Correlation Between Serum Uric Acid, Serum Homocysteine Level and Interleukin- 17 in Lupus Nephritis Patients

Overview

Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystem autoimmune disease characterized by pathogenic autoantibodies production against nuclear structures . SLE affecting mainly women of childbearing age and is characterized by unpredictable flares and remissions. Disease severity varied from a mild episodic disorder to a rapidly progressive life-threatening illness. The kidney is the most commonly involved visceral organ in SLE. Therefore, identifying new noninvasive biomarkers of LN severity and outcome is mandatory. IL-17 is a potent pro-infammatory cytokine that amplifes T-cell activation and stimulates fibroblast cells, endothelial, and epithelial cells to produce several pro-infammatory mediators, including IL-1β, IL-6, and TNF-α. IL-17 receptor signaling enhances the expression of multiple pro-infammatory mediators. Hence, IL-17 enhances the production of neutrophil-attracting chemokines

Detailed description

Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystem autoimmune disease characterized by pathogenic autoantibodies production against nuclear structures. SLE affecting mainly women of childbearing age and is characterized by unpredictable flares and remissions. Disease severity varied from a mild episodic disorder to a rapidly progressive life-threatening illness. The kidney is the most commonly involved visceral organ in SLE Lupus nephritis (LN) is one of the most serious manifestations of SLE since it is associated with significant morbidity and mortality and affects up to 60% of SLE patients. Nephritic syndrome and acute kidney injuries can complicate LN and increase the risk of end stage renal disease (ESRD) . Early diagnosis of renal involvement in SLE patients is important to improve the long-term outcome and increase the survival rate .

LN is diagnosed by either the presence of proteinuria (\>0.5 g/day), active urinary sediment (with red blood cell, granular, tubular and/or mixed casts), or an unexplained rise in serum creatinine. A renal biopsy is known to be the gold standard for the diagnosis of LN because it gives information and details about the pattern and severity of kidney affection as well as the exclusion of other mimics of LN . Each of these factors weighs heavily on treatment choices. However, kidney biopsy is an invasive technique, and it is contraindicated in some situations such as bleeding and infection, associated with renal biopsy .

Therefore, identifying new noninvasive biomarkers of LN severity and outcome is mandatory. IL-17 is a potent pro-infammatory cytokine that amplifes T-cell activation and stimulates fibroblast cells, endothelial, and epithelial cells to produce several pro-infammatory mediators, including IL-1β, IL-6, and TNF-α. IL-17 receptor signaling enhances the expression of multiple pro-infammatory mediators. Hence, IL-17 enhances the production of neutrophil-attracting chemokines .

Few studies focused on the importance of IL-17 in SLE, particularly LN, and its relation to different disease activity parameters, so we aimed to explore its relation with uric acid and homocysteine in LN.

Also, Lupus nephritis (LN) is closely associated with hyperuricemia, and uric acid is the metabolite of purine that is excreted mainly in urine and considered a risk factor for renal involvement in systemic lupus erythematosus (SLE).

We postulated that patients with lupus nephritis are more likely to have elevated homocysteine levels. Homocysteine is metabolized by two alternative pathways, including its remethylation and transsulfuration. Elevated serum homocysteine can occur in 5 to 10 percent of the population. Increased serum homocysteine levels are seen in approximately 15% of patients with systemic lupus erythematosus.

Interventions

• Diagnostic test interleukin- 17
  focused on the importance of IL-17 in SLE, and its relation to different disease activity

Primary outcome measures

• SLE disease activity index (SLEDAI) will be assessed [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• ● Aged ≥18 years.

• SLE patients fulfilling the SLE International Collaborating Clinics (SLICC) classification criteria and matched controls.
• Patients cooperative and can answer questions.
• Patients who are able and willing to give written informed consent

Exclusion criteria

• ● Individuals with other autoimmune diseases.

• Patients receive any hyperuricemia treatment
• Pregnancy
• Malignancy
• Diabetes.
• Hypertension.
• Heart failure.
• Hepatic diseases.
• Chronic renal failure other than lupus nephritis.
• Renal artery stenosis.
• Renal vein thrombosis.
• Intrarenal arteriovenous fistula.
• Obstructive nephropathy.
• Urinary tract obstruction that could affect RI of intra renal arteries.
• Uncooperative patients.
• Patients not able and willing to give written informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

Egypt · 1 center

• Sohag university Hospital — Sohag

Publications

• Alforaih N, Whittall-Garcia L, Touma Z. A Review of Lupus Nephritis. J Appl Lab Med. 2022 Oct 29;7(6):1450-1467. doi: 10.1093/jalm/jfac036. PMID 35932197
• Zhu S, Qian Y. IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clin Sci (Lond). 2012 Jun;122(11):487-511. doi: 10.1042/CS20110496. PMID 22324470
• Ameer MA, Chaudhry H, Mushtaq J, Khan OS, Babar M, Hashim T, Zeb S, Tariq MA, Patlolla SR, Ali J, Hashim SN, Hashim S. An Overview of Systemic Lupus Erythematosus (SLE) Pathogenesis, Classification, and Management. Cureus. 2022 Oct 15;14(10):e30330. doi: 10.7759/cureus.30330. eCollection 2022 Oct. PMID 36407159
• Anstee QM, Castera L, Loomba R. Impact of non-invasive biomarkers on hepatology practice: Past, present and future. J Hepatol. 2022 Jun;76(6):1362-1378. doi: 10.1016/j.jhep.2022.03.026. PMID 35589256

Identifiers

NCT: NCT07017868 · Soh-Med--25-4-07MS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗