Search Results (672)

Background and Clinical Significance: Chromothripsis represents a catastrophic genomic event in plasma cell myeloma (PCM) associated with poor prognosis. We report a case of newly diagnosed PCM with complex cytogenetic abnormalities indicative of genomic instability. Case Presentation: A 67-year-old man presented with acute dyspnea and was found to have severe acute kidney injury, anemia, hypercalcemia, and IgG lambda monoclonal gammopathy. Bone marrow biopsy revealed plasma cell infiltration. Comprehensive FISH analysis demonstrated a complex pattern with gain of 1q, monosomy 13, and multiple numeric and structural abnormalities affecting chromosomes 5, 9, and 15, suggestive of a chromothripsis-like pattern. Despite requiring hemodialysis, the patient achieved complete renal recovery and >99% reduction in serum-free light chains after one cycle of CyBorD plus daratumumab, which was continued for four cycles. Follow-up bone marrow evaluation at three months confirmed complete histologic, flow cytometric, and cytogenetic remission, allowing for preparation for autologous stem cell transplantation. Conclusions: This case demonstrates that exceptional clinical responses can be achieved in high-risk disease with contemporary quadruplet regimens. While the long-term durability of such responses in genomically unstable cases remains uncertain, this case highlights the importance of comprehensive cytogenetic characterization to identify and monitor genomic instability in PCM. Full article

Chronic kidney disease (CKD) represents a growing medical, diagnostic and social challenge, and it is estimated to effect 8.5–9.8% of the global population and requires expensive modes of treatment, such as hemodialysis or renal transplants. Currently, a diagnosis of CKD is set based on the level of creatinine in the blood, which is the gold standard of renal function diagnostics. Unfortunately, decrease in GFR is secondary to damage of the kidney parenchyma and indicates that the best time to start more aggressive treatment has already passed. Therefore, several non-invasive methods have been proposed for predicting increased risk of CKD progression; however, in most of the cases kidney biopsy is essential. Currently, the greatest hopes for a method that can confirm CKD are associated with the development of MRI, the most tissue-specific imaging method, and it is already proven to be capable to detect inflammatory and edematous changes, fibrosis, as well as perfusion and oxygenation disturbances. Therefore, in our manuscript we decided to present up-to-date knowledge about kidney MRI from a clinical point of view. Full article

Chronic kidney disease is rising worldwide, and kidney transplantation remains the preferred modality of kidney replacement therapy. However, long-term graft survival continues to be limited by chronic alloimmune injury, particularly antibody-mediated rejection (ABMR) and its chronic active form. This narrative review synthesizes contemporary evidence on the immunopathogenesis, epidemiology, diagnosis, and management of kidney allograft rejection, with a deliberate focus on studies from the last five years and on United States and European cohorts. We summarize current concepts of T cell–mediated rejection (TCMR), ABMR, mixed and donor-specific antibody (DSA)–negative phenotypes, and the evolution of the Banff classification, highlighting how chronic active ABMR has emerged as a leading cause of death-censored graft loss. We then critically appraise the conventional diagnostic triad of creatinine/eGFR, DSA, and biopsy and review emerging tools, including donor-derived cell-free DNA, urinary chemokines such as CXCL9 and CXCL10, additional blood- and urine-based biomarkers, and biopsy transcriptomics. We also examine how artificial intelligence and machine learning may support digital pathology, multimodal risk prediction, and data integration, while recognizing the current challenges of biological interpretability, external validation, and clinical implementation. Finally, we propose a rejection-focused precision-medicine framework and outline key research gaps, including multicenter validation, trial-ready endpoints, and governance for AI-enabled pathways. Overall, the field is moving from isolated diagnostic signals toward integrated, biologically informed, and clinically actionable approaches to rejection detection and risk stratification. Full article

RCC remains a therapeutically challenging malignancy, particularly in its metastatic stage, in which treatment resistance and limited response durability persist despite recent advances in immunotherapy and targeted therapies. Although immune checkpoint inhibitors (ICIs) have significantly improved outcomes for a subset of patients, reliable prognostic and predictive biomarkers to guide therapy selection are still lacking. Current clinical models, such as the International Metastatic RCC Database Consortium (IMDC) risk score, offer only limited insight into the molecular and immunologic complexity of RCC. Emerging molecular biomarkers implicated in resistance mechanisms reflect the underlying heterogeneity of RCC and may inform future therapeutic strategies. Kidney Injury Molecule-1 (KIM-1), a transmembrane protein that is up-regulated in RCC and detectable in circulation, has demonstrated potential as a non-invasive biomarker for diagnosis, prognosis, and treatment monitoring. Liquid-biopsy approaches, including the analysis of circulating tumour DNA (ctDNA), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), are also gaining traction due to their minimally invasive nature and potential for real-time disease monitoring. This review aims to provide a structured overview of emerging biomarkers in metastatic RCC, critically evaluate their current clinical applicability, and propose a biologically informed framework for their integration into clinical decision-making. In addition, we propose a conceptual IMDC-Plus framework that integrates clinical, biological, and early dynamic markers to improve risk stratification in the era of immunotherapy (IO). Full article

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) represents a dynamic and multistage pathological process driven by maladaptive intercellular communication. Rather than resulting from isolated cellular injury, AKI-CKD progression unfolds through a spatially and temporally coordinated dysregulation of cellular networks. In the acute phase, damaged tubular epithelial cells act as instigators, releasing damage-associated molecular patterns (DAMPs) and activating a storm of inflammatory crosstalk among immune cells, endothelium, and fibroblasts. During the subacute repair phase, imbalance in macrophage polarization (M1 persistence/M2 dysfunction) and the emergence of senescent tubular cells with a senescence-associated secretory phenotype (SASP) together create a pro-fibrotic microenvironment. In the chronic phase, activated myofibroblasts—derived from multiple sources—establish self-sustaining feedback loops via autocrine signaling, mechanical memory from the stiffened extracellular matrix (ECM), and ongoing dialogue with immune and resident cells, ultimately leading to irreversible fibrosis. Current therapeutic strategies focused on single molecular targets often fail to disrupt this resilient network homeostasis. Therefore, we propose a paradigm shift toward spatiotemporally precise network-remodeling therapies, which require integrated use of liquid biopsy-based staging, smart nanocarriers for cell-specific delivery, and AI-powered multi-omics modeling. This review systematically delineates the evolving cell-to-cell communication networks across AKI-CKD continuum and highlights innovative strategies to intercept disease progression by targeting the pathophysiology of cellular crosstalk. Full article

Background: Hypothermic machine perfusion (HMP) has been associated with reduced delayed graft function compared with static cold storage (SCS). However, the molecular mechanisms underlying these differences during cold preservation remain incompletely understood. This study compared cold-storage-related biochemical and histological changes in kidneys preserved by HMP versus SCS using a Lewis rat model prior to transplantation. Methods: Following isolation, rat kidneys were flushed with cold saline (4 °C). Left kidneys were preserved by HMP at constant flow using Belzer’s machine perfusion solution (MPS) at 4 °C, while right kidneys were stored using SCS in University of Wisconsin solution at 4 °C. After four hours of preservation, kidneys were processed for biochemical and histological analysis. Fresh biopsies were evaluated for mitochondrial complex respiration. Western blotting was performed to assess expression of NDUFS3, a complex I subunit. Histological staining for nitrotyrosine and kidney injury markers was compared across groups. Results: Mitochondrial complex respiration did not differ significantly between the SCS and HMP groups. Western blot analysis demonstrated significantly increased NDUFS3 expression in HMP-preserved kidneys compared with SCS and control kidneys. Histological evaluation revealed elevated tubular staining of nitrotyrosine and kidney injury markers in SCS kidneys relative to controls, whereas HMP preservation markedly attenuated these increases. Conclusions: HMP mitigates cold-storage-induced oxidative stress and reduces expression of kidney injury markers after four hours of preservation. These molecular findings suggest a protective effect of HMP during cold preservation. Future studies with longer preservation times and transplantation models are needed to determine whether these improvements translate into enhanced post-transplant kidney function. Full article

Decisions regarding the use of adjuvant systemic therapy in genitourinary (GU) malignancies—including bladder, kidney, and prostate cancers—are currently driven by clinicopathologic risk factors, which incompletely capture individual risk of residual disease. Consequently, patient selection for adjuvant treatment remains imprecise, leading to both overtreatment of cancers unlikely to recur and undertreatment of those with occult residual disease. Circulating tumor DNA (ctDNA), a minimally invasive liquid biopsy biomarker for minimal residual disease, has emerged as a promising tool to refine adjuvant treatment decision-making. Detection of ctDNA reflects persistent tumor-derived genomic material and often precedes radiographic recurrence, whereas ctDNA negativity is consistently associated with favorable oncologic outcomes. In this review, we summarize the evolving evidence supporting the use of ctDNA to guide adjuvant therapy decisions in bladder, kidney, and prostate cancers. This is not a comprehensive review on all of the potential applications of ctDNA in these malignancies. Rather, we aim to highlight disease-specific, adjuvant-guiding applications, including post-neoadjuvant and post-cystectomy decision-making in bladder cancer and emerging proof-of-concept data in renal cell carcinoma, and explore the potential application of ctDNA in the post-prostatectomy setting. Collectively, these data suggest that ctDNA may enable a paradigm shift toward biologically informed escalation and de-escalation of adjuvant therapy across GU malignancies, while underscoring the need for prospective validation in biomarker-driven clinical trials. Full article

Background and Objectives: Rituximab, a monoclonal antibody targeting CD20+ B-cells, is used in autoimmune diseases and B-cell malignancies. Recently, rituximab has been used as an induction agent in kidney transplantation. Our study evaluates the efficacy of rituximab induction on biopsy-proven acute rejection (BPAR), patient survival, and graft survival in ABO-compatible patients. Materials and Methods: A systematic literature search was performed across five databases, following PRISMA guidelines, and the protocol was registered in PROSPERO (CRD42024603984). The inclusion criteria consisted of randomized controlled trials (RCTs), exploring the impact of rituximab induction on eligible kidney transplant recipients with BPAR, graft, and patient survival as the primary outcomes. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by the random-effects model. The risk of bias was assessed via the Cochrane ROB-2 tool across five domains. Results: From an initial 859 potentially relevant studies, three RCTs, including 454 patients, met the inclusion criteria. At 6 months, rituximab was associated with a non-significant reduction in the risk of BPAR (RR 0.76; 95% CI, 0.50–1.15; I² = 0%). Similarly, patient survival remained unchanged at 6 months (RR 1.01; 95% CI, 0.98–1.04; I² = 0%). Due to significant heterogeneity, long-term outcomes were assessed using narrative synthesis, which revealed no additional benefit for rituximab in terms of graft or patient survival. Furthermore, potential safety concerns—especially in terms of infection risk—were noted. The certainty of this evidence was low, due to clinical heterogeneity in the included studies causing very serious indirectness. Conclusions: Induction with rituximab provides no significant benefit over standard regimens. Thus, its routine use in ABO-compatible renal transplants may not be justified. The available evidence is of low certainty. Further trials are needed before drawing a firm conclusion and to determine the best dosage, timing, and combinations. Full article

Chronic kidney disease (CKD) is a major global health burden leading to a loss of kidney function via podocyte damage, a non-regenerative renal cell type. Early detection of podocyte injury is crucial but remains limited, highlighting the need for non-invasive biomarkers. Therefore, we analysed urinary exosomal microRNAs (miRNAs) in relation to podocyte morphology in biopsies from 65 CKD patients, including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and healthy controls. Global profiling distinguished CKD patients from controls, with miR-606 consistently upregulated and miR-431 downregulated. In podocytopathies, MCD displayed a predominantly suppressed miRNA profile, with miR-141, miR-429, and miR-660 as key candidates, whereas FSGS exhibited elevated miR-181c, miR-3610, miR-663b, miR-4651, and miR-429. Super-resolution morphometry revealed diffuse foot process effacement in MCD and heterogeneous, focally disrupted architecture in FSGS, providing a structural context for the molecular findings. Regression analyses linked these miRNAs to filtration slit density and length, proteinuria, and 25-Hydroxy-vitamin-D3 levels, integrating molecular, structural, and clinical readouts. These results define a coherent miRNA signature of podocyte injury that distinguishes CKD entities and correlates molecular changes with disease severity. Combining urinary exosomal miRNAs with morphometric analysis facilitates early, non-invasive identification of podocyte damage, enabling earlier therapeutic intervention in podocytopathies. Full article

Background/Objectives: Kidney injury is a frequent complication of multiple myeloma (MM) and monoclonal gammopathies. Podocyte stress markers, such as urinary nephrin and podocin, have been studied in other renal diseases but their utility in paraprotein-related kidney disease remains unclear. This pilot study investigated the association of urinary nephrin and podocin levels with albuminuria and biopsy-proven podocytopathy in patients with paraprotein-related diseases. Methods: We retrospectively analyzed 75 patients with plasma cell dyscrasias, including MM and MGRS, along with 11 healthy controls. Urinary podocin and nephrin mRNA levels were measured using qPCR, and urinary podocin protein levels were quantified via ELISA. Associations were assessed between these biomarkers and urinary protein-to-creatinine ratio (uPCR), albumin-to-creatinine ratio (uACR), and histologically confirmed podocytopathia. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Results: Higher urinary podocin protein levels were significantly associated with lower uACR (p = 0.007) and uPCR (p = 0.026). Neither podocin nor nephrin mRNA showed significant associations with proteinuria metrics. ROC analysis indicated that podocin ELISA (AUC = 0.350) and podocin mRNA (AUC = 0.510) lacked diagnostic accuracy for predicting renal involvement. The presence of urinary tract infection (UTI) was a significant confounder, leading to increased levels of podocin and nephrin mRNA. Conclusions: Urinary podocin shows a trend toward elevation in MM/MGRS patients with histological podocyte injury. The study revealed an unexpected inverse association between urinary podocin and albuminuria, suggesting complex release kinetics or stage mismatches in this population. Given the confounding effect of UTIs, and the pilot nature of this study, further research is required to validate these podocyte proteins as biomarkers in paraprotein-related kidney disease. Full article

Background: The etiopathogenesis of juvenile systemic lupus erythematosus (JSLE), a complex and complicated illness, is unknown. Genetic, environmental, and dysregulated immune system responses are all thought to contribute to the disease’s etiology. Important immunological molecules that regulate different immune cells and are associated with autoimmune disorders are TNFSF4 and IKZF1. Thus, our purpose was to discover if TNFSF4 and IKZF1 mutations left the Egyptian population genetically predisposed to SLE. Methods: Using real-time polymerase chain reaction (RT-PCR), polymorphism analysis of the TNFSF4 rs1234315 C/T and IKZF1 rs11980379 C/T genes was performed on extracted DNA from JSLE patients and healthy controls. Results: TNFSF4 frequencies (rs1234315 T allele, CT, TT genotypes, dominant and recessive models) were substantially associated with a higher incidence of JSLE (p < 0.05) compared to healthy controls. Conversely, IKZF1 frequencies (rs11980379 T allele, TC, TT genotypes, and dominant model) significantly correlated with a lower incidence of JSLE. Furthermore, the TC + CC rs11980379 genotype was identified as significantly associated with lower kidney biopsy grades and a lower incidence of lupus nephritis. Conclusions: Our findings suggest that TNFSF4 and IKZF1 polymorphisms affect vulnerability to juvenile SLE. Full article

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease in which renal involvement is a major determinant of prognosis and is classically dominated by amyloid A (AA) amyloidosis. Non-amyloid renal manifestations are uncommon and poorly characterized. We report a case of clinically overt FMF associated with anti-phospholipase A2 receptor (PLA2R) antibody-positive membranous nephropathy (MN). A 46-year-old man with recurrent febrile episodes fulfilling Tel Hashomer criteria for FMF developed progressive proteinuria with detectable anti-PLA2R antibodies. Genetic testing identified a heterozygous missense MEFV variant in exon 10 (p.Lys695Arg), a mutation with variable penetrance and conflicting pathogenic classification. Kidney biopsy demonstrated PLA2R-positive MN, excluding amyloidosis. After initial conservative management, the patient progressed to nephrotic syndrome complicated by renal vein thrombosis, requiring immunosuppressive therapy according to the Ponticelli regimen in addition to colchicine and anticoagulation, resulting in clinical and immunological remission. In parallel, we performed a systematic review of the literature, identifying only isolated reports of biopsy-proven MN in FMF patients. This case highlights the diagnostic importance of kidney biopsy in FMF patients with proteinuria and illustrates that immune-mediated glomerular disease may occur even in association with non-founder or variably penetrant MEFV mutations, requiring disease-specific management beyond standard autoinflammatory control. Full article

Background and Clinical Significance: Sarcoidosis is a systemic inflammatory disorder characterized by noncaseating granulomas. While pulmonary involvement is common, isolated renal involvement is rare and diagnostically challenging. We report a case emphasizing the utility of urinary tubular markers for early detection. Case Presentation: A 60-year-old woman with a history of suspected ocular sarcoidosis presented with progressive renal impairment and constitutional symptoms. Initial workup for systemic sarcoidosis was negative, leading to a misdiagnosis of chronic fatigue syndrome. Her rising serum creatinine was initially attributed to dehydration. However, a marked elevation in urinary β2-microglobulin (33,736 μg/L) prompted a renal biopsy, which revealed granulomatous tubulointerstitial nephritis. Following prednisolone therapy, her renal function improved, and her fatigue resolved completely. Conclusions: This case demonstrates that the kidney can be the primary site for histological diagnosis in the absence of pulmonary lesions. Incorporating urinary β2-microglobulin into routine monitoring may facilitate the early detection of renal sarcoidosis, preventing diagnostic delays. Full article

According to the Global Burden of Disease 2019 analysis, there were 606,300 new cases of chronic kidney disease due to glomerulonephritis worldwide, with 17.3 million prevalent cases and 183,700 deaths More interestingly, between 1990 and 2019, the global burden of glomerulonephritis increased by 77% in incidence and 81% in prevalence, mainly due to demographic aging and population growth. Among primary glomerulopathies, IgA Nephropathy (IgAN), also known as Berger’s disease, is the most common primary glomerulopathy worldwide, with significant geographic and ethnic variation in incidence, with the highest prevalence in Europe and Asia and the lowest in Africa. Its pathogenesis reflects a complex interaction between polygenic susceptibility and environmental modifiers, mucosal immune activation, infections of the upper respiratory and gastrointestinal tracts, dietary factors, and alterations in the gut microbiome. In addition, IgAN increasingly coexists with other chronic diseases, such as hypertension and diabetes, which complicates both diagnosis and treatment in aging societies. All these observations suggest that in the coming years, the epidemiology of IgAN will gradually transform from a description of “case counts” to a predictive tool that integrates genetic, environmental, and molecular biomarker data. In this sense, epidemiology is increasingly becoming the foundation of precision nephrology—allowing not only for disease risk prediction but also for the design of effective therapeutic strategies. The conceptual shift in IgAN—from a disease defined by biopsy prevalence to one understood through integrative epidemiology—illustrates the broader transition of GN research toward biomarker-based risk stratification and precision medicine. This review focuses on IgA nephropathy as the most prevalent primary glomerulonephritis and uses it as a reference disease to illustrate broader epidemiological patterns, outcome trajectories, and methodological limitations relevant to primary glomerulonephritides. Full article

Background/Objectives: Personalized treatment approaches are increasingly recognized as essential in the management of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), given the substantial heterogeneity in disease severity and patient characteristics. Kidney biopsy has the potential to serve as an effective tool for personalized treatment decision-making in patients with AAV. This study aimed to investigate the association of kidney biopsy with intensive immunosuppressive therapy and clinical outcomes in patients with AAV and kidney impairment. Methods: In this retrospective study, propensity score overlap weighting was applied to compare intensive immunosuppressive therapy and clinical outcomes (ESKD, death, combined ESKD and death, and infectious complications) between patients with AAV who underwent kidney biopsy and those who did not. Results: Out of 74 patients with AAV, 38 underwent kidney biopsy. Overlap weight analysis revealed that kidney biopsy was significantly associated with intensive immunosuppressive therapy (risk difference [RD], 28.9%; 95% confidence interval [CI], 0.017 to 0.562). Kidney biopsy was not associated with combined ESKD and death (RD, −0.2%; 95% CI, −0.302 to 0.298), death (RD, −3.8%; 95% CI, −0.264 to 0.189), ESKD (RD, −7.3%; 95% CI, −0.353 to 0.207), and infectious complications (RD, −25.9%; 95% CI, −0.537 to 0.020). Conclusions: In this observational cohort, kidney biopsy was associated with intensification of immunosuppressive therapy. However, after adjustment using overlap weighting, no statistically significant difference in clinical outcomes was detected, and the reduced effective sample size limited statistical power. These findings should be interpreted cautiously, as causal inference regarding the prognostic impact of kidney biopsy remains limited. Full article