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.

OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to &lt;75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c &lt;7.5% (58 mmol/mol) or ≥7.5%. RESULTS Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c &lt;7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

No abstract

Background: This prespecified subgroup analysis of the FIDELIO-DKD trial aimed to evaluate the efficacy and safety of finerenone in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) in China. Methods: Three hundred and seventy-two participants were recruited from 67 centers in China and randomized 1:1 to oral finerenone or placebo with standard therapy for T2DM. The primary composite outcome included kidney failure, sustained decrease of estimated glomerular filtration rate (eGFR) ≥ 40% from baseline over at least 4 weeks, or renal death. The key secondary composite outcome included death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results: After a median follow-up of 30 months, the finerenone group showed a relative risk reduction (RRR) of 41% (hazard ratio [HR]=0.59, 95% confidence interval [CI], 0.39 to 0.88; p=0.009) for the primary composite outcome compared with placebo, consistent across its components with treatment benefits with finerenone. Based on an absolute between-group difference of 12.2% after 30 months, the number of patients who needed to be treated (NNT) with finerenone to prevent one primary outcome event was eight (95%CI: 4 to 84). For the key secondary composite outcome, the finerenone group showed a RRR of 25% (HR=0.75, 95% CI, 0.38 to 1.48; p=0.408). Adverse events were similar between the two groups. The effects of finerenone on blood pressure were modest. No gynecomastia events were reported in the study. Hyperkalemia leading to discontinuation occurred in eight (4.3%) and two (1.1%) participants in the finerenone and control groups, respectively. The incidence of acute kidney injury was comparable between the two groups (1.6% vs. 1.6%). Conclusions: Finerenone resulted in lower risks of CKD progression than placebo and a balanced safety profile in Chinese patients with CKD and T2DM.

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