NDT Plus最新文献

{"title":"Klotho: A Potential Therapeutic Target in Aging and Neurodegeneration Beyond Chronic Kidney Disease","authors":"Mehmet Kanbay, Sidar Copur, Lasin Ozbek, Ali Mutlu, Daniel Cejka, Paola Ciceri, Mario Cozzolino, Mathias Loberg Haarhaus","doi":"10.1093/ckj/sfad276","DOIUrl":"https://doi.org/10.1093/ckj/sfad276","url":null,"abstract":"Abstract Klotho, a multifunctional protein, acts as a co-receptor in FGF23, and exerts its impact through various molecular pathways, including Wnt, HIF, IGF-1 pathways. The physiological significance of Klotho is the regulation of vitamin D and phosphate metabolism, as well as serving as a vital component in aging and neurodegeneration. The role of Klotho in aging and neurodegeneration in particular has gained considerable attention. Hereby, in this narrative review, we highlighted several key insights into the molecular basis and physiological function of Klotho and synthesized current research on the role of Klotho in neurodegeneration and aging. Klotho deficiency was associated with cognitive impairment, reduced growth, diminished longevity, and the development of age-related diseases in vivo. Serum Klotho levels showed a decline in individuals with advanced age and those affected by chronic kidney disease, establishing its potential diagnostic significance. Additionally, multiple medications have been demonstrated to influence Klotho levels. Therefore, this comprehensive review suggests that Klotho could open the door to novel interventions aimed at addressing the challenges of aging and neurodegenerative disorders.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"6 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135874548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria","authors":"Daniel Rodríguez, Ekaterina Gurevich, Soroush Mohammadi Jouabadi, Eva Maria Pastor Arroyo, Alexander Ritter, Sandrine Estoppey Younes, Carsten A Wagner, Pedro Henrique Imenez Silva, Harald Seeger, Nilufar Mohebbi","doi":"10.1093/ckj/sfad256","DOIUrl":"https://doi.org/10.1093/ckj/sfad256","url":null,"abstract":"ABSTRACT Background Kidney stones are frequent in industrialized countries with a lifetime risk of 10 to 15%. A high percentage of individuals experience recurrence. Calcium-containing stones account for more than 80% of kidney stones. Diet, environmental factors, behavior, and genetic variants contribute to the development of kidney stones. Osteocytes excrete the 21 kDa glycoprotein sclerostin, which inhibits bone formation by osteoblasts. Animal data suggests that sclerostin might directly or indirectly regulate calcium excretion via the kidney. As hypercalciuria is one of the most relevant risk factors for kidney stones, sclerostin might possess pathogenic relevance in nephrolithiasis. Methods We performed a prospective cross-sectional observational controlled study in 150 recurrent kidney stone formers (rKSF) to analyse the association of sclerostin with known stone risk factors and important modulators of calcium-phosphate metabolism. Serum sclerostin levels were determined at the first visit. As controls, we used 388 non-stone formers from a large Swiss epidemiological cohort. Results Sclerostin was mildly increased in rKSF in comparison to controls. This finding was more pronounced in women compared to men. Logistic regression indicated an association of serum sclerostin with rKSF status. In hypercalciuric individuals, sclerostin levels were not different from normocalciuric patients. In Spearman correlation analysis we found a positive correlation between sclerostin, age, and BMI and a negative correlation with eGFR. There was a weak correlation with iPTH and intact FGF 23. In contrast, serum sclerostin levels were not associated with 25-OH Vitamin D3, 1,25-dihydroxy-Vitamin D3, urinary calcium and phosphate or other urinary lithogenic risk factors. Conclusion This is the first prospective controlled study investigating serum sclerostin in rKSF. Sclerostin levels were increased in rKSF independent of hypercalciuria and significantly associated with the status as rKSF. It appears that mechanisms other than hypercalciuria may be involved and thus further studies are required to elucidate underlying pathways.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"205 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135510076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Should we enlarge the indication for kidney biopsy in diabetics? The con part","authors":"Alberto Ortiz","doi":"10.1093/ckj/sfad267","DOIUrl":"https://doi.org/10.1093/ckj/sfad267","url":null,"abstract":"Abstract Diabetes is the most common cause of chronic kidney disease (CKD), a condition found in 850 million persons and projected to become the fifth global cause of death by 2040. Research is needed that examines kidney tissue to characterize distinct phenotypes in patients with DM and CKD so as to identify non-invasive biomarker signatures and develop targeted therapeutic approaches. However, from a routine care point of view, kidney biopsy is likely overused in patients with CKD and DM, as most biopsy results are not expected to be associated with a therapeutic approach that differs from standard kidney protection with triple or quadruple therapy (renin-angiotensin system blockade. SGLT2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists and GLP1 receptor agonists). Moreover, expanding the kidney biopsy criteria will increase the absolute number of complications from kidney biopsies, that may reach 27 000 to 108 000 deaths of persons that would derive little benefit from kidney biopsy if all people with DM and severe CKD were biopsied globally. Finally, limited resources should be optimally allocated. The cost of one kidney biopsy may fund 7000 semiquantitative urinary albumin:creatinine ratio assessments that may identify earlier stages of the disease and allow treatment that prevents progression to a stage in which kidney biopsy may be considered.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"1 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134908206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Should we enlarge the indication for kidney biopsy in patients with diabetes? The pro part","authors":"Loreto Gesualdo, Marco Fiorentino, Francesca Conserva, Paola Pontrelli","doi":"10.1093/ckj/sfad266","DOIUrl":"https://doi.org/10.1093/ckj/sfad266","url":null,"abstract":"Abstract Diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) represent intricate challenges in diagnosis and treatment within the context of the global diabetes epidemic. As the prevalence of diabetes continues to escalate, effective management of renal complications becomes paramount. Recent advancements in comprehending the multifaceted nature of renal damage, fueled by insights from histopathological investigations, offer unprecedented prospects for refining diagnostic strategies and customizing therapeutic interventions. Renal biopsies have risen as indispensable tools for unraveling the diverse phenotypes of renal damage in diabetes. The pioneering Mazzucco's study identified three classes of renal damage in T2DM patients: classical diabetic glomerulosclerosis (DN), vascular and ischemic glomerular changes (NDRD), and other glomerulonephritides in the presence (DN+NDRD, mixed forms) or absence of DN (NDRD). The prevalence of these classes varies widely in published studies, influenced by factors such as ethnicity, geography, and selection criteria for renal biopsy. Moreover, the international RPS consensus classification system has stratified the classical diabetic nephropathy into progressive categories of renal impairment, a breakthrough that aids in prognostication. Histopathological scrutiny, particularly the intricate correlation between glomerular and tubulointerstitial lesions, contributes profoundly to enhancing our grasp of the phenotype's heterogeneity. This amplified comprehension holds the potential to steer personalized treatment strategies. Cutting-edge interventions, encompassing sodium-glucose cotransporter 2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRAs), and anti-endothelin receptor agents, are broadening the arsenal against renal injury in diabetes. When combined with the profound insights garnered from histopathological, omics, imaging and clinical data these therapeutic avenues promise a transformative shift towards precision-driven care paradigms. Collaborative efforts uniting researchers, clinicians, and patients are indispensable for propelling our knowledge of diabetic renal damage and ameliorating patient outcomes. The fusion of histopathological, omics and imaging findings into clinical decision-making harbors the potential to customize interventions and optimize care for individuals grappling with diabetes-associated renal complications. Furthermore, groundbreaking initiatives like the iBeat Study within the BEAT-DKD project (https://www.beat-dkd.eu/), elucidating distinct phenotypes of renal damage within diabetes, underscore the imperative necessity of integrating histopathological data into the broader framework of diabetic renal management.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"40 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136376461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney biopsy in diabetic kidney disease. Yes, but in very selected cases","authors":"Carmine Zoccali","doi":"10.1093/ckj/sfad268","DOIUrl":"https://doi.org/10.1093/ckj/sfad268","url":null,"abstract":"Abstract The debate on kidney biopsy in diabetic kidney disease (DKD) is multifaceted. Loreto Gesualdo and colleagues argue for its broader application, claiming that biopsies can offer precise diagnostic data and guide personalized treatment plans. On the other hand, Alberto Ortiz opposes this, citing insufficient evidence, resource constraints, and potential risks. He suggests that alternative diagnostic methods, such as advanced imaging techniques and serological markers will obviate the need of biopsy in most patients. Both sides agree on the need for individualized patient care and open discussions between healthcare providers and patients about the procedure's risks and benefits. The application of kidney biopsy in these patients needs to consider clinical evidence, practical limitations, and patient preferences and demands a balanced, case-by-case approach. Overall, this moderator believes that, although fundamental in clinical research, kidney biopsy in DKD is infrequently needed.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"99 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136377137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characteristics of circulating B cells and kidney cells at the single-cell level in special types of primary membranous nephropathy","authors":"Xiaoqian Feng, Qilin Chen, Jinjie Zhong, Sijie Yu, Yue Wang, Yaru Jiang, Junli Wan, Longfei Li, Huimin Jiang, Liping Peng, Anshuo Wang, Gaofu Zhang, Mo Wang, Haiping Yang, Qiu Li","doi":"10.1093/ckj/sfad215","DOIUrl":"https://doi.org/10.1093/ckj/sfad215","url":null,"abstract":"ABSTRACT Background Although primary membranous nephropathy (pMN) associated with podocyte autoantibodies (POS) is becoming well-known, the molecular characteristics of the specific type of pMN that is negative for podocyte autoantibodies (NEG) is still unclear. Methods We performed single-cell transcriptome sequencing and single-cell B cell receptor sequencing on circulating CD19+ cells and kidney cells of a NEG paediatric patient with pMN. The single-cell datasets of POS patients and healthy control individuals were included for integrative analysis. Results The gene expression characteristics and clonal expansion of naïve and memory B cells in the NEG patient changed significantly. We found that a group of CD38+ naïve B cells expanded in the NEG patient, which had the functional characteristics of cell activation. In addition, the conversion between immunoglobulin M (IgM)/IgD and IgG1 in the NEG patient was increased. Parietal epithelial cells (PECs) and podocytes shared similar signature genes (WT1, CLIC5), and new candidate marker genes for PECs, such as NID2, CAV1 and THY1, might contribute to the definition of cell subsets. PECs might have undergone significant changes in the disease, mainly manifested by changes in the expression of CCN2, PLAAT4 and SEPTIN2. The scores of gene sets related to extracellular matrix, cell adhesion and calcium channel in podocytes of the NEG patient was significantly increased. The gene expression of sodium transporter in a group of proximal tubule cells in the disease was significantly increased, especially SLC5A12, which might be related to the oedema of patients. Conclusions Our research demonstrated the cell type–specific molecular features in the circulation and kidney of the NEG pMN patient.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"189 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135169227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT-2 inhibitors and finerenone in non-diabetic CKD: a step into the (near) future?","authors":"Marieta P Theodorakopoulou, Pantelis A Sarafidis","doi":"10.1093/ckj/sfad272","DOIUrl":"https://doi.org/10.1093/ckj/sfad272","url":null,"abstract":"","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"7 12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135413138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The need for better donor engagement and outreach with legacy living kidney donors","authors":"Katya Loban, Ahsan Alam, Shaifali Sandal","doi":"10.1093/ckj/sfad271","DOIUrl":"https://doi.org/10.1093/ckj/sfad271","url":null,"abstract":"","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135780261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic Ultra Low Dose Rituximab to maintain remission in Relapsing Adult Minimal Change Disease","authors":"Wing-Yin Leung, Henry H L Wu, Alexander Woywodt, Arvind Ponnusamy","doi":"10.1093/ckj/sfad270","DOIUrl":"https://doi.org/10.1093/ckj/sfad270","url":null,"abstract":"","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135780030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and clinical characterization of familial renal glucosuria","authors":"Lubin Xu, Ruohuan Zhao, Yumo Zhao, Xueqing Tang, Nuo Si, Xiuzhi Guo, Cai Yue, Min Nie, Limeng Chen","doi":"10.1093/ckj/sfad265","DOIUrl":"https://doi.org/10.1093/ckj/sfad265","url":null,"abstract":"Abstract Background Familial renal glucosuria (FRG) is a hereditary disorder caused by variants in SLC5A2, encoding sodium-glucose cotransporter 2 (SGLT2). In this study, we aimed to characterize proximal tubule solute transport, glucagon secretion, and genotype-phenotype relationship in FRG patients. Methods We sequenced SLC5A2 and PDZK1IP1 in 21 FRG patients and measured the renal threshold of glucose (RTG) in 15 patients. We built an open-source online calculator of RTG, evaluated the proximal tubule transport of amino acid, uric acid, and phosphate, and explored glucagon secretion after glucose ingestion in FRG patients. Results We identified 12 novel SLC5A2 variants (G484D, R564W, A212S, c.574 + 1G > C, W649*, S592Cfs*6, Q579*, Y339*, V39F, G491E, A464E, and G360D) in our cohort and yielded 111 SLC5A2 variants from literature review. RTG in our cohort ranged from 1.0 to 9.2 mmol/L. Patients with two SLC5A2 variants had lower RTG (3.9 vs. 6.2 mmol/L) and higher 24-hour urinary glucose excretion (24hUG) than single-variant carriers (291.0 vs. 40.01 mmol/1.73m2). Patients with homozygous missense or in-frame indels had mean 24hUG of 457.2 mmol/1.73m2, comparable to those with homozygous truncating variants (445.0 mmol/1.73m2) and significantly more than those with homozygous splicing variants (196.6 mmol/1.73m2). Patients with homozygous missense variants involving conservative residues (582.0 mmol/1.73m2) had more 24hUG than those with variants at non-conservative residues (257.6 mmol/1.73m2). Four out of 14 tested patients had mild aminoaciduria. The RTG of FRG patients had no significant correlation to phosphate reabsorption but a potential negative correlation to the fractional excretion of uric acid. Postprandial suppression of glucagon secretion was absent in most FRG patients. Conclusions We built a comprehensive map showing the impact of SLC5A2 variant type and variant location on glucosuria severity. Our results highlighted the role of key residues in maintaining the transport function of SGLT2 and the functional link between glucosuria and reabsorption of amino acid and uric acid in FRG patients.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136034340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}