Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a group of inherited renal disorders characterized by progressive decline in kidney function, with UMOD being the most frequently mutated gene. This study aimed to delineate critical molecular pathways and candidate genes involved in ADTKD-UMOD through integrated transcriptomic profiling and experimental validation, including newly added analyses of early stage disease and human samples. Transcriptomic datasets (GSE214491, GSE139585, GSE97093) from ADTKD-UMOD murine kidney tissues were analyzed for differentially expressed genes (DEGs) with the criteria: |log2 fold change| ≥ 1.5 and p < 0.05. Functional enrichment was assessed by GO and KEGG analyses, and hub genes were identified using protein-protein interaction networks. Immune cell infiltration was estimated by CIBERSORT. The key candidate gene LCN2 was validated in HEK293 cells expressing mutant UMOD (C195R) by qPCR and in an expanded analysis of serum from patients with ADTKD-UMOD by ELISA. In GSE214491 (6 mutant vs 6 wild type mice), 302 DEGs were identified at 4 months, and an additional 117 DEGs were newly characterized at 1 month, when histological disease was minimal. GSE139585 revealed 12 DEGs, and GSE97093 showed 83 and 16 DEGs in male and female cohorts, respectively. Across datasets, Lcn2 was consistently identified as a significant DEG and central hub gene and was already significantly elevated in 1-month-old ADTKD-UMOD (R186S) mice. Functional enrichment implicated pathways related to cell activation, metabolic processes, and inflammation. In UMOD (C195R)-mutant HEK293 cells, LCN2 mRNA was higher than in wild-type cells (2.95 ± 0.31 vs. 1.12 ± 0.19, p < 0.01), as were CASP1 (5.38 ± 0.95 vs. 0.48 ± 0.08, p < 0.001) and GSDME (1.69 ± 0.21 vs. 1.00 ± 0.09, p < 0.001). In human specimens, serum LCN2 protein levels were elevated in patients compared with healthy controls (4,204.06 ± 239.51 vs. 3,078.02 ± 88.41 pg/mL, p < 0.01). LCN2 protein emerges as a reproducible biomarker and plausible pathogenic mediator across distinct UMOD mutations, with concordant evidence from mouse models, cell experiments, and patient samples, thereby providing a strengthened rationale for its further mechanistic and translational investigation in ADTKD-UMOD. Autosomal dominant tubulointerstitial kidney disease caused by changes in the UMOD gene (ADTKD-UMOD) is an inherited kidney disorder that gradually leads to loss of kidney function. Although the genetic cause is known, the biological processes that drive kidney damage in this condition are not fully understood. Identifying early molecular changes may help improve diagnosis and guide future treatments. In this study, we analyzed publicly available transcriptome data from mouse models carrying Umod mutations. We compared diseased and healthy kidney tissues to identify genes that were consistently altered. We then performed laboratory experiments in kidney cells and examined blood samples from patients to confirm our findings. Across multiple datasets and experimental models, LCN2 was repeatedly increased. This increase was observed even at early stages of disease, before major structural kidney damage was visible. Higher LCN2 protein levels were also detected in the blood of patients with ADTKD-UMOD compared with healthy individuals. These findings suggest that LCN2 protein may serve as a measurable indicator of disease activity and may play a role in the processes that lead to kidney injury in ADTKD-UMOD.
Fabry disease is an X-linked lysosomal storage disease that leads to the intracellular accumulation of glycosphingolipids in many tissues and fluids, including the kidneys. We report a single family with Fabry disease that includes seven patients carrying the pathogenic variant c.797A>C in the GLA gene, with remarkable variability in kidney involvement, assessed based on clinical, biological, and histological data. The patients were monitored for 2-9 years, and all received enzyme replacement therapy. Kidney involvement was variable and included severely decreased GFR with significant proteinuria, mildly to moderately decreased GFR with proteinuria, mildly decreased GFR with microalbuminuria or normoalbuminuria, hyperfiltration with normoalbuminuria, and preserved kidney function. All patients who underwent kidney biopsy presented with Fabry-specific lesions and, in some cases, chronic histological damage. This study provides valuable insights into kidney involvement evaluated through kidney biopsy, personalized management strategies for family members according to their phenotype, and long-term follow-up of kidney function. We underscore the importance of molecular screening of the GLA gene in all family members for early identification of the disease and early initiation of specific treatments that can prevent or delay the progression of this disease.
Daidzein is a naturally occurring isoflavone phytoestrogen, mainly found in leguminous plants. This component exerts anti-inflammatory effects by regulating inflammatory cells via multiple targets, blocking core inflammatory pathways, and inhibiting the release of inflammatory factors. It also scavenges reactive oxygen species, activates the antioxidant enzyme system, and regulates antioxidant signaling pathways to achieve antioxidant effects. By regulating these two core pathological processes, it exerts protective effects in diseases such as cancer, cardiovascular disease, and acute kidney injury, based on preclinical evidence. The development of nanodelivery systems has effectively improved the physicochemical properties of daidzein, enhanced its bioavailability, and enabled disease-targeted delivery. Most previous reviews have either focused exclusively on daidzein or broadly covered the pharmacological activities of isoflavones, yet have largely overlooked the dual anti-inflammatory and antioxidant mechanisms specific to daidzein. This review summarizes these mechanisms and their preclinical effects on various diseases, including cancer, cardiovascular diseases, and acute kidney injury. It also reviews the pharmacokinetic limitations of daidzein and recent progress in nanodelivery strategies aimed at enhancing its bioavailability and bioactivity. Overall, this review serves as a reference for the future standardized comparison of nanocarriers, targeted therapies, and clinical applications.
The development of new technologies enabling rapid, frequent, and reagent-free monitoring of kidney function is recognized as being of paramount importance. In this work, mid-(MIR) and near-infrared (NIR) spectroscopy were compared for the prediction of key renal biomarkers-creatinine, urea and albumin-using 54 serum solutions mimicking the biochemical profiles of five stages of chronic kidney disease (CKD). MIR spectra were acquired in a high-throughput microplate platform after a simple dehydration step, while the NIR spectra were obtained directly from liquid serum using a fiber optic probe. After evaluating several spectral pre-processing methods and targeted spectral regions, excellent regression models (R2 > 0.9 for the best models) were obtained for the three biomarkers. MIR provided highly accurate urea predictions, whereas optimized NIR sub-regions enabled excellent estimation of creatinine and albumin. Both MIR and NIR, associated with supervised classification methods, enabled us to successfully distinguish healthy from diseased profiles and to identify the diseases state with AUC > 0.93. These findings highlight the complementary value of MIR and NIR spectroscopy for kidney disease assessment and their potential integration into point-of-care diagnostic systems.
Functional magnetic resonance imaging (fMRI) is a promising method to assess kidney injury noninvasively. This study aimed to explore the value of fMRI in assessing subclinical rejection and provide potential monitoring methods for non-invasive rejection screening in kidney transplantation. Based on the kidney transplantation cohort of the Second Affiliated Hospital of Nanjing Medical University, 46 cases of patients who underwent protocol renal biopsy and fMRI at 3 months or 12 months post-transplantation were included in this study. They were divided into the subclinical rejection group and the normal group according to the pathological results. Various fMRI parameters, including blood oxygenation level-dependent (BOLD) imaging, intravoxel incoherent motion (IVIM) imaging, and diffusion kurtosis imaging (DKI), were used to assess the oxygenation, microcirculation perfusion, and tissue microstructural changes of renal grafts. Multivariate analysis was performed to evaluate the role of different imaging parameters in subclinical rejection. Additionally, the receiver operating characteristic (ROC) curve analysis were used to compare the diagnostic performance of imaging parameters, clinical indicators, and the combined model in diagnosing subclinical rejection. Comparing the imaging parameters of 17 cases in the subclinical rejection group with those of 29 cases in the normal group, it was found that there were statistical differences between two groups in cortical apparent transverse relaxation rate (R2*), cortical axial diffusion (Da), cortical axial kurtosis (Ka), medullary fractional anisotropy (FA) and medullary Da. Among them, cortical Ka and medullary Da were independent predictors of subclinical rejection. In the evaluation of diagnostic performance, when MRI parameters were combined with clinical indicators, the AUC increased to 81.3%, which was better than either fMRI parameters (76.1%) or clinical indicators (73%) alone, with a sensitivity of 76.5% and a specificity of 86.2%. fMRI could provide key imaging information for subclinical rejection in kidney transplantation. DKI parameters, cortical Ka, and medullary Da have high diagnostic value for subclinical rejection. Combining fMRI parameters with clinical indicators could further improve the identification of subclinical rejection and provide a new fMRI-based approach for non-invasive rejection screening in kidney transplantation.
Diabetic kidney disease (DKD) has emerged as the leading cause of end-stage renal disease (ESRD) internationally due to the rising prevalence of diabetes mellitus. DKD is not only a secondary disease caused by continuous glucose metabolism disorder but also a chronic inflammatory disease characterized by high expression of pro-inflammatory factors and a large number of immune cell infiltration. Macrophages are the main immune cells infiltrating in the kidney, which can polarize into pro-inflammatory M1 and anti-inflammatory M2 phenotypes under the high control of the surrounding microenvironment. M1 and M2 macrophages can coexist at times but have distinct functional characteristics in the same population. Studies have confirmed that the accumulation and polarization of macrophages is a risk factor for the progression of DKD. Natural products contribute to alleviate kidney damage by suppressing macrophage recruitment and activation, which may be a potential treatment for DKD. This review describes the phenotype and polarization of macrophages, as well as their role in DKD animal models and patients, outlines the molecular mechanism of macrophage recruitment and activation in DKD, further discusses the cross-action between macrophages and other kidney cells, and emphatically summarizes natural products targeting macrophages, which is of great significance for future basic research and clinical management of DKD.
Kidney transplantation is the preferred treatment for suitable patients with end-stage renal disease; however, access to transplantation declines dramatically with increasing HLA sensitization. While the acceptable mismatch (AM) program by Eurotransplant improves transplantability for highly sensitized candidates, a clinically relevant subgroup with extremely low donor frequency or ineligible for AM remains disadvantaged. In carefully selected cases, the controlled delisting of unacceptable HLA antigens and the use of peri-transplant desensitization (e.g., imlifidase) may enable transplantation. In order to provide better guidance, this German expert consensus report was compiled by the Kidney and Immunology Commissions of the German Transplantation Society and the Organ Transplantation Commission of the German Society for Immunogenetics. Within the German legal framework of urgency and chances for success, the report proposes a practical guide for candidate selection, multidisciplinary governance, risk-adapted HLA delisting, assessment of organ offers, use of imlifidase, perioperative immunosuppression, prophylaxis for infection, post-transplant monitoring, and management of antibody-mediated rejection. These recommendations are intended for experienced transplant centers and aim to balance transplant opportunity against immunological risk in highly sensitized kidney transplant candidates. The primary scope of this article is highly sensitized adult wait-listed candidates considered for deceased-donor kidney transplantation after compatibility-preserving pathways have been exhausted or are unlikely to succeed; HLA-incompatible living-donor transplantation with imlifidase is addressed separately as a potential off-label scenario for selected highly sensitized patients.
Kidney involvement in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) significantly increases morbidity and risk of mortality, particularly with progression to end-stage kidney disease (ESKD). This review focused on the cumulative incidence of ESKD in patients with AAV and assessed how changes in estimated glomerular filtration rate (eGFR) impact the risk of developing ESKD. Literature searches were performed in the PubMed, EMBASE and Cochrane Library databases, focusing on studies published in 2019-2024 with at least 100 participants and a minimum follow-up of 3 years. Combined estimates of the cumulative incidence of ESKD and hazard ratios (HRs) quantifying the relationship between eGFR and ESKD risk were calculated. A total of 49 studies (19,301 patients) reported the incidence of ESKD, while 19 studies (4513 patients) reported the relationship between eGFR and ESKD risk. ESKD incidence ranged from 2.9 to 59.6% at 1 year of follow-up, and from 9.4 to 51.4% at 10 years. The meta-analysis found that ESKD incidence was 14.2% and 24.8% at 1 and 10 years of follow-up, respectively, and that 1 mL/min/1.73 m2 higher eGFR at diagnosis and at 6 months after diagnosis were associated with 5-6% and 7-8% reductions in ESKD risk, respectively. This review indicates that patients with AAV remain at high risk of ESKD, with lower eGFR at diagnosis and at 6 months after diagnosis associated with poorer kidney outcomes. However, the pooled estimates should be used with caution, given the high heterogeneity in patient characteristics across studies.
Objective: The aim of this study was to evaluate the safety and efficacy of robot-assisted laparoscopic ureteroureterostomy (RALUU) and laparoscopic ureteroureterostomy (LUU) for duplicated kidney malformations in infants. Methods: This retrospective comparative cohort included infants with duplicated kidney malformations who underwent RALUU or LUU between May 2021 and April 2025. Perioperative variables assessed included operative duration, blood loss, oral feeding time, FLACC pain score, hospital stay, and complications. Follow-up outcomes included changes in anteroposterior pelvic diameter (APD), ureteral diameter (UD), and renal function (RF) of the affected upper moiety, assessed using renal ultrasonography and radionuclide imaging, with preoperative measurements serving as the baseline reference. The minimum follow-up duration was 12 months. Surgical success was determined based on fulfillment of all three criteria: resolution or alleviation of clinical symptoms, a reduction in APD and UD, and preserved or improved upper-moiety renal function compared with baseline. Results: The final cohort consisted of 52 infants (RALUU, n = 28; LUU, n = 24). Demographic and clinical profiles were comparable between groups. RALUU was associated with a shorter operative duration than LUU (139.6 ± 16.6 vs. 151.8 ± 21.6 min, p = 0.029). Estimated blood loss, time to oral feeding, FLACC pain score, and hospital stay were comparable. Postoperative complications were observed in 2 RALUU patients and 3 LUU patients. One patient in the LUU group developed urine leakage, which was managed conservatively. Postoperative urinary tract infection occurred in 2 patients in each group. No patient required secondary surgery. At a mean follow-up of 26.8 ± 10.4 and 28.1 ± 11.7 months in the RALUU and LUU groups, both groups showed significant reductions in APD and UD, with preserved RF and a modest postoperative increase. Conclusions: Both RALUU and LUU were safe and effective for duplicated kidney malformations in infants. RALUU was associated with a shorter operative time, while postoperative recovery, complication rates, and follow-up outcomes were comparable.
The kidney is an organ rich in peroxisomes, which play a pivotal role in fatty acid oxidation and ROS decomposition. Importantly, peroxisomal dysfunction contributes to the development and progression of various renal diseases. Therefore, we aimed to elucidate whether peroxisomes affect renal damage and fibrosis over time using a unilateral ureteral obstruction (UUO) mouse model. Expression levels of peroxisome-related factors and ROS- and hypoxia-related genes in UUO mice were measured in a time-dependent manner. UUO led to renal damage and fibrosis progression over time; it significantly increased the protein expression levels of ATG5 and ATG7, while it decreased PMP70 and PEX14 protein expression. In particular, UUO increased the protein expression level of pexophagy receptor NBR1. Although the number of peroxisomes decreased, the protein expression levels of peroxisomal biogenesis-related proteins such as PEX11b, PEX16, and PEX19 remained constant. Decreased lipid metabolism due to reductions in ACOX1, DBP, and catalase caused by UUO and increased ROS production through peroxisomal degradation and mitochondrial antioxidant enzyme dysfunction were observed. Additionally, HIF-1α protein levels gradually increased in the UUO mice, whereas those of HIF-2α initially increased and then decreased. UUO is characterized by a progressive, chronological reduction in peroxisomal markers. Our findings indicate that peroxisomal degradation and associated metabolic dysfunction are tightly correlated with the progression of kidney injury and fibrosis, suggesting a potential involvement of compromised peroxisomal homeostasis in renal pathogenesis rather than proving a direct causal mechanism. Maintaining peroxisomal quality control may nevertheless represent a potential therapeutic avenue for chronic kidney disease.
Oxidative stress contributes to kidney and ureteral calculi, but the specific genes and mechanisms remain unclear. This study integrates methylation quantitative trait loci (mQTL), expression QTL (eQTL), and protein QTL (pQTL) data with genome-wide association study (GWAS) data to identify oxidative stress-related genes linked to calculi. Summary data-based mendelian randomization (SMR) and colocalization analyses were performed using GWAS data from FinnGen (discovery) and UK Biobank (UKB; validation) to identify oxidative stress-related genes associated with calculus risk. External validation employed a genetic hypercalciuric stone-forming (GHS) rat transcriptomic dataset. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, together with protein-protein interaction (PPI) network, were used to characterize functional pathways and central regulators. SMR and colocalization analyses in FinnGen identified 172 mQTLs, 27 eQTLs, and 5 pQTLs associated with calculus risk, with subsets validated in UKB. Multi-omics integration highlighted CREM (cg26679713) and MAPT (cg21705961) as key candidates, showing hypermethylation-associated upregulation. CREM was consistently associated with increased risk in both SMR analysis and the GHS model, whereas MAPT showed a protective association in SMR but was upregulated in GHS kidneys. GO and KEGG enrichment of 75 nonredundant genes from eQTL- and pQTL-level associations indicated predominant roles in oxidative stress and inflammation, and enrichment in FoxO, TNF, apoptosis, and IL-17/Th17 pathways. PPI analysis identified 11 hub genes linked to oxidative stress and inflammation. Oxidative stress-related genes, particularly CREM and MAPT, are potential modulators of kidney and ureteral calculi risk, warranting further mechanistic and translational investigation.
Background: To investigate the protective effects of Phellodendron amurense Rupr. polysaccharides (PAP), alkaloids, and flavonoids in alleviating diabetic kidney disease (DKD) and to elucidate the role of the PI3K/AKT/GSK-3β/Nrf2 signaling pathway. Methods: Active components were extracted and quantified. In vitro, high-glucose (HG)-induced human kidney-2 (HK-2) cells were used to screen the optimal fraction via CCK-8, reactive oxygen species (ROS), TdT-mediated dUTP Nick-End Labeling (TUNEL), and Western Blot (WB) assays. In vivo, a DKD rat model was established using 2% Streptozotocin (STZ) and a high-fat with high-sugar diet. Rats were treated with PAP and LY294002. Renal damage and signaling pathway proteins were evaluated using histological staining and WB. Results: Among the tested components, PAP conferred the most pronounced cytoprotection against HG-induced injury in HK-2 cells. PAP significantly reduced glomerular damage, collagen deposition, and glycogen accumulation in the kidneys of DKD rats. Mechanistically, PAP activated the PI3K/AKT/GSK-3β/Nrf2 pathway, upregulating HO-1 and NQO1, while inhibiting the TGF-β1/Smad2 pathway and Bcl-2/Bax-mediated apoptosis. These protective effects were significantly attenuated by LY294002. Conclusions: Among the tested fractions under the present experimental conditions, PAP exhibited the most pronounced protective activity. These protective effects were partially mediated through the PI3K/AKT/GSK-3β/Nrf2 pathway, which enhanced antioxidant capacity while reducing fibrosis and apoptosis.
Ischemia-reperfusion injury (IRI) contributes to graft dysfunction in solid organ transplantation, with the pancreas vulnerable due to its fragile vasculature. Endothelial glycocalyx (eGCX) disruption is central to this process. This study prospectively examined perioperative endothelial injury in pancreas transplantation. Fifty-two recipients were included, of whom 47 underwent simultaneous pancreas-kidney (SPK) transplantation and 5 pancreas retransplantation. Biomarkers of eGCX degradation (syndecan-1, heparan sulfate (HS) and hyaluronan) and endothelial injury (soluble thrombomodulin, VEGF and soluble VEGFR1) were measured in plasma preoperatively, 10 min after pancreas reperfusion, 24 h later, and at discharge. Associations with donor type and early post-transplant outcomes were explored. A marker endothelial injury was evident within 10 min of pancreas reperfusion, before kidney implantation, characterized by increased syndecan-1, HS, and sVEGFR1, together with decreased VEGF. Hyaluronan peaked at 24 h, consistent with a broader systemic endothelial response. Controlled donation after circulatory death donors showed higher syndecan-1 levels at 10 min PR and higher VEGF at 24 h. Seven recipients developed pancreas graft loss, which was linked to lower VEGF at 10 min post-reperfusion and lower hyaluronan levels both before surgery and at discharge. Kidney acute tubular necrosis was related with higher preoperative HS and elevated 24 h sVEGFR1. Among recipients with functioning grafts, preoperative endothelial biomarkers were linked to postoperative complications. Pancreas transplantation triggers early endothelial injury and glycocalyx shedding, particularly in a predominant SPK setting. Perioperative endothelial biomarkers may have a value for early risk stratification after transplantation.
Kidney injury is an important manifestation of post-resuscitation syndrome and a significant factor leading to high mortality rates after cardiopulmonary resuscitation (CPR).This study aimed to develop and validate a multivariable nomogram to predict estimated glomerular filtration rate (eGFR) after CPR to assess the degree of kidney injury and provide protective strategies. The clinical data of patients after CPR admitted to Tianjin Medical University General Hospital from January 2017 to June 2024 and Tianjin Medical University General Hospital Airport Hospital from January 2017 to December 2019 were retrospectively analyzed. The patients those who met the inclusion criteria were randomly divided into training and validation cohorts at a ratio of 7∶3.We obtained clinical data from January 2021 to June 2023 at First Affiliated Hospital of Hebei North University as external validation. Univariate and multivariate linear regression methods were used to identify independent risk factors for 7d-eGFR after CPR, develop and validate (internal and external) a multivariate nomogram model. Calibration curve, Bland-Altman plot, and paired-T validation were used to validate the predictive performance of the model. We included 439 patients after CPR, of whom 307 were in training cohort and 132 were in validation cohort. And 105 patients were included as an external validation cohort. Multivariable linear analysis showed that age (beta coefficient [β], 95% confidence interval: -0.344 [-0.528, -0.160]), hypertension (-3.610 [-5.968, -1.252]), diabetes mellitus (-2.992 [-5.295, -0.689]), no flow time (-0.577 [-0.996, -0.158]), baseline eGFR (0.349 [0.269∼0.429]), ACR (-0.042 [-0.073, -0.011]), lactic acid (-0.650 [-1.214,-0.086]) were the independent risk factors for eGFR after CPR. A composite nomogram predicted eGFR with good accuracy in training (97.07%), internal validation (95.45%), and external validation (91.08%) cohorts. The nomogram model has good predictive ability for AKI and CKD in training (AUC = 0.933 and 0.882), internal validation (AUC = 0.915 and 0.859), and external validation (AUC = 0.823 and 0.784) cohorts. The developed nomogram could be used to predict 7d-eGFR after CPR, which helped to accurately quantify kidney function levels and early predict the probability of AKI and CKD progression, achieving early detection and intervention, thereby improving the prognosis of patients after CPR.
Despite advancements in hemodialysis (HD) technology, mortality remains unacceptably high in end-stage kidney disease (ESKD) patients, with cardiovascular disease (CVD) as the leading cause. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a critical contributor to CVD pathogenesis. However, longitudinal evidence on trends in CKD-MBD biomarker (calcium, phosphorus, parathyroid hormone [PTH]) target attainment and its association with clinical outcomes in Chinese HD patients remains limited. Utilizing data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS, 2009-2022), this multicenter cohort included 4,650 maintenance HD patients across 45 facilities in Beijing, Shanghai, and Guangzhou. Through multistage cluster sampling, we analyzed decade-long trends in CKD-MBD target achievement (per KDIGO and Chinese guidelines) and evaluated associations with all-cause and cardiovascular mortality using multivariable Cox models. Over the decade, phosphorus target attainment (3.5-5.5 mg/dL) significantly improved (32.8%→43.2%, Δ + 31.7%), yet achievement of stricter targets (2.5-4.5 mg/dL) remained suboptimal (24.4%). Calcium target rates (8.4-10.2 mg/dL) increased from 66.3% to 70.5%, paralleled by rising hypercalcemia (>10.2 mg/dL: 9.5%→12.7%). Triple target attainment (calcium+phosphorus+PTH) improved from 10.8% to 22.5%. Survival analysis suggested that achieving phosphorus targets was independently associated with lower all-cause mortality (HR = 0.77, 95% CI 0.64-0.93) and cardiovascular mortality (HR = 0.73, 0.58-0.93), while stricter phosphorus targets did not show additional associations with improved outcomes. Concurrent triple target achievement was associated with a 39.6% reduction in cardiovascular mortality risk (HR = 0.60, 0.38-0.96). While single-parameter CKD-MBD management has progressed in Chinese HD patients, multiparameter synergistic control remains inadequate. Achieving phosphorus targets appears to be strongly associated with survival benefits. Further optimization of guideline implementation, particularly through integrated management of multiple parameters, may contribute to reducing cardiovascular events and mortality.
Renal tubular epithelial cells (RTECs) are increasingly recognized as key players in kidney diseases. They integrate metabolic, inflammatory, and fibrotic signals. This article reviews new data suggesting that RTECs could function as central integrators within diagnostic networks, linking cellular stress responses to detectable blood and urine biomarkers. We discuss the latest advances in multi-omics, extracellular vesicles, and single-cell technologies that enable precise identification of RTEC states. Finally, we discuss the potential of RTEC-centric diagnostics and highlight current limitations in early disease recognition, stratification, and the development of personalized therapeutic interventions.
Kidney diseases, which are broadly classified into acute kidney injury (AKI) and chronic kidney disease (CKD), represent a significant and ongoing health burden in China and across the globe. AKI is a clinical syndrome marked by a rapid decline in renal function within 48 h due to diverse causes. Despite its high prevalence among hospitalized patients as a common complication, current therapeutic outcomes remain unsatisfactory. Therefore, a critical step toward resolving this issue is the precise identification of the specific cell types that drive renal regeneration during AKI repair. Renal fibrosis, pathologically characterized by excessive extracellular matrix (ECM) deposition, is the common final pathway of CKD and significantly impairs patient's quality of life and prognosis. The focal nature of fibrotic lesions has prompted systematic investigations into the fibrotic microenvironment. Myofibroblasts are the central effector cells driving pathological ECM deposition. Nevertheless, their cellular origins remain elusive. A thorough understanding of myofibroblast origins, along with the composition and regulatory factors of the fibrotic microenvironment, is therefore crucial for developing effective treatments for renal fibrosis. The kidney is a complex organ with intricate anatomical structures and diverse cellular composition. Traditional investigative methods which rely on conventional pathology and low-resolution molecular biology have been unable to capture cellular heterogeneity at single-cell resolution. This limitation has obscured functional distinctions among cell subpopulations and their critical spatial context, thereby leading to an inadequate understanding of intercellular communication. Fortunately, the advent of single-cell and spatial transcriptomics has revolutionized kidney research by enabling comprehensive profiling of functional signatures and intercellular crosstalk within the renal microenvironment. This review summarizes the current applications of single-cell and spatial transcriptomics in renal regeneration and fibrosis. Furthermore, it introduces emerging technologies, such as proximity-dependent labeling, while rarely applied in kidney research to date, hold significant potential. Our aim is to provide researchers with insightful strategies for their future application in this field.
Infections are a leading cause of morbidity and mortality in pediatric solid organ transplant recipients (SOT). Comprehensive data in this population is limited. We included pediatric SOT from the Swiss national cohort aged 0-18 years prospectively from 2008 to 2022. Using standardized definitions, all clinically relevant infections during the first year after transplant were analyzed. Associations with age, organ type, and rejection episodes were assessed. A total of 285 pediatric SOT were included, with kidney (41%) and liver (37%) transplants being the most common. During the first-year post-transplant, 53% (151/285) of patients experienced at least one infection, totaling 360. The overall incidence was 1.36 infection/person/year. Viral infections predominated (53%), followed by bacterial (41%) and fungal infections (6%). Patients receiving liver and lung transplants had higher infection rates (1.91 and 2.53 per person-year, respectively). In multivariate analysis type of transplant and male sex remained associated with increased risk of infection. Viral infections were overrepresented in younger recipients, while bacterial infections were most frequent in the first 3 months post-transplant. Pediatric SOT recipients face a substantial burden of infection. This underscores the need for specific prevention, early recognition, and coordinated management strategies to reduce infection-related morbidity.
Acute kidney injury (AKI) is a serious complication of COVID-19 inpatients, requiring early identification of high-risk individuals by dynamic biomarkers. We evaluated the association between longitudinal peripheral blood count (PBC) trajectories and AKI in these patients by joint model analysis. In a prospective cohort of 3,691 hospitalized adults with COVID-19 from six tertiary hospitals in China, longitudinal lymphocyte, neutrophil, and platelet counts and four derived ratios (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], neutrophil-to-platelet ratio [NPR], and neutrophil-to-lymphocyte-platelet ratio [NLPR]) were analyzed. A joint model was performed to evaluate the associations between PBC trajectories and in-hospital AKI. PBC thresholds on admission were identified by restricted cubic splines for further stratified joint model analyses. Competing-risk joint models were then performed to evaluate the associations between PBC trajectories and renal recovery. Among 3,691 COVID-19 inpatients, 768 (20.8%) developed AKI during hospitalization. Joint model analysis revealed that trajectories of all seven PBC parameters were significantly associated with AKI risk (all p < 0.001). Increasing lymphocyte (hazard ratio [HR] = 0.46, 95% confidence interval [CI] 0.39-0.53) and platelet (HR = 0.63, 95% CI 0.55-0.72) levels were associated with decreasing AKI risk, while elevated neutrophils (HR = 3.33, 95% CI 2.70-4.13) and PBC ratios (NLR, NPR, PLR, NLPR) were associated with increased AKI risk. Stratified analyses showed that in patients with lower NLR and NPR baseline levels, larger risk magnitudes were observed. No significant associations were observed between biomarker trajectories and renal recovery. By joint model analyses, dynamic PBC trajectories enabled individualized, real-time AKI risk evaluation in COVID-19 patients.
Background/Objectives Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family of amine oxidases involved in collagen cross-linking, has emerged as a key mediator of pathological extracellular matrix remodeling and tissue fibrosis. Dysregulated LOXL2 activity has been implicated in various fibrotic diseases; however, its role in fibrosis-driven chronic kidney injury, particularly in the context of calcineurin inhibitor-induced kidney toxicity, remains incompletely defined. Methods To investigate the contribution of LOXL2 inhibitor to cyclosporine A (CsA)-induced nephropathy, a well-established model of progressive tubulointerstitial fibrosis, male CD-1 mice were administered either saline or CsA (15 mg/kg/day, intraperitoneally) for 8 weeks. After 4 weeks of CsA exposure, CsA-treated mice were further divided into two groups and received either vehicle or a LOXL2 inhibitor (10 mg/kg/day, oral gavage) for an additional 4 weeks. Kidney function, albuminuria, histological fibrosis, inflammatory cell infiltration, and profibrotic gene expression were assessed. Results In a murine model of CsA-induced nephropathy, pharmacological inhibition of LOXL2 markedly improved kidney outcomes. LOXL2 inhibition significantly reduced albuminuria and ameliorated kidney dysfunction. In parallel, tubulointerstitial fibrosis was substantially attenuated, accompanied by reduced myofibroblast activation and extracellular matrix accumulation. These protective effects were associated with downregulation of profibrotic and inflammatory mediators and inhibition of TGF-β-related downstream signaling pathways activated by CsA. Conclusions The present preclinical findings suggest that Compound #765-mediated LOXL2 inhibition may offer a potential therapeutic benefit in CsA-induced fibrosis, though further validation is warranted.