Introduction:Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are crucial in managing proteinuria in chronic kidney disease (CKD), yet individual responses vary. Whether urinary glucose excretion, a direct pharmacodynamic marker of SGLT2is, could predict proteinuria reduction efficacy remains unclear and has not been specifically investigated. Methods:We enrolled 277 CKD patients treated with empagliflozin (10 mg/day) between July 2024 and September 2025 at a single center, stratifying them into low (<46.4 mmol/L, n = 69) and high (≥46.4 mmol/L, n = 208) urinary glucose groups by 24-h urinary glucose levels after 3 months of treatment. We evaluated changes in proteinuria levels following 3 and 6 months of medication across the different urinary glucose groups. Changes in laboratory values over time were analyzed using paired Wilcoxon signed-rank tests. Results:Proteinuria was significantly reduced at both 3 (-0.42 g/24 h [95% confidence interval [CI]: -0.55 to -0.32]) and 6 months (-0.46 g/24 h [95% CI: -0.61 to -0.33]) after treatment initiation. After adjusting for covariates, urinary glucose excretion predicted proteinuria reduction from 3 to 6 months (β = 2.47, 95% CI: 0.49-4.45, p = 0.015), with higher urinary glucose correlating with greater proteinuria decline. The high urinary glucose group had significant proteinuria reduction from baseline at 3 and 6 months (p < 0.001), unlike the low group. Following propensity score adjustment for age, sex, body mass index, baseline estimated glomerular filtration rate (eGFR), and renin-angiotensin-aldosterone system inhibitors use, the high urinary glucose group had a significantly higher relative risk of ≥30% proteinuria reduction (risk ratio = 2.82, 95% CI: 1.20-6.65, p = 0.017), particularly in patients with baseline proteinuria ≥1 g/24 h. Urinary glucose concentration was weakly positively correlated with 6-month eGFR change (r = 0.17, p = 0.011). Conclusions:Urinary glucose concentration can serve as a predictor of SGLT2i-mediated proteinuria reduction, providing a practical clinical reference for personalized CKD management.
Background:Predicting early progression of diabetic kidney disease (DKD) remains challenging. The neutrophil-derived peptide LL37 is implicated in kidney inflammation, yet its role and prognostic value in DKD remain unclear. Methods:RNA sequencing dataset was analyzed to examine the expression of CAMP (encoding LL37) and myeloperoxidase (MPO) in peripheral blood from diabetic mellitus patients. A clinical cohort of 94 biopsy-proven DKD patients and 63 healthy controls (HCs) was established. Serum LL37 and MPO-DNA complexes were measured using enzyme-linked immunosorbent assay. The correlation between serum LL37 and MPO-DNA complex levels and kidney function was assessed and assessed their association with DKD progression using restricted cubic spline analysis and Cox proportional hazards regression models. Results:Bioinformatics analysis revealed significantly elevated CAMP expression in DM patients, with strong neutrophil infiltration. In the clinical cohort, serum LL37 levels were significantly higher in DKD patients than in HC, showing discriminatory power for DKD diagnosis (AUC = 0.90, 95% CI: 0.85-0.96). Serum LL37 and MPO-DNA complex levels correlate with elevated serum creatinine and reduced eGFR. After a median follow-up of 39 months, 60 patients (63.83%) experienced renal progression events. After adjusting for confounding factors, elevated serum LL37 and MPO-DNA complex levels were independent risk factors for DKD progression (per Ln-transformed HRs: 2.290 [95% CI: 1.491-3.518] and 1.833 [95% CI: 1.261-2.664], respectively). Conclusion:Elevated serum LL37 and MPO-DNA complex levels are independently associated with kidney disease progression in patients with DKD, and increased circulating LL37 may be closely linked to neutrophil activation.
Chronic hyperkalemia in patients with chronic kidney disease (CKD) often limits the use of vital renin-angiotensin-aldosterone system inhibitors (RAASi). This prospective cohort study compared the efficacy and safety of patiromer (n=40) versus sodium polystyrene sulfonate (SPS) (n=40) for chronic hyperkalemia management in 80 adult CKD patients. Over a six-month follow-up, both agents effectively reduced serum potassium from similar baseline levels (patiromer: 5.73 ± 0.59 mmol/L; SPS: 5.62 ± 0.50 mmol/L) with no significant difference in efficacy (p>0.05). However, key differences in the clinical impact on RAASi therapy emerged, alongside numerical but statistically non-significant differences in tolerability. Patients receiving patiromer had a significantly lower rate of RAASi therapy discontinuation compared to the SPS group (5.2% vs. 36.3%; p=0.033), enabling continuation of guideline-directed medical therapy. A trend towards poorer compliance was noted in the SPS group (22.5% vs. 7.5%; p=0.060). An exploratory analysis revealed that patiromer initiation significantly increased tacrolimus levels in post-kidney transplant recipients (p=0.003), necessitating dose adjustments. While both agents showed comparable potassium-lowering efficacy, patiromer's numerical advantages in tolerability and significant benefit in maintaining RAASi therapy position it as a valuable therapeutic option in this high-risk population.
Introduction:Kidney disease is a major global health burden with limited regenerative treatment options. Induced pluripotent stem cells (iPSCs) offer patient-specific pluripotency and the potential to generate renal cells and organoids, making them a promising approach for kidney repair. Methods:A systematic literature search was conducted in PubMed, ScienceDirect, Web of Science, and Cochrane Library for peer-reviewed studies investigating the therapeutic application of iPSCs in kidney disease up to February 2026. Risk of bias was assessed using the SYRCLE tool. Random effects meta-analyses were performed, and subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity. Result:In this search, 23 preclinical studies encompassing 372 animals met the inclusion criteria, and no eligible human trials were identified. iPSC-based therapy was associated with reduced mortality (OR = 0.17; 95% CI: 0.05-0.52; p = 0.002) and improvements in blood urea nitrogen, serum creatinine, and histological injury scores. Subgroup and meta-regression analyses suggested that therapeutic response was influenced by biological factors, including cell type, disease model, delivery route, and treatment conditions. Notably, stronger effects were observed in acute kidney injury models and with direct iPSC-based interventions. However, substantial heterogeneity was observed across most renal outcomes (I 2 > 90%), indicating considerable variability among studies. Conclusion:iPSC-based therapy demonstrates beneficial effects in experimental kidney disease, particularly in acute models. However, the high degree of heterogeneity, potential risk of bias, and limited safety data constrain the reliability and generalizability of these findings. Further optimization of therapeutic strategies and rigorous long-term safety evaluations are required to support clinical translation.
Introduction:Pegmolesatide selectively binds to the erythropoietin receptor homodimer with higher binding stability and prolonged residency than erythropoietin, potentially offering an improved therapeutic profile for anemia management in chronic kidney disease (CKD) patients. This post hoc analysis of two randomized phase 3 trials compared pegmolesatide with epoetin alfa to further evaluate pegmolesatide's potential benefits. Methods:This analysis included a total of 545 patients: 372 with dialysis-dependent (DD)-CKD (248 pegmolesatide, 124 epoetin alfa) and 173 with non-dialysis-dependent (NDD)-CKD (115 pegmolesatide, 58 epoetin alfa). The proportion of patients maintaining mean hemoglobin (Hb) levels ≥10 g/dL and intraindividual hemoglobin variability (Hb-Var) were analyzed. Cardiovascular (CV) safety was assessed using five-point major adverse cardiovascular events (MACE), expanded CV events, and three-point MACE. Results:During the efficacy evaluation period (weeks 17-24), pegmolesatide showed numerically higher proportions of patients who maintained mean Hb levels ≥10 g/dL versus epoetin alfa in both DD-CKD {91.8% vs. 88.6%; difference: 7.1% (95% confidence interval [CI]: 0.1, 14.2); p = 0.2802} and NDD-CKD (87.0% vs. 85.4%; difference: 3.3% [95% CI: -8.1, 14.6]; p = 0.6091) patients. From the efficacy evaluation period to the extended period (weeks 17-52), patients receiving pegmolesatide exhibited lower Hb-Var compared with those receiving epoetin alfa as measured by within-patient residual standard deviation (DD-CKD: 0.678 g/dL vs. 0.730 g/dL, p = 0.0061; NDD-CKD: 0.647 g/dL vs. 0.677 g/dL, p = 0.3158). The incidences of five-point MACE (DD-CKD: 3.7% vs. 6.5%, hazard ratio [HR] = 0.54 [95% CI: 0.21, 1.39]; NDD-CKD: 0.9% vs. 6.9%, HR = 0.14 [95% CI: 0.02, 1.28]), expanded CV events (DD-CKD: 9.8% vs. 11.3%, HR = 0.83 [95% CI: 0.43, 1.61]; NDD-CKD: 5.2% vs. 12.1%, HR = 0.49 [95% CI: 0.16, 1.45]) and three-point MACE (DD-CKD: 2.0% vs. 3.2%, HR = 0.60 [95% CI: 0.16, 2.23]; NDD-CKD: 0 vs. 1.7%, HR not estimable) were consistently lower in the pegmolesatide group across both patient populations. Conclusion:Pegmolesatide showed effectiveness in Hb management for both NDD-CKD and DD-CKD populations, with overall numerically favorable CV safety outcomes compared to epoetin alfa.
Introduction:Iron deficiency is prevalent in chronic kidney disease (CKD), particularly among patients with anemia. However, the prognostic value of routinely measured iron biomarkers, ferritin and transferrin saturation (TSAT), in non-dialysis-dependent (NDD) CKD remains incompletely defined. Methods:We conducted a multicenter retrospective cohort study using data from the China Renal Data System. Eligible hospitalized adults had anemia and NDD-CKD with baseline serum ferritin or TSAT measurements. Iron deficiency was defined as ferritin ≤100 ng/mL and/or TSAT ≤20%. The primary outcomes were CKD progression and all-cause mortality. Associations were assessed using multivariable Cox proportional hazards models; Fine and Gray competing risk models and prespecified subgroup analyses evaluated robustness. Results:Among 40,667 patients with anemic CKD, 38,307 had ferritin measurements, and 9,210 had TSAT measurements. Of these, 11,116 (29.02%) had ferritin ≤100 ng/mL and 3,295 (35.78%) had TSAT ≤20%. During follow-up, CKD progression occurred in 8,756 (22.86%) patients in the ferritin cohort and 2,459 (26.70%) in the TSAT cohort. In multivariable analyses, ferritin ≤100 ng/mL was associated with a modestly lower risk of CKD progression than levels greater than 100 ng/mL (adjusted hazard ratio [aHR], 0.95; 95% confidence interval [CI], 0.90-0.99), with similar results in competing risk analyses. TSAT ≤20% was not associated with CKD progression (aHR, 1.04; 95% CI, 0.95-1.13). For all-cause mortality, ferritin ≤100 ng/mL was not independently associated with risk (aHR, 0.99; 95% CI, 0.93-1.06), whereas TSAT ≤20% was associated with higher risk (aHR, 1.19; 95% CI, 1.06-1.36). CRP-stratified analyses indicated that ferritin ≤100 ng/mL was associated with lower CKD progression risk only among patients with CRP ≤10 mg/L, suggesting that the prognostic association of ferritin varied by inflammatory status. Conclusion:In Chinese adults with anemia and NDD-CKD, ferritin and TSAT showed divergent prognostic associations. TSAT ≤20% identified higher mortality risk, whereas ferritin ≤100 ng/mL was associated with a modestly lower observed risk of CKD progression in an inflammation-dependent pattern. These findings support routine, context-aware assessment of iron indices, particularly TSAT, in anemic NDD-CKD.
Background: Acute kidney injury (AKI) remains a major clinical problem characterized by high morbidity and an increased risk of progression to chronic kidney disease (CKD). Immune cell infiltration and activation are important features of AKI; however, the upstream mechanisms that shape this inflammatory response are not fully understood. Emerging evidence suggests that gut microbiota dysbiosis and systemic immune activation may contribute to renal injury, but the functional significance of the gut-kidney axis in AKI pathogenesis remains to be further clarified. Summary: This review synthesizes current evidence regarding gut-kidney crosstalk in AKI, with a focus on the immunometabolic impact of microbiota-derived metabolites. We discuss the potential roles of short-chain fatty acids, indole derivatives, indoxyl sulfate (IS), p-cresol sulfate (PCS), and trimethylamine-N-oxide (TMAO) in regulating T and B lymphocytes, macrophages, neutrophils, and other immune cell populations. Importantly, we distinguish direct AKI-related evidence from findings extrapolated from CKD, uremic conditions, or broader microbiome-immunity studies. Potential therapeutic interventions, including pharmacological modulation and probiotic strategies aimed at restoring gut-kidney homeostasis, are also highlighted. Key Messages: The gut-kidney axis is increasingly recognized as a potential contributor to immune-mediated injury and repair in AKI. However, the causal roles and temporal dynamics of several gut-derived uremic toxins, including IS, PCS, and TMAO, remain incompletely defined in AKI. By integrating direct AKI evidence with indirect evidence from CKD and broader microbiome-immunity studies, this review provides a more balanced conceptual framework for understanding renal immunopathology and identifying potential microbiome-targeted strategies to mitigate AKI and its progression to CKD.
Introduction:Vascular endothelial injury is a critical driver of renal dysfunction and glomerulosclerosis in chronic kidney disease (CKD). While endothelial damage-induced inflammation contributes to sclerosis, the underlying mechanisms remain unclear. Although miR-214 has been implicated in renal fibrosis, its role in vascular endothelial cells during glomerulosclerosis is undefined. Methods:In this study, we investigated miR-214 expression and function in renal endothelial cells using five-sixths nephrectomy (5/6Nx) mice, endothelial-specific and smooth muscle-specific miR-214 knockout models, CD31-enriched primary renal endothelial cells, and mouse aortic endothelial cells. Transcriptome analysis, bioinformatic prediction, luciferase reporter assays, cytokine profiling, and pro-inflammatory stimulation experiments were performed to evaluate the regulatory relationship between miR-214 and RELA-associated inflammatory signaling. Results:We observed significant miR-214 upregulation in renal endothelial cells of 5/6Nx mice. Endothelial-specific knockout of miR-214 aggravated glomerulosclerosis and endothelial dysfunction, whereas smooth muscle-specific knockout showed no significant effect. Transcriptome analysis revealed that miR-214 inhibition altered the NF-κB pathway, specifically upregulating RELA. Bioinformatic prediction and luciferase reporter assays supported a direct interaction between miR-214 and the RELA 3'-UTR in vitro. In CD31-enriched primary renal endothelial cells, modulation of miR-214 levels inversely regulated RELA expression. Cytokine profiling showed that miR-214 suppression enhanced pro-inflammatory secretion. Furthermore, pro-inflammatory stimulation experiments demonstrated that inhibition of miR-214 amplified RELA-associated endothelial inflammatory activation, while miR-214 overexpression attenuated it. Conclusion:Collectively, these results suggest that endothelial miR-214 protects against glomerulosclerosis by restraining RELA-associated inflammatory signaling, highlighting endothelial-targeted modulation of miR-214 as a potential therapeutic strategy for CKD-related glomerular injury.
Introduction: Hypouricemia is an often-overlooked condition. Isolated persistent hypouricemia is rare and may be associated with uncommon genetic disorders, such as familial renal hypouricemia or xanthinuria. Methods: Fifteen non-consanguineous adult patients were included in this single-center study. Secondary causes of hypouricemia, including malnutrition, SIADH, cirrhosis, uricosuric drug use, and full-blown Fanconi syndrome, were excluded. Patients were classified as hyperuricosuric or hypouricosuric based on urinary uric acid levels. Clinical or whole-exome sequencing was performed, and variant pathogenicity was assessed using in silico prediction tools. Results: Ten patients were female (66.7%), and four were hypouricosuric (26.7%). Three patients (20%) had also glucosuria without diabetes mellitus and full-blown Fanconi syndrome. Thirteen patients (86.7%) carried at least one rare variant (variant of unknown significance, likely pathogenic, or pathogenic) in genes associated with hypouricemia: 1 patient with homozygous SLC2A9, one with homozygous SLC22A12, five with heterozygous SLC22A12 (1 patient carried two variants; compound heterozygosity could not be confirmed), one with heterozygous CLCN5, one with homozygous XDH, two with homozygous MOCOS, one with heterozygous MOCS1, and one with two heterozygous SLC5A2 variants. This study reports, for the first time, the co-occurrence of familial renal glucosuria and familial renal hypouricemia, as well as the coexistence of xanthinuria type 2 and familial renal glucosuria in 2 patients. Finally, 1 female patient with hyperuricosuric hypouricemia carried a likely pathogenic FTL variant and a mitochondrial DNA variant of unknown significance, which may represent candidate genes and require confirmation in larger cohorts and functional studies. Conclusion: Our study expands the clinical and genetic spectrum of persistent hypouricemia. Genetic testing has a high diagnostic yield and should be considered in patients with unexplained persistent hypouricemia.
Introduction:Kidney stone disease (KSD) is multifactorial, and the genetic basis is poorly understood among the East Asian population. This study aims to elucidate comprehensive genetic factors associated with KSD. Methods:We conducted a genome-wide association study (GWAS) on Taiwanese Han Chinese individuals from the Taiwan Biobank to investigate genetic predispositions to KSD. A total of 108,483 participants were included, of whom 7,635 reported having KSD. A phenome-wide association study (PheWAS) leveraging the National Health Insurance Research Database was used to verify GWAS findings and explore disease associations. We also assessed individual genetic risk for KSD using a polygenic risk score (PRS). Results:Our analysis identified significant associations with KSD at single-nucleotide polymorphisms rs1481012 (odds ratio = 1.13, p = 5.53 × 10-11) and rs12872074 (odds ratio = 1.16, p = 4.77 × 10-17) on chromosomes 4 and 13, respectively. We pinpointed ABCG2, DGKH, and a novel locus PKD2. Biological pathways, including protein dimerization and CD4+ T-cell regulation, were identified in gene-set analysis. PheWAS confirmed the association of these lead variants with calculus of kidney and various phenotypes. PRS reached an area under the receiver operating characteristic curve of 0.97 on the discovery sample. Conclusion:This comprehensive study highlights the significant genetic contributors to KSD in an East Asian population. Our findings underscore the potential of using a national health database to validate our analyses and reveal novel disease correlations, which supported immune dysregulation in disease pathogenesis. PRS highlights the contribution of genetic variants to KSD risk and suggests potential for future clinical application, although validation in independent populations will be required to determine its predictive utility.
Background: It has been recognized that Periodic acid–Schiff (PAS) staining of amyloid deposits reveals weak or negative in the majority of AL amyloidosis. However, a subset of patients exhibits PAS-positive deposits, and their clinicopathological significance remains unclear. Methods: We retrospectively analyzed 269 patients with renal biopsy-proven AL amyloidosis from our institution; 72 were classified as PAS-positive and 197 as PAS-negative. Baseline demographics, clinical data, renal pathology features, treatment strategies, and prognostic information were collected. Multivariable linear regression and Cox proportional hazards models were used to determine the impact of PAS-positive amyloid deposition on renal function and patients’ outcomes. Results: Compared with the PAS-negative group, PAS-positive patients had higher serum creatinine (94.40 vs. 79 μmol/L, P = 0.005) and increased renal insufficiency ratio (31.94 % vs. 14.72%, P = 0.002). Histopathology showed more severe glomerular and interstitial amyloid deposition (P = 0.037, P = 0.049, respectively). In multivariable linear regression, PAS-positive deposits (β = 0.158, P = 0.005) were independently associated with higher serum creatinine. PAS-positive patients showed significantly worse renal survival (HR 3.05, 95% CI: 1.40 – 6.65, P = 0.005), independent of age, treatment regimens, renal stage, and pathological cores. Meanwhile, PAS-positive staining was an adverse prognostic factor (HR 2.34, 95% CI: 1.24 – 4.43, P = 0.009) for overall survival after adjusting for AL-type, age, treatment, organ involvement, interstitial fibrosis and tubular atrophy, and total amyloid burden. Conclusion: PAS-positive amyloid deposits are associated with more severe renal injury and poorer prognosis in AL amyloidosis.
Background: Predicting early progression of diabetic kidney disease (DKD) remains challenging. The neutrophil-derived peptide LL37 is implicated in kidney inflammation, yet its role and prognostic value in DKD remains unclear. Methods: RNA sequencing dataset was analyzed to examine the expression of CAMP (encoding LL37) and myeloperoxidase (MPO) in peripheral blood from diabetic mellitus patients. A clinical cohort of 94 biopsy-proven DKD patients and 63 healthy controls (HC) was established. Serum LL37 and MPO-DNA complexes were measured using enzyme-linked immunosorbent assay. The correlation between serum LL37 and MPO-DNA complex levels and kidney function was assessed, and assessed their association with DKD progression using restricted cubic spline analysis and Cox proportional hazards regression models. Results: Bioinformatics analysis revealed significantly elevated CAMP expression in DM patients, with strong neutrophil infiltration. In the clinical cohort, serum LL37 levels were significantly higher in DKD patients than in HC, showing discriminatory power for DKD diagnosis (AUC=0.90, 95%CI: 0.85-0.96). Serum LL37 and MPO-DNA complex levels correlate with elevated serum creatinine and reduced eGFR. After a median follow-up of 39 months, 60 patients (63.83%) experienced renal progression events. After adjusting for confounding factors, elevated serum LL37 and MPO-DNA complex levels were independent risk factors for DKD progression [per Ln-transformed HRs: 2.290 (95% CI: 1.491-3.518) and 1.833 (95% CI: 1.261-2.664), respectively]. Conclusion: Elevated serum LL37 and MPO-DNA complex levels are independently associated with kidney disease progression in patients with DKD, and increased circulating LL37 may be closely linked to neutrophil activation.
Introduction： Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are crucial in managing proteinuria in chronic kidney disease (CKD), yet individual responses vary. Whether urinary glucose excretion, a direct pharmacodynamic marker of SGLT2is, could predict proteinuria reduction efficacy remains unclear and has not been specifically investigated. Methods： We enrolled 277 CKD patients treated with empagliflozin (10mg/day) between July 2024 and September 2025 at a single center, stratifying them into low (<46.4 mmol/L, n=69) and high (≥46.4 mmol/L, n=208) urinary glucose groups by 24-hour urinary glucose levels after 3 months of treatment. We evaluated changes in proteinuria levels following 3 and 6 months of medication across the different urinary glucose groups. Changes in laboratory values over time were analyzed using paired Wilcoxon signed-rank tests. Results： Proteinuria was significantly reduced at both 3 [−0.42 g/24 h (95% CI −0.55 to −0.32)] and 6 months [−0.46 g/24 h (95% CI −0.61 to −0.33)] after treatment initiation. After adjusting for covariates, urinary glucose excretion predicted proteinuria reduction from 3 to 6 months (β=2.47, 95% CI: 0.49-4.45, p=0.015), with higher urinary glucose correlating with greater proteinuria decline. The high urinary glucose group had significant proteinuria reduction from baseline at 3 and 6 months (p<0.001), unlike the low group. Following propensity-score adjustment for age, sex, and Body Mass Index (BMI), baseline estimated glomerular filtration rate (eGFR), and renin-angiotensin-aldosterone system (RAAS) inhibitors use, a significantly higher relative risk of ≥30% proteinuria reduction in the high urinary glucose group (RR=2.82, 95% CI: 1.20-6.65, p=0.017), particularly in patients with baseline proteinuria ≥1g/24h. Urinary glucose concentration was weakly positively correlated with 6-month eGFR change (r=0.17, p=0.011). Conclusions： Urinary glucose concentration can serve as a predictor of SGLT2i-mediated proteinuria reduction, providing a practical clinical reference for personalized CKD management.
Introduction:End-stage kidney disease (ESKD) is a growing global public health burden, with millions of patients dependent on maintenance hemodialysis (MHD). Conventional center-based MHD imposes significant constraints on patient flexibility, accessibility, and quality of life, while home hemodialysis faces substantial implementation barriers in China. Advances in digital health technologies - including artificial intelligence, internet of things (IoT), and real-time data analytics - offer opportunities to fundamentally transform dialysis care delivery. This study presents the protocol for the first clinical trial evaluating a mobile intelligent hemodialysis platform in mainland China. Methods:This is a prospective, single-center, exploratory clinical trial to be conducted at Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine. Twenty adult ESKD patients (aged 18-75 years) receiving regular MHD 3 times weekly for at least 3 months will be enrolled. Participants will undergo a single 4-h hemodialysis session on the mobile intelligent dialysis platform, a specialized medical vehicle integrating water purification, dialysis equipment, and an intelligent clinical decision support system across six functional zones. The primary endpoint is the successful session completion rate, defined as completion without platform-related technical failure or premature termination. Secondary endpoints include dialysis adequacy (urea reduction ratio ≥65%; Kt/V >1.2), hemodynamic stability, and pre- to post-dialysis changes in biochemical parameters. Safety assessments include continuous vital sign monitoring and adverse event grading according to Common Terminology Criteria for Adverse Events (CTC-AE) version 4.0. The study has been approved by the Ethics Committee of Ren Ji Hospital (approval number: LY2024-313-A) and registered in the Chinese Clinical Trial Registry (ChiCTR2500100356). Conclusion:This trial is expected to demonstrate that the mobile intelligent hemodialysis platform can achieve high session completion rates, adequate dialysis efficiency, and a safety profile comparable to conventional center-based dialysis. If validated, this platform has the potential to improve service accessibility, reduce indirect costs, enhance patient autonomy, and provide a resilient dialysis option in public health emergencies and disaster settings, representing a meaningful paradigm shift in dialysis care delivery.
Introduction: Cancer patients are at risk for acute kidney injury (AKI) due to anticancer agents, tumor lysis syndrome, sepsis, and contrast-induced nephropathy. Renal replacement therapy (RRT) is associated with longer hospital stays, higher healthcare costs, and significant healthcare resource consumption. Therefore, early detection of severe AKI requiring RRT and the implementation of preventive measures are crucial. We comprehensively evaluated the associations with RRT by cancer site among Japanese cancer patients undergoing treatment through use of Hospital-Based Cancer Registry (HBCR) data linked to administrative data in a multicenter cohort study. Methods: Patients were classified into three groups based on the timing of RRT after the initiation of cancer treatment: acute phase (≤30 days), post-acute phase (after 30 days), and no RRT. The hazard ratios (HRs) and subdistribution HRs for RRT incidence were evaluated by cancer site (colon, lung, stomach, liver, kidney, esophagus, pancreas, and hematologic malignancies) using Cox proportional hazards and Fine-Gray competing-risk models adjusted for patient characteristics, comorbidities, and diuretic use. The 1-year cumulative incidence of RRT was also calculated. Results: A total of 230,850 patients were analyzed. Among them, 386 patients received RRT at ≤30 days after cancer treatment initiation (acute phase), 479 patients received RRT at >30 days (post-acute phase), and 229,985 patients did not receive RRT. In the Cox proportional hazards regression model, the HRs for RRT were significantly higher in the acute phase among patients with colorectal cancer (HR: 1.72, p < 0.001), liver cancer (HR: 1.80, p = 0.006), kidney cancer (HR: 2.49, p < 0.001), and hematologic malignancies (HR: 4.06, p < 0.001) when compared according to cancer site. In the post-acute phase, only hematologic malignancies showed a significantly increased HR for RRT (HR: 2.65, p < 0.001). The 1-year cumulative incidence of RRT among all patients was 0.413%. Conclusion: The risk of RRT after cancer treatment was increased during the acute phase in patients with colorectal, liver, and kidney cancer and those with hematologic malignancies. Patients with hematologic malignancies always had a higher HR for RRT, but the HR was particularly high in the acute phase.
Introduction: 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. Methods: 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. Results: 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). Conclusion: 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.
Introduction: 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. Methods: 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. Results: 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%. Conclusion: 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.
Introduction:This study evaluated the clinicopathological profiles and prognostic trajectories of nondiabetic renal disease (NDRD) subtypes coexisting with type 2 diabetes mellitus (T2D). Methods:The study cohort comprised of 123 patients with predominant NDRD subtypes: IgA nephropathy (T2D-IgAN, n = 52), membranous nephropathy (T2D-MN, n = 48), and podocytopathies (T2D-Podo, n = 23). Multivariate Cox regression was used to identify prognostic factors for renal outcomes over a median follow-up period of 80 months (interquartile range 62-102). Results:T2D-MN patients exhibited distinct characteristics compared to T2D-IgAN and T2D-Podo, including advanced age, higher incidence of nephrotic-range proteinuria and elevated total cholesterol. This group also demonstrated a greater susceptibility to atherosclerotic plaque formation. Pathological analysis revealed more severe glomerular sclerosis, interstitial inflammation, and C3 deposition in T2D-IgAN. Multivariate Cox regression identified three independent predictors of renal endpoints: glomerular C3 deposition (HR 3.021, 95% CI: 1.084-8.419), preserved estimated glomerular filtration rate (>60 mL/min/1.73 m2; HR 0.296, 95% CI: 0.110-0.796), and prolonged T2D duration (>10 years; HR 4.168, 95% CI: 1.389-12.503). Conclusion:These findings suggest that integrating clinical and pathological parameters enhances the prognostic accuracy of NDRD in patients with diabetes, enabling timely therapeutic interventions to mitigate complications in high-risk cases.
Introduction: Pulmonary hypertension (PH) is a major complication in patients undergoing maintenance hemodialysis (MHD), significantly elevating the risk of cardiovascular events and mortality and severely impairing quality of life. Methods: In this single-center retrospective study, 1,077 MHD patients were enrolled. PH was diagnosed via echocardiography, and relevant clinical data were collected. Results: The prevalence of PH was 33.8% (364 cases). Nonlinear regression analysis indicated a significant inverse correlation between serum magnesium levels and PH. Notably, the risk of PH increased substantially when serum magnesium fell below 0.98 mmol/L. After adjusting for confounders (age, hemoglobin, serum phosphorus, NT-proBNP, left ventricular ejection fraction, extracellular water ratio, and pleural effusion), patients in the high-magnesium group (≥0.98 mmol/L) exhibited a 49.9% lower risk of PH (p = 0.026). Survival analysis further confirmed that hypomagnesemia was associated with a 65% and 89% increase in mortality risk among non-PH and PH patients, respectively. Conclusion: This study provides the evidence that hypomagnesemia is an independent risk factor for PH in MHD patients and is closely associated with adverse clinical outcomes. Management of hypomagnesemia is particularly crucial in MHD patients with PH.
Introduction: This study aimed to explore the ameliorative effects of enoxolone on renal fibrosis in diabetic kidney disease (DKD) and elucidate its underlying molecular mechanisms, thereby proposing a novel candidate drug and providing a theoretical foundation for clinical anti-fibrotic therapy in DKD. Methods: We analyzed the single-cell transcriptome dataset GSE209781 and integrated it with the connectivity map database to identify potential therapeutic compounds for DKD. Molecular docking and surface plasmon resonance techniques were employed to verify the binding interaction between enoxolone and Smad3. In vitro experiments involved human renal tubular epithelial HK2 cells and primary mouse tubular epithelial cells derived from Smad3-knockout (Smad3-KO) mice, which were stimulated with high glucose and advanced glycation end-products (HG+AGEs). Co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), quantitative real-time polymerase chain reaction (qPCR), and Western blot analyses were conducted to assess the effects of enoxolone on the Smad3-Smad4 interaction, binding of Smad3 to the COL1A1 promoter, and expression of fibrotic genes. An in vivo streptozotocin-induced DKD mouse model with adeno-associated virus-mediated Smad3 overexpression was established to evaluate renal function, fibrosis, and associated molecular changes. Results: Enoxolone was identified as a key candidate capable of reversing collagen expression disorder in proximal tubular epithelial cells treated with high glucose and AGEs. It binds directly to the Arg292 site in the MH2 domain of Smad3 with a high affinity. Enoxolone significantly inhibited the formation of the Smad3-Smad4 complex, reduced the enrichment of Smad3 on the COL1A1 promoter, and downregulated COL1A1 expression. In DKD mice, enoxolone reduced blood urea nitrogen, serum creatinine, and renal hydroxyproline levels and alleviated collagen deposition and tubular injury, whereas Smad3 overexpression reversed these effects. Conclusion: Enoxolone targets Arg292 of Smad3, inhibiting Smad3-Smad4 complex formation and downstream pro-fibrotic gene transcription, thereby attenuating renal fibrosis in DKD. Enoxolone has emerged as a promising anti-fibrotic candidate for the treatment of DKD.
