Chuan-Ming Hao

Background: Omicron variants of COVID-19 have driven global waves of infection. Hemodialysis patients are particularly vulnerable to severe outcomes. However, clinical data on the impact of Omicron infection in hemodialysis patients remain limited. Methods: We retrospectively collected clinical data on hemodialysis patients infected with the COVID-19 Omicron variant at Huashan Hospital between March 31 and May 3, 2022, a period marked by a rapid increase in COVID-19 cases. Patients were categorized into two groups based on chest CT: the non-COVID-19 pneumonia group and the COVID-19 pneumonia group. Additionally, 74 diabetic patients who did not receive hemodialysis and who contracted COVID-19 during the study period were analyzed as controls. Results: A total of 150 hemodialysis patients were admitted to the hospital during this period, and 3 were excluded because of a lack of chest CT. At admission, 105 (71.4%) patients were diagnosed with COVID-19 pneumonia on the basis of chest CT. In contrast, 41.9% of non-hemodialysis diabetic patients exhibited manifestations of COVID-19 pneumonia. In dialysis patients, compared to the non-pneumonia group, the pneumonia group was older (65.7 ± 12.0 vs. 59.9 ± 16.3 years; p = 0.041) and had a higher prevalence of diabetes (39.0% vs. 11.9%; p = 0.003). The median time from the initial positive RT‒PCR result for SARS-CoV-2 to the first negative result was similar between the two groups. Serum levels of fibrinogen, NT-pro-BNP, and creatinine were independent factors associated with CT-defined COVID-19 pneumonia Conclusions: Hemodialysis patients had a higher prevalence of COVID-19 pneumonia. The fibrinogen level was an independent factor associated with CT-defined COVID-19 pneumonia.

Key Points: Susceptibility to ischemia-reperfusion–induced AKI was sexually dimorphic and associated with sex difference in KYNU expression and de novo NAD ⁺ flux. Androgen-dependent deficiency in kynureninase expression impaired NAD ⁺ de novo synthesis under stress, contributing to male mice susceptibility to kidney injury. Kynureninase deletion in female mice abrogated protection against ischemia‑reperfusion injury, which was rescued by nicotinamide mononucleotide treatment. Background: Biological sex is recognized as a modulator of AKI, whereas the underlying molecular mechanisms remain incompletely understood. Methods: An ischemia-reperfusion injury–induced AKI model was established on adult male and female wild-type and female kynureninase ( Kynu ) knockout ( Kynu ^−/− ) mice. Prepubertal wild-type mice were gonadectomized and euthanized 5 weeks later. ¹³ C-tryptophan was administered by tail vein injection, and renal levels of NAD ⁺ and metabolites in the de novo pathway were examined using high-performance liquid chromatography. Quinolinic acid (QA) and nicotinamide mononucleotide were administered by oral gavage or intraperitoneal injection. Results: Male mice were more susceptible to ischemic kidney injury, accompanied by a more pronounced decrease in NAD ⁺ levels compared with female mice. Further experiments demonstrated that the expression of KYNU, a central enzyme in the de novo NAD ⁺ biosynthetic pathway, was significantly downregulated in male kidneys. High-performance liquid chromatography analysis revealed that male mice exhibited significantly lower renal QA (a downstream metabolite of KYNU) and reduced tryptophan-derived NAD ⁺ after ischemia-reperfusion injury compared with females, reflecting impaired NAD ⁺ de novo biosynthesis. Notably, QA supplementation effectively alleviated the exacerbated kidney injury observed in male mice. In addition, castration markedly elevated renal Kynu expression to levels comparable with those in females, which decreased again after testosterone supplementation. Furthermore, genetic ablation of Kynu replicated the decreased renal QA and NAD ⁺ levels observed in male mice, accompanied by exacerbated kidney damage. Supplementation with nicotinamide mononucleotide, an NAD ⁺ precursor, significantly alleviated AKI in Kynu ^−/− mice. Conclusions: Androgen-dependent KYNU downregulation was found in the adult mouse kidney. Disrupted NAD ⁺ de novo biosynthesis caused by Kynu deficiency mediated the sex-biased susceptibility to AKI.

Worldwide, CKD is seen in one in nine adults; type 2 diabetes (T2D) is the most common cause. The population of just two countries in Asia, India and China, constitutes about 35% of the global population and is larger than the population of Africa or the combined populations of Europe and the Americas. CKD Global Outcomes (Kidney Disease Improving Global Outcomes) Clinical Practice Guideline for the Evaluation and Management of CKD recommends the use of foundational therapies such as lifestyle modifications, detection and treatment of hypertension, and pharmacologic management to forestall cardiovascular and kidney complications of T2D, including renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists such as finerenone, and glucagon-like peptide 1 receptor agonists. However, the implementation of these guidelines may be limited by real-world considerations, especially in Asia. This continent represents low-, middle-, and high-income countries and a variety of health care systems and policies. In this narrative review, the authors comprising of experts in the management of CKD in T2D in Asia, convened through video conferencing and online survey to discuss the perceived barriers to the implementation of guidelines with a focus on implementing the use of finerenone in CKD in T2D, particularly on the following: ( 1 ) the management of hypertension as an important comorbidity of T2D leading to CKD; ( 2 ) perceived barriers to screening for CKD in T2D; and ( 3 ) the use of finerenone in T2D with CKD, including its effects on Asian patients and perceived barriers to implementing the use of finerenone in the region.

Introduction: Erythropoietin and roxadustat are commonly used to manage anemia in hemodialysis-dependent chronic kidney disease (CKD) patients, but the comparative safety and effectiveness are unknown. Methods: This is a retrospective cohort study. Data were extracted from Tianjin Healthcare and Medical Big Data Platform. We screened all patients with CKD stage G5 and anemia (hemoglobin <100 g/L) who were treated with either erythropoietin or roxadustat between January 1, 2015, and December 31, 2021. The primary endpoints included expanded composite of major adverse cardiovascular events (MACE+), cardio-cerebrovascular events, and thromboembolic events in the peridialytic period, defined as the duration from the time of estimated glomerular filtration rate decrease to <15 mL/min × 1.73 m2 to 3 months after dialysis initiation. A propensity score-matched analysis (1:1 ratio; caliper width: 0.02) was conducted to minimize the impact of confounding factors. Results: The initial screen identified a total of 40,324 patients; 1,092 were included in the propensity score-matched analysis (546 in each group). In comparison to the roxadustat group, the erythropoietin group had a lower rate of MACE+ events within 6 months (13.4% vs. 21.2%, p < 0.001) and 12 months of treatment initiation (17.0% vs. 24.0%, p = 0.004), as well as within 3 months of hemodialysis initiation (12.9% vs. 28.7%, p < 0.001). The rate of cardio-cerebrovascular events was also lower in the erythropoietin group within 6 months (38.5% vs. 50.7%, p < 0.001) and 12 months of treatment initiation (49.1% vs. 56.2%, p < 0.001). The rate of thromboembolic events did not differ between the two groups. Conclusion: Peridialytic erythropoietin was associated with a more favorable cardiovascular safety profile versus roxadustat in hemodialysis-dependent CKD patients.

Background: Rituximab has been shown effective in patients with primary membranous nephropathy refractory to glucocorticoids plus cyclophosphamide (GC + CTX) or calcineurin inhibitors (CNIs), but the response rates remain limited. Compared with rituximab, obinutuzumab is a humanized anti-CD20 monoclonal antibody with greater B-cell depletion capacity. This study was performed to investigate the effectiveness of obinutuzumab compared with rituximab in treating patients with refractory primary membranous nephropathy. Methods: A retrospective study was conducted at Huashan Hospital, Fudan University between 1 January 2015 and 31 July 2024, and included adult patients with primary membranous nephropathy who met the following criteria: (i) resistance to GC + CTX and/or CNI regimens, (ii) dependence on CNIs or (iii) relapse within 1 year after CTX discontinuation. The patients subsequently received either obinutuzumab or rituximab. The primary endpoint was treatment response, which was defined as overall remission of nephrotic syndrome with no need for rescue therapy after obinutuzumab versus rituximab treatment. The secondary measures included immunological remission and safety profiles. Results: Among the 51 participants, 20 received obinutuzumab and 31 received rituximab. The response rate was significantly greater in patients receiving obinutuzumab than in those receiving rituximab (90.0% vs 38.7%, P < .001) during a follow-up period of 24 [interquartile range (IQR) 10–34] months. Cox proportional hazards survival regression analysis also revealed the superior effectiveness of obinutuzumab (P < .001). Immunological remission rates were higher in patients receiving obinutuzumab at both 3 months (75.0% vs 20.0%, P < .001) and 6 months (87.5% vs 21.4%, P < .001). The safety profiles of the two treatments were comparable. Among the 19 non-responders treated with rituximab, 10 subsequently received obinutuzumab, and 8 achieved remission during a follow-up period of 20.0 (IQR 18.5–22.3) months. Conclusion: This retrospective study suggests that obinutuzumab is an effective treatment option for patients with primary membranous nephropathy refractory to GC + CTX, CNI and rituximab regimens.

Obinutuzumab is a humanized and glycoengineered anti-CD20 monoclonal antibody that has been shown to induce profounder B-cell depletion than rituximab. The effectiveness and safety of obinutuzumab in the treatment of membranous nephropathy remain unclear. This was a retrospective study conducted in Huashan Hospital, Fudan University between December 1st, 2021 and November 31st, 2023. Patients with membranous nephropathy were included to assess the effectiveness and safety of obinutuzumab and prevalence of severe pneumonia during the outbreak of COVID-19 in China. Eighteen patients were included in the study assessing the effectiveness of obinutuzumab. After a 12-month follow-up, 14 patients (78%) achieved remission, with 6 (33%) achieving complete remission and 8 (44%) achieving partial remission. Among the 18 obinutuzumab-treated patients contracting COVID-19 for the first time, 6 (33%) developed severe pneumonia, and one died. In contrast, two of the 37 patients receiving glucocorticoids combined with cyclophosphamide, and none of the 44 patients on calcineurin inhibitors or the 46 patients on rituximab developed severe pneumonia. However, compared to patients receiving rituximab or glucocorticoids plus cyclophosphamide, the obinutuzumab-treated patients had a longer duration of membranous nephropathy and immunosuppressive therapy. Therefore, cardinal matching was employed to balance these baseline characteristics. Due to small sample size for each regimen, patients receiving all the 3 non-obinutuzumab immunosuppressive regimens were grouped as a control cohort. After matching for age, gender, remission status, duration of membranous nephropathy, duration of immunosuppressive therapy, and ongoing immunosuppression, the obinutuzumab-treated patients still had a significantly higher incidence of severe pneumonia compared to those on other regimens (P = 0.019). Obinutuzumab was an effective treatment option for patients with membranous nephropathy. On the other hand, it was associated with a higher incidence of severe pneumonia following COVID-19 infection compared to other immunosuppressive regimens.

The purpose of this study was to analyze the clinical, pathological, prognostic features and treatment response of the coexistence of focal segmental glomerulosclerosis lesions with idiopathic membranous nephropathy.

BACKGROUND: Prostacyclin is a fundamental signaling pathway traditionally associated with the cardiovascular system and protection against thrombosis but which also has regulatory functions in fibrosis, proliferation, and immunity. Prevailing dogma states that prostacyclin is principally derived from vascular endothelium, although it is known that other cells can also synthesize it. However, the role of nonendothelial sources in prostacyclin production has not been systematically evaluated resulting in an underappreciation of their importance relative to better characterized endothelial sources. METHODS: To address this, we have used novel endothelial cell–specific and fibroblast-specific COX (cyclo-oxygenase) and prostacyclin synthase knockout mice and cells freshly isolated from mouse and human lung tissue. We have assessed prostacyclin release by immunoassay and thrombosis in vivo using an FeCl ₃ -induced carotid artery injury model. RESULTS: We found that in arteries, endothelial cells are the main source of prostacyclin but that in the lung, and other tissues, prostacyclin production occurs largely independently of endothelial and vascular smooth muscle cells. Instead, in mouse and human lung, prostacyclin production was strongly associated with fibroblasts. By comparison, microvascular endothelial cells from the lung showed weak prostacyclin synthetic capacity compared with those isolated from large arteries. Prostacyclin derived from fibroblasts and other nonendothelial sources was seen to contribute to antithrombotic protection. CONCLUSIONS: These observations define a new paradigm in prostacyclin biology in which fibroblast/nonendothelial-derived prostacyclin works in parallel with endothelium-derived prostanoids to control thrombotic risk and potentially a broad range of other biology. Although generation of prostacyclin by fibroblasts has been shown previously, the scale and systemic activity was unappreciated. As such, this represents a basic change in our understanding and may provide new insight into how diseases of the lung result in cardiovascular risk.