Long-term renal outcomes of mesangial proliferative lupus nephritis in Chinese patients.

OBJECTIVE: This study aimed to explore the long-term outcomes of mesangial proliferative lupus nephritis (LN class II) and the factors associated with its relapse and histological transformation in Chinese patients. METHODS: 104 SLE patients with biopsy-proven LN class II were included and divided into proteinuria group (proteinuria ≥ 0.4 g/24 h, with or without microscopic hematuria) and hematuria group (microscopic hematuria with proteinuria < 0.4 g/24 h).Patients were treated with glucocorticoid alone (GC monotherapy) or GC in combination with other immunosuppressant (combination therapy). The rates of remission, relapse, histological transformation, end-stage renal disease (ESRD), adverse events, and risk factors related to the outcomes were analyzed. RESULTS: During the median follow-up of 77.5 (IQR 58-116.5) months, all the 104 patients achieved remission. Relapse occurred in 69 cases (66.3%), of which 37 were of renal relapse (35.6%). Histological transformation was found in 14 of the 16 (87.5%) cases who received repeated renal biopsy after renal relapse. At the end of follow-up, 3 (2.9%) patients developed ESRD. There were no significant differences in the rates of relapse, histological transformation, adverse events and in the time from remission to relapse between the proteinuria group and the hematuria group. In contrast, the cumulative relapse rate in the GC monotherapy group was much higher than that in the combination group (P < 0.01). Adverse events occurred in 55 (57.3%) patients during follow-up. CONCLUSIONS: Patients with LN class II have high rates of relapse and renal histological transformation and need optimal maintenance therapy. KEY POINTS: • The rates of relapse and histological transformation are high in patients with LN class II. • Patients with LN class II are suggested to receive combination therapy and consider repeat renal biopsy after renal relapse.

Hydrogen sulfide alleviates the anxiety-like and depressive-like behaviors of type 1 diabetic mice via inhibiting inflammation and ferroptosis.

Studies reported that sodium hydrosulfide (NaHS) can remit the depressive-like and anxiety-like behaviors induced by type 1 diabetes mellitus (T1DM). However, the mechanism is still unclear. In this study, we aimed to investigate the mechanism of NaHS on T1DM. Mice were randomly divided into four groups, including the control group (CON group), DM group, DM + 5.6 mg/kg NaHS group, and CON + 5.6 mg/kg NaHS group. Data showed that NaHS did attenuate the depressive-like and anxiety-like behaviors by OFT, EPM test, FST, and TST. Results suggest that NaHS markedly alleviated the ferroptosis in the prefrontal cortex (PFC) of diabetic mice by reducing iron deposition and oxidative stress, increasing the expression of GPX4 and SLC7A11. Moreover, NaHS could dampen the activation of microglias and the release of pro-inflammatory cytokines, enhance the protein expression of sirtuin 6 (Sirt6) and the interaction between Sirt6 and the acetylation of histoneH3 lysine9 (H3K9ac), and decrease the protein expressions of the Notch1 receptor and H3K9ac. In vitro experiment, NaHS ameliorated the ferroptosis via increasing the protein expressions of SLC7A11, glutathione peroxidase 4 (GPX4), and cystathionine ß-synthase (CBS), reducing the pro-inflammatory cytokines, decreasing the levels of Fe2+, MDA, ROS, and lipid ROS. In conclusion, our results suggested that NaHS did alleviate anxiety-like and depressive-like behaviors. It can inhibit inflammation via modulating Sirt6 and was able to decrease the ferroptosis in the PFC of type 1 diabetic mice and the BV2 cells.

Clinical-Morphological Features and Outcomes of Lupus Podocytopathy.

BACKGROUND AND OBJECTIVES: Lupus podocytopathy, which is characterized by diffuse foot process effacement without peripheral capillary wall immune deposits and glomerular proliferation, has been described in SLE patients with nephrotic syndrome in case reports and small series. This study aimed to better characterize the incidence, clinical-morphologic features, and outcomes of such patients from a large Chinese cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Lupus podocytopathy was identified from 3750 biopsies of SLE patients obtained from 2000 to 2013 that showed mild glomerular histology in patients with a clinical sign of nephrotic syndrome. The biopsy results were divided into three groups: glomerular minimal change, mesangial proliferation, and FSGS. RESULTS: Fifty (1.33%) cases were identified as lupus podocytopathy and included minimal change in 13 cases, mesangial proliferation in 28 cases, and FSGS in nine cases. Extensive foot process effacement appeared in all the biopsies and mesangial electron-dense deposits were present in 47 biopsies. All patients demonstrated nephrotic syndrome, and the median proteinuria was 5.72 g/24 h (interquartile range [IQR], 3.82, 6.92). Seventeen (34%) cases presented with AKI. Forty-seven (94%) patients achieved remission after immunosuppressive therapy for a median time of 4 weeks (IQR, 2, 8). Compared with the patients with minimal change and mesangial proliferation, patients with FSGS showed significantly higher incidence of AKI and severe tubule-interstitial injury and a much lower complete remission rate. During follow-up of a median of 62 (IQR, 36, 84) months, renal relapses occurred in 28 (59.6%) patients. No patient died or developed ESRD. CONCLUSIONS: The findings from this cohort study suggest that lupus podocytopathy may represent a special entity of lupus nephritis with distinct clinical-morphologic features. The differences in AKI incidence, tubular injury severity, and response to treatment between the patients with minimal change/mesangial proliferation and those with FSGS patterns indicate two different subtypes of lupus podocytopathy.

Long-term outcome of IgA nephropathy patients with recurrent macroscopic hematuria.

BACKGROUND/AIMS: The long-term renal outcomes of patients with IgA nephropathy (IgAN) who present with recurrent macroscopic hematuria (RMH) have not been described in previous studies. METHODS: Patients with biopsy-proven primary IgAN in Jinling Hospital were divided into three groups according to different patterns of macroscopic hematuria (MH): RMH, isolated MH (IMH), and those without a history of MH (NMH). RESULTS: A total of 1,155 patients were enrolled in the study (158 in the RMH group, 256 in the IMH group, and 741 in the NMH group). At biopsy, patients with RMH were younger, had lower median proteinuria, a lower incidence of hypertension, and a higher estimated glomerular filtration rate than those in the NMH group. Pathologically, patients with RMH had a lower level of mesangial hypercellularity and segmental glomerulosclerosis as well as less tubular atrophy than those with NMH. The demographic and clinical features of patients with IMH fell between patients with RMH and those with NMH. During a median follow-up of 7.9 years, the 5-, 10- and 20-year cumulative renal survival after biopsy, as calculated by K-M methods, were 98, 91, and 91% in the RMH group, 95, 89, and 64% in the IMH group, and 95, 79, and 57% in the NMH group. The renal survival in patients with RMH was significantly better than patients with NMH or IMH. CONCLUSIONS: The long-term prognosis of patients who present with RMH is significantly better than patients with NMH or IMH.