Search Results (160)

Background: Fabry disease is a rare X-linked lysosomal storage disorder associated with progressive renal, cardiac, and neurological complications. Enzyme replacement therapy (ERT) has been the standard treatment for more than two decades, but its long-term impact on renal outcomes remains debated. Methods: We conducted a systematic review and meta-analysis of studies reporting renal outcomes in Fabry patients under long-term follow-up, including both ERT-treated and untreated cohorts. Electronic databases were searched up to October 2023. Data were extracted on estimated glomerular filtration rate (eGFR) slope, proteinuria, and clinical events. Random-effects models were used to calculate pooled effect sizes, and subgroup analyses were performed by treatment status and baseline risk factors. Results: Sixteen studies involving 2191 patients were included. Pooled analyses demonstrated a significant decline in eGFR over time across Fabry cohorts. Crucially, baseline proteinuria was identified as a significant prognostic factor; male patients with baseline UPCR > 0.5 g/g experienced a significantly faster decline in eGFR compared to those with UPCR < 0.5 g/g (p = 0.011). While direct comparisons between ERT and non-ERT groups did not consistently reach statistical significance, trends suggested a slower decline in ERT-treated patients, particularly in those with preserved renal function and lower proteinuria. Patients with baseline eGFR < 60 mL/min/1.73 m² had a significantly higher risk of clinical events compared with those with preserved renal function. Conclusions: Fabry patients experience progressive renal decline despite available therapies. Although direct comparisons between ERT and non-ERT groups did not consistently reach statistical significance, our quantitative analysis highlighted baseline proteinuria as a major determinant of renal trajectory. Patients with baseline UPCR > 0.5 g/g exhibited a significantly faster decline in eGFR, emphasizing the importance of early diagnosis and intervention before significant glomerular damage occurs. The limitations of the analysis include the small number of studies, heterogeneity in renal function definitions, exclusion of advanced kidney disease, and methodological constraints related to effect size reporting and risk-of-bias assessment. Full article

Background: Switching stable liver transplant (LT) recipients from twice-daily immediate-release tacrolimus (IR-Tac) to once-daily MeltDose^® extended-release tacrolimus (LCPT) has been proven safe and well tolerated. Moreover, the switch has been associated with enhanced treatment adherence, improvement of tremors, and preserved renal function. Here, we hypothesized that switching to LCPT early after LT may enhance long-term patient outcomes significantly. Methods: This single-center, observational study investigated the long-term safety of LCPT in a large cohort of LT recipients (n = 100). Allograft function, emerging adverse events, the incidence of rejection reactions, renal function, lipid and glucose metabolism, and treatment adherence were assessed over 24 months. Results: In 56% of patients, the switch was conducted within 4 weeks post-transplantation. Adverse events occurred in 90% of patients during the 24-month follow-up, including gastrointestinal complications (28%), neurological symptoms (28%), skin disorders (26%), metabolic disorders (22%), and fatigue (18%). Seven patients (7%) developed renal insufficiency, and five patients (5%) developed renal failure. Three episodes of chronic graft rejection reactions (3%) and a single transplant failure (1%) were observed over 24 months. LCPT was discontinued in 10 patients. Liver and renal function markers, blood lipids (cholesterol and triglycerides), and glucose levels remained stable over the 24-month follow-up. However, 58% of LT recipients had one of their liver function markers elevated at baseline (i.e., before the switch), 28% had low glomerular filtration rate (GFR < 60 mL/min/1.73 m²), and 18% had high serum creatinine (>1.3 mg/dL). In these subgroups, the early switch to LCPT was associated with a significant decrease in liver enzymes (p < 0.001 for alanine transaminase; p = 0.032 for gamma-glutamyl transferase; and p < 0.001 for total bilirubin) and a significant decrease in serum creatinine levels (p < 0.001). Self-reported treatment adherence was good and consistent throughout the study. Conclusions: The early switch from IR-Tac to LCPT was safe and effective in our cohort and may be particularly beneficial for patients with suboptimal liver and renal function following LT. Full article

Background: Cardiometabolic disorders such as hypertension and diabetes are major contributors to chronic kidney disease and often coexist, amplifying dysfunction and metabolic imbalance that favor renal injury and nephrolithiasis. Although pharmacological therapies exist for blood pressure and glycemic control, few target these mechanisms simultaneously. Rosmarinic acid (RA), a polyphenolic compound, exhibits antioxidant, anti-inflammatory, and nephroprotective effects, but its role in combined models of hypertension, diabetes, and nephrolithiasis remains unexplored. Objectives: This study investigated the therapeutic potential of RA in an experimental model combining hypertension, diabetes mellitus, and nephrolithiasis. Methods: Male Wistar spontaneously hypertensive (SHR) and normotensive rats were assigned to eight groups, including controls, comorbid groups, and treatments with RA (10 mg/kg) or hydrochlorothiazide (HCTZ; 5 mg/kg). Diabetes was induced by streptozotocin and nephrolithiasis by ethylene glycol plus ammonium chloride. Hemodynamic, biochemical, oxidative stress, and histological parameters were assessed. Results: SHR exhibited sustained hypertension, further aggravated by diabetes and nephrolithiasis. RA stabilized arterial pressure progression, whereas HCTZ significantly reduced blood pressure. RA and HCTZ treatments decreased urinary calcium oxalate crystal formation by 47.34 and 58.99%, respectively, and partially restored renal morphology. RA restored superoxide dismutase activity, preserved nitrite levels, and reduced lipid peroxidation, indicating antioxidant and endothelial protection. Neither treatment normalized glycemia or fully recovered renal function. Histological analysis showed attenuation of tubular and glomerular alterations in treated groups, particularly with RA. Conclusions: Overall, RA exerted antioxidant, nephroprotective, and antilithogenic effects in this complex comorbidity model, supporting its potential as a complementary therapeutic agent in chronic metabolic and renal disorders. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major metabolic disorder associated with progressive microvascular complications such as nephropathy, retinopathy, and neuropathy. Early detection of diabetic nephropathy (DN) remains challenging, as conventional markers such as urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are influenced by non-renal factors and lack sensitivity for subclinical injury. Sirtuin 2 (SIRT2), a cytoplasmic NAD⁺-dependent deacetylase involved in oxidative stress and inflammatory regulation, has recently been implicated in renal pathophysiology. This study aimed to assess the relationship between serum SIRT2 levels and the presence of diabetic nephropathy and to evaluate its potential utility as a complementary biomarker reflecting early renal injury. Methods: In this single-center, cross-sectional study, 180 participants aged 18–80 years were enrolled: 60 healthy controls, 60 T2DM patients without nephropathy (T2DM − DN), and 60 T2DM patients with nephropathy (T2DM + DN). Serum SIRT2 concentrations were quantified using a validated ELISA. Group comparisons, multinomial logistic regression, and receiver operating characteristic (ROC) curve analyses were performed to assess associations between SIRT2 and renal indices (UACR and eGFR). Statistical significance was set at p < 0.05. Results: Serum SIRT2 concentrations showed a progressive elevation across study groups (p < 0.001), with median levels of 6.13 ng/mL in healthy controls, 8.53 ng/mL in T2DM − DN, and 33.19 ng/mL in T2DM + DN. ROC analysis revealed good diagnostic performance for differentiating DN from healthy controls (AUC = 0.813, sensitivity 75%, and specificity 78.3%). Multivariable regression analysis identified SIRT2 as an independent correlate of DN after adjusting for metabolic and renal covariates (adjusted OR = 1.22, 95% CI 1.11–1.35, p < 0.001). Conclusions: Serum SIRT2 levels were observed to increase in parallel with the presence and severity of diabetic nephropathy and remained independently associated with the condition after adjustment for conventional risk factors. These findings suggest that SIRT2 may serve as a feasible complementary biomarker reflecting renal injury processes not captured by traditional measures. Further longitudinal studies are warranted to clarify its prognostic significance and potential for clinical integration. Full article

Nephrotic syndrome (NS) is a systemic disorder characterized not only by glomerular dysfunction but also by profound dysregulation of lipid metabolism and microvascular integrity. Adipose tissue, as a central lipid-handling and endocrine organ, undergoes structural and functional remodeling in chronic renal conditions yet remains underexplored in this context. The aim of this manuscript is to integrate adipose tissue imaging into the diagnostic and mechanistic framework of NS. To establish this perspective, we first summarize current knowledge on adipose tissue architecture and imaging in both physiological states and renal disease. We then present a multimodal imaging approach—combining ultrasound (US), histology, and atomic force microscopy (AFM)—applied to human adipose tissue as a potential diagnostic and pathophysiological marker in NS. Original imaging from our laboratory experience is presented as a demonstrative material, complemented by literature synthesis. Given that different modalities of imaging-based characterization of adipose tissue are sparse across the literature, this pictorial review offers a guide to identifying structural biomarkers of adipose remodeling in NS. By bridging imaging modalities with metabolic and vascular perturbations observed in NS, this work aims to guide future research toward the clinical application of adipose tissue imaging in renal disease. This provides insights into cell size heterogeneity, vascular topology, and subcellular features such as membrane wrinkles and nanodomain organization. We propose that such morphometric parameters, accessible via minimally invasive biopsies, could serve as surrogate markers of adipose remodeling in nephrotic syndrome. This sets the stage for integrating adipose tissue imaging into the diagnostic and mechanistic evaluation of systemic features in NS. Full article

Aim: Nephrotic syndrome (NS) represents a complex glomerular disorder with significant clinical heterogeneity across pediatric and adult populations. Although glucocorticosteroids have constituted the mainstay of therapeutic intervention for more than six decades, primary treatment resistance manifests in approximately 20% of pediatric patients and 50% of adult cohorts. Steroid-resistant nephrotic syndrome (SRNS) is associated with substantially greater morbidity compared to steroid-sensitive nephrotic syndrome (SSNS), characterized by both iatrogenic glucocorticoid toxicity and progressive nephron loss with attendant decline in renal function. Based on this, the current study aims to develop a robust machine learning (ML) model integrated with explainable artificial intelligence (XAI) to distinguish SRNS and identify important biomarker candidate metabolites. Methods: In the study, biomarker candidate compounds obtained from proton nuclear magnetic resonance (1 H NMR) metabolomics analyses on plasma samples taken from 41 patients with NS (27 SSNS and 14 SRNS) were used. We developed ML models to predict steroid resistance in pediatric NS using metabolomic data. After preprocessing with MICE-LightGBM imputation for missing values (<30%) and standardization, the dataset was randomly split into training (80%) and testing (20%) sets, repeated 100 times for robust evaluation. Four supervised algorithms (XGBoost, LightGBM, AdaBoost, and Random Forest) were trained and evaluated using AUC, sensitivity, specificity, F1-score, accuracy, and Brier score. XAI methods including SHAP (for global feature importance and model interpretability) and LIME (for individual patient-level explanations) were applied to identify key metabolomic biomarkers and ensure clinical transparency of predictions. Results: Among four ML algorithms evaluated, Random Forest demonstrated superior performance with the highest accuracy (0.87 ± 0.12), sensitivity (0.90 ± 0.18), AUC (0.92 ± 0.09), and lowest Brier score (0.20 ± 0.03), followed by LightGBM, AdaBoost, and XGBoost. The superiority of the Random Forest model was confirmed by paired t-tests, which revealed significantly higher AUC and lower Brier scores compared to all other algorithms (p < 0.05). SHAP analysis identified key metabolomic biomarkers consistently across all models, including glucose, creatine, 1-methylhistidine, homocysteine, and acetone. Low glucose and creatine levels were positively associated with steroid resistance risk, while higher propylene glycol and carnitine concentrations increased SRNS probability. LIME analysis provided patient-specific interpretability, confirming these metabolomic patterns at individual level. The XAI approach successfully identified clinically relevant metabolomic signatures for predicting steroid resistance with high accuracy and interpretability. Conclusions: The present study successfully identified candidate metabolomic biomarkers capable of predicting SRNS prior to treatment initiation and elucidating critical molecular mechanisms underlying steroid resistance regulation. Full article

Background/Objectives: Glyphosate-based herbicides (GBHs) are widely used agrochemicals implicated in nephrotoxicity through mechanisms involving oxidative stress, inflammation, and tissue remodeling. Natural peptides such as melittin possess potent anti-inflammatory and antioxidant properties; however, their therapeutic use is limited by instability and toxicity. Nanotechnology-based encapsulation presents a promising approach to overcoming these challenges. Objective: This study aimed to evaluate the protective effects of melittin-loaded chitosan–TPP nanoparticles (MEL-NPs) against glyphosate-induced nephrotoxicity in rats, with emphasis on oxidative, inflammatory, and apoptotic pathways. Methods: Female Wistar rats were divided into four groups: control, glyphosate (5 mg/kg/day, 25 days), glyphosate + free melittin, and glyphosate + MEL-NPs (40 µg/kg, orally, 3 times/week). Renal function biomarkers, oxidative stress parameters (MDA, GSH, SOD, CAT, NO), cytokines (TNF-α, IL-6), and serum protein/iron indices were assessed. Western blotting (Nrf2, NGAL), histopathology (H&E), and immunohistochemistry (Bax) were performed. Nanoparticles were characterized by TEM, FTIR, and UV–Vis spectroscopy. Results: Glyphosate exposure caused renal dysfunction, including elevated plasma urea and creatinine levels, and reduced creatinine clearance, indicating impaired glomerular filtration efficiency, oxidative stress (↑increased MDA, NO; ↓decreased GSH, SOD), and upregulation of pro-inflammatory cytokines. Histology revealed tubular degeneration and inflammatory infiltration, while NGAL and Bax were strongly induced. Nrf2 expression was elevated as a compensatory response. Free melittin partially ameliorated these alterations, whereas MEL-NPs provided superior protection, restoring renal function, normalizing oxidative balance, reducing NGAL and Bax expression, and preserving renal histoarchitecture. Conclusions: Melittin nanoparticles confer robust renoprotection against glyphosate-induced nephrotoxicity in rats by modulating oxidative stress, suppressing inflammation, and regulating Nrf2/Bax signaling. These findings highlight nano-melittin as a promising therapeutic platform for managing herbicide-related renal disorders. Full article

Background: Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD), driven by mechanisms distinct from the general population. Fibroblast Growth Factor 23 (FGF-23), a phosphaturic hormone elevated early in CKD, has been mechanistically linked to left ventricular hypertrophy, vascular dysfunction, and disordered mineral metabolism. This study examines the associations between FGF-23 and key renal, mineral, and cardiovascular parameters and its utility in risk stratification. Methods: We conducted a cross-sectional study of 60 adults with CKD stages 1–5. Serum FGF-23 was quantified using ELISA, alongside measures of iPTH, phosphorus, calcium, and eGFR (Estimated Glomerular Filtration Rate). Cardiovascular evaluation included transthoracic echocardiography and carotid intima-media thickness (CIMT). Associations were analyzed using Spearman correlations, ROC analysis, and multivariable logistic regression. Results: FGF-23 levels were significantly associated with declining eGFR (r = –0.288; p < 0.05), elevated iPTH (Intact Parathyroid Hormone) (r = 0.361; p < 0.05), and serum phosphorus (r = 0.335; p < 0.05). Patients with structural cardiac abnormalities (left atrial enlargement or left ventricular hypertrophy) exhibited higher FGF-23 concentrations (154 vs. 128 pg/mL; p = 0.027). FGF-23 alone predicted high cardiovascular risk with moderate accuracy (AUC 0.70; sensitivity 76%; specificity 67%). A composite model including iPTH and eGFR improved discriminatory power (AUC 0.76). Conclusions: FGF-23 correlates with subclinical cardiovascular remodeling and key mineral abnormalities in CKD. Its integration with iPTH and eGFR enhances cardiovascular risk stratification, supporting its potential as a multidimensional biomarker in early CKD. However, the cross-sectional design and modest correlation strengths limit causal inference and generalizability of the findings. Full article

Diabetic kidney disease (DKD), as one of the most serious microvascular complications of diabetes, is the main cause of end-stage renal disease in the world. Lipid peroxidation plays a crucial role in the development and progression of DKD. Under conditions of high glucose and insulin resistance, renal lipid metabolism disorders result in abnormal accumulation of polyunsaturated fatty acids (PUFAs), which undergo lipid peroxidation via free radical chain reactions to generate reactive aldehydes. These substances not only directly damage the cell structure but can also be used as signaling molecules that activate pathways related to inflammation, fibrosis, and ferroptosis, eventually leading to glomerular sclerosis and tubulointerstitial fibrosis. Natural products have shown considerable application prospects in the treatment of DKD due to their multi-functional properties, including anti-inflammatory, antioxidant, and lipid-metabolism-regulating effects. To elucidate this, we conducted a systematic review of the literature available in electronic databases (including PubMed, Web of Science, and Scopus, and Google Scholar) from January 2000 to May 2025. This study further discusses the therapeutic effect and mechanism of natural products targeting lipid peroxidation in DKD. The results indicate that natural products are promising anti-lipid peroxidation drugs. Further clinical trials will be necessary to verify the safety and effectiveness of these natural compounds in clinical applications, thereby laying the foundation for developing novel treatment strategies for DKD. Full article

Hyperuricemia (HUA) is a metabolic disorder characterized by abnormal purine metabolism within the body. Ampelopsis japonica (Thunb.) Makino has traditionally been utilized in the treatment of various kidney diseases; however, its specific anti-hyperuricemic effects and the underlying mechanisms warrant further investigation. This study investigates the mechanism of action by which A. japonica extract (AJE) addresses HUA using a combination of pharmacology techniques, including network pharmacology and metabolomics. A HUA mouse model was established using potassium oxonate and hypoxanthine. AJE intervention significantly reduced serum uric acid and creatinine levels in HUA mice and markedly decreased glomerular atrophy and renal tubular degeneration. Metabolic profiling revealed distinct metabolic profiles between AJE-intervention and control groups, further demonstrating that AJE corrected disruptions in arginine biosynthesis, purine metabolism, pyrimidine metabolism, and arachidonic acid metabolism. The results of the network pharmacology-based study indicate that AJE can alleviate HUA by modulating the TNF pathway and the Toll-like receptor pathway. The mechanisms of action of AJE in HUA involve the inhibition of xanthine oxidase (XOD) to reduce uric acid synthesis, downregulation of URAT1 and GLUT9 to decrease uric acid reabsorption, and suppression of the TLR4/NF-κB pathway to mitigate inflammation in the HUA mouse model. Therefore, AJE demonstrates significant potential as a therapeutic intervention for HUA and its associated renal complications. Full article

Myalgic Encephalomyelitis (ME) is a complex, multisystem disorder with poorly understood pathophysiological mechanisms. SMPDL3B, a membrane-associated protein expressed in renal podocytes, is essential for lipid raft integrity and glomerular barrier function. We hypothesize that reduced membrane-bound SMPDL3B may contribute to podocyte dysfunction and impaired renal physiology in ME. To investigate this, we quantified soluble SMPDL3B in plasma and urine as a surrogate marker of membrane-bound SMPDL3B status and assessed renal clearance and plasma metabolomic profiles. In a cross-sectional study of 56 ME patients and 16 matched healthy controls, ME patients exhibited significantly lower urine-to-plasma ratios of soluble SMPDL3B and reduced renal clearance, suggesting podocyte-related abnormalities. Plasma metabolomics revealed dysregulation of metabolites associated with renal impairment, including succinic acid, benzoic acid, phenyllactic acid, 1,5-anhydroglucitol, histidine, and citrate. In ME patients, plasma SMPDL3B levels inversely correlated with 1,5-anhydroglucitol concentrations and renal clearance. Multivariable modeling identified the urine-to-plasma SMPDL3B ratio as an independent predictor of clearance. Female ME patients showed more pronounced SMPDL3B alterations, reduced clearance, and greater symptom severity. Non-linear associations between soluble SMPDL3B and lipid species further suggest systemic metabolic remodeling. These findings support soluble SMPDL3B as a potential non-invasive biomarker of renal-podocyte involvement in ME, highlighting sex-specific differences that may inform future therapeutic strategies. Full article

Chronic kidney disease (CKD) is a progressive disorder that is characterized by the gradual loss of kidney function, often leading to end-stage renal failure. Recent research has highlighted the role of gut dysbiosis and its metabolic byproducts in the pathogenesis of CKD, with a particular focus on short-chain fatty acids (SCFAs). SCFAs, including acetate, propionate, and butyrate, are primarily produced by the fermentation of dietary fibers by the gut microbiota and are known for their systemic anti-inflammatory and immunomodulatory properties. In CKD, gut dysbiosis results in a reduction in SCFA-producing bacteria and an increase in uremic toxin-producing microorganisms, contributing to systemic inflammation, oxidative stress, and renal fibrosis. The depletion of SCFAs has been shown to exacerbate glomerular injury, whereas their presence supports integrity of the glomerular barrier and confers protection against damage. These protective effects are mediated by several mechanisms, including the modulation of immune responses, preservation of epithelial barrier function, and activation of specific receptors, such as G protein-coupled receptor 41 (GPR41), GPR43, and GPR109A. The present review provides a comprehensive overview of current understanding of SCFA-mediated pathways in glomerular protection during CKD progression. It highlights the therapeutic potential of targeting the gut–kidney axis to mitigate CKD progression by examining the complex interplay between gut microbiota and disease development, with a particular focus on strategies to protect the glomerular structure and function. Full article

Galectin-3 (Gal-3), a multifunctional protein, plays a pivotal role in a wide range of physiological and pathological processes in the human body. Substantial evidence has linked its overexpression and secretion to the pathogenesis of various conditions, including diabetes mellitus, heart failure, fibrosis, atherosclerosis, and chronic kidney disease. Diabetes mellitus, a persistent metabolic disorder, exerts profound effects on both renal and cardiovascular systems. Contemporary research has investigated a range of various biomarkers aimed at predicting the early onset of renal and cardiac dysfunction in diabetic patients. An early decline in glomerular filtration rate (GFR) may occur even with normal urinary albumin excretion. Given that NT-proBNP concentrations are influenced by GFR, there is a critical need to identify biomarkers capable of detecting early cardio–renal injury in individuals with diabetes. Elevated Gal-3 levels in diabetic patients have been associated with an increased risk of all-cause mortality, cardiovascular disease, and progressive kidney failure and may serve as an indicator of subclinical cardiac and renal dysfunction. Incorporating Gal-3 assessment into clinical practice has the potential to improve diagnostic precision and support personalized management for cardiovascular, renal, and metabolic disorders. This review aims to elucidate the role of Gal-3 as a pivotal biomarker for diagnosis, prognosis, and therapeutic guidance in general in different types of diseases which involve cardio–renal complications. Full article

The neutrophil-to-lymphocyte ratio (NLR) has emerged as a readily accessible, cost-effective biomarker reflecting systemic inflammation. Chronic low-grade inflammation plays a pivotal role in the pathogenesis and progression of metabolic and cardiovascular disorders including chronic kidney disease (CKD), hypertension, diabetes mellitus, and cardiovascular disease (CVD). This review critically evaluates the current evidence on NLR as a prognostic marker across these interconnected conditions. A comprehensive literature search was conducted focusing on clinical and epidemiological studies investigating the association between NLR and CKD, hypertension, diabetes, and cardiovascular outcomes. Mechanistic insights into inflammation-driven pathophysiology and the predictive utility of NLR in disease progression and adverse events were synthesized. Elevated NLR is consistently associated with increased risk and severity of CKD, correlating with glomerular filtration decline, proteinuria, and mortality. In hypertension, higher NLR levels are linked to non-dipper blood pressure patterns, arterial stiffness, and increased cardiovascular risk. Among diabetic patients, NLR correlates with poor glycemic control and vascular complications. In cardiovascular disease, elevated NLR predicts major adverse cardiovascular events (MACE) and all-cause mortality, reflecting underlying immune dysregulation and endothelial dysfunction. Despite promising findings, direct comparisons with established inflammatory biomarkers remain limited, and heterogeneity exists across populations. NLR represents a simple yet powerful inflammatory biomarker with significant prognostic value in CKD, hypertension, diabetes, and cardiovascular disease. Its integration into clinical risk stratification models could enhance personalized medicine approaches. Future research should focus on longitudinal studies, validation in diverse cohorts, and comparative analyses with other inflammatory markers to fully delineate NLR’s clinical utility. Full article

Background and Clinical Significance: Membranoproliferative glomerulonephritis (MPGN) is a rare and heterogeneous pattern of immune-mediated glomerular injury, often associated with infections, autoimmune disorders, or monoclonal gammopathies. Idiopathic cases remain a diagnostic challenge and frequently require empirical immunosuppressive treatment. There is increasing interest in environmental triggers that may activate the immune system in genetically or immunologically predisposed individuals. We report an unusual case of idiopathic immune complex-mediated MPGN with a relapsing course potentially associated with vaccine-induced immune reactivation. Case Presentation: A 35-year-old male with no significant medical history aside from untreated dyslipidemia and active smoking presented with a hypertensive emergency and acute kidney injury (AKI). Laboratory investigations revealed nephrotic-range proteinuria, microscopic hematuria, and reduced estimated glomerular filtration rate (eGFR). Kidney biopsy demonstrated type I immune complex-mediated MPGN with a diffuse endocapillary proliferative pattern and granular subendothelial deposits (IgG+++, C3+++, C1q++). An extensive work-up ruled out secondary causes, supporting a diagnosis of idiopathic MPGN. Immunosuppressive therapy with corticosteroids and mycophenolate mofetil led to a partial clinical response. However, after receiving multiple vaccinations, the patient experienced clinical deterioration. A second biopsy revealed persistent proliferative changes and new deposits of IgM++, C4d++, and both kappa and lambda light chains. This prompted a reintroduction of immunosuppressive therapy, which resulted in subsequent clinical improvement. Conclusions: This case supports the hypothesis that vaccine-induced immune reactivation may serve as a potential trigger for disease relapse in idiopathic MPGN. Clinicians should remain alert to environmental stimuli that may influence disease activity in immune-mediated glomerulopathies. Further research is needed to elucidate the underlying immunopathogenic mechanisms. Full article