Kidney Diseases最新文献

Introduction: Shear-wave elastography (SWE) is a promising noninvasive technique for measuring renal fibrosis after transplantation. This study aimed to develop an interpretable model to predict allograft deterioration in kidney transplant recipients and evaluate the predictive ability of SWE features.

Methods: In this prospective cohort study, we performed SWE examinations on kidney transplant recipients at Renji Hospital between October 2020 and August 2023. The primary outcome was a composite of a 40% decline in estimated glomerular filtration rate or end-stage kidney disease. A total of 396 patients with stable renal allograft function were included. Five machine learning methods were used to construct predictive models.

Results: Among all participants, 69 (17.4%) individuals reached the outcome. The XGBoost model with the addition of SWE features achieved the highest predictive performance with 20 repeats of nested tenfold cross-validation AUC of 0.870 (95% CI: 0.862-0.878) in the training dataset and 0.868 (95% CI: 0.801-0.935) in the validation dataset. Patients with higher medullary or cortical tissue stiffness had worse prognoses. A high level (>10 kPa) of medullary SWE was an independent risk predictor (adjusted OR, 2.68; 95% CI, 1.12-6.41).

Conclusion: The joint use of SWE parameters and laboratory data significantly improved the risk prediction performance for a faster decline in allograft function. This interpretable XGBoost model may provide a readily available system to guide patient monitoring using noninvasive methods.

Introduction: Neutrophil extracellular traps (NETs) contribute to inflammation and are implicated in autoimmune diseases; however, their role in IgA nephropathy (IgAN) remains unclear. This study aimed to investigate the involvement of NETosis in IgAN and its impact on renal injury and mesangial cell function, utilizing patient samples, mouse models, and in vitro assays.

Methods: RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from IgAN patients to identify differentially expressed genes (DEGs) and NETosis-related pathways. An IgAN mouse model was established using bovine serum albumin, carbon tetrachloride, and lipopolysaccharide. Mice were treated with the peptidyl arginine deiminase-4 inhibitor GSK484 to evaluate the effects of NETosis inhibition. In vitro assays assessed the impact of NETosis on mesangial cells.

Results: RNA sequencing identified 905 DEGs in IgAN patients, with significant enrichment in neutrophil and NETosis pathways. Serum levels of NETosis markers - citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase - were elevated in IgAN patients, with CitH3 levels correlating with Gd-IgA1. Inhibiting NETosis with GSK484 reduced CitH3 levels in IgAN mice and improved clinical outcomes, including decreased proteinuria and increased serum albumin. Histological analysis revealed reduced mesangial proliferation. In vitro, NETosis enhanced tumor necrosis factor-α (TNF-α) release from mesangial cells, an effect that was mitigated by GSK484. RNA-seq analysis of kidneys from GSK484-treated IgAN mice also revealed significant alterations in the PPAR signaling pathway. Additionally, TNF-α treatment of mesangial cells resulted in reduced PPARα expression, suggesting that NETosis may modulate this pathway through the release of TNF-α by mesangial cells.

Conclusion: Our findings demonstrate that NETosis is upregulated in IgAN and plays a key role in its pathogenesis by promoting inflammatory cytokine release. Inhibition of NETosis improves both clinical and pathological outcomes, highlighting its potential as a therapeutic approach for managing IgAN.

Introduction: Renal vascular lesions (RVLs) are a common histopathological feature in lupus nephritis (LN). Despite their frequent occurrence, the clinical significance and prognostic impact of RVLs remain poorly understood. The main objectives of our study were to investigate the clinicopathological characteristics associated with RVLs in LN and to assess their prognostic implications in patients with LN.

Methods: We conducted a retrospective analysis of baseline clinical and pathological data, as well as outcomes, for patients diagnosed with biopsy-confirmed lupus nephritis between September 1, 2008, and October 31, 2021. Patients were initially stratified into two groups based on the presence or absence of vascular disease at baseline. Subsequently, they were further categorized into four groups according to the severity of vascular disease. Comparisons were made across these groups with respect to clinical and laboratory parameters, pathological features, and prognostic outcomes. The composite endpoint was defined as death, end-stage renal disease (ESRD), or a ≥30% increase in serum creatinine. Survival analysis was performed using the Kaplan-Meier method to compare the renal survival and overall survival between groups with different severities of RVLs. The log-rank test was employed for univariate survival analysis, and multivariate analysis of survival outcomes was performed using the Cox regression model.

Results: In a group of 225 patients, RVLs were found in 101 kidney biopsies, with 72 of these being mild. Among 156 patients with proliferative lupus nephritis, 77 had RVLs. Patients with RVLs were older and exhibited higher levels of serum creatinine, blood urea, uric acid, C-reactive protein, and significantly higher chronicity index and SLEDAI scores. They also had more severe tubulointerstitial lesions, worse clinical manifestations, and lower complete remission rates. Their estimated glomerular filtration rate was lower (p < 0.05). Compared to the NRVLs group, patients in the RVLs group had a lower renal survival rate and overall survival rate, and a significant difference was observed between the groups (p < 0.05). Importantly, the severity of vascular lesions was associated with a lower renal survival rate and overall survival rate, especially in proliferative lupus nephritis.

Conclusion: RVLs are a common pathological feature in lupus nephritis and are particularly prevalent among patients with proliferative lupus nephritis. The presence and severity of RVLs are associated with more severe clinicopathological manifestations and a lower complete remission rate in lupus nephritis patients. Furthermore, they are predictive of poorer long-term outcomes, with a particularly pronounced impact on those with proliferative lupus nephritis.

Background: Kidney diseases are a prevalent global health concern, and despite ongoing research, there remains a lack of fully effective clinical treatments to prevent or halt their progression. Consequently, it is encouraged to identify novel biomarkers, establish early diagnostic methods, pinpoint key molecular pathways, and develop innovative therapeutic targets for more effective management of renal disorders.

Summary: Interferons (IFNs), a group of cytokines, play pivotal roles in immune responses, particularly in antiviral and antiproliferative activities. IFNs trigger a cascade of signaling events that lead to the induction of interferon-stimulated genes (ISGs), which are essential for controlling viral infections and regulating immune responses. This review explores the impact of interferon-related genes on renal disorders, focusing on the mechanisms, therapeutic approaches, and consequences of enhanced interferon signaling in the kidney.

Key messages: Most diagnostic and therapeutic strategies targeting ISGs are still far from clinical implementation. The better understanding of ISG-regulated pathophysiology and the progress of new intervention approaches are expected to facilitate the clinical translation of ISGs-based diagnosis and therapy of kidney diseases.

Introduction: With the aging of population, dementia has emerged as a major public health concern, imposing a heavy society burden. However, the relationship between acute kidney injury (AKI) and the risk of dementia remains uncertain.

Methods: A total of 1,256,756 participants from the China Renal Data System (CRDS) database and 492,250 individuals from the UK biobank (UKB) dataset were included in the study. The study investigated the associations between AKI and the onset of dementia. The exposure of interest was AKI. The outcome in both the CRDS and UKB cohorts was dementia.

Results: The CRDS cohort identified 7,878 patients with new-onset dementia, while the UKB recorded 9,926 dementia cases during follow-up. AKI showed a significant association with the risk of dementia in both the CRDS (adjusted HR: 1.22; 95% confidence interval [CI]: 1.13-1.30, p < 0.001) and UKB cohorts (adjusted HR: 1.64; 95% CI 1.29-1.98, p = 0.005). In the CRDS cohort, patients with more severe AKI (stage 2-3 AKI) (aHR: 1.25; 95% CI 1.09-1.42, p = 0.008) exhibited a higher adjusted HR for dementia compared to those at AKI stage 1 (aHR: 1.21; 95% CI 1.11-1.30, p < 0.001). The association between AKI and dementia remained consistent across different subgroups in both cohorts.

Conclusion: Our findings demonstrated that AKI was associated with an elevated risk of all-cause dementia. Consequently, patients with history of AKI episodes necessitate vigilant monitoring for prevention of dementia.

Introduction: Purinergic signaling has been recognized as important extracellular regulator in multiple physiological and pathophysiological conditions. Adenosine triphosphate-purinergic receptor P2Y2 signaling pathway is associated with glomerular nephritis (GN), diabetic nephropathy (DN), and chronic kidney disease. Recently, there has been evidence that global knockout of P2Y2 exacerbated bilateral ischemic reperfusion-induced acute kidney injury (AKI). However, its role in cisplatin-induced AKI (CIA) remains unknown. Cisplatin is a platinum-containing antineoplastic drug widely used in variety of solid malignant tumors. Nephrotoxicity is one of the major serious side effect that limit its clinical use. In the present study, we investigated whether inhibition of P2Y2 has an effect on CIA.

Methods: We used AR-C118925 (AR-C), a selective antagonist of P2Y2, and gene transfection for interruption of the P2Y2 pathway. Mice were pretreated with AR-C (10 mg/kg/day) and then challenged with cisplatin at a dose of 20 mg/kg. Seventy-two hours after cisplatin administration, all mice developed kidney failure. Knockdown and overexpression of P2Y2 in mice and mouse proximal tubular cells (mPTCs) were employed to validate that ARC acts through P2Y2 receptor.

Results: AR-C markedly ameliorated cisplatin-induced nephrotoxicity evidenced by improved renal function, renal morphology, and tubular injury marker expression. Further analysis of the mechanism revealed that AR-C significantly reduced kidney oxidative stress, inflammation, apoptosis, and necroptosis. Consistently, AR-C protects mPTCs from injury caused by cisplatin. To verify that AR-C acts through the P2Y2 receptor, we knocked down P2Y2 in mice or in mPTC cells. Both showed beneficial effects, while overexpression of P2Y2 promotes cisplatin-induced cell death.

Conclusion: Taken together, our study, for the first time revealed that P2Y2 plays an important role in CIA by regulating oxidative stress, inflammation, apoptosis, and necroptosis and its inhibitor, AR-C, is a potential drug for treating CIA.

Introduction: Patient adherence is important for long-term outcomes of peritoneal dialysis (PD). Artificial intelligence is a good tool to manage patients. However, there are limited data regarding its impact on the patient adherence and the effect of patient adherence on serum phosphate, calcium, and intact parathyroid hormone (iPTH) control in PD patients.

Methods: This was a single-center, prospective cohort study including PD patients in Guangdong Provincial People's Hospital. Adult patients (age ≥18 years) who were included in the smart PD care program from September 1, 2020, to April 31, 2023, were enrolled. Patient adherence was assessed using the patient-reported daily PD prescription data and calculated as the total days with PD ultrafiltration reported divided by the total days of follow-up. Good adherence was defined as the reporting rate ≥80%. The primary outcome was serum phosphate, calcium, and iPTH values achieved the treatment targets at 12-month follow-up. Unadjusted and adjusted generalized estimating equations were used to evaluate the association of patient adherence with the serum phosphorus, serum calcium, and iPTH control.

Results: A total of 267 patients were included in this study. The mean age of the whole cohort was 43.3 ± 12.8 years, 130 (48.7%) were females, and 52 (19.5%) had diabetes. Patient adherence improved after being included in the smart PD care program and the overall patient adherence during 12-month follow-up was 77.1% ± 26.4%, 93.0% ± 7.4%, and 50.9% ± 25.6% for the entire cohort, patients with good adherence, and those with poor adherence, respectively. Compared to patients with poor adherence, those with good adherence were associated with a better serum calcium (adjusted OR: 3.76; 95% CI: 2.67-5.30; p < 0.001) and iPTH control (adjusted OR: 2.20; 95% CI: 1.56-3.11; p < 0.001) but not for serum phosphorus control (adjusted OR: 1.31; 95% CI: 0.89-1.91; p = 0.17) after being adjusted for potential confounders. Results were similar when assessing the relationship between patient adherence and the longitudinal changes of serum calcium, iPTH, and phosphorus during follow-up.

Conclusions: Smart PD care program was effective in improving patient adherence. Good patient adherence was associated with better serum calcium and iPTH control but not for phosphorus control in PD patients. Further studies should be done to evaluate the effect of the smart PD care program on long-term patient outcomes.

Introduction: Various types of acute kidney injury (AKI) are associated with triglyceride (TG) accumulation in renal tubular epithelial cells, but the role and mechanisms of TG accumulation in AKI remain unclear. This study aimed to explore the impact of low-density lipoprotein (LDL) receptor-related protein-1 (LRP1), a protein that mediates TG endocytosis, on ischemia-reperfusion injury (IRI)-induced AKI and TG accumulation in renal tubular epithelial cells.

Methods: We established an IRI-induced AKI mouse model and assessed LRP1 expression by Western blot, RT-qPCR, and immunofluorescence. The LRP1 antagonist receptor-associated protein (RAP) was used to evaluate the effect of LRP1 on AKI and renal TG accumulation in the AKI mouse model. We applied a carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced hypoxia-reoxygenation model to HK-2 cells in vitro. The effects of very low-density lipoproteins (VLDLs) and LRP1 silencing on TG levels, cell viability, and apoptosis in HK-2 cells were observed.

Results: We observed significant TG accumulation in renal tissue during IRI-AKI, accompanied by upregulation of LRP1 in renal tubular epithelial cells. After intervention with the LRP1 antagonist RAP, AKI was significantly alleviated, and TG levels in renal tissue were notably reduced. However, in the in vitro model, although VLDL increased TG levels in HK-2 cells in both normal culture and hypoxia-reoxygenation conditions, it did not alleviate the decrease in cell viability induced by CCCP. In the absence of exogenous VLDL, silencing LRP1 still reduced CCCP-induced TG accumulation and cell apoptosis, although the reduction in TG levels was less pronounced compared to the presence of exogenous VLDL.

Conclusion: Our study demonstrated that the increased expression of LRP1 on renal tubular epithelial cells contributes to IRI-induced AKI and TG accumulation. The injury effects of LRP1 on the renal tubules are independent of TG endocytosis. Targeting the inhibition of LRP1 may emerge as a novel therapeutic strategy for AKI.

Introduction: The prevalence of urinary myeloid bodies in Fabry disease patients and their correlation with renal involvement remains unclear.

Methods: This single-center, retrospective study included 25 patients with Fabry disease and 27 controls. We analyzed 24-h urine samples for the presence of urinary myeloid bodies and evaluated clinical data, including serum creatinine, estimated glomerular filtration rate (eGFR), 24-h urinary protein levels, α-Gal A, and Lyso-GL-3. Seven Fabry patients underwent analysis of urine samples before and after 1 year of enzyme replacement therapy (ERT).

Results: Urinary myeloid bodies were detected in 84% of Fabry patients (21 out of 25), with no significant gender differences. None of the healthy controls or patients with other renal disease patients had urinary myeloid bodies. Among the Fabry patients with myeloid bodies, 48% had no proteinuria, and 52% were in CKD1 stage G1. Furthermore, urinary myeloid bodies were detected in 4 patients under the age of 20, despite the absence of or only minimal proteinuria, and these patients all exhibited a substantial number of myeloid bodies. After 1 year of ERT, significant reductions in both the count (p = 0.043) and area ratio (p = 0.028) of myeloid bodies were observed.

Conclusion: Urinary myeloid bodies are specific to Fabry disease and are associated with early renal injury, even in the absence of proteinuria. These findings suggest that urinary myeloid bodies may serve as a noninvasive biomarker for the early diagnosis of Fabry disease and for monitoring the efficacy of ERT.

Introduction: Kidney injury molecule-1 (KIM-1), encoded by the Hepatitis A Virus Cellular Receptor 1 (HAVCR1) gene, plays a crucial role in kidney injury progression. Although serum and urinary KIM-1 levels are established biomarkers for kidney damage, the relationship between KIM-1 levels, HAVCR1 gene polymorphism, and chronic kidney disease (CKD) stages remains unclear. This study aimed to investigate KIM-1 as a potential biomarker for CKD progression in the Thai population and explore its association with genetic polymorphisms in the HAVCR1 gene.

Methods: A total of 250 patients with CKD were recruited from Khon Kaen, Thailand. Serum and urinary KIM-1 levels were measured using an indirect enzyme-linked immunosorbent assay. Single-nucleotide polymorphism (SNP) genotyping was conducted using the TaqMan assay to assess the associations between KIM-1 levels, SNPs, and CKD progression. Statistical analyses were conducted to assess the correlations between estimated glomerular filtration rate (eGFR), KIM-1 levels, and SNPs.

Results: Serum and urinary KIM-1 levels showed a significant negative correlation with eGFR, indicating higher KIM-1 levels in patients with more advanced CKD. However, the rs6555820 SNP in the HAVCR1 gene did not show a significant association with KIM-1 levels or eGFR. Interestingly, a significant association between rs6555820 and gender was observed, implying a potential gender-dependent genetic impact.

Conclusion: Serum and urinary KIM-1 levels have been found to be associated with CKD stages and eGFR, suggesting their potential as biomarkers for assessing CKD severity. However, no direct associations were observed between the SNP rs6555820 and KIM-1 levels or eGFR. Further research is required to elucidate the genetic mechanisms underlying CKD progression.