Serum Ceramides Level in Systemic Lupus Erythematosus (SLE) Patients as a Novel Marker for Renal Impairment

1. Estimation of serum ceramides level in SLE patients as anovel marker for renal impairment
2. Correlation serum ceramides level with histological classification of LN,C3,C4,ANA,ANTI DS DNA ,CRP ,ESR , eGFR , creatinine /protein ratio
3. Follow up estimation of ceramides level in LN patients after 3 cycles of treatment

Study Overview

• Status: Unknown
• Conditions: Systemic Lupus
• Intervention / Treatment: Diagnostic test: serum ceramides level in blood

Detailed Description

Systemic lupus erythrematosus (SLE) is an autoimmune disease with increasing prevalence and incidence , The clinical manifestation is multifaceted and targets the musculoskeletal system, the skin and different organs like lung and kidney From 30-80% of SLE patients develop lupus nephritis (LN) which often leads to chronic kidney disease (CKD) and end-stage renal disease (ESRD) and is associated with an overall poor prognosis and high mortality Diagnosis of LN is made by kidney biopsy, which still remains the gold standard Histological evaluation distinguish between different stages of LN upon morphological changes within the kidney . However, noninvasive methods to diagnose and guide LN therapy are currently not established in the clinic. On the other hand, an early diagnosis is important for the therapeutic success and thereby lowers the risk of ESRD In this context, classical clinical markers for renal dysfunction are insufficient for an early assessment of the need for renal biopsies and subsequently to decide about the optimal therapy. Even though traditional biomarkers like antids DNA antibodies and complement deficiency are widely accepted as diagnostic instruments to assess disease activity, their specificity is rather low, and they appear to be more suitable to confirm diagnosis of SLE and LN in an already likely clinical setting Ceramides are a family of waxy lipid molecules ,composed of sphingosine and fatty acide ,found in high concentration with in the cell membrane of eukaryocyte cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer Ceramides and other sphingolipids found in cell membrane were purely supporting structural elements,also participate in variety of cellular signaling, regulating differentiation, proliferation, Programmed cell death(PCD) Sphingolipids are a heterogenous group of lipids with more than 400 single compounds formed by structural and chemical modifications of a sphingosine backbone Recent studies reveal that blood sphingolipids not only have important signaling properties but also serve as biomarkers in various renal disease Patyna etal in 2019 concluded that ceramides in blood could act as potent biomarker for renal impairment in patient

• Study Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 58 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Prospective analytic (cross_section) study will be carried out on patients admitted to assiut university hospital internal medicine department.

Description

Inclusion Criteria:

• Forty five patients will SLE with and without renal impairment diagnosed as SLE according to SLICC classification criteria for SLE

Exclusion Criteria:

• Malignant tumor ,infectious diseases, Alzheimer disease ,type 2 diabetes mellitus vitamin D intaker, obesty , cardiovascular disease (HTN,HF ,ischemic heart disease)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Crossover
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients proven having (SLE); 20 patients proven to have systemic lupus Erthematosus without renal impairment (eGFR) ≥ 80 ml/min/1.73 m2 and albumin / creatinine ≤ 30 mg/g)	Diagnostic test: serum ceramides level in blood; Serum ceramides ( sphingolipid measurement, plasma (EDTA as anticoagulant) and serum separation was performed immediately after blood drawing by two-time scentrifugation at 750 x g for 5 min (4°C). Lipid extraction from plasma and/or serum samples (10 µl each) and subsequent LC-MS/MS)
patients proven to have (LN) by renal biopsy; Group (2) 25 patients proven to have LN by renal biopsy before starting treatment and after 3 cycle of treatment (eGFR < 80 ml/min/1.73 m2 and albumin/creatinine ratio > 30 mg/g)	Diagnostic test: serum ceramides level in blood; Serum ceramides ( sphingolipid measurement, plasma (EDTA as anticoagulant) and serum separation was performed immediately after blood drawing by two-time scentrifugation at 750 x g for 5 min (4°C). Lipid extraction from plasma and/or serum samples (10 µl each) and subsequent LC-MS/MS)
healthy control; (20) patients healthy control matched in age and sex	Diagnostic test: serum ceramides level in blood; Serum ceramides ( sphingolipid measurement, plasma (EDTA as anticoagulant) and serum separation was performed immediately after blood drawing by two-time scentrifugation at 750 x g for 5 min (4°C). Lipid extraction from plasma and/or serum samples (10 µl each) and subsequent LC-MS/MS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimation of serum ceramides level in SLE patients as anovel marker for renal impairment	Correlation serum ceramides level with histological classification of LN,C3,C4,ANA,ANTI DS DNA ,CRP ,ESR , eGFR , creatinine /protein ratio	base line

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Patyna S, Buttner S, Eckes T, Obermuller N, Bartel C, Braner A, Trautmann S, Thomas D, Geiger H, Pfeilschifter J, Koch A. Blood ceramides as novel markers for renal impairment in systemic lupus erythematosus. Prostaglandins Other Lipid Mediat. 2019 Oct;144:106348. doi: 10.1016/j.prostaglandins.2019.106348. Epub 2019 Jul 10.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2020
• Primary Completion (Anticipated): February 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: serum ceramides level in (SLE)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No