Complement 3(C3)-dominant Glomerulonephritis (GN) are rare diseases resulting from alternative complement pathway dysregulation, include C3 Glomerulopathy(C3G), paraprotein associated GN and C3 dominant infection-related glomerulonephritis (IRGN). To our knowledge long-term follow-up studies of clinical profile and outcomes of this rare disorder are sparse. We studied kidney histopathology baseline findings, outcomes, treatment, and its complications of C3-dominant GN in our setting. We studied the clinical, pathological profiles and outcomes of patients with C3-dominant GN. Design: Single centre, retrospective, case record based observational study. Consecutive patients of C3-dominant GN on kidney biopsy from 2013 to 2023. Demography, laboratory and histopathological data, treatment and outcomes were studied. Of 2175 kidney biopsies, 141(6.48%) showed C3-dominant Glomerulonephritis; 74 (52.5%) C3G, 67(47.5%) IRGN. Median age was 43 years (IQR 29-59.5), males 90 (63.8%). Preceding skin/throat infections were seen in 32/141 (22.7%). At presentation median serum creatinine was 1.7mg/dL (IQR: 1.2-3.6), eGFR <60ml/min/1.73m2 in 91/141 (64.5%), 111/141 (78.7%) had low serum C3 levels. Nephrotic proteinuria was seen in 65/141 (46%), Crescents in 45(31.9%). Remission was partial in 38/141(27%), complete in 45/141(31.9%) and 31/141(22%) progressed to End stage kidney disease (ESKD). On immunosuppression commonest infection was pneumonia in 15/70 (21.4%) and 27/141(19.1%) died at an average follow up of 25.7 months. Diabetes mellitus, percentage sclerosis and presence of crescents predicted development of CKD stage 5. Over ten years, C3-dominant GN represented 6.48% of kidney biopsies. Nephrotic proteinuria and kidney failure are common at presentation with 58% achieving some remission, 22 % going on to ESKD and mortality of 19%.

Background Acute glomerulonephritis (GN) is an acute episode of glomerular injury that affects both children and older adults. However, up-to-date data on its incidence, prevalence, mortality, and disability-adjusted life years (DALYs) remain limited. This study aims to provide the latest global trends and underlying health inequalities associated with acute GN. Methods Incidence, prevalence, mortality, and DALYs per 100,000 population were reported at global, regional, and national levels, along with the Estimated Annual Percentage Change (EAPC). Global trends were analyzed by age, sex, and sociodemographic index (SDI), with forward projections estimated for the year 2040. Results Globally, there were 528,368 (95% Uncertainty Interval [UI], 446,739 to 613,211) incident cases, 35,452 (95% UI, 30,151 to 41,655) prevalent cases, 10,761 (95% UI, 7,668 to 13,463) deaths, and 312,303 (95% UI, 208,981 to 393,514) DALYs attributed to acute GN in 2021. Children aged <14 years and older adults aged >85 years experienced the most severe burden. Frontier analysis revealed that middle SDI countries had the greatest potential to reduce the disease burden. Although the disease burden of acute GN has declined over the past three decades, our projections indicate that its incidence and prevalence will increase by 2040 due to population growth and aging. Conclusion The global disease burden of acute GN has decreased; however, population growth and aging may be associated with rising incidence and prevalence by 2040. Middle SDI regions bear a disproportionate burden of acute GN, particularly among children and older adults.

ObjectivesWe aimed to evaluate the safety and efficacy of cotrimoxazole for preventing infections in patients with glomerulonephritis (GN) receiving rituximab (RTX) therapy.Study design and methodsThis single-center, open-label randomized controlled trial enrolled 150 patients with GN who received RTX at Xijing Hospital between October 2022 and December 2023. Participants were randomized 1:1 to either the cotrimoxazole prophylaxis group (n = 75) or the non-cotrimoxazole group (n = 75). The primary endpoint was the cumulative incidence of infection over a 180-day follow-up period. Secondary endpoints included the incidence of severe infections and the rate of adverse events (AEs) attributed to cotrimoxazole.InterventionAll patients received RTX at a dose of 1000 mg intravenously on days 1 and 14. CD19 + B-cell counts were monitored monthly for 6-month post-initial infusion; if CD19 + B cells remained detectable at the 6-month mark, an additional 1000-mg RTX dose was administered.Cotrimoxazole prophylaxis protocolPatients in the intervention group initiated oral cotrimoxazole on the same day as their first RTX infusion, with one tablet daily for seven consecutive days. Prophylaxis was repeated for 7 days following each subsequent RTX infusion, resulting in a total of 14 days of prophylaxis over the study period.The non-cotrimoxazole groupThey received no cotrimoxazole prophylaxis.ResultsOver 180 days of follow-up, 8 infectious episodes occurred in 7 patients in the cotrimoxazole group, compared with 19 episodes in 16 patients in the control group. The annualized incidence density of infections (per 100 person-years) was 20.80 (95% CI 11.36–30.24) in the cotrimoxazole group versus 54.83 (95% CI 43.09–66.57) in the control group. The hazard ratio (HR) for the cumulative incidence of infection was 0.39 (95% CI 0.17–0.88; log-rank test, P = 0.029), indicating a significant reduction in infection risk with cotrimoxazole prophylaxis.ConclusionsOur findings demonstrate that cotrimoxazole prophylaxis for 1-week post-RTX infusion effectively prevents post-RTX infectious complications, reduces infection-related mortality, and does not elevate the risk of serious AEs. However, it should be noted that this study was a single-center investigation without a placebo control.Trial registrationThe study was registered on the Chinese Clinical Trial Registry (trial registration identifier: ChiCTR2200063564).Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04491-3.

Urinary tract infections are among the most common bacterial infections worldwide, with increasing antimicrobial resistance posing a significant public health challenge. This study aimed to determine the demographic distribution, antimicrobial susceptibility patterns of uropathogens, and the clinical implications of UTIs in patients with renal comorbidities in the Al-Baha region of Saudi Arabia. A retrospective, cross-sectional study was conducted at King Fahad Hospital, Al-Baha, from January 2021 to September 2022. A total of 1126 culture-positive UTI cases were included. Patient demographics, uropathogen distribution, antimicrobial resistance profiles, and clinical characteristics were extracted from hospital records. Subgroup analysis was performed for 32 patients with renal comorbidities, including end-stage renal disease (ESRD), glomerulonephritis (GN), and kidney transplant recipients (KTs). Statistical analysis was performed using SPSS version 25. Most cases occurred in patients aged >70 years (43.2%) and females (68.29%). Escherichia coli (38.09%) and Klebsiella pneumoniae (14.02%) were the leading pathogens. High resistance to ampicillin (47–67%), cotrimoxazole (35–37%), and third-generation cephalosporins (34–47%) was observed, whereas carbapenems and aminoglycosides remained largely effective. Among the 32 patients with renal comorbidities, E. coli (43.8%), Staphylococcus aureus (25%), and Enterococcus spp. (18.8%) were the most common isolates. Dysuria (46.87%) and fever (31.25%) were the most frequent clinical presentations. Treatment regimens in this subgroup often required multidrug combinations, reflecting higher resistance burdens. Uropathogens in the Al-Baha region shows rising resistance to first-line antibiotics, with vulnerable populations such as patients with renal comorbidities experiencing distinct pathogen distributions and treatment challenges. Continuous surveillance, prudent antibiotic use, and targeted strategies for high-risk patients are essential to mitigate the impact of multidrug-resistant UTIs in Saudi Arabia.

To investigate urinary thrombin levels in patients with glomerulonephritis (GN), evaluate their relationship with the morphological type of GN, disease activity, and assess the diagnostic value of thrombinuria. Methods. A cross-sectional study was conducted in 72 patients with biopsy-proven GN and 40 healthy controls. Serum and urinary concentrations of thrombin, IL-6, TNF-α, and TGF-β1 were measured using ELISA. Clinical data and renal biopsy findings were analyzed. Statistical methods included correlation and group comparison tests. Results. Urinary thrombin was markedly elevated in GN patients compared with controls (median 9.4 vs. 0.38 ng/ml; p = 0.013), while serum thrombin showed no significant difference. Thrombinuria was detected in 80.6% of patients and correlated positively with daily proteinuria (r = 0.514), urinary IL-6 (r = 0.438), and urinary TNF-α (r = 0.372). An inverse correlation was observed with urinary TGF-β1 (r = –0.534) and the chronicity index (r = –0.783), suggesting that thrombinuria characterizes active inflammatory phases, while its decline accompanies fibrotic remodeling. No significant associations were found between serum thrombin and systemic inflammatory markers. Conclusions. Thrombinuria may reflect local activation of coagulation–inflammation pathways. It demonstrates associations with proteinuria, pro-inflammatory cytokines. These results suggest that thrombinuria could serve as a potential non-invasive biomarker of disease activity in GN; however, due to the cross-sectional design and limited sample size, the findings should be interpreted with caution and confirmed in larger longitudinal studies.

Pauci-immune glomerulonephritis (GN) is a typical renal manifestation of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, patients positive for ANCA can present with kidney pathologies other than pauci-immune GN. This study aimed to investigate and compare the characteristics of ANCA-positive patients diagnosed with pauci-immune GN to those with non-pauci-immune kidney diseases, based on kidney biopsy findings. We retrospectively analyzed the electronic medical records of ANCA-positive patients who underwent kidney biopsy from January 2010 to October 2023 at a single tertiary center in Seoul, Republic of Korea. Logistic regression analysis was performed to identify variables associated with the diagnosis ofpauci-immune GNin this cohort. Of 268 ANCA-positive patients, 195 (72.8%) were diagnosed with pauci-immune GN, while 73 (27.2%) had other kidney diseases. The most common pathologies in the non-pauci-immune GN group were IgA nephropathy (20.5%) and lupus nephritis (16.4%). Compared to the non-pauci-immune GN group, patients with pauci-immune GN exhibited higher platelet counts and C-reactive protein (CRP) levels, along with lower estimated glomerular filtration rate (eGFR). Urine abnormalities, categorized by the presence or absence of hematuria and/or proteinuria, differed significantly between the groups. Multivariate analysis identified hematuria and pulmonary involvement as significant predictors of pauci-immune GN. Approximately 70% of our ANCA-positive patients who underwent kidney biopsy were diagnosed with pauci-immune GN. Predictive factors for pauci-immune GN included platelet count, CRP levels, eGFR, hematuria, and pulmonary involvement. Identifying these clinical and laboratorymarkers may be valuable for improving the diagnostic approach towards AAV-related kidney manifestations.

Molecular insights into chronic glomerulonephritis and dopamine interplay.

Glomerulonephritis (GN) is a group of kidney disorders marked by glomerular damage, leading to proteinuria, hematuria, hypertension, and impaired kidney function. Despite advancements in diagnostics, kidney biopsy remains the gold standard for diagnosis. The prevalence of GN varies globally, with Latin America showing a significant increase in incidence rates. This systematic review adhered to PRISMA guidelines and included observational studies from PubMed, Embase, Cochrane, and SciELO databases. Studies were selected based on their focus on the prevalence of GN and its subtypes in Latin America from 2000 onward. The quality of the studies was assessed using the Newcastle-Ottawa Scale adapted for cross-sectional studies. Following the search, a total of 4336 articles were screened. Of these, 49 underwent full-text review, and 35 met the inclusion criteria, encompassing 61,979 kidney biopsies analyzed across studies conducted in Latin America. The studies spanned a time frame of 1-35years, with a mean age at biopsy ranging from 28 to 57years. Focal Segmental Glomerulosclerosis (FSGS) and Lupus Nephrtis were the most frequent primary and secondary glomerulopathies. Nephrotic syndrome was the leading indication for biopsy, and electron microscopy was only reported in 17 studies. Few studies reported data on estimated glomerular filtration rate (eGFR), interstitial fibrosis, and tubular atrophy. Furthermore, subclassification of FSGS into primary and secondary forms was performed in only four studies. Most countries in Latin America reported kidney biopsy rates below 50 per million population per year (pmp/yr), substantially lower than those observed in high-income countries, where rates commonly exceed 100-200 pmp/yr. The epidemiology of glomerulonephritis in Latin America is heterogeneous, with marked regional differences and predominance of FSGS as the leading primary GN; however, data on primary FSGS (pFSGS) are lacking. Compared to high-income countries, most Latin American countries report significantly lower rates of kidney biopsies per million population, which, combined with limited diagnostic resources, may contribute to the underdiagnosis and potential misclassification of glomerular diseases.

BackgroundThe epidemiology of biopsy-proven kidney disease varies geographically, yet data from Central Germany are lacking, hindering local disease understanding and healthcare planning. We aimed to characterize the spectrum, trends, and predictors of kidney diseases in this region.MethodsWe retrospectively analyzed 1,029 native kidney biopsies from a tertiary center in Saxony-Anhalt (2010–2021), assessing demographic, clinical, and histopathological data. Temporal trends were compared between two 6-year periods. Multivariate logistic regression identified predictors for major diagnoses.ResultsMean patient age was 54.3 years (65% male). Primary glomerulonephritis (GN) was the most common diagnosis (50.4%), led by IgA nephropathy (IgAN) (23.0%), diabetic nephropathy (DN) (10.0%), and vasculitis-associated GN (8.7%). Trend analysis revealed a significant decrease in primary GN (56.4% to 46.5%; p < 0.001) and an increase in vascular nephropathies (2.7% to 10.6%; p < 0.001). Male sex was an independent predictor for IgAN (OR 1.41), while younger age and female sex predicted Minimal Change Disease or Lupus Nephritis.ConclusionThis first study from Central Germany reveals a unique epidemiological profile with a high burden of IgAN, DN, and vasculitis. We observed a significant temporal shift from primary GNs towards vascular diseases, reflecting the rising prevalence of metabolic syndrome and hypertensive conditions. These findings underscore evolving challenges in nephrology and support the need for a national German kidney biopsy registry to monitor and address these trends.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12882-025-04617-y.

Leptospira interrogans serovar Copenhageni infection and exudative glomerulonephritis in rehabilitated gray seals (Halichoerus grypus) and harbor seals (Phoca vitulina) in Ireland.

Children with chronic kidney disease (CKD) face increased morbidity, mortality, and reduced quality of life. Uremic neuropathy (UN) is a common neurological complication, but data on its relationship with dialysis in pediatric populations are limited. This prospective study aimed to assess the prevalence of UN in children with end-stage renal disease (ESRD) in a Tunisian population and explore the association between dialysis and UN. Conducted between July and September 2023 in the nephrology and neurophysiology units of a Tunisian hospital, the study included 31 children with CKD G5. Clinical data, biological analyses, and nerve conduction studies via electroneuromyography (EMG) were performed at baseline and six months later. Participants were divided into pre-dialysis and dialysis groups for comparison. The mean age was 11 ± 3.5 years, and the average age at CKD diagnosis was 7.5 ± 4.2 years. UN was diagnosed in 45% of participants using EMG, including 13% with silent neuropathy. Axonal neuropathy was predominant, with no cases of demyelinating neuropathy identified. Initial comparisons between dialysis and pre-dialysis groups showed no significant differences in UN characteristics. However, clinical neuropathy, weight-for-age, and glomerular nephritis were significantly associated with UN. Follow-up revealed a significant improvement in UN in the dialysis group. From this study, we conclude the importance of screening for UN in pediatric ESRD care and recommend routine EMG evaluations, even in asymptomatic patients, to ensure early diagnosis and management.

Children with chronic kidney disease (CKD) face increased morbidity, mortality, and reduced quality of life. Uremic neuropathy (UN) is a common neurological complication, but data on its relationship with dialysis in pediatric populations are limited. This prospective study aimed to assess the prevalence of UN in children with end-stage renal disease (ESRD) in a Tunisian population and explore the association between dialysis and UN. Conducted between July and September 2023 in the nephrology and neurophysiology units of a Tunisian hospital, the study included 31 children with CKD G5. Clinical data, biological analyses, and nerve conduction studies via electroneuromyography (EMG) were performed at baseline and six months later. Participants were divided into pre-dialysis and dialysis groups for comparison. The mean age was 11 ± 3.5 years, and the average age at CKD diagnosis was 7.5 ± 4.2 years. UN was diagnosed in 45% of participants using EMG, including 13% with silent neuropathy. Axonal neuropathy was predominant, with no cases of demyelinating neuropathy identified. Initial comparisons between dialysis and pre-dialysis groups showed no significant differences in UN characteristics. However, clinical neuropathy, weight-for-age, and glomerular nephritis were significantly associated with UN. Follow-up revealed a significant improvement in UN in the dialysis group. From this study, we conclude the importance of screening for UN in pediatric ESRD care and recommend routine EMG evaluations, even in asymptomatic patients, to ensure early diagnosis and management.

HepatitisE virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic manifestations, particularly renal disease. While the underlying pathomechanisms are still largely unknown, these manifestations are thought to develop either directly, i.e., by HEV infection of the respective organ, or indirectly, i.e., via immunologic reactions. Herein, we describe the development of de novo immune complex-mediated glomerulonephritis (GN) associated with the glomerular deposition of anewly described form of the HEV open reading frame2 (ORF2) capsid protein in patients with chronic or acute hepatitisE. We performed immunostaining, electron and deconvolution microscopy, and laser-capture microdissection combined with mass spectrometry to specifically investigate the glomerular compartment. In akidney transplant recipient with chronic hepatitisE, we show that GN developed in parallel with increasing glomerular deposits of the HEV ORF2 protein, which significantly colocalizes with IgG, thus forming immune complexes. Interestingly, the glomerular HEV ORF2 protein does not correspond to the expected secreted and glycosylated form of the viral capsid protein but rather has the molecular weight of atruncated non-glycosylated form. Importantly, it is not associated with HEV RNA and, in contrast to the situation in liver cells, no productive HEV infection of kidney cells is detected. Patients with acute hepatitisE show similar but less pronounced deposits. Our results establish alink between the production of HEV ORF2 protein and the development of hepatitisE-associated GN. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides amechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide atool for etiology-based diagnosis of hepatitisE-associated GN, establish hepatitisE-associated GN as adistinct entity, and suggest therapeutic implications.

Introduction: Novel molecular tools have the potential to improve current clinical and histology-based risk classification systems for various medical renal diseases including glomerulonephritis (GN). We aimed to assess the utility of gene expression for improving biopsy-based risk prediction in patients with GN with and without crescent formation. Methods: This retrospective case-control study used NanoString nCounter to measure the expression of 54 previously described inflammation, nephron injury, endothelium, and crescent-related genes in 335 archival, formalin-fixed paraffin-embedded native kidney biopsies, including a 288-biopsy discovery cohort representing a broad spectrum of crescentic GN subtypes, and an independent 47-biopsy validation cohort focused on ANCA-associated crescentic GN. Clinical, histologic, and gene expression data were compared. Results: Discovery cohort analysis demonstrated increased expression of 13 genes in crescentic GN cases that developed end-stage renal disease (ESRD) versus those that did not (false discovery rate <0.05). Within the 75-biopsy subset of ANCA-associated crescentic GN cases in the discovery cohort, this 13-gene set was found to be independently predictive of ESRD in multivariate Cox proportional hazards regression analysis (p = 0.015), with significant differentiation of high and low risk patients in the Kaplan-Meier renal survival analysis (log-rank test, p = 0.002). However, validation cohort analysis did not demonstrate significant improvement in risk stratification with the 13-gene set when compared with established clinicopathologic models. Conclusion: These results suggest that biopsy-based gene expression may provide the opportunity for improved risk stratification in crescentic GN; however, the genes evaluated in this study appear to have limited added clinical utility over existing risk scores.

Autoimmune glomerulonephritis (GN) emerges when self-reactive humoral and cellular immunity converge in the kidney. Combined immunofluorescence and electron microscopy aids in classifying GN; however, more stratification strategies are required for personalized therapy. We aimed to review biopsy-anchored clinicopathologic classification and pathophysiology of GN-associated disorders based on immunofluorescence and electron microscopy. Additionally, we sought to integrate mechanistic insights from multiomics and spatial profiling that resolve the composition and spatial organization of the cellular "neighborhoods" that drive injury and repair across IgA vasculitis/nephropathy, lupus nephritis, antiglomerular basement membrane disease, and antineutrophil cytoplasmic antibody-associated vasculitis. Although inciting antigens, immune complexes, and deposition patterns vary among entities, downstream injury pathways overlap. The convergent programs include complement activation, including locally produced renal complement, Fc receptor-driven myeloid effector functions, neutrophil extracellular traps with nucleic-acid sensing, the reprogramming of monocytes/macrophages, interleukin (IL)-23/IL-17, and type 1 interferon-primed cytotoxicity of T cells, and epithelial stress responses in podocytes and parietal epithelial cells. Despite diverse triggers, autoimmune GNs share targetable injury pathways. Integrating biopsy-defined immune deposits and the accompanying inflammatory context with spatial, single-cell, and proteomic readouts enables mechanistic subtyping and pathway-aligned therapy. Tailoring treatment to individual dominant injury programs may improve renal outcomes and reduce adverse effects.

Abstract Background and Aims Glomerulonephritis (GN) is characterized by inflammation of the glomeruli, leading to impaired kidney function and, in some cases, chronic kidney disease (CKD). This process can result in global fibrosis beyond the site of initial glomerular injury. Peroxisome proliferator-activator receptor γ (PPARγ), a nuclear receptor involved in lipid and glucose metabolism, has been implicated in modulating the inflammatory response in renal fibrosis and has been suggested as a potential therapeutic target for this condition. Dysregulation of lipid metabolism has been associated with inflammation and fibrotic processes in the kidney. Thus, a better understanding of the specific lipidome changes associated with renal fibrosis and CKD could provide relevant information to tackle this pathology best. Method Here, we present an in-depth renal lipidome study assessed mainly by matrix-assisted laser desorption/ionization-image mass spectrometry (MALDI-IMS) of control and GN mice. We used the nephrotoxic serum (NTS)-induced crescentic GN as a transition model from glomerular insult to CKD progression and mainly focused on tubular epithelial cells (TECs) lipidome. GN was induced on male mice with C57BL6/J background by retroorbital injection of sheep anti-mouse GBM NTS. Mice were euthanized at day 21 post-injection, at the stage of CKD progression, and snapped frozen kidney sections of 15 μm thickness were prepared in a cryostat. MALDI-IMS analyses were performed at 10 µm of spatial resolution using a MALDI-LTQ-Orbitrap XL. Renal biopsy specimens for MALDI-IMS analysis after the completion of diagnostic workup were obtained from patients diagnosed with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and GN or normal kidneys. They were used after informed consent and approval from and following the guidelines of the local ethics committee (IRB00003888, FWA00005831). Lipid assignment was based on comparing the experimental m/z and the species in the software's LIPID MAPS database. After MALDI-IMS, immunofluorescent staining of the different tubular segments was performed over the same tissue section to correlate each structure with its lipid fingerprint. Additionally, key enzymes involved in lipid metabolism were assessed by RT-qPCR for the two study groups. Results Sixteen lipid families were identified by MALDI-IMS, accounting for 167 different lipid species in all the samples. The control and GN kidneys confirmed up to eight different lipid fingerprints. GN condition was associated with increased phosphatidylcholine (PC) and ether/vinyl ether phosphatidylethanolamine (PE-O/P) levels and decreased HexCer and PS species. These results were consistent with the modification in some enzyme expressions involved in phospholipid biosynthesis. We also observed a marked loss of PPARγ expression in epithelial cells in GN samples, especially highlighted in proximal tubules. Some features point to the proximal tubules as the most affected kidney region in GN: A higher number of modified individual lipid species were accounted for in proximal tubules. This region had a positive correlation between the increase in PC/PE ratio and the urea and creatinine sera levels. In agreement with these results, similar profiles were observed in proximal tubules of ANCA GN kidney biopsies. A higher concentration of carnitine, a biomarker of proximal tubule injury, was found in the urine of GN mice. Conclusion MALDI-IMS characterized the lipid composition of different kidney regions and identified GN-CKD-related changes. Modification in the expression of enzymes involved in lipid biosynthesis is consistent with some of the changes in lipid composition observed in GN. Our results identify a lipidomic signature of GN-induced CKD progression in the proximal tubule, including loss of PPARγ.

Abstract Background and Aims Chronic primary glomerulonephritis (GN) significantly impacts patients on physical, emotional, and economic levels due to its symptoms and prognosis. The existing literature on the subject is scarce. Thus, this collaborative study with the National Federation of Associations for the Fight Against Kidney Diseases (ALCER, according to Spanish spelling), aims to describe the impact on the psycho-emotional and economic well-being of GN from the perspective of the patient and their caregivers. To our knowledge, this is the first report to comprehensively assess the burden of the disease in several domains in a large GN population. Method Market research study conducted through online questionnaires to patients with a biopsy-confirmed diagnosis of GN, including immunoglobulin A (IgA) nephropathy, IgA vasculitis, lupus nephritis, complement 3 glomerulopathy, immune complex-mediated membranoproliferative GNs, monoclonal gammopathies of renal significance, membranous nephropathy, focal segmental glomerulosclerosis, minimal change podocytopathy and anti-neutrophil cytoplasmic antibodies associated vasculitis, aged ≥12 years and their caregivers (for &amp;lt;18 years patients). Two questionnaires were developed with the collaboration of a multidisciplinary scientific committee: (1) targeting adult patients (≥18 years); (2) designed for adolescent patients (between 12 and 17 years) and their caregivers. Patients were invited to participate by nephrologists (81 clinical nephrologists and 15 pediatric nephrologists) across 52 hospitals representing all regions of Spain, with confirmed GN diagnosis. Questionnaires included questions grouped into 5 domains: sociodemographic and clinical characteristics, impact of the disease (psycho-emotional well-being, daily life activities, relationships, academic and work environment), patient journey in the health system, treatment, and economic impact. Results 360 patients participated: 337 adult and 23 adolescent patients with their respective caregivers. 50.8% of the total patients were men with a mean (SD) age of 44.8 (18.3) years, being 46.9 (17.1) years for adults and 14.3 (1.2) for adolescents. Overall, 71.9% of the patients reported an impact on their psycho-emotional well-being related to GN; this was more prominent in transplanted patients (81.5%). The primary concern among patients was the loss of quality of life (73.1%), followed by the need for dialysis (51.7%), the need for a transplant (40.6%) and risk of early death (38.1%). Patients experienced a fluctuating psycho-emotional journey throughout the different stages of the disease (Fig. 1), predominantly characterized by concern and sadness prior to being placed on the transplant waiting list, which shifted to hope after being listed. Beyond the described psycho-emotional impact, GN significantly affects patients' work and family life: 34.4% of adult patients have given up or postponed having children due to GN, 56.2% of working patients reported an impact on their work environment, and up to 38.9% of post-transplant patients were unable to fully develop their careers. Additionally, GN impacts other aspects of patients' lives, including leisure activities (83.1%), diet (84.2%), sports (77.0%), sleep (70.3%), and relationships (31.1%). Conclusion This study underscores the significant and multifaceted burden of chronic primary GN on patients’ physical, emotional, and economic well-being. The high prevalence of psycho-emotional distress, coupled with substantial impacts on daily activities, work, and family life, reveals a clear unmet need for these patients. The findings highlight the urgent need for innovative measures and therapies aimed at reducing the disease burden.

Abstract Background and Aims Studies determining the relation between soluble urokinase-type plasminogen activator receptor (suPAR) levels and clinical outcomes in glomerulonephritis (GN) are limited. In this study, we aimed to investigate the association between suPAR levels and renal outcomes in patients with GN. Method A total of 96 patients diagnosed with primary GN on renal biopsy in two tertiary hospitals between 2013 and 2020, who underwent both baseline and follow-up sampling and consented to participate, were included. Serum suPAR levels were measured at the time of biopsy and during follow-up. The association between serum suPAR levels and the reduction of renal function and proteinuria was analyzed. Results The most common GN was IgA nephropathy, followed by focal segmental glomerulosclerosis, membranous nephropathy and minimal change disease. The median follow-up duration was 2.3 years. Ln(suPAR) levels, logarithmically transformed on a natural log of suPAR showed no significant difference according to the type of GN at the time of biopsy (P = 0.42), but there was a significant difference at follow-up (P = 0.018). Ln(suPAR) levels were significantly higher in patients with an eGFR less than 60 ml/min/1.73 m2 compared to those with an eGFR of 60 ml/min/1.73 m2 or higher at both baseline (P = 0.02) and follow-up (P = 0.001). There was a significant difference in the change in Ln(suPAR) per year (%/year) among GN groups (P &amp;lt; 0.001). Higher baseline Ln(suPAR) levels were significantly associated with eGFR decline in the Cox proportional hazards model (HR 1.760, 95% CI 1.101–2.813, P = 0.018), although they were not significantly associated with a reduction in the urine protein-to-creatinine ratio (UPCR) (HR 1.540, 95% CI 0.988–2.386, P = 0.057). Kaplan-Meier analysis showed that patients in the highest tertile of Ln(suPAR) at the time of biopsy exhibited a faster eGFR decline (P = 0.019). However, there was no statistical significance for reduction of UPCR (P = 0.065). Multivariate regression analysis identified Ln(suPAR) (P &amp;lt; 0.001) and UPCR (P = 0.043) at the time of biopsy as independent factors influencing Ln(suPAR) levels at follow-up. Receiver operating characteristic (ROC) analyses demonstrated a modest improvement in predictive power for eGFR and reduction of UPCR when incorporating suPAR into models that included age, sex, hypertension, diabetes, type of GN, UPCR and the presence or absence of eGFR less than 60 ml/min/1.73 m2 at baseline. Conclusion Higher suPAR levels at the time of biopsy are associated with eGFR decline in patients with GN, although they are not significantly associated with the reduction of proteinuria. suPAR could be suggested as a potential marker for renal outcomes in GN.

Abstract Background and Aims The presence of dysmorphic microhematuria has been related to the presence of glomerulonephritis (GN). Detection of dysmorphia is a qualitative analysis observer-dependent of the urinary sample. Therefore, this technique has a high specificity with variable sensitivity. The objective of our study was to evaluate a cohort of patients with diagnosis of GN and to study the prevalence of dysmorphic and isomorphic microhematuria and to evaluate factors associated with the presence of dysmorphia. Method Retrospective study of patients diagnosed with GN associated with microhematuria in our hospital from 2013 to 2024. Clinical and analytical characteristics of the patients were analyzed comparing patients who presented or not dysmorphic red blood cells (dRBCs). Results A total of 119 patients diagnosed with GN were included: 68 men (57.1%), mean age 51.6 (±19) years, 55.5% (n = 66) hypertension and 8.4% (n = 10) diabetes mellitus. At the time of the kidney biopsy, creatinine 1.8 [0.9–3.6] mg/dl, eGFR 44 [15–81] mL/min/m2 and albumin/creatinine ratio 650 [281–1634]mg/gr. The indications of kidney biopsy were proteinuria and microhematuria (n = 52, 43.7%), microhematuria (n = 22, 18.5%), proteinuria (n = 14, 11.8%) and acute kidney injury (n = 13, 10.9%). The GN diagnosis were: IgA nephropathy (n = 34, 28.6%), extracapillary GN (n = 16, 13.4%), and thrombotic microangiopathy (n = 12, 10.1%). A total of 105 patients (88.2%) had microhematuria, of which 51 (48.6%) had dysmorphia. In patients with cryoglobulinemia, anti-glomerular basement membrane disease and IgA Nephropathy, a higher percentage of dysmorphia was detected (80%, 57% and 51.6%, respectively P = 0.013). A higher prevalence of dysmorphia was also observed in patients with acute kidney injury, proteinuria and microhematuria as indication of kidney biopsy, (P = 0.046). Furthermore, patients with hypertension (P = 0.013) and men (P = 0.038) presented more prevalence of dysmorphic hematuria. However, patients who did not present dysmorphia had a higher ischemic heart disease (P = 0.019), antiplatelet agents (P = 0.016), protein/creatinine ratio (P = 0.043) and positive urine culture (P = 0.046). In the logistic regression analysis, lower protein/creatinine ratio in urine (1.03–9.09 OR: 3.06, P = 0.044) was the only variable associated with the presence of dysmorphia. A ROC curve was obtained with an area under the curve of 0.72 (0.619–0.822 P &amp;lt; 0.001). The sensitivity was 31.9% and specificity of 91.5%. Conclusion In our cohort diagnosed with GN and microhematuria, dysmorphia was detected in approximately half of patients. The absence of hypertension, ischemic heart disease, antiplatelet agents, negative urine culture and lower level of proteinuria were related to the presence of dysmorphia, with a sensitivity of 31.9% and a specificity of 91.5%.

Abstract Background and Aims Identifying systemic proteome signatures in glomerulonephritis (GN) requires further investigation. Plasma proteome profiling may offer a non-invasive alternative to distinguish GN subtypes without kidney biopsy. Method In this study, we analyzed plasma samples from GN patients at baseline biopsy using the OLINK assay, measuring over 5,000 protein levels. The cohort included 35 patients with IgA nephropathy (IgAN), 14 with primary focal segmental glomerulosclerosis (FSGS), 55 with minimal change disease (MCD), and 24 with anti-PLA2R antibody-positive membranous nephropathy (MN). The control group consisted of 40 healthy individuals with normal kidney function. A machine-learning approach employing elastic net regression with 5-fold cross-validation was applied. Results Principal component analysis (PCA) revealed clear discrimination between GN patients and controls. Variance in plasma proteome profiles was primarily driven by disease category (P = 0.001) rather than proteinuria severity (P = 0.40). A model incorporating 150 plasma proteins achieved high discriminatory power for GN, with an overall ROC-AUC of 0.99. Subtype-specific performance was also strong: MCD (AUC = 0.96), IgAN (AUC = 0.96), and MN (AUC = 0.944). However, the performance was relatively low with FSGS (AUC = 0.86). Top predictive proteins varied by GN subtype. For instance, high MERTK, LUC7L, IL4R levels were indicative of MCD, while high SYNM and DDAH1 levels were associated with FSGS. IgAN was characterized by elevated PRG2 and HAVCR1, and MN by high SPOCK1. Conclusion In conclusion, distinct plasma proteome signatures exist for each GN subtype, providing a promising tool for non-invasive diagnosis and disease classification.