IgA nephropathy (IgAN) is the most common glomerulonephritis in children. Although exosomes contribute to renal injury, their role in IgAN remains unclear. This pilot study tested whether urinary exosomal C3a normalized to creatinine (uE-C3a/Cr) reflects glomerular injury and activates NF-κB signaling. We enrolled 70 children with IgAN, 43 with other glomerulopathies, and 30 healthy controls. After isolating exosomes, we quantified uE-C3a/Cr and assessed correlations with clinical and pathological parameters. In parallel, IgAN model rats were examined for renal exosomal C3a (rE-C3a), NF-κB phosphorylation, and inflammatory cytokines. In vitro, rat mesangial cells were exposed to patient-derived IgAN exosomes, with or without a C3aR antagonist. uE-C3a/Cr was elevated in IgAN patients, correlating with log24 h-UP (ρ = 0.480, P < 0.001) and Oxford C score (ρ = 0.565, P < 0.001). The AUC for IgAN vs. non-IgAN was 0.637. In follow-up, uE-C3a/Cr decreased in remission patients; at 12 weeks, non-remission patients in the IST group had higher levels than remission patients (P < 0.001). In IgAN rats, rE-C3a was upregulated alongside an enhanced p-p65/t-p65 ratio and elevated MCP-1 and IL-6. Exosomes from IgAN patient urine promoted rat mesangial cell proliferation and enhanced NF-κB phosphorylation and cytokines; these effects were partially reversed by C3aR antagonist. uE-C3a/Cr is not a disease-specific diagnostic marker for IgAN, but may serve as a non-invasive marker for monitoring disease activity and treatment response. Exosomal C3a appears to activate mesangial NF-κB through C3a/C3aR, pointing to C3aR as a therapeutic target in IgAN. Larger cohorts must validate these findings. This study integrates clinical, in vivo, and in vitro evidence. Urinary exosomal C3a appears to reflect renal injury in pediatric IgAN and may activate mesangial NF-κB via C3a/C3aR.
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by cyst formation, kidney enlargement, and extrarenal complications. While the role of genetic mutations in PKD1, PKD2, and other minor genes is well established, the influence of circadian rhythms and sleep disturbances on disease progression remains underexplored. The circadian timing system, coordinated by the central clock in the suprachiasmatic nucleus and synchronized with peripheral clocks in the kidneys, regulates key physiological processes, including glomerular filtration rate (GFR), sodium handling, blood pressure, and hormone secretion. In ADPKD, circadian disruption driven by intrinsic molecular alterations and exacerbated by sleep disorders contributes to sympathetic nervous system activation, renin-angiotensin-aldosterone system (RAAS) dysregulation, and elevated vasopressin levels, all of which accelerate cyst growth and hypertension. Mechanistic links also involve the activation of the mTOR pathway, impaired fatty acid oxidation, and altered gut microbiota composition. These disturbances impair kidney function and increase the risk of cardiovascular disease. Chronotherapy and targeted sleep hygiene interventions offer promising adjunctive strategies for mitigating circadian misalignment in ADPKD. Timed administration of antihypertensives, diuretics, and disease-modifying agents, such as tolvaptan, along with melatonin supplementation, structured light exposure, and optimized physical activity patterns, may enhance therapeutic efficacy and improve quality of life (QoL). Future research should prioritize longitudinal and interventional studies incorporating circadian biomarkers to evaluate the impact of aligning therapeutic interventions with biological rhythms on kidney and cardiovascular outcomes in ADPKD.
The gut-kidney axis is a potential mechanism underlying kidney dysfunction. However, the relationship between chronic kidney disease (CKD) and bowel habit subtypes, especially the coexistence of constipation and diarrhea, remains unknown. We investigated the association of bowel habit subtypes including the no-constipation/diarrhea, constipation-only, diarrhea-only and coexisting constipation/diarrhea groups with new onset of CKD during a 10-year follow-up period in 14,876 Japanese adults (men/women: 9,620/5,256, mean age: 47 years) who underwent annual health examinations. During a median follow-up of 7.0 years, 2,281 participants (men/women: 1,571/710) developed CKD. Multivariable Cox proportional hazards models analysis after adjustment for age, sex and several confounders showed that hazard ratio (HR) for the development of CKD was significantly higher in the coexisting constipation/diarrhea group (HR [95
Dietary intake assessment is necessary for developing appropriate nutritional management aimed at improving patient outcomes. We investigated the association of dietary intake at dialysis initiation, as calculated using data of meal intake rates, with adverse outcomes. Data were collected retrospectively from patients starting hemodialysis (HD) or peritoneal dialysis (PD) during 2016–2018. Dietary energy intake (DEI) and dietary protein intake (DPI) were calculated based on data of nutritional contents of meals provided for patients and meal intake rates recorded by nurses during three days from dialysis initiation. We assessed the association between each of DEI and DPI and primary outcomes: death and hospitalization within 2 years. This study examined 114 patients starting HD or PD, with median age of 72 (72
