Glomerular diseases最新文献

{"title":"Anti-Glomerular Basement Membrane Disease in Association with Pembrolizumab Treated with Rituximab in Addition to Standard Care: A Case Report.","authors":"Tony Lopez, Mukunthan Srikantharajah, Stephen McAdoo","doi":"10.1159/000547089","DOIUrl":"10.1159/000547089","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors have significantly improved the prognosis of patients with certain malignancies; however, they can also be associated with diverse autoimmune organ toxicities, including those affecting the kidney.</p><p><strong>Case presentation: </strong>A 75-year-old man was referred to the nephrology team with a progressive decline in kidney function over a 3-month period. His medical history included a diagnosis of non-small cell lung cancer for which he had been treated with pembrolizumab immunotherapy for the past 18 months (15 cycles). At referral, serum creatinine had risen from a baseline of 140 µmol/L to 208 µmol/L. Urinalysis showed blood and protein, and his urine protein creatinine ratio was 457 mg/mmol. An autoimmune screen yielded a positive anti-glomerular basement membrane (anti-GBM) antibody result (23 IU/L, normal range <7). He underwent a kidney biopsy. Light microscopy demonstrated focal and necrotising crescentic glomerulonephritis and eosinophilic tubulointerstitial nephritis. Immunofluorescence revealed linear IgG deposition along glomerular basement membranes. The patient did not have any clinical or radiographic evidence of pulmonary haemorrhage. A diagnosis of anti-GBM glomerulonephritis was made, and the patient received treatment with corticosteroids, seven cycles of plasma exchange, oral cyclophosphamide (total dose 3.3 g) and two intravenous doses of 1 g rituximab. The patient achieved a negative anti-GBM status within 1 week of presentation. Despite treatment for anti-GBM disease and cessation of pembrolizumab, his kidney function continued to decline, and his cancer progressed. Six months after diagnosis, he presented unwell to the hospital and received treatment for a presumed chest infection. Unfortunately, his condition deteriorated during this inpatient stay, and he passed away peacefully (6.7 months after induction treatment).</p><p><strong>Conclusion: </strong>This case demonstrates a rare but important diagnosis of anti-GBM disease during pembrolizumab therapy. It highlights the challenges of managing immunosuppression and chemotherapy options in patients who are frail and with impaired kidney function.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"344-351"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Punctate Podocyte IgG Staining Does Not Differentiate Primary from Secondary Minimal Change Disease.","authors":"Matthew Leong, Chen Yu Jamie Lee, Michifumi Yamashita, Daisuke Kiyozawa, Man-Hoon Han, Cynthia C Nast","doi":"10.1159/000547193","DOIUrl":"10.1159/000547193","url":null,"abstract":"<p><strong>Introduction: </strong>Punctate IgG staining of podocytes (\"dusting\") identified by immunofluorescence recently has been described in a subset of minimal change disease (MCD), possibly correlating with anti-nephrin or other autoantibodies. Whether dusting is associated with other clinicopathologic features of MCD remains unclear, but identification of these associations could provide insight into MCD mechanisms, prognosis, and therapeutic strategies.</p><p><strong>Methods: </strong>Cases with a diagnosis of MCD over 8.5 years at one institution were retrospectively reviewed, including reexamination of IgG immunofluorescence and electron microscopy when necessary. Demographic, clinical, and ultrastructural feature data were collected. Cases were divided into presumed primary and secondary MCD based on clinical associations and they were assessed for dusting frequency.</p><p><strong>Results: </strong>A total of 371 cases were included, of which 73% were primary MCD and 16.4% were pediatric. Dusting frequency among MCD etiologies ranged from 45 to 63% and did not differ between children and adults, or in primary versus any secondary MCD association. Dusting was positively correlated with the degree of podocyte foot process effacement (<i>p</i> < 0.005) and actin cytoskeletal condensation (<i>p</i> = 0.001). Otherwise, dusting was not associated with other ultrastructural features of proteinuric kidney disease or with podocyte ballooning clusters.</p><p><strong>Conclusion: </strong>Podocyte IgG dusting was not specific for any one etiologic trigger of MCD or age category. This suggests that autoantibodies may induce MCD irrespective of a primary (idiopathic) versus a presumed secondary cause, which may alter the diagnostic and therapeutic approach. Additionally, podocyte ultrastructural features associated with dusting may reflect mechanisms of autoantibody-induced injury, or may represent a feature of disease severity and/or temporal progression.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"316-327"},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum NF-κB-Regulated Biomarkers of Proliferative Lupus Nephritis.","authors":"Nicholas A Shoctor, Makayla P Brady, Rebecca R Lightman, Kristen N Overton, Shweta Tandon, Steven P Mathis, Madhavi J Rane, Michelle T Barati, Cristina G Arriens, David W Powell, Dawn J Caster","doi":"10.1159/000547044","DOIUrl":"10.1159/000547044","url":null,"abstract":"<p><strong>Introduction: </strong>Lupus nephritis (LN) is kidney inflammation that commonly occurs from systemic lupus erythematosus. NF-κB activity is increased in LN patients, leading to elevated circulating concentrations of immune modulators that contribute to LN pathophysiology. This study sought to investigate this phenomenon with the aim of discovering novel serum biomarkers for LN.</p><p><strong>Methods: </strong>A multiplex antibody-based assay was performed with serum from 24 LN patients and 7 healthy controls (HCs) to determine if 48 NF-κB-regulated proteins were elevated in LN patients. Confirmation ELISAs were performed on stem cell factor (SCF), macrophage colony-stimulating factor (M-CSF), and interleukin-2 receptor alpha (IL-2Rα) subunit in a separate sample cohort of 27 LN patients and 10 HC. Follow-up ELISAs were performed on samples obtained from the same patients during LN remission to determine if these candidates were reliable predictors of disease activity. Comparisons of protein levels between LN patients and HC were performed using a series of 2-tailed Mann-Whitney tests. Paired samples were analyzed using a Wilcoxon matched pairs test. Two-tailed Spearman's correlation analyses were used to compare serum protein concentrations with LN clinical parameters. All <i>p</i> values were adjusted for multiple comparisons.</p><p><strong>Results: </strong>SCF, M-CSF, and IL-2Rα were significantly elevated in LN serum. Elevated serum SCF and M-CSF were significantly correlated with elevated urine protein to creatinine ratio, decreased estimated glomerular filtration rate, and elevated serum creatinine. Elevated serum IL-2Rα was significantly correlated with elevated serum creatinine. Serum SCF concentration was significantly decreased during LN remission in paired samples from individuals, but it was not a good predictor at the population level (AUC = 0.6265).</p><p><strong>Conclusion: </strong>We identified the NF-κB-regulated proteins SCF, M-CSF, and IL-2Rα as candidate serum biomarkers for consideration in monitoring LN activity. Our findings also indicate the importance for follow-up mechanistic studies pertaining to these inflammatory mediators.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"328-343"},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic Characteristics of Intraglomerular Malignancy in Kidney Biopsies.","authors":"Chen Yu Jamie Lee, Cynthia C Nast, Jean Hou, Mark Haas, Mercury Y Lin, Michifumi Yamashita, Hae Yoon Grace Choung","doi":"10.1159/000547065","DOIUrl":"10.1159/000547065","url":null,"abstract":"<p><strong>Introduction: </strong>Intraglomerular malignancy (IGM) is a rare finding, with current data limited to case reports and small, often postmortem, series. This study aimed to characterize the clinicopathologic features of kidney biopsy cases with IGM.</p><p><strong>Methods: </strong>Renal biopsy cases diagnosed with IGM from January 2000 to June 2023 at Cedars Sinai Medical Center were retrospectively reviewed. Demographic data, clinical characteristics, and pathologic data were collected, and cases were divided into hematologic (HEME) versus non-hematologic (non-HEME) malignancy.</p><p><strong>Results: </strong>We identified 9 patients with IGM. Five were hematolymphoid in origin, and 4 were from metastatic solid tumor (2 carcinomas from the lung, 1 neuroendocrine tumor of likely lung origin, and 1 from the head and neck). All patients presented with proteinuria and hematuria, and 89% had renal dysfunction. The median serum creatinine was 2.9 (IQR 1.7-5.7) mg/dL. All non-HEME patients had an established malignant diagnosis at the time of kidney biopsy, whereas all HEME cases were initially or concurrently diagnosed at the time of biopsy. Two of the non-HEME biopsies showed extracapillary hypercellularity due to malignant cells, a feature not seen in HEME cases. Of the 8 patients with follow-up available, 7 (88%) died within a median of 69 (IQR 4-161) days.</p><p><strong>Conclusion: </strong>IGM is a rare presentation of disseminated malignancy, often indicating advanced disease with poor prognosis. Nephropathologists should be aware of IGM as a histologic mimicker of endocapillary hypercellularity or cellular crescent formation. Similarly, the provision of complete clinical history is critical for accurate biopsy assessment and to avoid this diagnostic pitfall. Given its high mortality rate and the short interval between tissue diagnosis and death, the identification of IGM should prompt urgent medical attention.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"304-315"},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney Biopsy in 613 Elderly Brazilian Patients: Clinicopathological Correlations.","authors":"Gisane Cavalcanti Rodrigues, Michelle Tiveron Passos Riguetti, Gianna Mastroianni Kirsztajn","doi":"10.1159/000546391","DOIUrl":"10.1159/000546391","url":null,"abstract":"<p><strong>Introduction: </strong>According to the Brazilian Dialysis Survey 2022 glomerular diseases are among the three main causes of chronic kidney disease in the elderly. The distribution and presentation of such kidney diseases specifically in elderly need additional and more recent data in Brazil.</p><p><strong>Methods: </strong>Retrospective analysis of 613 native kidney biopsies from patients aged 60 years and above, in a single center, of the five regions of Brazil, performed from 2015 to 2020.</p><p><strong>Results: </strong>Most patients were males with a mean age of 67.5 years. Nephrotic syndrome (NS) was the main clinical indication (52.4%), followed by asymptomatic urinary abnormalities (AUA, 21.4%), rapidly progressive glomerulonephritis (RPGN, 10.1%), and acute renal failure (ARF, 6.1%). In the group aged 80 years and over, indications were significantly increased due to acute conditions (ARF and RPGN) compared to other groups. Membranous nephropathy (MN) was the most common histopathological diagnosis, followed by pauci-immune glomerulonephritis (PIGN, 12.7%) and diabetic nephropathy (DN, 10.3%). DN was more frequent in the younger elderly, amyloidosis between 70 and 79 years old, and PIGN in those aged 80 or older. Younger men had higher frequencies of IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS); younger women had more PIGN, amyloidosis, and minimal change disease (MCD); 80 or more women had more PIGN and chronic glomerulonephritis. The clinical presentation of NS was mainly associated with the histopathological findings of MN and MCD. AUA was more associated with MN and IgAN.</p><p><strong>Conclusion: </strong>In this study, the NS was the most frequent clinical presentation, and the most common histopathological finding was MN. We observed differences in glomerular disease frequencies between genders and age-groups in the elderly. Considering our findings, we emphasize the importance of kidney biopsy in this age-group due to the potential for improvement with specific treatments.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"278-287"},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes in the Nephrotic Syndrome Study Network: Disease Burden and Treatment Patterns over Time.","authors":"Yelena Drexler, Ambarish Athavale, Abigail R Smith, Qian Liu, Jarcy Zee, Laura H Mariani, Richard A Lafayette","doi":"10.1159/000546655","DOIUrl":"10.1159/000546655","url":null,"abstract":"<p><strong>Introduction: </strong>Among patients with proteinuric glomerular diseases, there is a paucity of high-quality evidence and substantial variation in practice patterns among nephrologists. Our objective was to describe the clinical presentation, treatment patterns, and outcomes of patients with biopsy-proven glomerular diseases in a contemporary, well-phenotyped, diverse cohort.</p><p><strong>Methods: </strong>The Nephrotic Syndrome Study Network (NEPTUNE) is a prospective observational cohort study of children and adults with proteinuric glomerular diseases enrolled at 23 centers in the USA and Canada since 2009. We included participants who underwent their first clinically indicated kidney biopsy demonstrating minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or membranous nephropathy (MN). We described demographic and clinical characteristics at the time of biopsy and baseline visits. We analyzed treatment patterns for participants with and without immunosuppressive therapy (IST) use prior to biopsy. We described clinical outcomes including complete remission (CR) and proteinuria, stratified by IST use, at biopsy and up to 36 months' follow-up.</p><p><strong>Results: </strong>Among 507 NEPTUNE participants who underwent biopsy, 203 were classified as having FSGS, 193 as having MCD, and 111 as having MN. Corticosteroid exposure was high overall and highest among MCD patients. Substantial heterogeneity in treatment choices was evident, particularly among those initiating second-line therapy. The rate of kidney failure was highest, and CR rates were lowest, among patients with FSGS, who experienced ∼50% cumulative probability of first remission at 36 months after biopsy. At 36 months, 49.5% of all patients were not in CR; 19.3% were not in CR despite being on IST. Additionally, 20.2% of patients had proteinuria >1.5 g/g; among those on IST at their 36-month visit, 26.3% had UPCR >1.5 g/g.</p><p><strong>Conclusion: </strong>A substantial proportion of patients were not in remission and had persistent proteinuria despite being on IST 3 years after their first biopsy.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"288-303"},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial Idiopathic Glomerular Disease due to a Unique Renal-Predominant Phenotype of MYH9-Related Disease: A Case Report.","authors":"Natasha S Freeman, Kelsie Bogyo, Andrew Beenken, Jordan G Nestor, Simone Sanna-Cherchi, Pietro A Canetta","doi":"10.1159/000546242","DOIUrl":"10.1159/000546242","url":null,"abstract":"<p><strong>Introduction: </strong>MYH9-related disease (MYH9-RD) is a rare genetic cause of proteinuric kidney disease. It typically manifests as a syndromic condition, presenting with macrocytic thrombocytopenia, sensorineural hearing loss (SNHL), chronic glomerulopathy, elevated liver enzymes, and early-onset bilateral cataracts. In accordance with CARE guidelines, we present a case report of a father and daughter with renal-predominant MYH9-RD due to a recently described missense variant affecting the head domain of non-muscle myosin heavy chain IIA.</p><p><strong>Case presentations: </strong>Patient 1 was an 18-year-old woman with childhood proteinuria who presented with severely advanced kidney failure. Dialysis was initiated as a bridge to a living unrelated renal transplant (LURT). Family history was notable for proteinuric kidney disease in her father (patient 2). Eight years later, genetic testing identified a likely pathogenic missense variant in the head domain of the <i>MYH9</i> gene (c.1271G>A, p.R424Q). A predictive structural model was obtained via AlphaFold Protein Structure Database, in which the mutation interrupts hydrogen bonding and π-cation interactions, likely leading to protein misfolding. Subsequent clinical screening revealed persistent mild thrombocytopenia and elevated liver enzymes, without cataracts or SNHL. Patient 2 was a 53-year-old man with childhood proteinuria who eventually presented with stage 4 chronic kidney disease and soon after underwent LURT. After patient 1's genetic diagnosis, he was confirmed to have the same mutation by genetic testing. Subsequent screening revealed mild thrombocytopenia and elevated liver enzymes with hepatic steatosis progressing to cirrhosis, without cataracts or SNHL.</p><p><strong>Conclusion: </strong>The finding of this <i>MYH9</i> p.R424Q variant confirmed a diagnosis of MYH9-RD in these patients. <i>MYH9</i> variants affecting the head domain typically result in severe thrombocytopenia. This recently reported head domain variant caused severe renal manifestations with mild thrombocytopenia and no manifestations of SNHL or cataracts in both patients, suggesting that this variant causes a renal-predominant form of MYH9-RD.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"243-249"},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Events in Lupus Nephritis: A Systematic Review and Meta-Analysis.","authors":"Mehrbod Vakhshoori, Giv Heidari-Bateni, Roy O Mathew, Amir Abdipour, Noha S Daher, Swapnil Hiremath, Mohamed Hassanein, Mohadese Golsorkhi, Niloufar Ebrahimi, Arvind Kumar Singh, Sayna Norouzi","doi":"10.1159/000546177","DOIUrl":"10.1159/000546177","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic lupus erythematous (SLE) is known to be associated with cardiovascular events (CVEs). However, the incidence of CVE has not been thoroughly investigated in lupus nephritis (LN) patients. In this meta-analysis, we aimed to assess the incidence of CVE in patients with LN.</p><p><strong>Methods: </strong>We performed a literature search in PubMed, Scopus, and Web of Science database for studies reporting CVE (myocardial infarction [MI], heart failure, cerebrovascular accident [CVA] [i.e., ischemic or hemorrhagic stroke or transient ischemic attack], any cardiovascular- or cerebrovascular-related disease or death) in patients with LN. In addition, subgroup analyses were conducted according to geographical locations and kidney disease status. We also separately reported the incidence rate of MI, CVA, and cardiovascular- or cerebrovascular-related deaths, with CVE and MI risk in patients with LN.</p><p><strong>Results: </strong>Twenty-one records, encompassing 29,489 subjects, were included. The overall CVE incidence was 9% (95% confidence interval [CI]: 6-12%). Specifically, the incidence of MI (8 studies, <i>n</i> = 5,735), CVA (9 studies, <i>n</i> = 6,053), and mortality attributed to any cardiovascular or cerebrovascular disease (10 studies, <i>n</i> = 26,511) were 4% (95% CI: 2-7%), 4% (95% CI: 2-7%), and 5% (95% CI: 3-7%), respectively. Geographically, patients residing in Asia exhibited a lower incidence of CVE (2.3%, 95% CI: 1.6-3.3%) compared to those residing in North America (10.1%, 95% CI: 5.7-17.2%) and Europe (13.3%, 95% CI: 7.6-22.4%). Patients with LN had higher risk of CVE compared to SLE subjects (odds ratio: 1.18, 95% CI: 1.03-1.34, <i>p</i> = 0.014).</p><p><strong>Conclusion: </strong>CVE occurrence among individuals with LN is significant, and this disease entity increases CVE risk, highlighting the importance of implementing early therapeutic interventions to prevent poor outcomes.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"261-277"},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pitfalls in the Pathological Diagnosis of Glomerular Diseases: Why Stop at One?","authors":"David N Howell","doi":"10.1159/000546083","DOIUrl":"10.1159/000546083","url":null,"abstract":"<p><strong>Background: </strong>Renal pathologists face a number of challenges in evaluating kidney biopsies: one that is sometimes overlooked is the presence of multiple pathological processes in a single biopsy. Figuring out the interrelatedness (or lack thereof) of more than one form of renal abnormality can difficult. Several pitfalls in biopsy evaluation also await the unprepared diagnostician. This communication will examine these problems with illustrations from a single nephropathology practice dating back more than 3 decades.</p><p><strong>Summary: </strong>Paired processes in a biopsy can be related in many ways, including 2 lesions with a single root cause, 1 lesion that is a direct consequence of another, 1 lesion that results from the treatment of another, 2 lesions for which circumstantial evidence suggests a connection, and finally, 2 lesions occurring together entirely by chance. Failure to recognize a second lesion after a first has been identified can result from overintense focus on the first lesion, subtlety of the second lesion, unusual situations where the second lesion involves the absence rather than presence of something, instances where the first lesion obscures the second, and disease pairs where the findings for the second are a subset of those for first.</p><p><strong>Key messages: </strong>Detection and understanding of multiple pathological processes in a biopsy and avoiding pitfalls in their analysis requires the use of all available diagnostic modalities and thorough examination of all tissue received. Careful attention should be paid to the clinical record, but with the recognition that it may not always be entirely accurate or predictive of what will be found in the biopsy. Above all, pathologists must resist the temptation to think that their work is done when they find the first abnormality.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"250-260"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial Kidney Disease Phenocopying Hypertensive Nephropathy.","authors":"Fezile Ozdemir, D Deren Oygar, Ahmet Behlul, Salahi Ataç, Simge Bardak, Meral Yükseliş, Gregory Papagregoriou, Apostolos Malatras, Daniel P Gale, Guy H Neild, Constantinos Deltas, Cemal Gurkan","doi":"10.1159/000546094","DOIUrl":"10.1159/000546094","url":null,"abstract":"<p><strong>Introduction: </strong>Familial kidney disease is common in Cyprus and previous studies have found that the majority of families have mutations in Alport syndrome genes COL4A3/4/5. We have collected data from over 50 Turkish Cypriot families in whom kidney disease appears to follow an autosomal dominant pattern, and looked for pathological variants in these genes.</p><p><strong>Methods: </strong>Probands from 55 families underwent massive parallel DNA sequencing using a glomerular gene panel for familial hematuria, and whole-exome sequencing (WES) was also performed in 22 of them. Clinical records were reviewed.</p><p><strong>Results: </strong>Likely pathogenic variants were identified in 7 of the 55 families (COL4A3 [3], COL4A4 [2], and COL4A5 [2]), leaving 48 unsolved families. Among the latter a common missense variant of uncertain significance (COL4A4:p.G545A), was present in 5 families (9.1%). In contrast to families with a pathogenic variant in COL4A3/4 and a clear glomerular phenotype the 5 families (54 patients with clinical and genetic data), manifested near dominant susceptibility with incomplete penetrance, presenting with hypertension, variable and intermittent microscopic hematuria, and minimal proteinuria, <1 g/day until the estimated glomerular filtration rate (eGFR) fell below 30 mL/min, after which it increased in some individuals. Of those over age 50, 20% had reached end-stage by median age of 66 (48-80) years.</p><p><strong>Conclusions: </strong>We describe a kidney disease with mild hypertension that is more characteristic of a tubulointerstitial disease and phenocopies hypertensive nephropathy. While the variant COL4A4:p.G545A is not responsible for a Mendelian CKD phenotype, it appears to increases the susceptibility, acting as a hypomorphic variant contributing to Alport spectrum nephropathy. Early detection and treatment with ACE inhibitors should prolong kidney survival to an age where hemodialysis is avoided.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"5 1","pages":"233-242"},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}