Renal Assessment for Early Detection of Renal Impairment in Systemic Sclerosis and Systemic Lupus Erythematosus Patients

Обзор

* Evaluate renal resistive index in SSc and SLE patients for early detection of renal impairment. * Evaluate renal multi-parametric MRI in SSc and SLE patients for early detection of renal impairment. * Measure the serum levels of CD147 in SSc and SLE patients and its correlation with renal impairment. * Correlation between detected markers and other assessment tools.

Подробное описание

Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction, collagen deposition, and fibrosis in the skin and internal organs. Systemic lupus erythematosus (SLE) is a complex, multi-organ autoimmune disease. The presence of autoantibodies and circulating immune complexes can cause vasculitis and damage the endothelial cells, leading to multiple organ dysfunctions. Renal involvement in SSc, ranges from urinary abnormalities, reduction of glomerular filtration rate (GFR), and high resistive indices, to scleroderma renal crisis (SRC). Subclinical renal vasculopathy is characterized by progressive increase of intrarenal stiffness and reduction of parenchymal thickness due to post ischemic fibrosis secondary to the renal Raynaud phenomenon.Conversely, in SLE-related kidney manifestations, renal damage results from glomerular involve-ment secondary to immune-complex acti¬vation. Cluster of differentiation 147 (CD147) is, also named extracellular matrix metalloproteinase inducer (EMMPRIN), a transmembrane glycoprotein in the immunoglobulin superfamily that is widely expressed on the surface membrane of various cells. Higher levels of soluble CD147 were found in SSc patients compared to healthy controls and higher levels in SSc patients with scleroderma renal crisis (SRC). Suggesting that CD147 could be a useful tool for identifying SRC risk. In patients with active SLE, CD147 is overexpressed on CD3 T lymphocytes. Renal resistive index (RRI) is a useful non-invasive technique for evaluation of renal disease activity in SLE patients. It can differentiate between patients with active lupus nephritis (LN) and inactive LN. RRI was higher in SSc patients than other autoimmune diseases since subclinical renal vasculopathy is the main pathogenic mecha¬nism of all SSc renal manifestations.Multiparametric renal Magnetic Resonance Imaging (MRI) shows great promise as a non-invasive method to assess kidney structure and function without exposure to radiation or gadolinium contrast agents. In MRI microstructural changes of lupus nephritis kidney such as inflammatory cell infiltration or fibrosis could influence water molecular movement or diffusion, which indicates that diffusion-weigted imaging (DWI) may become a valuable tool in diagnosis of LN. However in systemic sclerosis there is decline of renal blood flow values that indicate microvascular pathology.

Вмешательства

• Устройство Renal multi-parametric MRI, Renal doppler ultrasound, Serum CD147
  Laboratory investigations: erythrocyte sedimentation rate (ESR) Serum C-reactive protein (CRP) complete blood picture (CBC) liver function tests (LFT): aspartate transaminase (AST), alanine transaminase (ALT), serum albumin, serum bilirubin. kidney function tests (KFT): serum creatinine and blood urea. Estimated glomerular filteration rate (eGFR) by CKD-EPI Creatinine Equation (2021). Complete urine analysis for: proteinuria, urinary casts (hyaline, granular), hematuria (RBCs/ high power fiel

Первичные конечные точки

• Evaluate serum levels of CD147 in SSc and SLE patients [Срок оценки: One year]
• Evaluate renal resistive index in SSC and SLE patients [Срок оценки: One year]
• Evaluate Multiparametric MRI in SSC and SLE [Срок оценки: One year]

Вторичные конечные точки (3)

• Utility of CD 147 in ssc and SLE patients [Срок оценки: One year]
• Utility of renal resistive index in SSC and SLE patients [Срок оценки: One year]
• Utility of Multiparametric MRI in SSC and SLE [Срок оценки: One year]

Критерии участия

Критерии включения

• Adult (aged above 18 years) SSc patients who fulfilled the 2013 European League Against Rheumatism/American College of Rheumatology (EULAR / ACR) for SSC \[13\] and 1980 ACR criteria \[14\].
• Adult SLE Patients who fulfilled the 2019 EULAR / ACR classification criteria for systemic lupus erythematosus \[15\]

Критерии исключения

• Individuals with other autoimmune diseases.
• Smoking.
• Infections as chest infection, hepatitis C, hepatitis B and HIV infection.
• Tumors as hepatocellular carcinoma.
• Hypertension, diabetes, heart failure, hepatic diseases, chronic renal failure, intrarenal arteriovenous fistula, obstructive nephropathy and urinary tract obstruction.
• Contraindication for MRI as implanted metallic devices.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Rosato E, Gigante A, Barbano B, Gasperini ML, Cianci R, Muscaritoli M. Prognostic Factors of Renal Involvement in Systemic Sclerosis. Kidney Blood Press Res. 2018;43(3):682-689. doi: 10.1159/000489740. Epub 2018 May 10. PMID 29763902
• Zhao T, Lin FA, Chen HP. Pattern of Nailfold Capillaroscopy in Patients With Systemic Lupus Erythematosus. Arch Rheumatol. 2020 Apr 20;35(4):568-574. doi: 10.46497/ArchRheumatol.2020.7763. eCollection 2020 Dec. PMID 33758813
• Gigante A, Barbano B, Gasperini ML, Zingaretti V, Cianci R, Rosato E. Renal Parenchymal Thickness in Patients with Systemic Sclerosis Is Related to Intrarenal Hemodynamic Variables and Raynaud Renal Phenomenon. J Rheumatol. 2020 Apr;47(4):567-571. doi: 10.3899/jrheum.190165. Epub 2019 Jun 15. PMID 31203218
• Pellicano C, Vaiarello V, Colalillo A, Gigante A, Iannazzo F, Rosato E. Role of kinurenic acid in the systemic sclerosis renal involvement. Clin Exp Med. 2023 Sep;23(5):1713-1719. doi: 10.1007/s10238-022-00962-6. Epub 2022 Nov 27. PMID 36436115
• Anders HJ, Fogo AB. Immunopathology of lupus nephritis. Semin Immunopathol. 2014 Jul;36(4):443-59. doi: 10.1007/s00281-013-0413-5. Epub 2014 Jan 9. PMID 24402709
• Muramatsu T. Basigin: a multifunctional membrane protein with an emerging role in infections by malaria parasites. Expert Opin Ther Targets. 2012 Oct;16(10):999-1011. doi: 10.1517/14728222.2012.711818. Epub 2012 Aug 11. PMID 22880881
• Yanaba K, Asano Y, Tada Y, Sugaya M, Kadono T, Hamaguchi Y, Sato S. Increased serum soluble CD147 levels in patients with systemic sclerosis: association with scleroderma renal crisis. Clin Rheumatol. 2012 May;31(5):835-9. doi: 10.1007/s10067-012-1949-9. PMID 22298186
• Pistol G, Matache C, Calugaru A, Stavaru C, Tanaseanu S, Ionescu R, Dumitrache S, Stefanescu M. Roles of CD147 on T lymphocytes activation and MMP-9 secretion in systemic lupus erythematosus. J Cell Mol Med. 2007 Mar-Apr;11(2):339-48. doi: 10.1111/j.1582-4934.2007.00022.x. PMID 17488482

Идентификаторы

NCT: NCT06287125 · Renal assess in SSc and SLE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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