Nephrology最新文献

Adult patients with a prior renal transplantation are at increased risk of accelerated cardiovascular disease. This study aims to identify key clinical and biochemical predictors of major adverse cardiovascular events (MACEs) in this population. Understanding these predictors may improve risk stratification and enhance long-term outcomes for kidney transplant recipients. A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing clinical and biochemical parameters in adult patients with a prior renal transplantation (2000-2024; English only; PROSPERO registration CRD42024596207). Data for a range of clinical and biochemical parameters were individually extracted, and those with low heterogeneity were then meta-analysed using a random-effects model for overall effect size and assessed through standardised mean difference (SMD) and odds ratios (ORs). The primary outcomes assessed were fatal or non-fatal cardiovascular events occurring after renal transplantation during hospitalisation and up to 10 years post discharge. Of 506 screened studies, 17 peer-reviewed articles met inclusion criteria and included a total of 181,938 renal transplant patients. The key novel predictors of MACE included pre-transplant haemodialysis (OR 2.562, 95% CI = 1.585-4.139, p < 0.001) and delayed graft function (OR 2.113, 95% CI = 1.397-3.198, p < 0.001). Importantly, transplant from a living donor (OR 0.463, 95% CI = 0.393-0.546, p < 0.001) was a protective factor. Traditional cardiovascular risk factor profiles were all predictors of MACE events (p < 0.05). This study identified several traditional and novel predictors of cardiovascular events in patients with pre-existing renal transplantation. Early recognition of these high-risk clinical predictors should prompt more aggressive monitoring and treatment.

Muscle symptoms including myalgia are common in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Muscle biopsy (MB) is sometimes used in the diagnosis of AAV, but which AAV patients benefit from MB remains unclear. We retrospectively assessed the clinical characteristics of Japanese AAV patients who underwent MB and examined the relationship between MB showing positive results for muscular vasculitis and kidney involvement. We enrolled all 38 of the 118 patients with AAV who also underwent MB. Clinical characteristics and histopathological findings on kidney biopsies were assessed in patients with MB showing positive or negative results for muscular vasculitis. Among the 38 patients, 34 (89.5%) were diagnosed with microscopic polyangiitis, and 17 patients (44.7%) showed positive MB. Myalgia and edema of the lower extremities were observed in 12 MB-positive patients, higher proportions than seen in MB-negative patients (70.6% vs. 38.1%, p = 0.046 and 70.6% vs. 33.3%, p = 0.022, respectively). Kidney involvement was more frequent in MB-positive patients (70.6%) than in MB-negative patients (28.6%, p = 0.010). Twelve of the 38 patients with MB underwent kidney biopsy. Proportions of crescents or vascular fibrinoid necrosis were higher in MB-positive patients than in MB-negative patients (83% vs. 33% and 67% vs. 20%, respectively). Myalgia and edema of the lower extremities may offer a guide to the utility of MB. Glomerulonephritis should be considered when muscular vasculitis is confirmed by MB.

Aim: Evaluate the area-level incidence of kidney failure due to diabetes among Australians aged ≤ 45 years.

Methods: Using Australian registry and census data (2000-2022), incidence rates and prevalence of kidney failure (defined as commencing kidney replacement therapy) due to diabetes among people aged ≤ 45 years were compared by geographical region.

Results: Incidence (per 100 000/year, 95% confidence interval) of kidney failure due to diabetes among people aged ≤ 45 years in Australia was 0.72 (0.68-0.77) in 2000-2011, and 1.13 (1.07-1.18) in 2012-2022 (incidence rate ratio [IRR] 1.56, 1.50-1.62). Between 2012 and 2022, there were 48 regions where the crude incidence of kidney failure due to diabetes was more than double the national average, the highest being 49.8 cases per 100 000 per year. Between 2012 and 2022, all jurisdictions had similar age-sex-adjusted point estimates for kidney failure incidence (range 0.78-1.48) except for the Northern Territory (15.8, 13.9-17.8). The most significant characteristics associated with the rate of incident kidney failure were residence in remote areas (IRR 13.9, 13.1-14.8, ref. major cities), socioeconomic disadvantage (IRR 2.96, 2.75-3.19, ref. advantaged areas), and Aboriginal and Torres Strait Islander ethnicity (IRR 24.2, 23.0-25.5). Between the eras, people born outside Australia had the largest increase in incident cases (IRR 2.47, 2.23-2.72) but had a lower overall incidence than those born in Australia (IRR 0.55, 0.52-0.59).

Conclusion: In Australia, there was an increase in the incidence of kidney failure due to diabetes among people aged ≤ 45 years in the last two decades. There was a strong relationship between the risk of kidney failure and social determinants of health, including place of residence, socioeconomic status and Indigenous status.

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: 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.

Aim: To study the effect and elucidate the underlying mechanisms of VDAC1-ΔC on autophagy in renal tubular epithelial cells injured by hypoxia/reoxygenation.

Methods: C57/BL6 mice were randomly divided into groups: sham operation group, IRI 1d group and IRI 2d group. The inner canthal blood of mice was collected to detect the levels of serum creatinine and urea nitrogen and kidney tissues were sampled, and sections were stained with Periodic acid-Schiff for morphological evaluation. The expression of VDAC1 in kidney tissue was detected by Western blot. An immortalised human proximal tubular epithelial cell line, HK-2 cells, were subjected to hypoxia/reoxygenation treatment. HK-2 cells were incubated under hypoxia for 6 h, followed by 6 and 24 h of reoxygenation, cells were divided into four groups: H6/R0 group, H6/R6 group, H6/R24 group and control group. The release of LDH and cytosolic ROS were assessed, the expression of autophagy-related proteins LC3 and p62 was detected by Western blot, autophagy flux was monitored by transfecting mRFP-GFP-LC3 lentivirus in HK2 cells, and cells were pretreated with bafilomycin A1 to further monitor the autophagy flux. VDAC1-cleavage-defective mutant in HK-2 cells silencing VDAC1 was established to examine the effect of VDAC1 cleavage on autophagy and hypoxia/reoxygenation injury.

Results: In vivo, IRI 1d/2d promoted the disorder of renal tubular structure and the cleavage of VDAC1 in kidney tissue; in vitro, hypoxia/reoxygenation promoted cytosolic ROS accumulation, LDH release, VDAC1 cleavage and induced autophagy and autophagic flux; reduced VDAC1 cleavage inhibited autophagy; and decreased cytosolic ROS accumulation and LDH release, thus alleviated cell injury.

Conclusion: In renal tubular epithelial cells injured by H/R, VDAC1 cleavage was increased, triggering an autophagic response, and VDAC1 cleavage promoted autophagy to regulate cell injury.

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.

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: 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.