Pub Date : 2024-01-01Epub Date: 2023-05-25DOI: 10.1159/000530657
Silvia Orisio, Marina Noris, Miriam Rigoldi, Elena Bresin, Norberto Perico, Matias Trillini, Roberta Donadelli, Annalisa Perna, Ariela Benigni, Giuseppe Remuzzi
Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the disease-causing variants observed in ADPKD patients are in two genes: PKD1 and PKD2.
Methods: 237 patients from 198 families with a clinical diagnosis of ADPKD were screened for PKD1 and PKD2 genetic variants using Sanger sequencing and multiple ligation-dependent probe amplification analysis.
Results: Disease-causing (diagnostic) variants were identified in 173 families (211 patients), 156 on PKD1 and 17 on PKD2. Variants of unknown significance were detected in 6 additional families, while no mutations were found in the remaining 19 families. Among the diagnostic variants detected, 51 were novel. In ten families, seven large rearrangements were found and the molecular breakpoints of 3 rearrangements were identified. Renal survival was significantly worse for PKD1-mutated patients, particularly those carrying truncating mutations. In patients with PKD1 truncating (PKD1-T) mutations, disease onset was significantly earlier than in patients with PKD1 non-truncating variants or PKD2-mutated patients.
Conclusions: Comprehensive genetic testing confirms its utility in diagnosing patients with ADPKD and contributes to explaining the clinical heterogeneity observed in this disease. Moreover, the genotype-phenotype correlation can allow for a more accurate disease prognosis.
{"title":"Mutation Analysis of PKD1 and PKD2 Genes in a Large Italian Cohort Reveals Novel Pathogenic Variants Including a Novel Complex Rearrangement.","authors":"Silvia Orisio, Marina Noris, Miriam Rigoldi, Elena Bresin, Norberto Perico, Matias Trillini, Roberta Donadelli, Annalisa Perna, Ariela Benigni, Giuseppe Remuzzi","doi":"10.1159/000530657","DOIUrl":"10.1159/000530657","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the disease-causing variants observed in ADPKD patients are in two genes: PKD1 and PKD2.</p><p><strong>Methods: </strong>237 patients from 198 families with a clinical diagnosis of ADPKD were screened for PKD1 and PKD2 genetic variants using Sanger sequencing and multiple ligation-dependent probe amplification analysis.</p><p><strong>Results: </strong>Disease-causing (diagnostic) variants were identified in 173 families (211 patients), 156 on PKD1 and 17 on PKD2. Variants of unknown significance were detected in 6 additional families, while no mutations were found in the remaining 19 families. Among the diagnostic variants detected, 51 were novel. In ten families, seven large rearrangements were found and the molecular breakpoints of 3 rearrangements were identified. Renal survival was significantly worse for PKD1-mutated patients, particularly those carrying truncating mutations. In patients with PKD1 truncating (PKD1-T) mutations, disease onset was significantly earlier than in patients with PKD1 non-truncating variants or PKD2-mutated patients.</p><p><strong>Conclusions: </strong>Comprehensive genetic testing confirms its utility in diagnosing patients with ADPKD and contributes to explaining the clinical heterogeneity observed in this disease. Moreover, the genotype-phenotype correlation can allow for a more accurate disease prognosis.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9893296","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}
Pub Date : 2024-01-01Epub Date: 2024-04-30DOI: 10.1159/000538820
Alshymaa Rafiek Eltahan, Zulfikar Pondor, Rosemary L Donne, David Lewis, Maharajan Raman, Paul Hinchliffe, Jan Cowperthwaite, Dimitrios Poulikakos
Background: Early identification of dysfunctional arteriovenous haemodialysis (HD) vascular access (VA) is important for timely referral and intervention.
Method: We retrospectively calculated VA risk score using Vasc-Alert surveillance software technology from HD treatment sessions in 2 satellite HD units over 18 months. We included in the analysis HD patients dialysing with arteriovenous fistula or graft (AVF/G) with available Vasc-Alert data for≥ 2 months. For group one (eventful) that included patients who developed vascular access thrombosis or stenosis over the study period, we collected Vasc-Alert risk score 2 months prior to the event and, for group two (uneventful), over 5 consecutive months. Vasc-Alert technology utilises routinely collected data during HD to calculate VA risk score and triggers an alert if the score is ≥7 in 3 consecutive dialysis sessions. Patients with >2 alerts (vascular access score ≥7) per month were considered to have positive alerts.
Results: From 140 HD patients, 81 patients dialysed via AVF/G. 77/81 had available Vasc-Alert data and were included in the final analysis. Out of 17 eventful patients, 11 (64.7%) had positive alerts 2 months prior to the vascular event. Out of the 60 patients without vascular events, 20 patients (33.3%) had positive alert. Vasc-Alert's sensitivity and specificity for vascular events were 64.7% and 66.6%, respectively. Within the 6 patients with thrombosed access, 2 patients (33.3%) detected by Vasc-Alert were not detected with clinical monitoring.
Conclusion: Vascular access risk score can be a useful non-invasive vascular access surveillance method to assist clinical decision making.
{"title":"Remote Surveillance Technology of Dialysis Arteriovenous Access: Retrospective Evaluation in a UK Renal Centre.","authors":"Alshymaa Rafiek Eltahan, Zulfikar Pondor, Rosemary L Donne, David Lewis, Maharajan Raman, Paul Hinchliffe, Jan Cowperthwaite, Dimitrios Poulikakos","doi":"10.1159/000538820","DOIUrl":"10.1159/000538820","url":null,"abstract":"<p><strong>Background: </strong>Early identification of dysfunctional arteriovenous haemodialysis (HD) vascular access (VA) is important for timely referral and intervention.</p><p><strong>Method: </strong>We retrospectively calculated VA risk score using Vasc-Alert surveillance software technology from HD treatment sessions in 2 satellite HD units over 18 months. We included in the analysis HD patients dialysing with arteriovenous fistula or graft (AVF/G) with available Vasc-Alert data for≥ 2 months. For group one (eventful) that included patients who developed vascular access thrombosis or stenosis over the study period, we collected Vasc-Alert risk score 2 months prior to the event and, for group two (uneventful), over 5 consecutive months. Vasc-Alert technology utilises routinely collected data during HD to calculate VA risk score and triggers an alert if the score is ≥7 in 3 consecutive dialysis sessions. Patients with >2 alerts (vascular access score ≥7) per month were considered to have positive alerts.</p><p><strong>Results: </strong>From 140 HD patients, 81 patients dialysed via AVF/G. 77/81 had available Vasc-Alert data and were included in the final analysis. Out of 17 eventful patients, 11 (64.7%) had positive alerts 2 months prior to the vascular event. Out of the 60 patients without vascular events, 20 patients (33.3%) had positive alert. Vasc-Alert's sensitivity and specificity for vascular events were 64.7% and 66.6%, respectively. Within the 6 patients with thrombosed access, 2 patients (33.3%) detected by Vasc-Alert were not detected with clinical monitoring.</p><p><strong>Conclusion: </strong>Vascular access risk score can be a useful non-invasive vascular access surveillance method to assist clinical decision making.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865356","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}
Pub Date : 2024-01-01Epub Date: 2024-03-08DOI: 10.1159/000538037
Gerrit van den Berg, Laura R Claus, Bert van der Zwaag, Phillis Lakeman, Lotte Kaasenbrood, John A Sayer, Marc R Lilien, Albertien M van Eerde
Medullary sponge kidney (MSK) is a description of radiographic features. However, the pathogenesis of MSK remains unclear. MSK is supposed to be the cause of secondary distal renal tubular acidosis (dRTA), although there are case reports suggesting that MSK is a complication of primary dRTA. In addition to these reports, we report 3 patients with metabolic acidosis and MSK, in whom primary dRTA is confirmed by molecular genetic analyses of SLC4A1 and ATP6V1B1 genes. With a comprehensive genetics-first approach using the 100,000 Genomes Rare Diseases Project dataset, the association between MSK and primary dRTA is examined. We showed that many patients with MSK phenotypes are genetically tested with a gene panel which does not contain dRTA-associated genes, revealing opportunities for missed genetic diagnosis. Our cases highlight that the radiological description of MSK is not a straightforward disease or clinical phenotype. Therefore, when an MSK appearance is noted, a broader set of causes should be considered including genetic causes of primary dRTA as the underlying reason for medullary imaging abnormalities.
{"title":"Medullary Sponge Kidney and Its Relationship with Primary Distal Renal Tubular Acidosis: Case Reports and a Comprehensive Genetics-First Approach.","authors":"Gerrit van den Berg, Laura R Claus, Bert van der Zwaag, Phillis Lakeman, Lotte Kaasenbrood, John A Sayer, Marc R Lilien, Albertien M van Eerde","doi":"10.1159/000538037","DOIUrl":"10.1159/000538037","url":null,"abstract":"<p><p>Medullary sponge kidney (MSK) is a description of radiographic features. However, the pathogenesis of MSK remains unclear. MSK is supposed to be the cause of secondary distal renal tubular acidosis (dRTA), although there are case reports suggesting that MSK is a complication of primary dRTA. In addition to these reports, we report 3 patients with metabolic acidosis and MSK, in whom primary dRTA is confirmed by molecular genetic analyses of SLC4A1 and ATP6V1B1 genes. With a comprehensive genetics-first approach using the 100,000 Genomes Rare Diseases Project dataset, the association between MSK and primary dRTA is examined. We showed that many patients with MSK phenotypes are genetically tested with a gene panel which does not contain dRTA-associated genes, revealing opportunities for missed genetic diagnosis. Our cases highlight that the radiological description of MSK is not a straightforward disease or clinical phenotype. Therefore, when an MSK appearance is noted, a broader set of causes should be considered including genetic causes of primary dRTA as the underlying reason for medullary imaging abnormalities.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049970","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}
Introduction: The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remain uncertain, warranting further research.
Methods: A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS + immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups.
Results: 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS + immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-h proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 mL/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable.
Conclusion: Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.
{"title":"Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1.","authors":"Xianjin Bi, Yanlin Yu, Siyan Zhou, Yue Zhou, Jinghong Zhao, Jiachuan Xiong","doi":"10.1159/000534788","DOIUrl":"10.1159/000534788","url":null,"abstract":"<p><strong>Introduction: </strong>The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remain uncertain, warranting further research.</p><p><strong>Methods: </strong>A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS + immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups.</p><p><strong>Results: </strong>296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS + immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-h proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 mL/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable.</p><p><strong>Conclusion: </strong>Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899077","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}
Introduction: 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®).
Methods: 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.
Results: 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 < 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.
Conclusions: Pediatric MesPGN increased the potential for PTF under high-shear flow conditions.
{"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 < 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":null,"pages":null},"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}
Pub Date : 2024-01-01Epub Date: 2024-01-12DOI: 10.1159/000536243
Pierre Delanaye, Etienne Cavalier, Thomas Stehlé, Hans Pottel
Background: 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.
Summary: 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.
Key messages: GFR is estimated by creatinine-based equations, but the most important for nephrologists is probably to know the limitations of these equations.
背景:在日常实践中,肾小球滤过率(GFR)是通过包括肾脏生物标志物在内的方程进行估算的。在这些生物标志物中,血清肌酐仍然是最常用的。然而,血清肌酐存在许多局限性,我们将在本综述中加以讨论。我们还将讨论以血肌酐为基础的方程是如何开发出来的,以及我们可以期望它们在估算 GFR 方面有怎样的表现。我们将介绍最近推出的欧洲肾功能联盟(EKFC)方程的优点。该方程可用于儿童和成人。该方程还可在不同人群中灵活使用:关键信息:肾小球滤过率是通过基于肌酐的方程估算出来的,但对肾病学家来说,最重要的可能是了解这些方程的局限性。
{"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":null,"pages":null},"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}
Pub Date : 2024-01-01Epub Date: 2024-02-01DOI: 10.1159/000536245
Anna M Drake, Jessica A Paynter, Arthur Yim, Jake A Tempo, Todd G Manning, Janelle Brennan, Kirby R Qin
Background: 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.
Methods: 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.
Results: 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%]).
Conclusion: 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.
{"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":null,"pages":null},"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}
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-01-01Epub Date: 2023-09-27DOI: 10.1159/000531913
Flóra Franciska Prepok, Karolina Kornélia Schnabel, Csaba Sumánszki, András Gellért Barta, András Tislér, Péter Reismann
Introduction: 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.
Methods: 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 (<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.
Results: 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.
Conclusion: Long-term suboptimal therapy adherence in PKU patients with high blood Phe levels may lead to deterioration in kidney function.
{"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 (<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":null,"pages":null},"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}
Pub Date : 2024-01-01Epub Date: 2023-11-13DOI: 10.1159/000531912
Yu Luo, Zhitao Cai, Xiongfei Wu, Feng Liu, Lian Li
Introduction: 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.
Method: 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.
Result: 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.
Conclusion: ATF3 mediates SOCS3 expression to promote the activation of mitophagy, thereby aggravating renal ischemia-reperfusion injury.
细胞因子信号传导抑制因子3 (Suppressor of cytokine signaling 3, SOCS3)在肾缺血再灌注(RI/R)损伤小鼠中高表达,具有调节线粒体自噬的潜力。在此基础上,本研究进一步探讨了SOCS3通过调节线粒体自噬影响RI/R的可能机制。方法:建立小鼠RI/R损伤模型和缺氧/再氧化(H/R)细胞模型,通过ELISA、qRT-PCR、Western blot、病理切片、CCK-8、流式细胞术和JC-1检测分析沉默SOCS3对上述模型小鼠损伤和线粒体自噬的影响。机制研究通过数据库分析和结合验证实验(染色质免疫沉淀(ChIP),双荧光素酶报告试验和共免疫沉淀(Co-IP))进行。确定结合靶点后,通过抢救实验验证靶基因与SOCS3的调控关系。结果:血尿素氮(BUN)和肌酐(Cr)水平的大幅升高验证了RI/R模型的成功。SOCS3在RI/R小鼠中表达上调。沉默的SOCS3可减轻RI/R小鼠的肾损伤和线粒体异常,并在分子水平上抑制线粒体自噬。同样,沉默的SOCS3减轻了H/ r诱导的细胞损伤和线粒体自噬。最后,我们确定激活转录因子3 (ATF3)与SOCS3启动子结合,SOCS3启动子与胰岛素样生长因子1受体(IGF1R)相互作用。救援实验证实了ATF3对SOCS3表达的影响及其调控机制。结论:ATF3介导SOCS3表达,促进线粒体自噬激活,从而加重肾缺血再灌注损伤。
{"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":null,"pages":null},"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}