Nephrology最新文献

Atypical hemolytic uremic syndrome is a thrombotic microangiopathy caused by the abnormal activation of the alternative complement pathway. Mutations in complement-related genes and autoantibodies against complement regulators are involved in the pathogenesis of this condition; the frequency of, and prognosis of patients harbouring, each genetic mutation varies based on the region and race. Complement factor I (CFI) mutations have been observed in 4%-8% of cases in Europe; however, they have not yet been reported in Japan. We present the first Japanese case of atypical hemolytic uremic syndrome in a patient harbouring a CFI mutation. An 83-year-old female patient presented with severe acute kidney injury, thrombocytopenia, and hemolytic anaemia following a femoral neck fracture. Plasma exchange and haemodialysis were initiated, resulting in improved kidney function and platelet count. However, the platelet count decreased when plasma exchange was discontinued. Therefore, we administered ravulizumab, an anti-complement 5 monoclonal antibody, which led to the maintenance of stable kidney function and platelet count. Genetic analysis revealed a CFI mutation, and the patient was treated with ravulizumab for 2 years without relapse. Individuals diagnosed with atypical hemolytic uremic syndrome harbouring CFI mutations experience poor outcomes, including low rates of remission, high rates of mortality, and progression to end-stage kidney disease. Our case serves as a crucial example demonstrating how prompt identification and appropriate management can lead to better patient outcomes.

Aim: To review the clinical characteristics and long-term outcomes of paediatric kidney transplants in Hong Kong.

Method: A retrospective cohort study was carried out on all paediatric kidney transplant recipients managed in the Paediatric Nephrology Centre in Hong Kong from 2009 to 2020. All recipients were under 21 at the time of transplant, with a minimal follow-up period of 2 years.

Results: Sixty-one patients (57.4% male; median age 13 years, IQR: 8.9-17.8) were followed for 6.4 years (IQR 4.3-9.6). The commonest causes of kidney failure were congenital abnormalities of the kidney and urinary tract (34.4%), followed by glomerular diseases (21.3%). 90.2% were deceased donor transplantation. Patient survival rates were 100%, 96.4%, and 96.4% at 1, 5, and 7 years, respectively, and the corresponding graft survival rates were 95.1%, 95.1%, and 89.9%. There were eight graft losses (13.1%). Rejection and chronic allograft nephropathy were the leading causes for graft loss after the first month. Donor age at or above 35 years and the presence of donor-specific antibodies with a history of antibody-mediated rejection (both p < 0.05) were associated with worse graft survival, while medication non-adherence was associated despite being marginally significant (p = 0.056). The rates of CMV syndrome and biopsy-proven BKV nephropathy were 19.7% and 13.1% respectively. 47.5% had short stature at the last follow-up.

Conclusion: Our paediatric kidney transplantation outcomes are favourable and comparable to international benchmarks. Preferential allocation of young donors below 35 to paediatric recipients, reinforce immunosuppressant compliance and early detection of DSA with prompt treatment of ABMR may improve allograft outcomes in paediatric recipients.

Aim: There is limited evidence to support the use of oral anticoagulation (OAC) in people with advanced chronic kidney disease (CKD) and atrial fibrillation (AF). The aim of this study is to characterise the practice patterns and priorities of clinicians in the management of non-valvular AF and primary prevention of AF-related stroke in people with stage 4-5D CKD.

Methods: This was an annonymous, multiple-choice, electronic survey distributed to and undertaken by nephrology and cardiology clinicians in Australia and New Zealand.

Results: Responses eligible for analysis were received from 181 clinicians (121 nephrology and 60 cardiology respondents). Management with close specialty collaboration was reported by 47% of all respondents. OAC use was predominantly based on estimated individual stroke risk (i.e., CHA₂DS₂-VASc score) in people with stage 4 CKD and kidney transplant recipients. In stage 5/5D CKD, nephrology respondents were more likely to withhold all antithrombotic therapy or individualise OAC use (p < 0.05), whilst cardiology respondents were more likely to defer OAC decision-making to another specialist (p < 0.01). Varied use and dosing of OAC agents were noted between specialties. Left atrial appendage occlusion experience was limited amongst nephrology respondents but cardiology respondents would consider in individualised cases. Impact of CKD severity was noted in some rate and/or rhythm control management decisions.

Conclusions: This survey provides important contemporary insights into the management of AF in people with advanced CKD in Australia and New Zealand. There was inter- and intra-specialty heterogeneity in practice, highlighting the need for multidisciplinary care and research to improve cardiovascular outcomes in this population.

Down syndrome (DS) is associated with a high prevalence of congenital heart, gastrointestinal, and endocrine anomalies, as well as a heightened risk for kidney and urinary tract abnormalities. The renal anomalies occur in up to 3.2% of DS cases at birth-four to five times higher than in the general population. Despite this, current DS management guidelines lack routine kidney evaluations, even though risk factors like neonatal acute kidney injury, renal hypoplasia and obesity may predispose DS children to chronic kidney disease (CKD). In a cross-sectional study, we analysed kidney size and function in 54 DS children. Results revealed that 25% of patients exhibited renal hypoplasia, 26% had an estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73 m² Among adolescents, 55.5% showed eGFR values below 90 mL/min/1.73 m² Additionally, 29.6% of the cohorts were overweight and 7.4% obese. There is a need for early kidney assessments in DS patients to detect initial renal decline and underscore the importance of close monitoring, particularly in adolescents. Further studies are needed to identify specific prognostic factors to better assess CKD risk in DS children, and limited research exists on renal replacement therapies for this population.

Aim: Anaemia is a significant complication of chronic kidney disease (CKD). However, its prevalence and treatment patterns in Asia are poorly understood. We sought to quantify prevalence of anaemia and its treatment in people with CKD across the region.

Methods: MEDLINE and Embase (inception to 2023) were systematically searched for observational studies of adults with CKD conducted in Asia that reported the prevalence of anaemia or its treatment. Additional relevant unpublished data were obtained from national experts. Summary estimates of the prevalence of anaemia and its treatment were determined using a random-effects meta-analysis according to country and study-specific CKD inclusion criteria.

Results: Eighty-six studies from 10 Asian countries reported data on 1 342 121 participants. The overall prevalence of anaemia in individuals with CKD was 42% (95% CI 33%-52%), with wide variation (12%-57% in studies including all CKD stages; 21%-96% in studies limited to individuals with kidney failure). Anaemia prevalence progressively increased with more advanced CKD (80% in Stage 5). Studies reporting data on anaemia treatment, particularly in early CKD, were limited. The prevalence of erythropoietin-stimulating agents (ESAs) and iron therapy was 40% (95% CI 24%-58%) and 21% (95% CI 14%-31%), respectively (ESA: 7%-29% in CKD, 63%-95% in kidney failure; iron: 6%-26% in CKD, 15%-88% in kidney failure).

Conclusion: Our findings indicate a significant, but widely varying, prevalence of anaemia and its treatment in people with CKD in Asia. Substantial variability in data availability and collection highlights the need for standardised reporting to facilitate the development of regionally relevant strategies for anaemia management in CKD.

A 73-year-old Japanese man with chronic kidney disease had no history of abnormal clotting or bleeding. Six days after receiving his third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BNT162b2; Pfizer/BioNTech), blood tests showed a marked prolongation of the prothrombin time-international normalised ratio and activated partial thromboplastin time, as well as a decrease in factor V (FV) activity. Three months later, he required dialysis owing to worsening heart and renal failure. After supplementation with FV, a flexible double-lumen catheter was inserted, and haemodialysis was initiated without the use of anticoagulants. The patient was found to be positive for FV inhibitors and was diagnosed with autoimmune acquired factor V deficiency (AiFVD). AiFVD is a rare autoimmune disease in which factor V inhibitors decrease FV activity. The patient did not undergo immunosuppressive therapy because he did not have severe bleeding symptoms, and he is currently able to continue dialysis without causing fatal bleeding. FV inhibitors can be induced by bovine thrombin, surgery, and infection, but have also been detected after SARS-CoV-2 infection. The development of various acquired coagulation factor inhibitors has been reported after SARS-CoV-2 infection or vaccination, but there have been no reports of AiFVD due to SARS-CoV-2 vaccination. To the best of our knowledge, this is the first report of AiFVD probably associated with SARS-CoV-2 vaccination. Although AiFVD is rare, physicians should be aware of its possibility after SARS-CoV-2 vaccination.

Aim: CD8⁺ regulatory T cells (Tregs) are cross-protective across multiple animal models of autoimmunity. Recently, specific peptides from a yeast-peptide-major histocompatibility complex library that expanded CD8⁺ Tregs in murine experimental multiple sclerosis were reported. Whether these peptides also expand CD8⁺ Tregs and protect against Heymann nephritis (HN), an experimental model of membranous nephropathy is unknown. We aimed to assess the efficacy of peptide vaccination to induce CD8⁺ Tregs in HN.

Methods: Lewis rats were immunised with Fx1A/complete Freund's adjuvant to induce HN and received peptide vaccination 1 week before (prevention vaccination) or 1 week after disease induction (treatment vaccination). To understand whether the effect of peptide vaccination was mediated by CD8⁺ Tregs, we adoptively transferred CD8⁺ T cells 1 week after peptide vaccination into HN rats.

Results: Prevention vaccination, but not treatment vaccination, significantly reduced anti-Fx1A autoantibody levels and serum creatinine. Both prevention and treatment vaccination reduced histological kidney injury. mRNA expression of Helios, the major CD8⁺ Treg transcription factor, was upregulated in both the spleen and kidney with prevention vaccination and in the kidney with treatment vaccination. Adoptive transfer of CD8⁺ T cells after peptide vaccination significantly reduced serum creatinine, proteinuria, histological kidney injury, anti-Fx1A autoantibody levels, germinal centre formation, and mRNA expression of markers of T follicular helper cells (Bcl6, interleukin-21), T helper 1 cells (interferon-γ, Tbet) and T helper 17 cells (interleukin-6, interleukin-17).

Conclusions: Peptide vaccination induces CD8⁺ Tregs that ameliorate induction of experimental membranous nephropathy which may represent a further peripheral regulation of autoimmunity.

Aim: Stroke is a leading cause of death and disability, with substantial healthcare implications. Chronic kidney disease (CKD) is similarly impactful, and emerging evidence links CKD to a higher stroke risk. Despite this, stroke risk assessment in CKD patients remains limited. This study explores the kidney failure risk equation (KFRE) as a predictive tool for ischaemic stroke in CKD patients.

Methods: This retrospective cohort study analysed CKD patients from a healthcare registry, excluding those with prior stroke, end-stage kidney disease, or kidney transplants. Acute ischemic stroke was the primary outcome, with deaths censored. Cox proportional hazards models evaluated associations between the 2-year and 5-year 4-variable KFRE scores and stroke risk.

Results: A total of 14,794 consecutive patients were included, with a median follow-up of 509 days. The median age of the cohort was 73 years (IQR:14 years), with 6251 females(42.3%), and the majority being of Chinese ethnicity (n = 10 759,73.5%). During the follow-up period, 155 patients (1.05%) experienced an ischemic stroke event, with a median time to stroke of 265 days (IQR:242 days). The 2-year (HR: 1.38 per 10% increase, 95% CI: [1.17-1.63], p < 0.001) and 5-year (HR:1.20 per 10% increase, 95% CI: [1.10-1.31], p < 0.001) 4-variable KFRE scores were significantly associated with an increased risk of ischemic stroke. These associations remained significant after adjusting for patient demographics, comorbidities, advanced CKD stage, glycated haemoglobin and lipid parameters.

Conclusion: CKD patients at elevated risk of kidney failure also face a significantly increased risk of acute ischaemic stroke. The KFRE could potentially be integrated into CKD management to assess this risk. Future large prospective cohort studies are necessary to validate these findings.

Aim: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterised by absolute or relative insufficiency of insulin secretion. The alkaloids from Rhizoma coptidis have potential hypoglycemic effects. Epiberberine (EPI), a protoberberine alkaloid extracted from Rhizome coptidis, has been found to regulate lipid metabolism. Our study aimed to investigate the antidiabetic effects of EPI on mice with T2DM, as well as its underlying mechanism.

Methods: The T2DM model in mice was established using a combination of high-fat diet and streptozotocin. Animals were divided into the control, T2DM, EPI-low dose (50 mg/kg EPI), EPI-medium dose (100 mg/kg EPI), EPI-high dose (200 mg/kg EPI) and metformin (MTF) (200 mg/kg MTF) groups. Body weight, water/food intake, serum lipids, blood glucose tolerance, insulin sensitivity, histopathological alterations, insulin signalling pathway and inflammation-related pathways in each group were detected.

Results: EPI significantly reduced blood glucose levels and water/food intake in T2DM mice. EPI reduced the levels of total cholesterol, total triglyceride, low-density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase, and elevated the levels of high-density lipoprotein cholesterol in serum. EPI effectively improved oral glucose tolerance, alleviated hepatic insulin resistance, decreased glycosylated haemoglobin levels and increased liver glycogen content. EPI ameliorated the histopathological alterations of skeletal muscle and liver in T2DM mice. EPI stimulated the insulin signalling pathway by increasing glucose transporter type 4 levels and activating insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase B in skeletal muscle and liver. EPI reduced the levels of proinflammatory cytokine in serum and inhibited the activation of mitogen-activated protein kinase signalling in skeletal muscle and liver of diabetic mice.

Conclusion: Overall, these data demonstrate that EPI alleviates the symptoms of T2DM, providing new insights into EPI as a therapeutic compound for the alleviation of T2DM.

Aim: Acute kidney injury (AKI) is the most common complication in the treatment of cisplatin, which is a clinically effective and classical anticancer drug. Orphan Nuclear Receptor Nur77 has been found to promote renal ischaemia-reperfusion injury. In this study, we aim to explore the effects of Nur77 on cisplatin-induced AKI (CI-AKI) and its underlying mechanism.

Methods: HK-2 cells treated with cisplatin were used to construct the CI-AKI model in vitro. Cell viability and cell proliferation were analysed using CCK-8 and EdU assays, respectively. Cell apoptosis was analysed by flow cytometry. The inflammation release level was detected using ELISA. Molecular abundance was evaluated using qPCR, Western blot and immunofluorescence. The interaction between Nur77 and SERPINA3 was clarified using ChIP and dual-luciferase reporter gene assays.

Results: Our works demonstrated that Nur77 and SERPINA3 expression were considerably ascended in cisplatin-induced HK-2 cells. The silence of SERPINA3 alleviated cisplatin-stimulated HK-2 cell injury, which was characterised by increased cell viability and proliferation, and decreased apoptosis and inflammatory cytokine release. In addition, Nur77 promotes SERPINA3 transcription by binding to the SERPINA3 promoter region (-182 to -175), thereby upregulating SERPINA3 expression and activating the Wnt/β-catenin pathway. Moreover, HK-2 cell injury induced by cisplatin was notably inhibited by the knockdown of Nur77. Furthermore, the efficacy of Nur77 downregulation on the cell injury in cisplatin-stimulated HK-2 cells was antagonised by SERPINA3 overexpression.

Conclusion: Taken together, our findings revealed that Nur77 knockdown resisted cisplatin-induced HK-2 cells injury through lessening the expression of SERPINA3 mediated by transcriptional regulation and inactivating the Wnt/β-catenin pathway.