Serum suPAR levels help differentiate steroid resistance from steroid-sensitive nephrotic syndrome in children

Peng, Zhaoyang; Mao, Jianhua; Chen, Xuejun; Cai, Fengqing; Gu, Weizhong; Fu, Haidong; Shen, Huijun; Wang, Jingjing; Jin, Xin; Zhu, Xinyuan; Liu, Aimin; Shu, Qiang; Du, Lizhong

doi:10.1007/s00467-014-2892-6

Cited by 19 publications

(19 citation statements)

References 28 publications

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“…Thus, 364 studies were initially included, among which 306 studies were excluded after reading the title and abstract. After reading the full text, another 29 studies were excluded; therefore, 29 studies were finally included 9–11 21–46. A flow chart of the study selection process is presented in figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…In total, there were 18 studies9 10 22–27 30 33–35 37 38 40–42 46 in which the concentrations of suPAR were compared between primary FSGS and the normal control group. The overall results showed that the level of suPAR in the primary FSGS group was significantly higher when compared with that in the normal control group (p<0.001; SMD: 2.56; 95% CI 1.85 to 3.28; I 2 =96.9%).…”

Section: Resultsmentioning

confidence: 99%

“…In a total of 19 studies,9 22 24–28 30 31 33–35 37 38 40 42 44–46 the concentrations of suPAR in primary FSGS and MCD were compared, and the results showed that the concentration of suPAR in primary FSGS was significantly higher compared with that in MCD (p<0.001; SMD: 1.72; 95% CI 1.17 to 2.28; I 2 =94.0%) (table 2).…”

Section: Resultsmentioning

confidence: 99%

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Serum soluble urokinase type plasminogen activated receptor and focal segmental glomerulosclerosis: a systematic review and meta-analysis

et al. 2019

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ObjectivesSoluble urokinase plasminogen activated receptor (suPAR) is a biomarker that may predict the occurrence of focal segmental glomerulosclerosis (FSGS); however, there is still controversy about whether suPAR can predict FSGS. In this study, we performed a systematic evaluation and meta-analysis to prove whether suPAR can predict FSGS, and to detect a threshold concentration of suPAR that can be used to diagnose FSGS. In addition, a threshold concentration of suPAR for the diagnosis of FSGS was proposed.DesignSystematic review and meta-analysis.Data sourcesWe systematically searched PubMed, Embase, Cochrane Library, Web of Science and China Biology Medicine databases for studies published from the inception dates to 1 December 2018.Eligibility criteria(1) Data involving the suPAR level were from blood samples; (2) FSGS was diagnosed by biopsy; and (3) randomised controlled trials, cohort studies, case–control studies and cross-sectional studies.Data extraction and synthesisInitially, a total of 364 studies were searched, among which 29 studies were finally included. In addition, seven studies described the cut-off value of suPAR, which ranged from 2992.6 to 5500 pg/mL.ResultsThe results showed that the suPAR levels in the primary FSGS group were significantly higher when compared with that in the normal control group (p<0.001; standard mean difference (SMD): 2.56; 95% CI 1.85 to 3.28), and significant differences were observed in the secondary FSGS and in the normal control group (p<0.001; SMD: 1.68; 95% CI 1.37 to 1.98). A suPAR concentration of 3000 pg/mL may be the best threshold for the diagnosis of primary FSGS (sensitivity=0.72; specificity=0.88; area under the curve=0.85).ConclusionOur results suggested that suPAR might be a potential biomarker for predicting primary and secondary FSGS. In addition, our data showed that a suPAR concentration of 3000 pg/mL might be used as a threshold for the diagnosis of FSGS.Trial registration numberCRD42019120948.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Serum soluble urokinase type plasminogen activated receptor and focal segmental glomerulosclerosis: a systematic review and meta-analysis

et al. 2019

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“…However, contradictory results had been declared. In 2015, Peng Z et al, showed that serum suPAR may help to differentiate steroid resistance from steroid-sensitive NS in children with high specificity but low sensitivity [21].…”

Section: Resultsmentioning

confidence: 99%

Nephronectin (NPNT) and the prediction of nephrotic syndrome response to steroid treatment

Watany

El‐Horany

2018

Eur J Hum Genet

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Steroid-resistant nephrotic syndrome represents about 10-20% of pediatrics' nephrotic syndrome. The regeneration of glomerular barrier seems pivotal for cessation of proteinuria. Nephronectin (NPNT) plays a major role in nephrogenesis, signal transduction, and epithelial-mesenchymal interactions. This study aims to preliminary assess NPNT as potential noninvasive biomarker of glomerular regeneration and its ability to identify steroid resistance. In this case control study, 80 retrospectively selected patients with nephrotic syndrome were enrolled in addition to 40 healthy controls. Forty patients were steroid sensitive (SSNS) and the other 40 patients were steroid-resistant (SRNS), NPTN concentration was measured using ELISA and NPNT mRNA expression was assayed using real-time PCR. NPTN concentrations were significantly higher in SSNS than both SRNS and controls (The means were 4.64 ± 3.05, 0.69 ± 0.44, and 1.63 ± 0.59, respectively). Moreover, NPTN concentrations were significantly lower in SRNS than controls. NPTN was significantly overexpressed in SSNS compared to both SRNS and controls (the means were 10.82 ± 7.39, 1.19 ± 0.94, and 1.04 ± 0.10, respectively) with no statistically significant difference between SRNS and controls. ROC curves analysis showed that both NPNT expression and NPNT serum level are of promising diagnostic performance (ROC 0.948 and 0.896, respectively). Regression analysis showed that both NPNT expression and NPNT serum level can be independent predictors of steroid resistance. The present study shows for the first time an enhanced expression of NPNT in steroid-sensitive nephrotic syndrome patients suggesting NPNT as a marker of glomerular regeneration. Also, serum NPNT can be a useful noninvasive biomarker of steroid resistance.

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“…It may be possible that suPAR plays a role in both genetic and non-genetic forms of rFSGS ( 9 ); even so rFSGS is generally less prominent in genetic forms of FSGS ( 8 ). Some reports show inconsistencies in associations of suPAR and rFSGS in patients with advanced CKD and reduced eGFR in pediatric ( 22 , 23 ) and adult FSGS patients ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

A Case Report of Adrenocorticotropic Hormone to Treat Recurrent Focal Segmental Glomerular Sclerosis Post-Transplantation and Biomarker Monitoring

et al. 2015

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Background: Recurrent focal segmental glomerular sclerosis (rFSGS) in renal transplant recipients (RTR) is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies.Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure, requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb), soluble urokinase-type plasminogen activator receptor (suPAR) serum level with suPAR-β3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab) titer.Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, β3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance), and high dose steroids, the Palb and suPAR-β3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation, we commenced adrenocorticotropic hormone (ACTH, Acthar® Gel), 80 units subcutaneously twice weekly. Four-weeks later, he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with <1 g of proteinuria.Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.

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Serum suPAR levels help differentiate steroid resistance from steroid-sensitive nephrotic syndrome in children

Abstract: From ROC curve analysis, we demonstrated the significance of the suPAR level in predicting SRNS with a high specificity but low sensitivity. However, the clinical value of suPAR to predict steroid resistance and guide therapy remains to be investigated further.

Cited by 19 publications

References 28 publications

Serum soluble urokinase type plasminogen activated receptor and focal segmental glomerulosclerosis: a systematic review and meta-analysis

Serum soluble urokinase type plasminogen activated receptor and focal segmental glomerulosclerosis: a systematic review and meta-analysis

Nephronectin (NPNT) and the prediction of nephrotic syndrome response to steroid treatment

A Case Report of Adrenocorticotropic Hormone to Treat Recurrent Focal Segmental Glomerular Sclerosis Post-Transplantation and Biomarker Monitoring

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