ObjectiveTo investigate the stiffness values obtained by acoustic radiation force impulse (ARFI) quantification in assessing renal histological fibrosis of chronic kidney disease (CKD).Methods163 patients with CKD and 32 healthy volunteers were enrolled between June 2013 and April 2014. ARFI quantification, given as shear wave velocity (SWV), was performed to measure renal parenchyma stiffness. Diagnostic performance of ARFI imaging and conventional ultrasound (US) were compared with histologic scores at renal biopsy. Intra- and inter-observer reliability of SWV measurement was analyzed.ResultsIn CKD patients, SWV measurements correlated significantly with pathological parameters (r = −0.422–−0.511, P<0.001), serum creatinine (r = −0.503, P<0.001), and glomerular filtration rate (r = 0.587, P<0.001). The mean SWV in kidneys with severely impaired (histologic score: ≥19 points) was significant lower than that mildly impaired (histologic score: ≤9 points), moderately impaired (histologic score: 10–18 points), and control groups (all P<0.001). Receiver operating characteristic (ROC) curves analyses indicated that the area under the ROC curve for the diagnosis of renal histological fibrosis using ARFI imaging was superior to these conventional US parameters. Using the optimal cut-off value of 2.65 m/s for the diagnosis of mildly impaired kidneys, 2.50 m/s for moderately impaired kidneys, and 2.33 m/s for severely impaired kidneys, the corresponding area under the ROC curves were 0.735, 0.744, and 0.895, respectively. Intra- and intre-observer agreement of SWV measurements were 0.709 (95% CI: 0.390–0.859, P<0.001) and 0.627 (95% CI: 0.233–0.818, P = 0.004), respectively.ConclusionsARFI may be an effective tool for evaluating renal histological fibrosis in CKD patients.

Background Focal segmental lesions (FSLs) are not uncommon in idiopathic membranous nephropathy (IMN). The reported percentage of IMN patients with focal segmental glomerulosclerosis (FSGS) lesions varies widely between studies. The objective of this study was to differentiate atypical FSL (aFSL) from typical FSGS in IMN and to analyse the clinicopathological predictors of primary outcome of IMN patients. Methods A total of 716 patients with biopsy-proven IMN between January 1, 2007 and December 31, 2017 were enrolled in the study. An atypical focal segmental lesion was defined as pure synechia, segmental hyperplasia of podocytes or thickening of the GBM accompanied by proliferation of the mesangial matrix, and absence of typical FSGS. The patients were divided into three groups: patients without FSL (FSL − ), patients with typical FSGS (FSGS + ), and patients with aFSL (aFSL + ).The primary outcome was a 50% decline in the initial estimated glomerular filtration rate or end-stage renal disease (ESRD) incidence. Secondary outcomes included all-cause death and ESRD. Results FSGS was present in 174 patients, while aFSL was noted in 161 patients. Systolic blood pressure was higher in both aFSL + group and FSGS + groups compared with the FSL − group. IMN patients without FSL and with aFSL had lower serum creatinine levels than IMN patients with FSGS. Both the FSGS + and aFSL + groups had higher levels of proteinuria and lower albumin levels than the FSL − group. Renal tissue lesions, including tubulointerstitial fibrosis, glomerular obsolescence, and vascular sclerosis were significantly more severe in the FSGS + group. Cox multivariate analysis showed that older age ≥ 60 years, eGFR< 60 ml/(min·1.73m 2 ), tubulointerstitial fibrosis area ≥ 15% and FSGS at biopsy were independent risk factors for the primary outcome. Conclusions No significant difference in outcome was found between the FSL − and aFSL + groups, although the patients with aFSL had lower levels of serum albumin and eGFR, higher level of urinary protein, more severe renal lesions with proliferation of the mesangial area,tubulointerstitial fibrosis and vascular sclerosis. FSGS, excluding atypical lesions, was an independent predictor of the primary outcome.

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Background: Cyclophosphamide (CTX) and cyclosporine (CsA) are used in idiopathic membranous nephropathy (IMN); however, limited data comparing their efficacy are available. We aimed to determine the baseline clinicopathological predictive factors of renal outcome in patients with IMN who received CTX or CsA. We also attempted to establish simple risk scores for predicting renal outcomes in IMN patients prescribed CsA-based initial treatment. Method: We retrospectively included 516 patients with biopsy-proven IMN from January 1, 2007 to October 31, 2019. The primary outcome was no remission and a decline of renal function in IMN patients who received CTX and CsA as initial treatment. Results: The CsA group showed higher complete remission (CR) rate at 6 months, and no significant difference in accumulative total remission between the two groups was observed in the initial 12 months. Independent predictors of primary outcomes were urine protein content and serum albumin in the CTX-based group and serum creatinine, triglyceride, and focal segmental glomerulosclerosis (FSGS) lesions in the CsA-based treatment group. The area under the receiver operating characteristic curve based on a three-variable risk score in predicting primary outcome was 0.791 (95% CI 0.720–0.862). IMN patients with FSGS lesions who received CsA-based initial treatment had a higher percentage of primary outcome and a lower CR rate. Conclusion: Serum creatinine, hypertriglyceridemia, and FSGS lesions were important predictors of a worse prognosis in CsA-based initial treatment patients. Our simple risk score was able to predict renal outcomes in IMN patients receiving CsA-based initial treatment with good discrimination. Name of the registry: Chinese Clinical TrialRegistry Trial registration number: ChiCTR2200059658 May 5, 2022 Retrospectively registered URL of trial registry record: https://www.chictr.org.cn/hvshowproject.aspx?id=168696

Aim: This study aimed to investigate the effect of norcantharidin (NCTD) on human mesangial cells (HMCs) apoptosis in vitro and further examine its molecular mechanism. Methods: HMCs were divided into 5 groups: control group, 25% fetal bovine serum (FBS)-treated group, and NCTD groups (NCTD [2.5, 5 and 10 µg/mL] + 25% FBS, respectively). Cell proliferation was determined by MTT assay, while apoptosis was evaluated by Hoechest 33258 staining, the level of cytochrome c, immunohistochemistry, and apoptotic-related proteins/gene expression. Results: Cell viability was inhibited in NCTD-treated HMCs in a dose-dependent manner. The number of apoptotic cells and the content of cytochrome c were significantly increased by NCTD treatment but that of mitochondrial membrane was decreased. Moreover, the expression of bcl-2 and caspase-3 was prompted by NCTD, but the expression of bax, MMP-2, and MMP-9 in 25% FBS-treated HMCs was inhibited. In addition, NCTD markedly unregulated the expression of apoptosis-related gene/protein, including p-Erk1/2, phosphorylated-Jun N-terminal kinase (JNK), p-p38, and p53. Conclusion: NCTD enhances 25% FBS-treated HMC apoptosis in vitro, and this effect may be attributed to the modulation of the ERK, JNK, and p38 mitogen-activated protein kinase signaling pathways.