Prognostic and Diagnostic Values of Novel Serum and Urine Biomarkers in Lupus Nephritis: A Systematic Review

Radin, Massimo; Miraglia, Paolo; Barinotti, Alice; Fenoglio, Roberta; Roccatello, Dario; Sciascia, Savino

doi:10.1159/000517852

Cited by 20 publications

(20 citation statements)

References 44 publications

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“…Lupus nephritis (LN) is seen in 50% of SLE patients and is a major cause of morbidity and mortality (1). Renal biopsy is considered the gold standard for the diagnosis of LN (2), but for its invasive, repeated biopsy is not safe and is rarely monitored. Thus, in LN patients,…”

Section: Introductionmentioning

confidence: 99%

Metabolic profiling reveals new serum signatures to discriminate lupus nephritis from systemic lupus erythematosus

et al. 2022

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BackgroundLupus nephritis (LN) occurs in 50% of patients with systemic lupus erythematosus (SLE), causing considerable morbidity and even mortality. Previous studies had shown the potential of metabolic profiling in the diagnosis of SLE or LN. However, few metabonomics studies have attempted to distinguish SLE from LN based on metabolic changes. The current study was designed to find new candidate serum signatures that could differentiate LN from SLE patients using a non-targeted metabonomics method based on ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).MethodMetabolic profiling of sera obtained from 21 healthy controls, 52 SLE patients and 43 LN patients. We used SPSS 25.0 for statistical analysis. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and metabolic pathway analysis were used to analyze the metabolic data.ResultsUpon comparison of SLE and LN groups, 28 differential metabolites were detected, the majority of which were lipids and amino acids. Glycerolphospholipid metabolism, pentose and glucuronate interconversions and porphyrin and chlorophyll metabolism were obviously enriched in LN patients versus those with SLE. Among the 28 characteristic metabolites, five key serum metabolites including SM d34:2, DG (18:3(9Z,12Z,15Z)/20:5(5Z,8Z,11Z,14Z,17Z)/0:0), nervonic acid, Cer-NS d27:4, and PC (18:3(6Z,9Z,12Z)/18:3(6Z,9Z,12Z) performed higher diagnostic performance in discriminating LN from SLE (all AUC > 0.75). Moreover, combined analysis of neuritic acid, C1q, and CysC (AUC = 0.916) produced the best combined diagnosis.ConclusionThis study identified five serum metabolites that are potential indicators for the differential diagnosis of SLE and LN. Glycerolphospholipid metabolism may play an important role in the development of SLE to LN. The metabolites we screened can provide more references for the diagnosis of LN and more support for the pathophysiological study of SLE progressed to LN.

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Section: Introductionmentioning

confidence: 99%

Metabolic profiling reveals new serum signatures to discriminate lupus nephritis from systemic lupus erythematosus

et al. 2022

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“…Renal biopsy is the gold standard for histological assessment of LN but has shortcomings in terms of sampling error, invasiveness, and the complication of hemorrhage ( 17 ). An alternative non-invasive and reproducible biomarker, such as urine CD163, is needed for evaluating LN ( 18 , 19 ). Specific urinary biomarkers that discriminate active LN could be instrumental in guiding its management ( 9 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

Urine Soluble CD163 Is a Promising Biomarker for the Diagnosis and Evaluation of Lupus Nephritis

et al. 2022

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IntroductionUrine-soluble CD163 (usCD163) is released from alternatively activated macrophages involved in the resolution of inflammation in glomeruli and plays an important role in glomerulonephritis. This study explored the role of usCD163 in patients with systemic lupus erythematosus (SLE).Materials and MethodsusCD163 concentrations were measured cross-sectionally in 261 SLE patients in Taiwan. Clinical and laboratory data were collected, and SLE disease activity scores were calculated to assess the correlation with usCD163.ResultsSLE patients with high usCD163 levels tended to be younger, with a higher hospital admission rate, higher prednisolone dose, lower estimated glomerular filtration rate, higher urine protein creatinine ratio (UPCR), more pyuria and hematuria, higher levels of inflammatory markers, higher rates of anemia, neutropenia, and lymphopenia, lower complement 3 (C3) levels, higher anti-double-stranded DNA antibody (anti-dsDNA Ab) levels, and higher disease activity scores (p < 0.05). usCD163 levels were significantly higher in patients with active lupus nephritis (LN) than in those with extrarenal or inactive SLE and correlated with UPCR, disease activity, and anti-dsDNA Ab levels. SLE patients with high usCD163 levels tended to have a higher chronic kidney disease stage.Discussion and conclusionThe usCD163 level correlates with the severity of LN and disease activity in renal SLE.

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“…Ten SRs on the diagnostic accuracy of new serum and urinary BMs in LN were selected. The SRs evaluated 7 distinct BMs in a total of 20 review arms (9 that analysed serum BMs [ 39 , 41 – 46 ], and 12 that analysed BMs in urine [ 37 , 39 , 43 , 44 , 47 – 49 ], as shown in Table 1 . The population evaluated in the primary studies was predominantly adults.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic test accuracy of novel biomarkers for lupus nephritis—An overview of systematic reviews

Guimarães

Furtado²,

Lucas³

et al. 2022

PLoS ONE

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Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan inflammatory involvement and a mortality rate that is 2.6-fold higher than individuals of the same age and sex in the general population. Approximately 50% of patients with SLE develop renal impairment (lupus nephritis). Delayed diagnosis of lupus nephritis is associated with a higher risk of progression to end-stage renal disease, the need for replacement therapy, and mortality. The initial clinical manifestations of lupus nephritis are often discrete or absent and are usually detected through complementary tests. Although widely used in clinical practice, their accuracy is limited. A great scientific effort has been exerted towards searching for new, more sensitive, and specific biomarkers in recent years. Some systematic reviews have individually evaluated new serum and urinary biomarkers tested in patients with lupus nephritis. This overview aimed to summarize systematic reviews on the accuracy of novel serum and urinary biomarkers for diagnosing lupus nephritis in patients with SLE, discussing how our results can guide the clinical management of the disease and the direction of research in this area. Methods The research question is “What is the accuracy of the new serum and urinary biomarkers studied for the diagnosis of LN in patients with SLE?”. We searched for systematic reviews of observational studies evaluating the diagnostic accuracy of new serum or urinary biomarkers of lupus nephritis. The following databases were included: PubMed, EMBASE, BIREME/LILACS, Scopus, Web of Science, and Cochrane, including gray literature found via Google Scholar and PROQUEST. Two authors assessed the reviews for inclusion, data extraction, and assessment of the risk of bias (ROBIS tool). Results Ten SRs on the diagnostic accuracy of new serum and urinary BMs in LN were selected. The SRs evaluated 7 distinct BMs: (a) antibodies (anti-Sm, anti-RNP, and anti-C1q), (b) cytokines (TWEAK and MCP-1), (c) a chemokine (IP-10), and (d) an acute phase glycoprotein (NGAL), in a total of 20 review arms (9 that analyzed serum BMs, and 12 that analyzed BMs in urine). The population evaluated in the primary studies was predominantly adults. Two SRs included strictly adults, 5 reviews also included studies in the paediatric population, and 4 did not report the age groups. The results of the evaluation with the ROBIS tool showed that most of the reviews had a low overall risk of bias. Conclusions There are 10 SRs of evidence relating to the diagnostic accuracy of serum and urinary biomarkers for lupus nephritis. Among the BMs evaluated, anti-C1q, urinary MCP-1, TWEAK, and NGAL stood out, highlighting the need for additional research, especially on LN diagnostic panels, and attempting to address methodological issues within diagnostic accuracy research. This would allow for a better understanding of their usefulness and possibly validate their clinical use in the future. Registration This project is registered on the International Prospective Registry of Systematic Reviews (PROSPERO) database (CRD42020196693).

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Prognostic and Diagnostic Values of Novel Serum and Urine Biomarkers in Lupus Nephritis: A Systematic Review

Cited by 20 publications

References 44 publications

Metabolic profiling reveals new serum signatures to discriminate lupus nephritis from systemic lupus erythematosus

Metabolic profiling reveals new serum signatures to discriminate lupus nephritis from systemic lupus erythematosus

Urine Soluble CD163 Is a Promising Biomarker for the Diagnosis and Evaluation of Lupus Nephritis

Diagnostic test accuracy of novel biomarkers for lupus nephritis—An overview of systematic reviews

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