Search Results (178)

The complement system is the primary defense mechanism against pathogens, acting through opsonization, the membrane attack complex, and classical, lectin, or alternative pathways. These pathways result in the production of key complement components, including C3a (complement component), C5a, and C3b, which recruit inflammatory cells. Complement dysregulation leads to renal disease through the overproduction of anaphylatoxins or inappropriate formation of the membrane attack complex. The levels of complement components have been shown to be useful as predictive markers in acute kidney injury, especially in conditions of alternative pathway activation, and in diseases of immune complex pathology such as lupus nephritis and IgA nephropathy. Genetic defects in complement regulatory proteins result in diseases such as C3 glomerulopathy or atypical hemolytic uremic syndrome, in which uncontrolled C3 convertase activity results in renal failure. Therapeutic interventions targeting complement components, including eculizumab or pegcetacoplan, improve patient outcomes in atypical hemolytic uremic syndrome and C3 glomerulopathy, respectively, while other interventions improve renal function in IgA nephropathy. These findings underscore the dual role of the complement system, which is not only implicated in the progression of renal diseases but also provides the potential for the development of therapeutic interventions for the treatment of various forms of nephropathy. Full article

Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by “Alport-like” multilamination of the glomerular basement membrane (GBM). Early recognition has therapeutic and prognostic implications. A previously healthy 4-year-old boy presented with generalized edema and nephrotic-range proteinuria. Glucocorticoids induced no remission; sequential calcineurin inhibition (cyclosporine, then tacrolimus) and a single dose of ofatumumab yielded only transient, partial reductions in proteinuria. A first biopsy elsewhere showed FSGS with nonspecific IgM/C3 trapping; electron microscopy (EM) was not performed. At age 10, repeat biopsy with EM revealed ~30% segmental foot-process effacement, focal GBM thickening (to 1740 nm), irregular lamina densa multilamination, and lamellar duplications without immune-complex deposits—features highly suggestive of hereditary GBM disease. Targeted sequencing identified compound-heterozygous MYO1E variants segregating in trans: a canonical splice-donor change (c.2785+1G>A) and a frameshift (c.3094_3097del; p.Thr1032Profs*73). Each parent was an unaffected heterozygous carrier; the sibling was negative. Supportive therapy with ramipril was continued. At last follow-up (January 2025), renal function was normal (serum creatinine 0.5 mg/dL; creatinine clearance 122 mL/min) with stable sub-nephrotic proteinuria (0.52 g/day; 16 mg/m² per hour) and normotension. This case broadens clinicopathologic recognition of MYO1E-associated nephropathy and highlights the teaching point that Alport-like GBM changes are not pathognomonic for type IV collagen disorders but may signal defects in podocyte cytoskeletal anchoring. 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: The benefit of specific B cell-targeted therapy in primary membranous nephropathy has been consistently demonstrated and is part of guideline-directed therapy. Though effective, Rituximab displays a highly variable response rate possibly owing to incomplete peripheral B cell depletion. Obinutuzumab is a second-generation anti-CD20 antibody which offers greater sustained peripheral B cell depletion and thus may result in improved clinical effect. This meta-analysis compares clinical efficacy of Obinutuzumab with Rituximab for the treatment of primary membranous nephropathy. Methods: A comprehensive search of PubMed, EMBASE, and Google Scholar was conducted on 10 October 2025. The search identified all studies which directly compared results of Obinutuzumab with Rituximab in the treatment of primary membranous nephropathy. Risk of bias was assessed using the Cochrane ROBINS-I tool. Data extraction and statistical analysis were performed using RevMan 5.1 software, assessing heterogeneity with the I² statistic. Results: Ultimately, three retrospective studies including a total of 161 participants were analyzed. The pooled estimated odds ratio for total clinical remission at 6 months was 2.84 (95% CI [1.42–5.69], p = 0.003, I² = 0%), and at 12 months was 12.25 ([95% CI 2.67–56.28]), p = 0.001, I² = 0%). The pooled estimated odds ratio for complete clinical remission at 6 months was 1.78 (95% CI [0.25–12.63], p = 0.57, I² = 0%) at 12 months was 4.12 (95% CI [1.36–12.48], p = 0.01, I² = 0%). The pooled estimated odds ratio for immunologic remission at 6 months was 6.18 (95% CI [1.57–24.39], p = 0.009, I² = 58%), and at 12 months was 5.56 (95% CI [1.50–20.64], p = 0.01, I² = 0%). The pooled estimated odds ratio for peripheral B cell depletion at 6 months was 3.91 (95% CI [0.99–15.40], p = 0.05, I² = 25%). Discussion: Obinutuzumab signals improvement in clinically relevant end points when compared with Rituximab for the treatment of primary membranous nephropathy but will require confirmation with head-to-head prospective data. The main limitations of this study include small sample sizes, geographic restriction, and retrospective design of the studies resulting in reduced generalizability. Other: There was no funding for this study. This review has been registered with PROSPERO (ID 1218735). Full article

The influence of gaseous components of tobacco smoke, e-cigarettes, and air pollutants on the development of glomerulonephritis has been the subject of numerous studies in recent years. Glomerulonephritis (GN) often leads to progressive kidney damage and chronic kidney disease (CKD), which is a global health problem. Genetic and autoimmune factors have been shown to contribute to their development. Yet, increasing attention is being given to environmental and lifestyle-related risk factors. This paper summarizes how specific substances found in tobacco smoke, e-cigarette smoke, and air pollutants contribute to the development and progression of GN. Particular emphasis is placed on substances such as formaldehyde, heavy metals, and particulate matter, which have been shown to trigger oxidative stress, immune dysregulation, and endothelial dysfunction. A clear understanding of the contributions of those agents to kidney inflammation is crucial for developing preventive strategies and improving public health awareness. We also highlight gaps in current research and suggest directions for future investigation. Understanding consequences of cigarette smoking should be promoted to encourage people to reduce their exposure to cigarette smoke, which could prevent many diseases. Full article

Membranous nephropathy is a disease that has been well documented, yet its etiopathogenesis has not been fully clarified and the distinction between its primary and secondary forms has not been completely categorized. The discovery of new antigens and antibodies reveals different percentages of positivity in secondary membranous nephropathy, which is a cause of great confusion and ambiguity not only in diagnosis but also in the choice of a therapeutic approach. The aim of this review is to summarize the literature on newly discovered antigens and antibodies, and to propose a pathogenetic model based on the role of the complement system and its activation pathways. In this model, antigens are categorized based on the type of immunoglobulin deposits and the putative complement pathways that they activate, which can help to differentiate primary from secondary membranous nephropathy. The model also reflects how the deposition of foreign antigens in the basement membrane can activate both the lectin and classical complement pathways, which may explain why positive antibodies are observed in both primary and secondary forms of membranous nephropathy. Full article

Primary glomerulonephritis encompasses a diverse group of kidney diseases with variable clinical trajectories and outcomes. Accurate prognostic stratification is critical for guiding individualized management and improving long-term renal survival. This narrative review synthesizes current evidence on the prognostic value of histological grading systems, circulating and urinary biomarkers, and integrative risk prediction models across major primary glomerulonephritis subtypes, including IgA nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis. Emphasis is placed on the utility of established classification systems (e.g., Oxford, MEST-C, chronicity scores), emerging tissue and fluid biomarkers (e.g., PLA2R antibodies, complement components, cytokine profiles), and the validation of multivariable prognostic tools and nomograms. We highlight areas of convergence between histopathologic lesions and molecular markers, as well as the evolving role of machine learning in predictive modeling. Ultimately, combining morphological, biochemical, and algorithmic tools holds promise for precision risk assessment and treatment tailoring in primary glomerulonephritis. Full article

Red blood cells (RBCs) play a key role in vascular origin pathologies such as nephropathy, retinopathy, and neuropathy. Altered RBCs also occur in the case of hereditary spherocytosis, hemoglobinopathies, sickle cell disease, thalassemia and hemolytic anemia. The consequence of damage to the cell membrane and cytoskeleton are changes in RBC deformability, which play an important role in microcirculation. In turn, oxidative changes in hemoglobin lead to impaired oxygen transport to cells and tissues and, consequently, to ischemia and hypoxia. In this review, we discuss the structure of normal and pathological RBCs, including, more broadly, red blood cells occurring in type 2 diabetes. We present factors that play a major role in RBC damage in this pathology. Finally, we characterize the participation of hemoglobin and heme in the induction of oxidative damage to biological material, including RBCs. Full article

Kidney toxicity remains a major dose-limiting complication of radiation therapy and platinum-based chemotherapy, yet the molecular determinants of renal susceptibility and resilience to these genotoxic treatments are incompletely understood. Podocytes are particularly vulnerable to such insults, and emerging evidence implicates lipid dysregulation in podocyte injury. This study investigated the role of sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B), a podocyte-enriched lipid-modulating enzyme, in radiation- and cisplatin-induced nephrotoxicity. Using a doxycycline-inducible, podocyte-specific SMPDL3B transgenic mouse model, renal injury was assessed following focal kidney irradiation, cisplatin administration, or their combination through functional assays, histopathology, ultrastructural analysis, immunofluorescence, and targeted lipidomics. Combined radiation and cisplatin exposure markedly reduced podocyte SMPDL3B expression, accompanied by podocyte depletion, glomerular basement membrane remodeling, proteinuria, and impaired renal function. These structural and functional abnormalities were associated with the selective accumulation of long-chain ceramide-1-phosphate species. In contrast, podocyte-specific induction of SMPDL3B preserved glomerular architecture, maintained renal function, and prevented pathological ceramide-1-phosphate elevation. Collectively, these findings identify SMPDL3B as a key regulator of podocyte stability and lipid homeostasis during chemoradiation stress. Enhancing SMPDL3B activity may represent a mechanistically grounded strategy to mitigate treatment-induced kidney injury while preserving anticancer efficacy. Full article

Background: Chronic kidney disease (CKD) affects up to 40% of individuals with diabetes mellitus. Given the fact that CKD in diabetics may result from various non-diabetic renal disorders, kidney biopsy remains essential in cases with atypical clinical presentation. The aim of this study was to assess the prevalence of diabetic nephropathy (DN) and other non-diabetic kidney diseases (NDKD) among diabetic patients who underwent renal biopsy. We also tried to find clinical and laboratory markers predicting the presence of DN in renal tissue. Methods: A retrospective analysis of all native renal biopsies in diabetic patients performed between 2010 and 2024 in one European nephrology center. Results: The cohort included 115 diabetic patients. DN was diagnosed in 43.5% individuals. Among NDKD cases, vasculitis (8.7%), membranous nephropathy (7.8%), and amyloidosis (7.8%) were most frequent. Compared with the NDKD group, patients with DN were younger, had a longer duration of DM, more often required insulin therapy, more frequently demonstrated diabetic retinopathy (DR) and nephrotic syndrome, and exhibited higher HbA1c levels. In multivariable logistic regression, younger age, need for insulin therapy, and presence of DR were the strongest predictors of DN. Conclusions: NDKD is common among DM patients. Patient’s younger age, the need for insulin therapy, and the presence of DR are strong predictive markers for diabetic nephropathy. Renal biopsy remains the most accurate method for diagnosis and should be considered in every case of suspected NDKD. Full article

Background: In recent years, Poland has observed fluctuations in kidney biopsy frequency and shifts in diagnostic patterns. These trends likely reflect evolving clinical practice, diagnostic advancements, and changing disease epidemiology. This study aimed to analyse these changes, assess biopsy-based diagnoses across age groups, and examine sex-related variability. Methods: We conducted a single-centre, retrospective study at a university hospital in southwestern Poland, covering 2010–2024. Data from 1969 kidney biopsies were collected, within 1291 native kidney cases analysed after excluding transplant recipients. Diagnoses were correlated with patients’ age, sex, presence of diabetes, and temporal trends, and compared with previous studies. Results: Biopsy numbers increased over time, peaking in 2021 (154 procedures). Most were performed in patients aged 40–64 years (46.1%), followed by 18–39 years (39.1%) and ≥65 years (14.8%), with a rising proportion of elderly patients. Repeated biopsies occurred in 7.7% (second) and 0.6% (third biopsy). The most frequent diagnoses were IgAN (16.9%), FSGS (14.7%), and lupus nephritis (11.4%). In patients ≥65 years, amyloidosis (13.6%), FSGS (13.1%), vasculitis (13.1%), and membranous nephropathy (12%) predominated. The most marked sex-related difference involved lupus nephritis, accounting for 20.3% of diagnoses in women, who made up 82.3% of lupus nephritis cases. While most diseases showed male predominance, this was not evident for several, including IgAN and diabetic nephropathy. Conclusions: Given CKD’s underdiagnosis and frequent late detection in Poland, updated multicentre studies are needed to better recognise disease patterns and raise public awareness. Full article

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide. One-third of patients with DN develop primary glomerulonephritis, and membranous nephropathy (MN) is the most common concurrent glomerulonephritis. Nephrotic syndrome (NS) due to DN and MN is often refractory to immunosuppressants because increased levels of low-density lipoprotein (LDL) not only accelerates kidney injury but also reduce the bioavailability of cyclosporine, a first-line immunosuppressant for MN. Given the pathological role of LDL, especially oxidized LDL, reducing LDL cholesterol levels can help achieve remission of NS and halt the progression of kidney injury. Although some lipoproteins are not excreted by the kidneys, excessive LDL, including oxidized LDL, can be considered uremic toxic-like factors that contribute to the development of NS or DN. We encountered a 74-year-old patient with concomitant DN and MN who achieved complete remission following additional LDL apheresis (LDL-A) with immunosuppressant therapy. Here, we provide a narrative review summarizing the role of LDL, especially ox-LDL, in the progression of DN and glomerulonephritis, including MN, and discuss the therapeutic rationale for LDL-A. We also present a representative case of concomitant MN and DN refractory to conventional immunosuppression who achieved clinical improvement following LDL-A. Full article

Background: PAR 1 (protease-activated receptor 1) and endothelin 1 are biomarkers that could be of significance in kidney diseases. Methods: We measured the plasma levels of PAR1 and endothelin 1 in patients with membranous nephropathy (n = 19), focal and segmental glomerulosclerosis (FSGS) (n = 30), systemic lupus erythematosus (SLE) (n = 22), IgA nephropathy (n = 16), mesangial proliferative (non-IgA) glomerulonephritis (n = 7), chronic kidney disease (CKD) (n = 27), and hemodialysis (n = 26), as well as a healthy control group (n = 22). Then, for two years, we tracked the patients’ clinical progress (creatinine, total protein, and albumin levels) and compared the outcomes with their initial PAR 1 and endothelin 1 levels. Moreover, we checked the correlations between PAR 1 and endothelin 1 and the results of anti-PAR1 and anti-ETAR (endothelin A receptor) evaluations. Results: Membranous nephropathy, FSGS, IgA nephropathy, CKD, and hemodialysis patients had higher PAR 1 levels than the control group. PAR 1 correlated with total protein, albumin in SLE, total protein in IgA nephropathy, and creatinine in CKD. Endothelin 1 correlated with albumin in membranous nephropathy, total protein, albumin, creatinine in FSGS, total protein in IgA nephropathy, total protein, and albumin in CKD. PAR 1 correlated with anti-PAR 1 in FSGS. Anti-ETAR correlated with anti-PAR 1 in membranous nephropathy, FSGS, and IgA nephropathy. Conclusions: PAR 1 levels are elevated in some kidney diseases compared to the healthy population. Both PAR 1 and endothelin 1 are supposed to be related to the clinical course of specific kidney diseases. Full article

Fabry disease (FD) is an X-linked lysosomal disorder caused by GLA mutations, typically associated with glycosphingolipid accumulation and a wide phenotypic spectrum. The p.R112H variant is generally linked to a non-classic predominantly renal phenotype with mild biochemical abnormalities and slow progression. We report the case of a young woman carrying the R112H mutation who exhibited early-onset kidney involvement and unusually rapid progression to end-stage renal disease. Clinical history, serial evaluations, and kidney biopsy findings initially supported a diagnosis of Fabry nephropathy; however, re-evaluation of the native kidney biopsy revealed marked remodeling and multilamellation of the glomerular basement membrane, suggesting Alport-like lesions. Subsequent genetic testing confirmed a heterozygous pathogenic COL4A4 variant (G912R), indicating coexistence of Fabry disease and autosomal dominant Alport syndrome. This dual genetic condition likely accounted for the accelerated decline in kidney function, in contrast with the typically mild phenotype associated with R112H. Our literature review indicates that coexistence of these two inherited nephropathies has not previously been confirmed either histologically or genetically. This case underscores the importance of integrating genetic and ultrastructural assessment in patients with atypical or rapidly progressive renal disease Full article

Membranous nephropathy (MN) is an immune complex-mediated glomerular disease defined by sub-epithelial deposits that trigger complement activation and podocyte injury. Its pathogenesis reflects loss of immune tolerance and may present as a kidney-limited autoimmune process or in association with underlying conditions (e.g., malignancy, infection, drugs, or systemic autoimmunity). Current diagnostic work-up integrates circulating antibodies—most commonly anti–phospholipase A2 receptor 1 (PLA2R1)—and kidney biopsy, which remains essential in PLA2R1-negative or atypical presentations and for antigen confirmation when serology is negative. In PLA2R1-negative MN, an expanding list of antigens is being recognized, potentially refining phenotyping and risk assessment; however, dedicated studies remain limited, and the clinical weight of many newly described antigens likely requires further validation before supporting an antigen-based classification. Uneven access to advanced diagnostics particularly affects PLA2R1-negative cases, underscoring the need for centralized testing and the development of reliable non-invasive biomarkers. Treatment has advanced with rituximab and other targeted therapies, but resistant and relapsing cases remain challenging, and the evidence base for PLA2R1-negative forms is comparatively limited. This review summarizes recent diagnostic and therapeutic advances, focusing on PLA2R1-negative MN. Full article