Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies

BioMed Research International

Lin

Wang

et al. 2020

Aims. Tenofovir (TDF) is an antiviral drug with potential risk of kidney injury. The study is aimed at comparing the incidence of acute kidney injury (AKI) between TDF and entecavir (ETV) treatment in hepatitis B virus- (HBV-) related acute on chronic liver failure (ACLF). Methods. Treatment-naive patients with HBV-related ACLF were included. Propensity score matching was used to balance the baseline characteristics between ETV and TDF groups. The risk of AKI and the efficacy of TDF and ETV were compared. Results. A total of 95 cases with HBV-related ACLF were included in this study, with 74.74% of male and a mean age of 47.01±14.71 years. The antiviral therapy was initiated within 2 days after admission, with 39 cases on the TDF group and 56 on the ETV group. Patients in the TDF group had higher AST, hemoglobin, and serum sodium levels and lower MELD-Na score. After propensity matching, 39 cases of TDF and 39 of ETV were included in the final analysis. No difference was found in the changes of creatinine and cystatin C from baseline to 4 weeks after treatment between ETV and TDF groups. AKI was developed in 1 (2.56%) patient in the ETV group and 2 (5.13%) in the TDF group within one month (P=0.556). Survival analysis revealed no significant difference in the 6-month mortality between the two groups (P=0.813). Cox analysis showed that the type of antiviral drug or the development of AKI was not an independent risk factor for the outcomes. Conclusions. Compared to ETV, TDF did not increase the risk of AKI nor the mortality in patients with HBV-related ACLF in the short time.

Section: Discussioncontrasting

confidence: 49%

The Risk of Acute Kidney Injury in Hepatitis B Virus-Related Acute on Chronic Liver Failure with Tenofovir Treatment

BioMed Research International

Lin

Wang

et al. 2020

“…Serum Cys-C indicates the real-time functional state of the kidney. It has been suggested to be an endogenous marker for predicting the early and accurate diagnosis of AKI [ 22 – 24 ]. We observed that Cys-C was detected at high levels in LPS-exposed mice, identifying renal dysfunction in the early stages of AKI.…”

Section: Discussionmentioning

confidence: 99%

Negative Regulation of Tec Kinase Alleviates LPS-Induced Acute Kidney Injury in Mice via theTLR4/NF-κB Signaling Pathway

BioMed Research International

Zhou

Jiang

et al. 2020

Tec kinase is an important mediator in inflammatory immune response that enhances the activity of neutrophils and macrophages. However, information on its function in lipopolysaccharide- (LPS-) induced acute kidney injury (AKI) is limited. This study is aimed at determining whether Tec kinase was a regulator in AKI. An AKI model in mice was successfully established using intraperitoneal LPS. Results showed that the serum levels of creatinine (Cr), blood urea nitrogen (BUN), and cystatin-C (Cys-C) increased after intraperitoneal LPS injection. Renal tissue sustained significantly severe injury as measured by pathological scores. Pretreatment with LFM-A13 improved the function of the kidney in mice and decreased the renal injury score. Enzyme-linked immunosorbent assay showed that LFM-A13 significantly reduced the release of IL-1β and TNF-α in mice exposed to LPS. LFM-A13 can evidently abrogate the expression of Tec protein, MyD88, TLR4, NF-κB p65, and Tec’s phosphorylated protein as determined by Western blot. Immunohistochemistry analysis revealed that LFM-A13 markedly downregulated the expression of Tec kinase in renal tubular epithelial cells. In vitro, Tec kinase protein was expressed highly in NRK-52E cells after LPS exposure. Tec-siRNA also decreased IL-1β and TNF-α production and obviously abolished phospho-p65 and phospho-IκBα expression in NRK-52E cell stimulated by LPS; however, Tec-siRNA increased the IκBα level. Altogether, these data suggested that Tec kinase can be a modulating protein in AKI through TLR4/NF-κB activation.

“…In contrast to the serum Creat concentrations, CysC was not affected by intra-variabilities such as gender and muscle mass, providing a more accurate measure of renal function [30, 31]. Evidence exists of the significant association of higher serum levels of CysC with increased microalbuminuria and lower GFR, which could reflect renal damage and impaired renal function [30].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic performance of serum cystatin C and complement component 1q in lupus nephritis

Yang

et al. 2019

Arthritis Res Ther

BackgroundThe information concerning non-invasive, easily obtainable, and accurate biomarkers for diagnosis of lupus nephritis (LN) is extremely limited. The aim of this study was to evaluate the diagnostic performance of cystatin C (CysC) and complement component 1q (C1q) for LN.MethodsA case-control study that included 905 patients with systemic lupus erythematosus (SLE) without LN (group SLE), 334 patients with active lupus nephritis (group LNA), 255 patients with inactive lupus nephritis (group LNI), and 497 healthy individuals (group HC) was performed in Mianyang Central Hospital from March 2017 to December 2018. The serum levels of CysC, C1q, urea (Urea), and creatinine (Creat) were measured, and 2 estimated glomerular filtration rates (eGFRCysC and eGFRCreat) were calculated by equations which were based on serum CysC established by our group and the modification of diet in renal disease (MDRD), respectively. ANOVA analysis or Kruskal-Wallis test was used for comparing the differences among the groups, and receiver operating characteristic (ROC) curve was applied to identify the diagnostic efficiencies of individual or combined multiple indicators.ResultsSignificantly elevated CysC and decreased C1q were observed in the LNA and LNI groups, which was in contrast to their levels in the SLE and HC groups. CysC (AUC = 0.906) or eGFRCysC (AUC = 0.907) assessed the highest diagnostic performance on LNA when detected individually, followed by C1q (AUC = 0.753). Joint utilization of C1q and CysC achieved very good performance (AUC = 0.933) which approximated to the best one observed in the combinations of C1q, Urea, CysC, eGFRCreat, and Creat (AUC = 0.975).ConclusionThe separately detected CysC (eGFRCysC) and C1q were superior to the conventional biomarkers Urea, Creat, and eGFRCreat in the diagnosis of LNA. Moreover, although the combined detection of Urea, Creat, C1q, CysC, and eGFRCreat had the greatest diagnostic performance, the joint utilization of CysC and C1q could be prioritized for rapid discrimination of LNA if the economic burden is taken into consideration.