Search Results (694)

Membranous nephropathy (MN) and minimal change disease (MCD) are the most common causes of nephrotic syndrome following hematopoietic stem cell transplantation (HSCT), a complication conventionally attributed to chronic graft-versus-host disease (GVHD). Paraneoplastic MCD is well described in lymphoid malignancies but is rarely reported in myeloid neoplasms. We report two cases of biopsy-confirmed MCD presenting as the initial manifestation of acute myeloid leukemia (AML) relapse following allogeneic HSCT. Both patients were White men in their sixties with relapsed/refractory AML who developed nephrotic-range proteinuria and acute kidney injury after matched unrelated donor HSCT without histologic evidence of GVHD. Renal biopsies confirmed MCD in both cases. Corticosteroid therapy was ineffective in halting renal deterioration; renal function improved only after initiation of leukemia-directed therapy, with one patient achieving dialysis independence. These cases highlight a rare paraneoplastic presentation of AML relapse. Nephrotic syndrome due to MCD may signal post-HSCT leukemia recurrence, and evaluation for AML relapse warrants consideration in steroid-refractory cases or those without concurrent GVHD. In such cases, control of the underlying malignancy, rather than escalation of immunosuppression, may be central to renal recovery. Full article

Background/Objectives: Pediatric IgA nephropathy (IgAN) is often considered to have a favorable early course. However, its progression is variable, and the prognostic value of histopathological classifications, such as MEST-C, remains incompletely defined in children. This study aimed to characterize clinicopathological features and the early disease course in pediatric IgAN and to descriptively examine histopathological findings and clinical outcomes. Methods: This retrospective, single-center study included children with biopsy-confirmed IgAN diagnosed between 2016 and 2025. Clinical, laboratory, and histopathological data were collected, and biopsies were assessed using the Oxford MEST-C classification. Follow-up data, including estimated glomerular filtration rate (eGFR), were analyzed descriptively, with follow-up extending from diagnosis to early 2026. Results: Fourteen patients were included, showing heterogeneous clinical presentations. Mesangial hypercellularity was observed in all cases (100%), with frequent endocapillary hypercellularity (78.6%) and segmental sclerosis (57.1%), consistent with a predominance of active lesions. Over a median follow-up of approximately five years, renal function remained stable in 57.1% of patients, declined in 21.4%, and improved in 14.3%, indicating variability in renal function during follow-up and potential reversibility in a subset of patients. One patient (7.1%) developed severe acute kidney injury requiring temporary dialysis, followed by full recovery. Given the descriptive design and limited sample size, no conclusions regarding associations between histopathological findings and renal outcomes can be drawn. Conclusions: Within this small cohort, pediatric IgAN showed variable renal function courses ranging from stability to decline or partial recovery. These findings should be considered descriptive and hypothesis-generating, supporting longitudinal monitoring in larger pediatric cohorts. Full article

Type 2 diabetes mellitus (T2DM) is a major driver of chronic kidney disease and cardiovascular morbidity worldwide. Extracellular vesicles (EVs), particularly exosomes, carry microRNAs (miRNAs) that reflect the pathophysiological state of their parent cells and represent promising non-invasive biomarkers. This review comprehensively examines the diagnostic and mechanistic roles of EV-derived miRNAs in diabetic nephropathy (DN) and cardiovascular diseases (CVDs) associated with T2DM. A PRISMA-guided literature search of PubMed, Scopus, Web of Science, and Embase identified 847 articles published between January 2020 and June 2026, of which 156 studies met the inclusion criteria. Several urinary exosomal miRNAs demonstrated significant diagnostic performance for DN, including miR-4534 (AUC = 0.786), miR-136-5p (sensitivity 72.2%, specificity 78.4%), and miR-142-3p. A meta-analysis of circulating miRNAs in diabetic kidney disease reported a pooled AUC of 0.79. In the cardiovascular setting, exosomal miR-155-5p (AUC = 0.901), miR-15a-3p (AUC = 0.874), and a four-miRNA panel (miR-433-3p/let-7b/miR-30-5p/miR-122-5p; AUC = 0.833) demonstrated strong diagnostic performance for ischemic heart disease and carotid atherosclerosis in T2DM. Mechanistically, key EV-associated miRNAs, including miR-21, miR-192, and the anti-fibrotic miR-29 family, participate in fibrosis, inflammation, oxidative stress, endothelial dysfunction, and cardiac remodeling pathways. EV-derived miRNAs therefore represent highly promising non-invasive biomarkers for the early diagnosis and monitoring of diabetic renal and cardiovascular complications. However, clinical translation requires standardized EV isolation and miRNA detection protocols, together with validation in large multicenter prospective cohorts. This review highlights the considerable diagnostic and translational potential of EV-derived miRNAs for precision medicine and liquid biopsy applications in T2DM complications. Full article

Introduction: Currently, chronic kidney disease (CKD) is detected based on glomerular filtration rate (GFR), proteinuria levels or kidney biopsy. However, the development of MRI techniques and AI algorithms gives hope to the assessment of CKD activity and kidney function with profound MRI image analysis. Methods: MRI images from healthy volunteers with no history of CKD were compared with those from CKD patients who had undergone both kidney MRI and kidney biopsy; the latter group was also divided into two subgroups based on CKD histopathological activity. Patients from both groups were scanned using either a 1.5 T or 3 T MRI scanner following sequential allocation (nine healthy controls and 28 CKD patients and 11 healthy volunteers and 43 CKD patients respectively for each scanner). Results: The final algorithm based on T1-weighted, T2-weighted and DWI images was able to distinguish patients with sensitivity ranging 77.78–87.50%, specificity 86.67–94.12% and precision 77.78–87.50%. Features of T1-weighted images and of T2-weighted images were found to correlate strongly with GFR with coefficients ranging from −0.5922 to −0.7090 and from 0.6126 to 0.6380, respectively. Conclusions: MRI image texture analysis may be suitable for assessing CKD activity, irrespective of the type of MRI scanner used. Furthermore, MRI image texture features correlate with eGFR values. Full article

Background/Objectives: Opportunistic infections remain clinically important after kidney transplantation and may contribute to morbidity and graft dysfunction in pediatric recipients. Data regarding their timing, spectrum and clinical course in children remain limited. Methods: We retrospectively reviewed pediatric kidney transplant recipients followed at a single tertiary center between 2014 and 2024. Demographic and clinical characteristics, infection type, timing after transplantation, management and outcomes were recorded. Infection incidence was assessed at the patient level, whereas pathogen distribution and timing were analyzed per infection episode. Results: Twenty-seven pediatric kidney transplant recipients were included, with a mean follow-up of 5.6 years. Ten patients (37.0%) developed at least one clinically significant opportunistic infection, and one patient experienced two distinct episodes, resulting in 11 infection events. BK virus was the most frequent pathogen, followed by fungal infections and cytomegalovirus (CMV). Five episodes (45.5%) occurred within the first post-transplant year, whereas six (54.5%) occurred later during follow-up. Late infections included CMV, fungal infections, BK virus and West Nile virus. Most infections resolved after targeted management without persistent graft impairment; however, one patient developed biopsy-confirmed BK virus-associated nephropathy with sustained graft dysfunction. No infection-related mortality was observed. Conclusions: Clinically significant opportunistic infections occurred both early and late after pediatric kidney transplantation, with more than half of all infectious episodes developing beyond the first post-transplant year. Although overall outcomes were favorable, BK virus-associated nephropathy remained clinically relevant because of its impact on graft function. Full article

Cardiorenal Syndrome (CRS) types depend on the primary impaired organ, Heart (Types I/II) or Kidney (Types III/IV), and are chronic (Types II/IV) or acute (Types I/III). Type V associates to a systemic disease. Diagnosis of CRS type via biochemical indices (e.g., B-type-natriuretic-peptide (BNP), neutrophil-gelatinase-associated-lipocalin (NGAL)) has not been documented absolutely, until now. Here we used advanced imaging facilities, atomic force microscope (AFM) and scanning electron microscope (SEM) for the biopsy of peripheral blood smears coming from CRS patients, aiming to investigate the possible existence of cellular indices associated with CRS pathology. Standard biochemical and hematological indices were comparatively recorded. Cylindrical micro/nano-metric Vesicles (mnVs) were observed in all CRS patients. In CRS patients with Types III/IV, the AFM/SEM data revealed an increased mnVs population and activated platelets that may represent their potential parent cells. In these patients, increased basic uraemic indices and BNP and NGAL levels were also observed. On the contrary, in patients with CRS Types I/II/V, the AFM/SEM data showed a comparatively smaller mnVs population, accompanied by lower levels of BNP and NGAL. According to our results, a higher mnVs population was observed in CRS Types III/IV, possibly released from platelets. The mnVs population may be associated with basic uraemic indices and increased BNP and NGAL levels. Full article

Background and Clinical Significance: IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory, immune-mediated multisystem disorder that can mimic neoplastic, infectious, or autoimmune conditions. Among its head-and-neck manifestations, IgG4-related dacryoadenitis and sialadenitis, historically referred to as Mikulicz disease, should be distinguished from the classical Mikulicz syndrome, which describes secondary lacrimal and salivary gland enlargement due to other systemic disorders. Renal involvement, most commonly in the form of IgG4-related tubulointerstitial nephritis (IgG4-TIN), is less frequent but carries major prognostic implications because delayed diagnosis may lead to irreversible kidney damage. Case Presentation: A 49-year-old man with no relevant past medical history presented with a 2-year history of intermittent polyuria and foamy urine. Laboratory testing revealed advanced kidney dysfunction, with serum creatinine of 4.2 mg/dL, estimated glomerular filtration rate of 16 mL/min/1.73 m², and proteinuria of 2874 mg/day. Physical examination showed bilateral parotid enlargement, upper eyelid edema, lacrimal gland enlargement, and sicca symptoms, raising suspicion for IgG4-related dacryoadenitis and sialadenitis (Mikulicz disease). Further work-up demonstrated marked eosinophilia, polyclonal hypergammaglobulinemia, and significantly elevated serum IgG4 levels (3180 mg/dL), while infectious serologies and autoimmune studies were negative. Kidney biopsy revealed plasma cell-rich tubulointerstitial nephritis with lymphoplasmacytic and eosinophilic infiltrates, interstitial fibrosis, tubular atrophy, and more than 40 IgG4-positive plasma cells per high-power field, supporting the diagnosis of IgG4-related tubulointerstitial nephritis in the setting of systemic IgG4-RD. Treatment with prednisone followed by mycophenolate mofetil led to improvement in glandular manifestations and a partial reduction in proteinuria, but renal recovery remained incomplete. The patient subsequently developed a severe pulmonary infection complicated by sepsis and oligoanuric acute kidney injury superimposed on chronic kidney disease, and ultimately progressed to end-stage kidney disease requiring chronic maintenance hemodialysis. Conclusions: This case highlights that a Mikulicz disease phenotype may represent the initial manifestation of systemic IgG4-RD and should prompt evaluation for extraglandular involvement, particularly renal disease. In patients with glandular enlargement, eosinophilia, hypergammaglobulinemia, and unexplained renal dysfunction, IgG4-RD should be actively considered. Kidney biopsy remains essential for diagnostic confirmation and prognostic assessment, as delayed recognition may result in irreversible renal damage and progression to end-stage kidney disease. Full article

Acute renal allograft rejection (AR) is immune-mediated. Recent evidence highlights some microRNAs as immune modulators. Few and conflicting studies have studied the impact of the MIR146A gene single-nucleotide polymorphism rs2910164 (C>G) on AR. We explored the association of rs2910164 with AR in a single-center cohort of 533 kidney transplant recipients (KTRs) by genotyping cases with biopsy-proven late AR (AR group, n = 35) and matched control KTRs without AR (non-AR group, n = 60). Genotyping was performed with real-time PCR. Multivariable logistic regression and Firth penalized logistic regression, as a sensitivity analysis, were used to adjust for confounding factors. Donor–recipient age difference was significantly higher in the AR group than in the non-AR group (23.37 ± 11.29 vs. 14.83 ± 10.54, p < 0.001). Recipient mean age in the AR group is lower than in the non-AR group (27.51 ± 10.34 vs. 32.83 ± 9.76 years, p = 0.014), while the opposite is observed with the donor mean age (49.57 ± 10.37 vs. 43.27 ± 10.27 years, p = 0.005). AR was associated with preformed donor-specific antibodies (DSAs) (45.7% vs. 8.3%, p = 0.000, OR = 9.263, 95% CI (2.988–28.720)), and with two HLA-A* mismatches (17.1% vs. 3.3%, p = 0.048, OR = 6.000, 95% CI (1.139–31.595)). Moreover, post-transplant viral infections, particularly with CMV and SARS-CoV-2, were associated with AR (p < 0.05). However, rs2910164 was not associated with AR across all the tested genetic models (p > 0.05). Our study provides population-specific negative association data on rs2910164 and AR. Larger multicentric studies and future meta-analyses are needed to clarify whether any effect is modest or context-dependent. Full article

Background: Distinguishing diabetic nephropathy (DN) from non-diabetic kidney disease (NDKD) in patients with diabetes remains clinically challenging, particularly when renal biopsy is not routinely performed. We aimed to identify clinical predictors of biopsy-proven NDKD. Methods: We conducted a retrospective cohort study of patients with type 2 diabetes who underwent native kidney biopsy at a tertiary referral center. Patients were classified as DN alone, mixed DN with NDKD, or pure NDKD. Baseline clinical and laboratory variables were analyzed. Logistic regression models were used to identify factors associated with NDKD. Results: Among 664 patients, 18.7% had DN alone, 27.0% had mixed lesions, and 54.3% had pure NDKD. In multivariable analysis, higher HbA1c, lower body mass index, lower low-density lipoprotein cholesterol, and higher urine albumin-to-creatinine ratio were independently associated with NDKD. For pure NDKD, lower HbA1c, lower serum albumin, lower body mass index, higher IgA levels, and absence of hypertension were significant predictors. Conclusions: NDKD is common among patients with diabetes undergoing biopsy and can be partially predicted using routinely available clinical parameters. These findings may aid in identifying patients who could benefit from timely renal biopsy and individualized management. Full article

Background: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Conventional clinical markers of renal function lack sufficient sensitivity for early diagnosis, whereas renal biopsy is unsuitable for routine monitoring because of its invasiveness. Objective: This narrative review aimed to evaluate recent advances in novel, non-invasive multimodal magnetic resonance imaging (MRI) biomarkers for the assessment of renal pathological alterations in DKD. Recent findings: Recent studies have demonstrated that multimodal MRI can non-invasively characterize several key pathological features of DKD, including renal hypoxia, microvascular dysfunction, ectopic fat deposition, and interstitial fibrosis. Furthermore, emerging evidence suggests that these imaging biomarkers may enhance risk stratification, monitor disease progression, and assess treatment efficacy, particularly in the presence of comorbidities and the advent of emerging therapies. Conclusions: Multimodal MRI shows considerable promise in translating advanced imaging biomarkers into clinical practice, facilitating the personalized management of DKD. However, future research must focus on establishing standardized imaging acquisition and analytical protocols, conducting prospective cohort studies to validate the association between imaging biomarkers and hard clinical endpoints, integrating artificial intelligence for automated analysis, and developing molecular imaging probes targeted at early disease pathways. Full article

Immune checkpoint receptors (ICRs) play a pivotal role in modulating antitumor immunity and have become central targets in the immunotherapy of genitourinary (GU) malignancies. This review provides a comprehensive overview of the fundamental mechanisms of ICR signaling, the expression and pathophysiological roles of these receptors in GU cancers (kidney, bladder, prostate, testicular, and penile), and the evolving therapeutic landscape. Key ICRs, including PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT, orchestrate complex signaling cascades that can lead to T-cell exhaustion and tumor immune evasion. Their expression varies significantly across GU cancer types, histological subtypes, and tumor stages, influencing prognosis and therapeutic response. Immune checkpoint inhibitors (ICIs) reinvigorate antitumor immunity by disrupting these inhibitory pathways and remodeling the tumor microenvironment (TME); however, resistance mechanisms (primary, adaptive, and acquired) and immune-related adverse events (irAEs) pose significant clinical challenges. Established biomarkers such as PD-L1 expression, tumor mutational burden (TMB), and microsatellite instability (MSI)/deficient mismatch repair (dMMR) status guide ICI use, but their predictive power has limitations. Consequently, emerging tissue-based (e.g., immune cell signatures, multiplex IHC/IF, spatial transcriptomics), liquid biopsy-based (e.g., ctDNA, CTCs, exosomes), and imaging-based (radiomics, AI-driven analysis) biomarkers are under active investigation to refine patient selection and monitor treatment efficacy. The therapeutic armamentarium is rapidly expanding with novel ICIs targeting new receptors, bispecific antibodies, and innovative combination strategies involving ICIs with chemotherapy, targeted therapies, radiotherapy, and other immunotherapies. Furthermore, ICIs are increasingly explored in neoadjuvant, adjuvant, and maintenance settings. This review highlights the dynamic progress in understanding ICR biology and its clinical translation, emphasizing the ongoing efforts to develop more personalized and effective immunotherapeutic strategies for patients with genitourinary tumors. Full article

Background: Crohn‘s disease (CD) is frequently complicated by extraintestinal manifestations, including axial spondyloarthritis (axSpA). Both diseases share genetic (HLA-B27, IL23R, ERAP1/2) and immunopathological mechanisms (Th17/IL-23 axis). Their co-occurrence increases the risk of systemic complications such as AA amyloidosis. Case presentation: We report a 42-year-old male with HLA-B27-positive axSpA who developed CD shortly after initiating secukinumab (IL-17A inhibitor). Following discontinuation of secukinumab and surgical management of CD, the patient experienced rapidly progressive AA amyloidosis affecting the kidneys and intestines, leading to acute kidney injury and requiring hemodialysis. Potential triggering factors included a preceding intestinal infection and self-administered infrared physiotherapy. Conclusions: Coexistent CD and axSpA significantly increases the risk of severe AA amyloidosis. IL-17 inhibitors should be used with extreme caution in patients with subclinical or active CD. Early screenings for proteinuria and low-threshold biopsy are essential to detect AA amyloidosis. In patients with both conditions, TNF-α or IL-12/23 inhibitors are preferred over IL-17 blockade. Full article

Diabetic kidney disease (DKD) lacks specific biomarkers reflecting the interplay between mitochondrial dysfunction and immune microenvironment remodeling. To address this, we integrated multi-dataset transcriptomics (GEO, MitoCarta 3.0, GeneCards) with Weighted Gene Co-expression Network Analysis, protein–protein interaction networks, and machine learning algorithms to identify key diagnostic genes. Single-nucleus RNA sequencing was utilized to map cell-type distributions. Subsequently, a single-center cohort of 70 biopsy-confirmed DKD patients was enrolled for validation of the key hub gene, HDAC6. We identified four hub genes: EGF (downregulated), HDAC6, TPM1, and VCAM1 (upregulated). All genes exhibited robust diagnostic efficacy, and single-nucleus analysis revealed distinct renal cell-type enrichment patterns. Clinically, high renal HDAC6 expression correlated with severe interstitial inflammation, elevated complement C3 and cystatin C, and reduced urinary ammonium (a clinical proxy for proximal tubular mitochondrial dysfunction). Crucially, high HDAC6 served as an independent risk factor for both renal endpoints and cardiorenal composite events. In conclusion, EGF, HDAC6, TPM1, and VCAM1 are key regulators in DKD. Specifically, intrarenal HDAC6 quantification serves as a precise histological metric for prognostic stratification and underscores its potential as a therapeutic target for DKD intervention. Full article

Background/Objectives: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE); it is associated with increased morbidity and mortality, underscoring the need for new diagnostic markers and therapeutic strategies. In this context, the exostosin 1 (EXT1)/exostosin 2 (EXT2) heterodimer has emerged as a novel antigen in membranous nephropathy associated with SLE. This study evaluated EXT1 prevalence in renal biopsies from patients with lupus membranous nephropathy (LMN) and compared clinical, laboratory, and histopathological characteristics on diagnosis and renal outcomes. Methods: This retrospective study included 97 LMN patients whose renal biopsy underwent immunohistochemistry (IHC) for EXT1. EXT1-positive and EXT1-negative groups were compared using descriptive analyses and repeated measures models. Results: EXT1 positivity was observed in 35% of the cohort, and is more frequent in pure LMN (40%) than in cases with a proliferative component (32%). Regarding SLE diagnostic criteria, EXT1-positive patients showed a higher frequency of antiphospholipid antibodies, although data were available for only a subset of patients. This group also exhibited lower serum creatinine levels, but without statistical significance. EXT1-negative patients more frequently received cyclophosphamide as induction therapy (57.6% vs. 34.5%; p = 0.041). No differences in clinical outcomes were observed during follow-up. Conclusions: EXT1 prevalence was consistent with the literature, reinforcing the epidemiological reproducibility of this marker. EXT1-positive and EXT1-negative groups did not differ regarding clinical presentation, disease progression, and renal outcomes, heightening the need for prospective studies to further elucidate the diagnostic and prognostic role of EXT1 in LMN. Full article

Background: Early external validation studies demonstrated the robust and consistent predictive performance of the International IgA Nephropathy Prediction Tool (IIgAN-PT) across diverse ethnic populations. However, emerging evidence suggests that, in contemporary cohorts of patients with IgA nephropathy, the IIgAN-PT increasingly tends to overestimate the risk of adverse renal outcomes. Subclassification of segmental glomerulosclerosis (S lesions) in the Oxford Classification system (MEST-C) could identify high-risk IgAN patients, with evidence that different S subclassifications respond differently to treatment. Our study aimed to evaluate the predictive performance of the IIgAN-PT in a contemporary Chinese external validation cohort and to optimize its prognostic accuracy by incorporating the most severe and prevalent pathological subclassification of S lesions, NOS⁺Adh⁺, into the original model. Methods: A total of 746 Chinese patients were included with biopsy-proven IgAN in this study. Major adverse kidney events (MAKEs) were defined as death from any cause, initiation of renal replacement therapy, or a 50% decline in eGFR. This study evaluated the discrimination and model fit of three predictive models. The performance of the original and modified IIgAN-PT models was compared and evaluated through reclassification, survival analysis, calibration, decision curve analyses and subgroup analyses. Results: In the study cohort, the median follow-up duration was 4.2 years, during which 77 patients experienced MAKEs. The discriminative ability of the three original models was relatively limited. In contrast, the modified IIgAN-PT incorporating the NOS⁺Adh⁺ subtype of S subclassification demonstrated improved global performance for predicting 5-year risk, achieving a C-index of 0.808 (95% CI, 0.756–0.861). Kaplan–Meier survival curves showed clear risk stratification, particularly between low- and intermediate-risk categories. Reclassification analyses (continuous NRI and IDI) and decision curve analysis further supported enhanced predictive performance, while calibration curves corrected the original model’s risk overestimation. The modified model maintained stable performance across clinically relevant subgroups, including patients with hypertension, proteinuria, or receiving immunosuppression. Conclusions: This study further confirms the independent and clinically relevant prognostic value of the S pathological subclassification. The modified IIgAN-PT model, incorporating the NOS⁺Adh⁺ subtype of S subclassification, demonstrated consistent performance in individualized risk assessment for patients with IgA nephropathy. Full article