Diabetic kidney disease (DKD) progression is driven by residual inflammation, potentially exacerbated by volatile organic compounds (VOCs). However, the impact of xylene exposure on the DKD immune microenvironment remains unclear. We evaluated the association between urinary VOC metabolites and DKD prevalence using NHANES data. Network toxicology and bulk transcriptomics (GSE142025) were integrated to identify core targets and profile immune infiltration. Single-cell RNA sequencing (GSE209781) validated macrophage heterogeneity and hub gene dynamics, and molecular docking assessed xylene-receptor binding affinities. Elevated urinary xylene metabolite (DPMA) correlated with increased DKD odds (OR = 4.03, 95% CI: 1.80-9.00). Multi-omics identified ITGAM, CSF1R, and CTSS as primary hub genes enriched in immune pathways. Both bulk and single-cell RNA sequencing analyses revealed that DKD tissues exhibited M2-like macrophage enrichment and an expansion of fibrotic SPP1+ subsets. This altered microenvironment positively correlated with hub gene upregulation along the macrophage developmental trajectory. Molecular docking suggested potential binding between xylene isomers and these receptors (binding free energies: -4.7 to -5.9 kcal/mol). Environmental xylene exposure is independently associated with higher DKD odds. These findings generate the hypothesis that xylene may interact with specific macrophage receptors (ITGAM, CSF1R, CTSS), potentially promoting M2-like macrophage polarization and fibrotic remodeling. This putative environmental-immunological axis warrants further experimental validation.

IgA nephropathy (IgAN) has a heterogeneous clinical course. We retrospectively studied 180 patients with biopsy-proven IgAN and at least 3 years of clinical follow-up. Patient-specific eGFR slopes were estimated from available measurements at biopsy and the 6-, 12-, 18-, 24-, 30-, and 36-month follow-up points. We built a post hoc multivariable model guided by clinical relevance. Oxford T was treated as categorical, with T0 as reference. The median eGFR slope was -1.12 mL/min/1.73 m2/year, and 35 patients (19.4%) met the operational rapid-progression threshold of < -5 mL/min/1.73 m2/year. In the primary model, higher ln(UACR + 1) predicted a steeper decline (β= -0.612, 95%CI -1.073 to -0.150). T2 lesions predicted a 3.87 mL/min/1.73 m2/year faster loss than T0 (β= -3.870, 95%CI -7.087 to -0.654), whereas T1 did not differ from T0. The model R2 was 0.159 (adjusted R2=0.130). UACR and T2 estimates remained negative under HC3 inference and after excluding influential observations, although T2 was less stable in some restricted analyses. Baseline albuminuria was the most consistent adverse marker of eGFR slope. T2 lesions were linked to faster decline as well, but this estimate derived from only 16 patients (8.9%) and lost statistical significance when analysis was restricted to ≥5 measurements, making the finding tentative and strictly hypothesis-generating.

Renal anemia is a prevalent complication in patients undergoing peritoneal dialysis (PD). Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, but comparisons with erythropoiesis-stimulating agents (ESAs) require consideration of the specific regimens used. We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed from inception to December 2025 for randomized controlled studies comparing roxadustat-based regimens with ESA-based regimens in adults receiving PD. Eligible evidence was restricted to PD-only randomized studies after rechecking dialysis modality and study design. Nineteen studies involving 1,636 participants were included. The average post-treatment hemoglobin level was higher in the roxadustat-based groups than in the study-specific ESA comparator groups (mean difference = 7.30 g/L, 95% CI: 5.43 to 9.16; I[2] = 62.6%). However, hemoglobin target-attainment data were not defined or reported consistently enough for quantitative synthesis. Post-treatment hematocrit and red blood cell count also differed between groups, with substantial heterogeneity. The pooled reported adverse-event rate yielded an RR of 0.45 (95% CI: 0.27 to 0.74), but definitions and ascertainment were not standardized. Effects on iron indices, inflammatory markers, lipid indices, and cardiovascular outcomes were exploratory. Grading of Recommendations Assessment, Development and Evaluation certainty was low for hemoglobin and low to very low for most secondary outcomes. Available evidence is insufficient to determine the comparative clinical superiority of roxadustat-based over ESA-based strategies in PD because final values were pooled and comparator regimens were heterogeneous. Evidence concerning hemoglobin target attainment, high-density lipoprotein cholesterol, and long-term safety remains insufficient.

Diabetic kidney disease (DKD) is a major cause of chronic kidney diseases. Panoptosis has emerged as a key contributor to renal injury. However, the specific panoptosis-related genes (PRGs) that drive diabetic tubular injury remain unknown. TNFSF10, a known regulator of apoptosis and inflammation, has been linked to podocyte injury in DKD, but its role in diabetic tubular injury remains unknown. To address this, we integrated weighted gene co-expression network analysis, machine learning algorithms, and clinical data from the Nephroseq database to identify PRGs associated with DKD. The biological function of the identified hub gene was further characterized by integrating single-cell and single-nucleus RNA sequencing data with analytical frameworks for cellular communication, trajectory inference, and regulatory network. In this study, we identified TNFSF10 as a conserved and robust hub PRG for DKD. TNFSF10 expression was significantly upregulated in DKD kidneys and inversely correlated with glomerular filtration rate. TNFSF10[high] kidneys exhibited elevated fibrosis and inflammation scores. scRNA/snRNA analysis revealed its predominant expression in injured proximal tubular cells. Importantly, TNFSF10[+] proximal tubular cells showed transcriptomic signatures consistent with panoptosis activation and inflammatory signaling, along with enhanced ligand-receptor interactions with fibroblasts and immune cells. Consistently, TNFSF10 treatment induced cell death and increased the expression of multiple inflammatory genes in vitro. Collectively, our results suggest that TNFSF10 is associated with tubular injury and kidney fibroinflammation in DKD. These exploratory findings suggest it may represent a promising candidate for DKD, and further in vivo functional validation is required to confirm its diagnostic and therapeutic potential.

Renal inflammation and fibrosis are pathological features of various types of kidney diseases. High-salt diet and aldosterone are risk factors for inducing kidney disease. Esaxerenone is the mineralocorticoid receptor blocker which is effective in treating hypertension. The aim of this study is to observe the effect of esaxerenone on renal inflammation in a rat model of high-salt diet plus aldosterone infusion. We found that rats treated with high-salt diet plus aldosterone showed more serious renal pathological injury. As well as, the expression of kidney injury molecule-1, toll-like receptor 4 (TLR4), phospho-nuclear factor kappa-B‌ (p-NF-κB), F4/80, interleukin-6, ‌tumor necrosis factor-alpha, and interferon gamma were increased (p < 0.05). In addition, high-salt diet plus aldosterone could upregulate the expression of transforming growth factor-beta‌ (TGF-β), p-Smad2, p-Smad3, alpha-smooth muscle actin, vimentin, and collagen I (p < 0.05). However, administration of esaxerenone could ameliorate high-salt diet plus aldosterone - induced these expressions and renal pathological injury (p < 0.05). These data suggest that esaxerenone may alleviate high-salt plus aldosterone-induced renal inflammation and fibrosis by regulating the TLR4/NF-κB and TGF-β/Smad signaling pathways.

Peritoneal dialysis (PD)-associated peritonitis is a leading cause of technique failure. We aimed to develop and internally validate a Cox regression‑based nomogram for predicting peritonitis‑free survival in incident PD patients. This single-center retrospective cohort study included 372 patients who underwent peritoneal dialysis between June 2018 and December 2024, with follow-up through December 2025. LASSO‑Cox regression was used to select predictors from 23 candidate variables. A nomogram was constructed to predict 6‑, 12‑, and 24‑month peritonitis‑free survival. Model performance was assessed by concordance index (C‑index), time‑dependent ROC, calibration curves, and decision curve analysis. Over a median follow‑up of 26.3 months, 92 (35.4%) and 34 (30.4%) peritonitis events occurred in the training and validation cohorts, respectively. Nine predictors (education, start age, BMI, hemoglobin, potassium, sodium, albumin, calcium, phosphorus) were retained. Independent predictors were lower education (≤9 vs >9 years: HR 1.93, 95% CI 1.03-3.64), lower hemoglobin (HR 0.99, 0.97-1.00), lower albumin (HR 0.92, 0.87-0.97), and lower phosphorus (HR 0.53, 0.29-0.99). The C‑index was 0.707 (95% CI 0.650-0.765). Time‑dependent ROCs in the training cohort were 75.8%, 77.5%, and 69.7% at 6, 12, and 24 months; in the validation cohort, they were 77.7%, 63.8%, and 58.4%, respectively. Calibration was satisfactory at 6 and 12 months (Brier scores 6.0%-11.1%), with wider clinical net benefit at 12-24 months. This nomogram using nine routinely available variables demonstrated moderate discrimination and satisfactory calibration for predicting peritonitis‑free survival in PD patients. While promising, the model requires external validation in larger, multicenter cohorts to confirm its generalizability before routine clinical use.

This study demonstrates that gamma-aminobutyric acid (GABA) ameliorates diabetic kidney disease (DKD) by modulating macrophage-driven inflammation and podocyte injury through the JAML/FPR2 signaling axis. In streptozotocin (STZ)-induced DKD mice, GABA administration significantly improved renal function by reducing serum creatinine, urea nitrogen, 24-hour urine protein, attenuated glomerular hypertrophy/mesangial expansion, and suppressed pro-inflammatory cytokine production (TNF-α, IL-1β, iNOS) in renal tissue and serum. GABA inhibited glomerular macrophage infiltration (CD68[+] cells) and M1 polarization while mitigating renal apoptosis and podocyte injury by restoring nephrin and podocin. In a high glucose (HG)-stimulated macrophage-podocyte co-culture model, GABA reduced HG-induced podocyte apoptosis in a macrophage ratio-dependent manner by reversing M1 polarization and inflammatory cytokine overproduction. Mechanistically, GABA normalized DKD-elevated JAML expression in renal tissues and podocytes, while JAML overexpression abolished GABA's renoprotective effects by reactivating inflammation, macrophage recruitment, and podocyte apoptosis. Co-IP confirmed JAML interacted with receptor formyl peptide receptor 2 (FPR2), which mediated DKD-driven macrophage infiltration, as FPR2 knockdown abrogated JAML-induced CD68[+] cell accumulation. Collectively, GABA alleviated DKD progression by disrupting the JAML/FPR2 axis to suppress macrophage-mediated inflammation and podocyte injury, highlighting its therapeutic potential for diabetic kidney disease.

Roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, is effective for treating renal anemia, with efficacy noninferior to erythropoiesis-stimulating agents. However, data on its adverse effects remain scarce. In medical practice, roxadustat administration reportedly leads to central hypothyroidism; however, the frequency of its occurrence remains unclear. We investigated thyroid function in patients undergoing dialysis who received roxadustat at Saiseikai Yokohamashi Tobu Hospital, with particular focus on the timing of the decrease in serum thyroid-stimulating hormone (TSH) levels after roxadustat initiation and the subsequent course of thyroid function. HIF-PH inhibitors were administered to 43 chronic kidney disease patients including dialysis. After 2 weeks of roxadustat administration, we extracted the data of 16 hemodialysis patients who exhibited absence of residual urine and were able to undergo blood tests. All patients revealed decreased serum TSH levels. In contrast, changes in serum free triiodothyronine and free thyroxine levels were minor. None of the patients reported fatigue, bradycardia, or constipation, which are common symptoms of hypothyroidism. Our findings revealed that roxadustat may cause TSH reduction after 2 weeks of administration, though some patients showed subclinical hypothyroidism with high TSH levels. In a few cases, TSH levels decreased to one-tenth of the normal values. Despite these rapid changes, none of the patients exhibited clinical symptoms. Hence, regular thyroid hormone level monitoring is necessary with roxadustat administration, regardless of patients' history of thyroid function.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by a 4-hit pathogenesis primarily driven by mucosal immune dysregulation in the gut-associated lymphoid tissue (GALT). However, the specific environmental triggers initiating this cascade remain elusive. We propose a novel hypothesis that chronic exposure to ubiquitous micro- and nano-plastics (MNPs) serves as a primary environmental catalyst for IgAN. Through a proposed 5-step cascade, we outline how ingested MNPs directly degrade intestinal tight junctions, precipitating a 'leaky gut' that permits the synergistic influx of plastics and commensal bacterial antigens into the GALT. Acting as a 'Trojan horse,' MNP-corona complexes evade immune detection but trigger chronic inflammation and B-cell dysregulation upon internalization by phagocytes. This persistent immune stimulation drives the aberrant production of galactose-deficient IgA1. Furthermore, we hypothesize that circulating MNPs co-deposit in the renal mesangium alongside immune complexes, acting as a dual generator of both systemic immune complexes and direct structural kidney injury. This potential gene-environment interaction is supported by the intersecting high prevalence of environmental MNPs and IgAN in Asia. Finally, we delineate future in vivo, observational, and epidemiological investigations required to establish this pathophysiological link.

Automated peritoneal dialysis (APD) is a widely used dialysis modality for patients with end-stage kidney disease (ESKD). However, controversy remains regarding the rate of residual kidney function (RKF) decline between patients treated with APD and continuous ambulatory peritoneal dialysis (CAPD). This study aimed to investigate the effect of peritoneal dialysis modality on the rate of RKF decline in Chinese patients with new-onset ESKD. We conducted a single-center retrospective study to explore the association between PD modalities and RKF decline. A total of 53 patients with new-onset ESKD were enrolled. Of these, 19 patients started with APD and 34 with CAPD. The rates of RKF decline were compared between two groups. Multivariate linear regression was performed to identify risk factors for rapid decline of RKF. Baseline RKF and urine output were comparable between the APD and CAPD groups. At 6 months after PD initiation, RKF was 1.9 ± 1.6 mL/min/1.73 m[2] in the APD group, significantly lower than 3.0 ± 1.7 mL/min/1.73 m[2] in the CAPD group (p = 0.043). The APD group had a significantly faster mean rate of RKF decline (-6.6 ± 2.5 vs. -4.3 ± 2.3 mL/min/1.73 m[2]/year, p = 0.002). In multivariate linear regression adjusted for established risk factors, APD use (vs. CAPD) (β = 0.93; p = 0.004) and baseline RKF (β = 0.38; p < 0.001) were significantly associated with accelerated RKF decline. Our findings indicate that Chinese patients initiating dialysis with APD experience faster RKF decline within the first 6 months compared with those starting PD with CAPD. Furthermore, high baseline RKF is associated with rapid RKF decline.