10.3390/ijms241914526

Parikh SV, Almaani S, Brodsky S, Rovin BH (2020) Update on Lupus Nephritis: Core Curriculum 2020, American Journal of Kidney Diseases, vol. 76, no. 2, pp. 265–281, Aug. https://doi.org/10.1053/j.ajkd.2019.10.017

Rojas-Rivera JE et al (2023) Aug., Diagnosis and treatment of lupus nephritis: a summary of the Consensus Document of the Spanish Group for the Study of Glomerular Diseases (GLOSEN), Clinical Kidney Journal, vol. 16, no. 9, pp. 1384–1402, https://doi.org/10.1093/ckj/sfad055

Lichtnekert J, Anders H-J, Lech M (2022) Lupus Nephritis: Current Perspectives and Moving Forward, JIR, vol. Volume 15, pp. 6533–6552, Dec. https://doi.org/10.2147/JIR.S363722

10.

Alforaih N, Whittall-Garcia L, Touma Z (2022) A Review of Lupus Nephritis, The Journal of Applied Laboratory Medicine, vol. 7, no. 6, pp. 1450–1467, Oct. https://doi.org/10.1093/jalm/jfac036

11.

Yap DYH, Tang CSO, Ma MKM, Lam MF, Chan TM (2012) Survival analysis and causes of mortality in patients with lupus nephritis, Nephrology Dialysis Transplantation, vol. 27, no. 8, pp. 3248–3254, Aug. https://doi.org/10.1093/ndt/gfs073

12.

Aringer M (2019) EULAR/ACR classification criteria for SLE, Seminars in Arthritis and Rheumatism, vol. 49, no. 3, pp. S14–S17, Dec. https://doi.org/10.1016/j.semarthrit.2019.09.009

13.

Kapsala NN et al (2021) Dec., From first symptoms to diagnosis of systemic lupus erythematosus: mapping the journey of patients in an observational study, Clinical and Experimental Rheumatology, https://doi.org/10.55563/clinexprheumatol/x3s9td

14.

Piga M et al (Feb. 2024) Clinical patterns of disease: from early systemic lupus erythematosus to late-onset disease. Best Pract Res Clin Rheumatol p. 101938. https://doi.org/10.1016/j.berh.2024.101938

15.

Nakano M et al (2019) Aug., Delayed lupus nephritis in the course of systemic lupus erythematosus is associated with a poorer treatment response: a multicentre, retrospective cohort study in Japan, Lupus, vol. 28, no. 9, pp. 1062–1073, https://doi.org/10.1177/0961203319860200

16.

Metry AM et al (2019) Jul., Systemic Lupus Erythematosus: Symptoms and Signs at Initial Presentations, AIAAMC, vol. 18, no. 2, pp. 142–150, https://doi.org/10.2174/1871523018666181128161828

17.

Aguilera-Pickens G, Abud-Mendoza C (Sep. 2018) Manifestaciones pulmonares en lupus eritematoso sistémico: afección pleural, neumonitis aguda, enfermedad intersticial crónica y hemorragia alveolar difusa. Reumatología Clínica 14(5):294–300. https://doi.org/10.1016/j.reuma.2018.03.012

18.

Moysidou G-S, Garantziotis P, Nikolopoulos D, Katsimbri P, Fanouriakis A, Boumpas DT (Feb. 2023) Relapses are common in severe hematologic systemic lupus erythematosus and may be prevented by early institution of immunosuppressive agents: Α real-life single-center study. Lupus 32(2):225–230. https://doi.org/10.1177/09612033221144425

19.

Voulgarelis M (2000) Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin, Annals of the Rheumatic Diseases, vol. 59, no. 3, pp. 217–222, Mar. https://doi.org/10.1136/ard.59.3.217

20.

Markvardsen LH, Christiansen I, Harbo T, Jakobsen J (Jan. 2014) Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders. Euro J Neurol 21(1):147–152. https://doi.org/10.1111/ene.12287

21.

Parodi A et al (2009) Nov., Macrophage activation syndrome in juvenile systemic lupus erythematosus: A multinational multicenter study of thirty-eight patients, Arthritis & Rheumatism, vol. 60, no. 11, pp. 3388–3399, https://doi.org/10.1002/art.24883

22.

Farshad S, Kanaan C, Savedchuk S, Karmo DS, Halalau A, Swami A (2019) Systemic Lupus Erythematosus (SLE) with Acute Nephritis, Antineutrophil Cytoplasmic Antibody- (ANCA-) Associated Vasculitis, and Thrombotic Thrombocytopenic Purpura (TTP): A Rare Case Report with Literature Review, Case Reports in Rheumatology, vol. pp. 1–5, Dec. 2019, https://doi.org/10.1155/2019/8750306

23.

Alonso MD et al (Sep. 2011) Systemic Lupus Erythematosus in Northwestern Spain: a 20-Year epidemiologic study. Medicine 90(5):350–358. https://doi.org/10.1097/MD.0b013e31822edf7f

24.

ACR AD HOC COMMITTEE ON NEUROPSYCHIATRIC LUPUS, NOMENCLATURE (Apr. 1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthr Rhuem 42(4):599–608. https://doi.org/10.1002/1529-0131(199904)42:4%3C599::AID-ANR2%3E3.0.CO;2-F

25.

Kosałka-Węgiel J et al (2023) Aug., Association between clinical features and course of systemic sclerosis and serum interleukin-8, vascular endothelial growth factor, basic fibroblast growth factor, and interferon alpha, Adv Clin Exp Med, vol. 33, no. 4, pp. 0–0, https://doi.org/10.17219/acem/168724

26.

Adiga A, Nugent K (Apr. 2017) Lupus Hepatitis and Autoimmune Hepatitis (Lupoid Hepatitis). Am J Med Sci 353(4):329–335. https://doi.org/10.1016/j.amjms.2016.10.014

27.

Kaczmarczyk K, Kosalka J, Soja J, Kuzniewski M, Musial J, Okon K (2014) Renal interstitial mast cell counts differ across classes of proliferative lupus nephritis, Folia Histochem Cytobiol, vol. 52, no. 3, pp. 218–224, Oct. https://doi.org/10.5603/FHC.2014.0025

28.

Wouk N (2021) End-Stage Renal Disease: Medical Management, Am Fam Physician, vol. 104, no. 5, pp. 493–499, Nov

29.

Chaker L, Razvi S, Bensenor IM, Azizi F, Pearce EN, Peeters RP (2022) Hypothyroidism, Nat Rev Dis Primers, vol. 8, no. 1, p. 30, May https://doi.org/10.1038/s41572-022-00357-7

30.

Ross DS et al (Oct. 2016) 2016 American Thyroid Association Guidelines for Diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 26(10):1343–1421. https://doi.org/10.1089/thy.2016.0229

31.

Firnhaber JM, Powell CS (2019) Lower Extremity Peripheral Artery Disease: Diagnosis and Treatment, Am Fam Physician, vol. 99, no. 6, pp. 362–369, Mar

32.

Murphy SP, Ibrahim NE, Januzzi JL (Aug. 2020) Heart failure with reduced ejection fraction: a review. JAMA 324(5):488. https://doi.org/10.1001/jama.2020.10262

33.

Levey AS, Titan SM, Powe NR, Coresh J, Inker LA, Kidney Disease, Race, and, Estimation GFR (2020) CJASN, vol. 15, no. 8, pp. 1203–1212, Aug. https://doi.org/10.2215/CJN.12791019

34.

Delfino J, Dos Santos TAFG, Skare TL (2020) Comparison of lupus patients with early and late onset nephritis: a study in 71 patients from a single referral center, Adv Rheumatol, vol. 60, no. 1, p. 5, Dec. https://doi.org/10.1186/s42358-019-0105-5

35.

Shabaka A, Landaluce-Triska E, Sánchez-Álvarez JE, Fernández-Juárez G (2022) Changing trends in presentation and indications of biopsy in lupus nephritis: data from the Spanish Registry of Glomerulonephritis, Clinical Kidney Journal, vol. 15, no. 4, pp. 703–708, Mar. https://doi.org/10.1093/ckj/sfab236

36.

Trentin F et al (2023) Apr., Gender differences in SLE: report from a cohort of 417 Caucasian patients, Lupus Sci Med, vol. 10, no. 1, p. e000880, https://doi.org/10.1136/lupus-2022-000880

37.

Islam SM, Rahman AKMM, Yasmin S, Giti S (2021) Clinico-histomorphologic characteristics of Lupus Nephritis, experience at a Center at Dhaka. Saudi J Kidney Dis Transpl 32(6):1754. https://doi.org/10.4103/1319-2442.352438CrossRefPubMed

38.

Das J et al (2023) Sep., Clinicopathological, Immunological, and Laboratory Parameters of Childhood Lupus Nephritis: A Study from Northeast India, J Lab Physicians, vol. 15, no. 03, pp. 361–364, https://doi.org/10.1055/s-0043-1768168

39.

De Araújo AS et al (2023) Júnior Feb., Development of an instrument to predict proliferative histological class in lupus nephritis based on clinical and laboratory data, Lupus, vol. 32, no. 2, pp. 216–224, https://doi.org/10.1177/09612033221143933

40.

Lacetera R et al (2023) Mar., Prevalence and clinical significance of ANCA positivity in lupus nephritis: a case series of 116 patients and literature review, J Nephrol, vol. 36, no. 4, pp. 1059–1070, https://doi.org/10.1007/s40620-023-01574-3

41.

Romero-Sánchez C et al (2020) Nov., Frecuencia de ANCA positivos en una población con síntomas clínicos sugestivos de enfermedad autoinmune y la interferencia de ANA en su interpretación, Reumatología Clínica, vol. 16, no. 6, pp. 473–479, https://doi.org/10.1016/j.reuma.2018.09.007

42.

Kang E-S et al (2023) Sep., Long-term renal outcomes of patients with non-proliferative lupus nephritis, Korean J Intern Med, vol. 38, no. 5, pp. 769–776, https://doi.org/10.3904/kjim.2022.339

43.

Suzuki E et al (2021) Dec., Comparison of renal remission and relapse-free rate in initial‐ and delayed‐onset lupus nephritis, Int J of Rheum Dis, vol. 24, no. 12, pp. 1500–1509, https://doi.org/10.1111/1756-185X.14228

44.

Pirson V, Enfrein A, Houssiau FA, Tamirou F (Aug. 2021) Absence of renal remission portends poor long-term kidney outcome in lupus nephritis. Lupus Sci Med 8(1):e000533. https://doi.org/10.1136/lupus-2021-000533

45.

Tang Z, Wang J-M, Qin J-M, Wen L-M (2023) Analysis of risk factors and development of a nomogram prediction model for lupus nephritis in systemic lupus erythematosus patients, Lupus, vol. 32, no. 9, pp. 1084–1092, Aug. https://doi.org/10.1177/09612033231189904

46.

Hsu T-C et al (Mar. 2023) Risk factors for subsequent lupus nephritis in patients with juvenile-onset systemic lupus erythematosus: a retrospective cohort study. Pediatr Rheumatol 21(1):28. https://doi.org/10.1186/s12969-023-00806-x

47.

Du K, Zhang X, Feng J, Zhong S, Qi J, Lin Z (2022) Renal response and its predictive factors of lupus nephritis: a 2-year real-world study of 56 hospital-based patients, Clin Rheumatol, vol. 41, no. 11, pp. 3363–3371, Nov. https://doi.org/10.1007/s10067-022-06258-0

48.

Duran E et al (2022) Aug., Differences and similarities of proliferative and non-proliferative forms of biopsy-proven lupus nephritis: Single centre, cross-disciplinary experience, Lupus, vol. 31, no. 9, pp. 1147–1156, https://doi.org/10.1177/09612033221106305

49.

Cho S-K et al (Dec. 2023) Risk of end-stage renal disease in patients with early-onset lupus nephritis: a population-based cohort study. Semin Arthritis Rheum 63:152308. https://doi.org/10.1016/j.semarthrit.2023.152308

50.

Fanouriakis A et al (Jan. 2024) EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis 83(1):15–29. https://doi.org/10.1136/ard-2023-224762

Title: Clinical and laboratory characteristics of early-onset and delayed-onset lupus nephritis patients: A single-center retrospective study
Authors: Joanna Kosałka-Węgiel
Radosław Dziedzic
Andżelika Siwiec-Koźlik
Magdalena Spałkowska
Mamert Milewski
Joanna Żuk-Kuwik
Lech Zaręba
Stanisława Bazan-Socha
Mariusz Korkosz
Publication date: 28-03-2024
Publisher: Springer Berlin Heidelberg
Keywords: Lupus Nephritis
Systemic Lupus Erythematosus
Published in: Rheumatology International
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-024-05579-4

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.