Nephron最新文献

{"title":"Immune Checkpoint Inhibitor-Associated Nephrotoxicity.","authors":"Omar Mamlouk, Farhad R Danesh","doi":"10.1159/000531297","DOIUrl":"10.1159/000531297","url":null,"abstract":"<p><strong>Context: </strong>The clinical indications for immune checkpoint inhibitors (ICIs) are rapidly expanding. However, adverse events affecting multiple organs, including kidneys leading to ICI-associated acute kidney injury (AKI), remain a significant challenge with ICI therapy. Although AKI is considered a rare complication, it can be severe and result in treatment interruption or discontinuation of ICIs. Despite a generally favorable kidney prognosis, the possibility of re-challenging ICI therapy remains a subject of debate, particularly for patients who have exhausted other treatment options or experienced severe AKI. Subject of Review: In a recent review article, Sprangers et al. provide a comprehensive overview of the possible mechanisms and clinical manifestations of ICI-associated AKI [Nat Rev Nephrol. 2022;18(12):794-805]. The authors propose a practical strategy for diagnosing and managing suspected cases of ICI-associated AKI, which includes identifying a subset of eligible patients who may be re-exposed to ICIs following an episode of AKI. Second Opinion: The authors of the review article offer several recommendations on the diagnosis and treatment of ICI-associated nephrotoxicity. While we generally agree with the recommendations proposed by the authors, it is important to acknowledge that the available data primarily rely on small retrospective studies, as the authors have recognized. In addition, there are two key questions that need be carefully addressed in future studies: (1) the optimal dose and duration of corticosteroids and the use of alternative immunosuppressive agents in patients with ICI-associated nephrotoxicity and (2) a clear guideline for restarting ICI treatment in patients with AKI who have not fully recovered their kidney function.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"11-15"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9606853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of NCAM1-Positive Lupus Nephritis with NCAM1 Antibody Titers Responsive to Rituximab.","authors":"Yifeng Wang, Ruiying Chen, Min Han, Shaojun Liu, Qionghong Xie, ChuanMing Hao","doi":"10.1159/000534037","DOIUrl":"10.1159/000534037","url":null,"abstract":"<p><p>Neural cell adhesion molecule 1 (NCAM1) is a recently identified new antigen of membranous nephropathy (MN) mostly secondary to systemic lupus erythematosus with a low positive rate of 6.6%, and its corresponding antibody was detected in patients' sera. Here, we reported a case of NCAM1-positive lupus nephritis (class V+III) developed from MN. The patient was refractory to multiple immunosuppressive regimens but achieved remission after the application of rituximab as an add-on therapy and showed a reduction of anti-NCAM1 antibody and proteinuria.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"312-318"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Renal Function in Adult Patients with Phenylketonuria.","authors":"Flóra Franciska Prepok, Karolina Kornélia Schnabel, Csaba Sumánszki, András Gellért Barta, András Tislér, Péter Reismann","doi":"10.1159/000531913","DOIUrl":"10.1159/000531913","url":null,"abstract":"<p><strong>Introduction: </strong>In phenylketonuria (PKU), toxic phenylalanine (Phe) can harm other organs beyond the brain. Furthermore, the lifelong therapy of PKU consists of consumption of increased amounts of amino-acid mixture that provoke hyperfiltration in the glomeruli. Therefore, the adherence to therapy in PKU might influence the long-term kidney function in PKU patients.</p><p><strong>Methods: </strong>Data from 41 adult, early treated PKU patients were analyzed in this 10-year, retrospective, monocentric study. Two subgroups were created according to their therapy adherence: one with long-term blood Phe levels in the therapeutic range (&lt;600 µmol/L), and one with suboptimal blood Phe levels. Renal function and metabolic parameters were collected over 10 years. Kidney function parameters were compared between the two groups and associations between blood Phe levels and kidney function were tested.</p><p><strong>Results: </strong>After 10 years, serum creatinine levels (p = 0.369) and estimated glomerular filtration rate (eGFR) (p = 0.723) did not change significantly from baseline in the good therapeutic group. The suboptimal therapeutic group's eGFR decreased in the same period (from 110.4 ± 14 mL/min/1.73 m2 to 94.2 ± 16 mL/min/1.73 m2, p = 0.017). At 10 years, the suboptimal therapeutic group had an increased serum creatinine level (81 ± 14.4 μmol/L vs. 71.5 ± 13 μmol/L, p = 0.038), and a decreased eGFR (94.2 ± 16 mL/min/1.73 m2 vs. 103.3 ± 13 mL/min/1.73 m2p = 0.031) compared to the good adhering group. Significant negative correlation between Phe levels and eGFR (r = -0.41, p = 0.008) was observed.</p><p><strong>Conclusion: </strong>Long-term suboptimal therapy adherence in PKU patients with high blood Phe levels may lead to deterioration in kidney function.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"195-203"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41128091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Mesangial Proliferative Glomerulonephritis Has Increased the Platelet Thrombus Formation Potentials under High-Shear Flow Condition.","authors":"Takashi Omae, Tomoaki Ishikawa, Kenichi Ogiwara, Keiji Nogami","doi":"10.1159/000534494","DOIUrl":"10.1159/000534494","url":null,"abstract":"<p><strong>Introduction: </strong>Blood coagulation is associated with glomerulonephritis (GN) pathophysiology. Using whole-blood-based rotational thromboelastometry, we recently reported that the degree of hypercoagulability in pediatric patients with immunoglobulin A nephropathy (IgAN), a GN, might be associated with pathological severity. To further clarify the coagulation status of mesangial proliferative GN (MesPGN), we assessed the platelet thrombus formation (PTF) under high-shear flow using a microchip-based flow chamber system (T-TAS®).</p><p><strong>Methods: </strong>Thirty-four pediatric patients definitively diagnosed with MesPGN by renal biopsy at Nara Medical University Hospital between 2015 and 2022 were enrolled, and 29 patients (case group; median age, 8.0 years) were assessed. Microchips coated with collagen (PL-chip) were used to assess PTF at high-shear in whole blood. The times to increase by 10 and 30 kPa (T10 and T30) from baseline were calculated and compared with those of the pediatric controls. Changes in the parameters during the treatment course and the relationship between pathological severity and the parameters were evaluated.</p><p><strong>Results: </strong>T10 and T30 parameters in the PL-chip were significantly shorter, and the area under the curves were greater in the case group than those in the control group (both p &lt; 0.05). Each parameter was enhanced during the 3-week treatment but improved after the end of treatment. No significant relationship was observed between pathological severity and these parameters. Little PTF difference was observed between IgAN and Henoch-Schönlein purpura nephritis.</p><p><strong>Conclusions: </strong>Pediatric MesPGN increased the potential for PTF under high-shear flow conditions.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"415-425"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41183176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glomerular Filtration Rate Estimation in Adults: Myths and Promises.","authors":"Pierre Delanaye, Etienne Cavalier, Thomas Stehlé, Hans Pottel","doi":"10.1159/000536243","DOIUrl":"10.1159/000536243","url":null,"abstract":"<p><strong>Background: </strong>In daily practice, glomerular filtration rate (GFR) is estimated with equations including renal biomarkers. Among these biomarkers, serum creatinine remains the most used. However, there are many limitations with serum creatinine, which we will discuss in the current review. We will also discuss how creatinine-based equations have been developed and what we can expect from them in terms of performance to estimate GFR.</p><p><strong>Summary: </strong>Different creatinine-based equations have been proposed. We will show the advantages of the recent European Kidney Function Consortium equation. This equation can be used in children and adults. This equation can also be used with some flexibility in different populations.</p><p><strong>Key messages: </strong>GFR is estimated by creatinine-based equations, but the most important for nephrologists is probably to know the limitations of these equations.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"408-414"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney Failure Secondary to Hereditary Xanthinuria due to a Homozygous Deletion of the XDH Gene in the Absence of Overt Kidney Stone Disease.","authors":"Pedro Lisboa Gonçalves, Hugo Diniz, Isabel Tavares, Sofia Dória, Juan Dong, McKenna Kyriss, Lynette Fairbanks, João Paulo Oliveira","doi":"10.1159/000536248","DOIUrl":"10.1159/000536248","url":null,"abstract":"<p><p>Hereditary xanthinuria (HXAN) is a rare metabolic disorder that results from mutations in either the xanthine dehydrogenase (XDH) or the molybdenum cofactor sulfurase genes (MOCOS), respectively defining HXAN type I and type II. Hypouricemia, hypouricosuria, and abnormally high plasma and urine levels of xanthine, causing susceptibility to xanthine nephrolithiasis and deposition of xanthine crystals in tissues, are the metabolic hallmarks of HXAN. Several pathogenic variants in the XDH gene have so far been identified in patients with HXAN type I, but the clinical phenotype associated with the whole deletion of the human XDH gene is unknown. Herein, we report the case of a woman diagnosed with HXAN, whose molecular genetic testing revealed a homozygous microdeletion involving the XDH gene. Distinctive features of her medical history were the diagnosis of arterial hypertension and microalbuminuria at 22 years of age; a single pregnancy at the age of 25, complicated by proteinuria and transient kidney function deterioration in the third trimester; unexplained severe hypouricemia incidentally discovered during pregnancy; inability to breastfeed her newborn daughter due to primary agalactia; chronic kidney disease (CKD) stage 3 diagnosed at age 35; and progression to end-stage kidney disease over the next 12 years. Protocol noninvasive laboratory and imaging investigation was not informative as to the cause of CKD. This is the first description of the clinical phenotype associated with a natural knockout of the human XDH gene. Despite the lack of kidney histopathology data, the striking similarities with the phenotypes exhibited by comparable murine models validate the latter as useful sources of mechanistic insights for the pathogenesis of the human disease, supporting the hypothesis that the absence of xanthine dehydrogenase activity might represent a susceptibility factor for chronic tubulointerstitial nephritis, even in patients without kidney stones.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"578-583"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription Factor ATF3 Mediating SOCS3 Expression Aggravates Renal Ischemia-Reperfusion Injury by Activating Mitophagy.","authors":"Yu Luo, Zhitao Cai, Xiongfei Wu, Feng Liu, Lian Li","doi":"10.1159/000531912","DOIUrl":"10.1159/000531912","url":null,"abstract":"<p><strong>Introduction: </strong>Suppressor of cytokine signaling 3 (SOCS3) is highly expressed in mice with renal ischemia/reperfusion (RI/R) injury and has the potential to regulate mitophagy. On this basis, this study further investigates the possible mechanism via which SOCS3 affects RI/R by regulating mitophagy.</p><p><strong>Method: </strong>After establishing a RI/R injury mouse model and a hypoxia/reoxygenation (H/R) cell model, the effects of silenced SOCS3 on injury and mitophagy in the above models were analyzed by ELISA, quantitative real-time polymerase chain reaction, Western blot, pathological sections, CCK-8 assay, flow cytometry, and JC-1 assay. Mechanistic studies were carried out with the help of database analysis and binding validation experiments (chromatin immunoprecipitation, dual-luciferase reporter assay, and co-immunoprecipitation). After the binding target was identified, the regulatory relationship between the target gene and SOCS3 was verified by rescue experiments.</p><p><strong>Result: </strong>The large increase in blood urea nitrogen (BUN) and creatinine (Cr) levels verified the success of the RI/R model. SOCS3 expression was up-regulated in RI/R mice. Silenced SOCS3 alleviated kidney damage and mitochondrial abnormalities in RI/R mice and inhibited mitophagy at the molecular level. Likewise, silenced SOCS3 alleviated H/R-induced cell damage and mitophagy. Finally, activating transcription factor 3 (ATF3) was determined to bind to the promoter of SOCS3, which interacted with insulin-like growth factor 1 receptor (IGF1R). Rescue experiments confirmed the effect of ATF3 on SOCS3 expression and the underlying regulatory mechanism.</p><p><strong>Conclusion: </strong>ATF3 mediates SOCS3 expression to promote the activation of mitophagy, thereby aggravating renal ischemia-reperfusion injury.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"230-244"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92155379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Renal Neoplasia in Autosomal Dominant Polycystic Kidney Disease: Systematic Review and Meta-Analysis.","authors":"Anna M Drake, Jessica A Paynter, Arthur Yim, Jake A Tempo, Todd G Manning, Janelle Brennan, Kirby R Qin","doi":"10.1159/000536245","DOIUrl":"10.1159/000536245","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition; however, its relationship with renal cell carcinoma (RCC) remains unclear. This paper aims to establish the prevalence of RCC and its subtypes amongst ADPKD patients.</p><p><strong>Methods: </strong>A database search was conducted to retrieve studies reporting RCC occurrence within ADPKD patients until July 2023. Key outcomes included number and subtype of RCC cases, and number of RCCs presenting incidentally. A random-effects meta-analysis was performed.</p><p><strong>Results: </strong>Our search yielded 569 articles, 16 met the inclusion criteria. Nephrectomy specimens from 1,147 ADPKD patients were identified. Of studies reporting per-kidney results (n = 13), 73 RCCs were detected amongst 1,493 kidneys, equating to a per-kidney prevalence of 4.3% (95% CI, 3.1-5.7, I2 = 15.7%). 75 ADPKD patients were found to have RCC (75/1,147), resulting in a per-person prevalence of 5.7% (95% CI, 3.7-7.9, I2 = 40.3%) (n = 16). As 7 patients had bilateral disease, 82 RCCs were detected in total. Of these, 39 were clear cell RCC, 35 were papillary and 8 were other. As such, papillary RCCs made up 41.1% (95% CI, 25.9-56.9, I2 = 18.1%) of detected cancers. The majority of RCCs were detected incidentally (72.5% [95% CI, 43.7-95.1, I2 = 66.9%]).</p><p><strong>Conclusion: </strong>ADPKD appears to be associated with the papillary RCC subtype. The clinical implications of these findings are unclear, however, may become apparent as outcomes and life expectancy amongst APDKD patients improve.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"457-467"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"8th Update on Fabry Disease: Biomarkers, Progression and Treatment Opportunities in 2024.","authors":"","doi":"10.1159/000539834","DOIUrl":"10.1159/000539834","url":null,"abstract":"<p><p>Fabry Update.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":"148 Suppl 1 ","pages":"1-76"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors and Clinical Outcomes of Renal Thrombotic Microangiopathy in Children with Lupus Nephritis in Terms of Pathological and Clinical Features.","authors":"Pei Zhang, Xiao Yang, Meng-Zhen Fu, Chun-Lin Gao, Xiang Fang, Zheng-Kun Xia","doi":"10.1159/000538240","DOIUrl":"10.1159/000538240","url":null,"abstract":"<p><strong>Background: </strong>Thrombotic microangiopathy (TMA) is an important risk factor for the prognosis of lupus nephritis (LN). Patients with LN complicated with TMA tend to be critically ill with high mortality and poor prognosis. In the present study, we retrospectively analyzed the clinical manifestations, laboratory results, renal pathological manifestations, and prognosis of children with LN-TMA and analyzed the risk factors for end-stage renal disease (ESRD) in children with LN-TMA.</p><p><strong>Methods: </strong>Seventy-four patients with LN and renal TMA (rTMA) were selected and compared to 128 LN controls without TMA (1:2 ratio) matched according to demographics, pathological type and treatments.</p><p><strong>Results: </strong>The mean values of systolic blood pressure, diastolic blood pressure (DBP), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), urinary protein quantitation (PRO), urine red blood cells, N-acetyl-β-D-glucosidase (NAG), retinol-binding protein, systemic lupus erythematosus disease activity score (SLEDAI), and activity index (AI) scores in the TMA group were all higher than those in the non-TMA group (p &lt; 0.05 and p &lt; 0.01). The mean values of complement C3, hemoglobin, platelets, estimated glomerular filtration rate, and chronic index (CI) score in the TMA group were all lower than those in the non-TMA group (p &lt; 0.05 and p &lt; 0.01). The number of cases of glomerular crescent, fibrous crescent, endocapillary proliferation, tubular atrophy, interstitial fibrosis, C3 and C1q deposition in the TMA group was higher than that in the non-TMA group (p &lt; 0.05 and p &lt; 0.01). The 3-year and 5-year renal survival rates in the TMA group (88.93% vs. 97.00%, p &lt; 0.05) and TMA group (61.41% vs. 82.31%, p &lt; 0.05) were significantly lower than those in the non-TMA group. Multivariate Cox regression analysis showed that serum creatinine before treatment (≥110 μmol/L), TMA and interstitial fibrosis were independent risk factors for the development of ESRD in LN children.</p><p><strong>Conclusion: </strong>The general condition of children with TMA is critical, and the prognosis is poor. Early detection, early treatment and the development of new treatments are key to improving LN-TMA outcomes in children.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"609-617"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}