Can sacubitril/valsartan become the promising drug to delay the progression of chronic kidney disease?

1 Introduction Chronic kidney disease(CKD)often coexists with or is a complication of cardiovascular disease.Previous studies have shown that CKD increases the risk of cardiovascular death and all-cause death and was considered to be a risk equivalent of coronary heart disease.[1,2]Adjusted for confounders,decreased glomerular filtration rate(GFR)and increased albuminuria are both independent risk factors for cardiovascular events.[3,4]The risk for cardiovascular death linearly increases with the decline of GFR in a certain range(<70 mL/min per 1.73 m^2)and the increase of albuminuria without a threshold effect[3].

Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave:a single-center cohort study

Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.

Severe mental disorders following anti-retroviral treatment in a patient on peritoneal dialysis: A case report and literature review

BACKGROUND Antiviral drugs are widely used in populations with viral infection caused by immunologic inadequacy.Because these drugs are mainly metabolized by the kidneys,patients with renal failure undergoing renal replacement therapy are prone to drug adverse effects and poisoning.Severe neurotoxicity caused by antiviral drugs is a rare but life-threatening complication.CASE SUMMARY This study reported one male patient on peritoneal dialysis who suffered from severe mental disorders after receiving an overdose of acyclovir and valacyclovir for the treatment of herpes zoster.The literature review suggested that hemodialysis is better than peritoneal dialysis to clear acyclovir from the circulation.The patient died after his consciousness deteriorated despite peritoneal dialysis and continuous blood purification.CONCLUSION This case emphasizes cautiousness when using anti-retroviral drugs in patients with uremia.Hemodialysis is optimal method to remove the drugs.

Mycophenolate mofetil plus prednisone for inducing remission of Henoch-Sch?nlein purpura nephritis: a retrospective study

Objective： The treatment of Henoch-Schonlein purpura （HSP） with moderate proteinuria remains con- troversial. We retrospectively analyzed the efficacy of immune suppressants, with a particular emphasis on myco- phenolate mofetil （MMF）. Methods： Ninety-five HSP patients with moderate proteinuria （1.0-3.5 g/24 h） after at least three months of therapy with angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） were divided into three groups： an MMF group （n=33） that received MMF 1.0-1.5 g/d combined with prednisone （0.4-0.5 mg/（kg.d））, a corticosteroid （CS） group （n=31） that received full-dose prednisone （0.8-1.0 mg/（kg.d））, and a control group （n=31）. Patients in the MMF and CS groups continued to take ACEI or ARB at the original dose. The patients in the control group continued to take ACEI or ARB but the dose was increased by （1.73±0.58）-fold. The patients were followed up for 6-78 months （median 28 months）. Results： The baseline proteinuria was higher in the MMF group （（2.1±0.9） g/24 h） than in the control group （（1.6±0.8） g/24 h） （P=0.039）. The proteinuria decreased sig- nificantly in all groups during follow-up, but only in the MMF group did it decrease significantly after the first month. At the end of follow-up, the proteinuria was （0.4±0.7） g/24 h in the MMF group and （0.4±0.4） g/24 h in the CS group, significantly lower than that in the control group （（0.9±1.1） g/24 h）. The remission rates in the MMF group, CS group, and control group were respectively 72.7%, 71.0%, and 48.4% at six months and 72.7%, 64.5%, and 45.2% at the end of follow-up. The overall number of reported adverse events was 17 in the MMF group, 30 in the CS group, and 6 in the control group （P〈0.001）. Conclusions： MMF with low-dose prednisone may be as effective as full-dose prednisone and tend to have fewer adverse events. Therefore, it is probably superior to conservative treatments of adult HSP patients with moderate proteinuria.

Lipopolysaccharide-induced podocyte injury is regulated by calcineurin/NFAT and TLR4/MyD88/NF-κB signaling pathways through angiopoietin-like protein 4

Podocyte injury is an important cause of proteinuria.Angiopoietin-like protein 4(Angptl4)is a secreted glycoprotein and has a role in proteinuria.However,the exact role of Angptl4 in podocyte injury and its upstream regulators has not been clarified.In this study,we used lipopolysaccharide(LPS)-induced mice and cultured podocytes as podocyte injury models.Our results indicated that LPS increased the expression of podocyte Angptl4 in vivo and in vitro.Furthermore,we showed that Angptl4 overexpression deteriorated LPS-induced podocyte injury by inducing podocyte cytoskeleton rearrangement,reducing the expression of synaptopodin while Angptl4 knockdown alleviated LPS-induced podocyte injury.In addition,we found that inhibitors and siRNA targeting TLR4/MyD88/NF-κB signaling inhibited the upregulation of Angptl4 in LPS-induced podocytes.Moreover,inhibitors and siRNA targeting calcineurin/NFAT signaling also relieved LPS-induced Angptl4 expression and podocyte injury in vivo and in vitro.Taken together,our study has elucidated that both of the TLR4/MyD88/NF-κB and calcineurin/NFAT signaling mediate the upregulation of Angptl4 in LPS-induced podocytes,which has important implications for further understanding the molecular mechanism of LPS-induced podocyte injury.

Corrigendum to“Lipopolysaccharide-induced podocyte injury is regulated by calcineurin/NFAT and TLR4/MyD88/NF-kB signaling pathways through Angiopoietin-like protein 4”[Genes&Diseases 9(2022)443e455]

The authors regret that some statistical errors were made in“Lipopolysaccharide-induced podocyte injury is regulated by calcineurin/NFAT and TLR4/MyD88/NF-kB signaling pathways through Angiopoietin-like protein 4”(Genes Dis,https://doi.org/10.1016/j.gendis.2020.07.005)at Figure 2G,Figure 3B and F,and Figure 4C and D for Angptl4 expression,Figure 5E for CaN expression.