Nephrology Dialysis Transplantation最新文献

{"title":"Mineralocorticoid receptor antagonism for non-diabetic kidney disease.","authors":"Frédéric Jaisser, Jonatan Barrera-Chimal","doi":"10.1093/ndt/gfae241","DOIUrl":"10.1093/ndt/gfae241","url":null,"abstract":"<p><p>The use of mineralocorticoid receptor antagonists (MRAs) in preclinical models of non-diabetic chronic kidney disease (CKD) has consistently shown a beneficial effect by preventing renal structural injury, reducing albuminuria and preserving renal function. In this context, MR activation in non-epithelial cells contributes to renal injury through the activation of inflammatory and fibrotic pathways, increasing oxidative stress and modulating renal hemodynamics. The protective effects of MRAs in animal models of CKD are not restricted to the kidney. Cardiovascular benefits, such as the prevention of cardiac fibrosis, hypoperfusion and vascular calcification, have also been observed. The translation of these preclinical findings into clinical practice has been difficult, mainly due to the lack of clinical studies testing the efficacy of steroidal MRAs in CKD patients due to their contraindication because of an increased risk of hyperkalemia in these patients. Here, we review the latest preclinical evidence showing new mechanisms by which MR inhibition results in beneficial effects against cardiorenal damage in non-diabetic kidney disease. Moreover, we summarize the clinical trials testing the safety and efficacy of steroidal and non-steroidal MRAs in patients with advanced non-diabetic CKD.</p><p><strong>Plain english summary: </strong>The mineralocorticoid receptor (MR) is known for its role in the regulation of sodium and potassium balance in the distal tubules of the kidney. However, under pathological conditions the activation of the MR in other renal cell types (including the vasculature and immune cells) leads to harmful effects, damaging the main structural components of the kidney, and ultimately causing renal dysfunction. Over the past 20 years, several studies performed in mouse and rat models of non-diabetic kidney disease have shown that using a specific drug class that inhibits the MR (MR antagonists: MRAs) positively impacts the preservation of the kidney structure and helps to prevent the decline of renal function, thus positioning MRAs as a good therapeutic option against kidney diseases from non-diabetic origin. In addition, the use of MRAs also benefited the cardiovascular system health as shown by improved cardiac structural and functional parameters as well as preventing the calcification of blood vessels. Nevertheless, an important barrier to translating these findings into clinical practice is that the use of MRAs could lead to increased serum potassium levels, particularly in kidney disease patients, an adverse effect that could lead to life-threatening cardiac arrhythmias. In this review, we summarize the latest data in animal models showing new evidences of MR benefits in non-diabetic kidney disease. In addition, we review the clinical trials that evaluated the safety and efficacy of MRAs in patients with advanced non-diabetic kidney disease including those that tested a new generation of MRAs (non-steroidal MRAs) and","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_1","pages":"i29-i36"},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination therapy as a new standard of care in diabetic and non-diabetic chronic kidney disease.","authors":"Brendon L Neuen, Emily K Yeung, Janani Rangaswami, Muthiah Vaduganathan","doi":"10.1093/ndt/gfae258","DOIUrl":"10.1093/ndt/gfae258","url":null,"abstract":"<p><p>Combination therapy, involving the use of multiple medications together, is becoming a new standard of care for chronic kidney disease (CKD). For people with CKD, combination therapy offers the promise of preventing kidney failure and reducing the risk of heart problems. This approach is appealing because different drugs target distinct mechanisms involved in CKD progression. For instance, some target immune responses, others reduce kidney inflammation and scarring, while others improve blood pressure within the kidneys. Data from large clinical trials suggest that each treatment works effectively on its own, regardless of other medications people are taking. Combining therapies can also reduce the risk of side effects of individual medications. This review highlights the evidence for combination therapy in CKD, explores how to improve its use, and discusses how future studies may answer remaining questions.</p><p><strong>Abstract: </strong>A range of therapies now exists to reduce the risk of kidney failure and cardiovascular events in people with type 2 diabetes, including renin-angiotensin system blockade, sodium-glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists. With multiple clinical trials underway, it is likely that at least some of these therapies-as well as additional agents such as endothelin receptor antagonists-will further demonstrate kidney-protective effects in people with CKD who do not have diabetes in the near future. For conditions such as IgA nephropathy, several therapies have recently been approved or are being evaluated in late phase trials. Thus combination therapy is emerging as a new standard for diabetic and non-diabetic chronic kidney disease (CKD). This approach is supported by randomized data suggesting that each therapeutic class offers independent and additive benefits in diabetic kidney disease, regardless of background therapy. Notably, the reduction in hyperkalaemia and fluid retention with SGLT2 inhibitors may enhance the tolerability and safety of other treatments. In this review, we present the rationale for combination therapy with evidence-based kidney therapies in diabetic and non-diabetic CKD. We also summarize randomized evidence supporting a multi-medicine approach, address safety considerations, review ongoing trials, and propose frameworks for implementing treatments aligned with patient risk to optimize person-centred care and reduce long-term risks of kidney failure and related complications.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_1","pages":"i59-i69"},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective endothelin A receptor antagonism in chronic kidney disease: improving clinical application.","authors":"Erik Moedt, Victor S Wasehuus, Hiddo J L Heerspink","doi":"10.1093/ndt/gfae214","DOIUrl":"10.1093/ndt/gfae214","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Endothelin-1 (ET-1) is a peptide that is involved in various chronic diseases including cardiovascular and kidney disease. ET-1 can bind to two receptors, endothelin A (ETA) and endothelin B (ETB), which are found in different organs and tissues. When ET-1 binds to the ETA receptor, it causes blood vessels to narrow, while binding of ET-1 to the ETB receptor causes blood vessels to widen. These receptors help regulate fluid and electrolyte balance in the kidneys, as well as the kidney's ability to filter various substances out of the body. Overactivation of ET-1 can occur in people with diabetes or obesity, which can damage the structure and function of the kidney.Studies in mice and humans with kidney disease have shown that blocking the ETA receptor improves kidney health. As a result, medicines that specifically block the ETA receptor, known as endothelin receptor antagonists (ERAs), are a promising option for treating these kidney diseases. The first ERA (sparsentan) is now available for use in patients with immunoglobulin A (IgA) nephropathy, a specific type of kidney disease. It should be noted that ERAs can cause side effects. Fluid retention, which can increase the risk of heart failure, is a side effect that is particularly observed in patients with type 2 diabetes and severe kidney disease. This side effect is less often observed in patients with IgA nephropathy or patients without diabetes.Treatment strategies to optimize safe and effective use of ETA blockers are being developed. Overall, these insights offer hope for better care of patients with kidney disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;Endothelin-1 (ET-1) is a 21-amino acid peptide involved in numerous cardiovascular and renal processes. ET-1 can bind to endothelin receptor A (ETA) and endothelin receptor B (ETB), which are found in various organs and tissues. In general, binding of ET-1 to the ETA receptor causes vasoconstriction, whereas activation of the ETB receptor leads to vasodilation. In the kidney, endothelin receptors regulate fluid and electrolyte balance, regional blood flow and glomerular filtration rate. In pathological conditions, ET-1 promotes kidney injury through adverse effects on the endothelial glycocalyx, podocytes and mesangial cells, and stimulating inflammation and fibrosis in the tubules. In experimental and clinical studies, inhibition of the ETA receptor has been shown beneficial in a variety of kidney diseases. These include diabetic kidney disease, immunoglobulin A nephropathy, focal segmental glomerulosclerosis and Alport syndrome. Accordingly, selective ETA endothelin receptor antagonists (ERA) may prove a viable therapeutic option in these diseases. However, clinical application is challenged by the occurrence of fluid retention which can lead to heart failure, in particular in patients with severe CKD. Concomitant use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) may mitigate these adverse effects through their diuretic actions.","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_1","pages":"i37-i46"},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design considerations for future renoprotection trials in the era of multiple therapies for chronic kidney disease.","authors":"Doreen Zhu, Parminder K Judge, Natalie Staplin, Richard Haynes, William G Herrington","doi":"10.1093/ndt/gfae210","DOIUrl":"https://doi.org/10.1093/ndt/gfae210","url":null,"abstract":"&lt;p&gt;&lt;p&gt;In the last 5-10 years, several large high-quality research trials testing new treatments versus a dummy treatment in patients with kidney disease have provided new discoveries, particularly among people with diabetes. Some of these trials included patients with a wide variety of kidney diseases and therefore provided important information on how effective the treatment is, and whether it is safe to use for many people (and not just those with a specific type of kidney disease). The findings are particularly important as they suggest that, once established, kidney disease progresses in similar ways regardless of the initiating cause. These new treatments importantly slow kidney disease progression but, even when used together, do not arrest the loss of kidney function. New research is still needed to test new potential treatments. Now that we have several drugs that can be used to treat kidney disease, there are new challenges when designing and conducting new trials. These include the reduced risk of kidney disease progression and heart disease (because of the new treatments available). Future research trials need to include a sufficiently large number of patients to be able to answer research questions reliably. In addition, different types of people and diseases should be included. In an age of increasing regulation and bureaucracy, conducting such trials is challenging. Simplifying the design and conduct of future trials by focusing only on the necessary components needed to answer the research key question(s) is important. Such trials reduce the burden of participation for patients and busy clinical staff, whilst still ensuring careful focus on patient safety and data quality. We hope more high-quality trials that are sufficiently large, inclusive and simple will be conducted in the future, so that kidney teams can offer better care to their patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;Nephrology has benefited from conducting increasingly large high-quality trials in the last 5-10 years. In addition to the long-standing known benefits of renin-angiotensin system inhibitors, we now have multiple pharmacotherapies that provide kidney and/or cardiovascular protection for certain types of patient with chronic kidney disease (CKD). These include sodium-glucose co-transporter 2 inhibitors (SGLT2i), a non-steroidal mineralocorticoid receptor antagonist and a glucagon-like peptide-1 receptor agonist. Trials of SGLT2i have had particularly important impact, as wide eligibility criteria in pivotal trials have enabled safety and efficacy across a wide range of causes of CKD to be demonstrated. These findings support the concept of final common pathways of CKD progression and should encourage similar trial designs recruiting broad ranges of patients at risk of CKD progression. This is important as these new drugs do not completely arrest CKD progression nor do they mitigate the full excess of cardiovascular disease. In the current era of multiple th","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_1","pages":"i70-i79"},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The era of combination of nephroprotective agents in CKD is there.","authors":"Michel Jadoul, Peter Rossing","doi":"10.1093/ndt/gfae260","DOIUrl":"10.1093/ndt/gfae260","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_1","pages":"i1-i2"},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cell Casts on Kidney Biopsy and Progression of IgA Nephropathy.","authors":"Yu-Xuan Yao, Chen Tang, Su- Fang Shi, Pei Chen, Xu-Jie Zhou, Ji-Cheng Lv, Li-Jun Liu, Hong Zhang","doi":"10.1093/ndt/gfaf023","DOIUrl":"https://doi.org/10.1093/ndt/gfaf023","url":null,"abstract":"<p><strong>Background: </strong>Renal red blood cell casts (RBCC) are common in IgA nephropathy (IgAN), but their role in kidney disease progression of patients with IgAN remains unclear.</p><p><strong>Methods: </strong>1425 patients in Peking University First Hospital IgAN (PKU-IgAN) cohort and 279 patients in TESTING trial were enrolled to test the association between RBCC and kidney outcome. RBCC was defined as positive (+) when at least one cast was identified within the renal tubules by light microscopy. Kidney endpoint was the composite of the first occurrence of a sustained 30% decrease in estimated glomerular filtration rate or end stage kidney disease or death due to kidney disease. Cox regression analysis was used.</p><p><strong>Results: </strong>In PKU-IgAN, 529 patients (37%) had RBCC; in TESTING trial, 78 patients (28%) had RBCC. Patients with RBCC had more crescentic lesions, and less segmental sclerosis compared with patients without RBCC. In PKU-IgAN, after a median follow-up of 54 months, 119 patients (22%) with RBCC and 260 patients (29%) without RBCC reached the composite kidney endpoint (P=0.009). In multivariable analysis, RBCC was independently associated with composite kidney endpoint (HR 0.79; 95%CI 0.63 - 0.99; P=0.038). RBCC and immunosuppressive therapy (IST) had an interaction (P=0.001). RBCC was independently associated with composite kidney endpoint in patients who received IST (HR 0.56; 95%CI 0.40 - 0.77; P<0.001). In TESTING trial, after a median follow-up of 57 months, 26 patients (33%) with RBCC and 96 patients (48%) without RBCC reached the composite kidney endpoint (P=0.041). In univariate analysis, RBCC was associated with composite kidney endpoint (HR 0.64; 95%CI 0.42 - 0.99; P=0.047).</p><p><strong>Conclusion: </strong>Renal RBCC was frequent in IgAN and was associated with a higher incidence of acute active lesions and better renal prognosis, especially in those who received IST, warranting particular attention.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination therapy: an upcoming paradigm to improve kidney and cardiovascular outcomes in chronic kidney disease.","authors":"Radica Z Alicic, Joshua J Neumiller, Katherine R Tuttle","doi":"10.1093/ndt/gfae212","DOIUrl":"10.1093/ndt/gfae212","url":null,"abstract":"&lt;p&gt;&lt;p&gt;In this article the authors review recent advances in the treatment of chronic kidney disease (CKD) with diabetes, and summarize evidence supporting combination therapy approaches to improve patient outcomes. Driven by the global rise in diabetes, the worldwide burden of CKD has nearly doubled since the 1990s. People with CKD have notably increased risks for premature cardiovascular disease (heart and blood vessels disease), kidney failure and death. CKD, diabetes, obesity and cardiovascular disease are closely interrelated and share common risk factors. These health conditions therefore comprise what is now known as cardiovascular-kidney-metabolic (CKM) syndrome. Recently approved medications, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone, represent agents capable of reducing metabolic, kidney and cardiovascular risk through complementary mechanisms of action. Current evidence supports use of these therapies in combination. Besides providing additive protective effects, combination therapy may also help reduce side effects. For instance, using an SGLT2 inhibitor in combination with finerenone helps decrease the risk for high potassium levels. Through the multipronged approach, combination therapy allows tailoring treatment for the individual patient characteristics and needs. Several planned and ongoing clinical trials continue to study the benefits of combination therapy in people with CKM syndrome. With building evidence supporting the use of combination therapy, it is crucial to raise awareness of the importance of this treatment approach and develop processes to incorporate new therapies into every day practice to support optimal care and improved outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;The global burden of chronic kidney disease (CKD) increased by nearly 90% in the period spanning 1990 to 2016, mostly attributed to an increase in the prevalence of CKD in diabetes. People living with CKD have an elevated lifetime risk for cardiovascular disease (CVD) when compared with the general population, with risk increasing in parallel with albuminuria and kidney function decline. Metabolic disease, CKD and CVD share common risk factors including neurohumoral activation, systemic inflammation and oxidative stress, thus prompting the introduction of a broader construct of cardiovascular-kidney-metabolic (CKM) syndrome. An important rationale for the introduction of this concept are recent and ongoing therapeutic advancements fundamentally changing CKM management. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone have shifted the therapeutic paradigm for patients with CKD and have emerged in rapid succession as cornerstones of guideline-directed medical therapy (GDMT).","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_1","pages":"i3-i17"},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upcoming drug targets for kidney protective effects in chronic kidney disease.","authors":"Massimo Nardone, Kevin Yau, Luxcia Kugathasan, Ayodele Odutayo, Mai Mohsen, Jean-Philippe Ouimet, Vikas S Sridhar, David Z I Cherney","doi":"10.1093/ndt/gfae216","DOIUrl":"https://doi.org/10.1093/ndt/gfae216","url":null,"abstract":"<p><p>People with chronic kidney disease (CKD) are at a high risk of heart disease and end-stage kidney disease. This review describes how new medications, such as glucagon-like peptide-1 receptor agonists (GLP1RA), aldosterone synthase inhibitors (ASi), soluble guanylate cyclase (sGC) and endothelin receptor antagonists (ERA), can lower heart-kidney risk in people with CKD. GLP1RA are already recommended for managing blood sugar in people with CKD and type 2 diabetes and have been shown to lower the risk of developing end-stage kidney disease. GLP1RA will likely soon be included in clinical guidelines, but further research is needed to understand how these medications protect the kidneys. ASi are another new medication that lower the protein found in urine. Larger trials are being done to see how well these medications work in slowing CKD. Lastly, both sGC agonists and ERAs have been shown to relax blood vessels to improve blood flow in the kidney, and reduce the amount of protein found in urine, both of which are critical to protecting kidneys. Larger clinical trials are being done to see if these medications prevent CKD from getting worse. In summary, this review describes the new and promising treatments for CKD. These therapies hold the potential to slow kidney disease and improve the wellbeing of patients. Further research of these new treatments is important for improving CKD care.</p><p><strong>Abstract: </strong>Despite recent advancements in the treatment of chronic kidney disease (CKD), identifying novel therapies beyond guideline-directed therapies that reduce residual cardiorenal risk remains imperative. In this review, we highlight the clinical evidence supporting emerging therapies for CKD, including glucagon-like peptide-1 receptor agonists (GLP1RA) and other incretin-based therapies, aldosterone synthase inhibitors (ASI), endothelin receptor antagonists (ERA), soluble guanylate cyclase (sGC) agonists and anti-inflammatory drugs. Long-acting GLP1RA are already recommended for glycemic control in patients with CKD and type 2 diabetes and the large, dedicated kidney outcome trial FLOW was recently stopped early for efficacy. Emerging clinical trial evidence supports the concept that ASI also provide additional benefit on top of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which remain a cornerstone of CKD treatment. Next, we consider the use of sGC agonists, which target nitric oxide bioavailability and thereby reduce albuminuria. Finally, we explore the therapeutic potential of ERA, which act through hemodynamic and anti-fibrotic mechanisms, thereby addressing a common final pathway in the development of CKD. Accordingly, our review highlights the changing therapeutic landscape for CKD with promising agents to further prevent the progression of kidney disease.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_1","pages":"i47-i58"},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral phosphate binders and incident osteoporotic fracture in patients on dialysis.","authors":"Ji Eun Kim, Jina Park, Yunyoung Jang, Eunjeong Kang, Yong Chul Kim, Dong Ki Kim, Kwon Wook Joo, Yon Su Kim, Hajeong Lee","doi":"10.1093/ndt/gfae139","DOIUrl":"10.1093/ndt/gfae139","url":null,"abstract":"<p><strong>Background: </strong>End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients.</p><p><strong>Methods: </strong>We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both CBPB and NCBPB (mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality.</p><p><strong>Results: </strong>Out of 69 368 incident dialysis patients, 22 326, 5020, 2853 and 39 169 were included in the CBPB, NCBPB, mixed and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared with non-users. Specifically, only the CBPB group showed a reduced risk of vertebral [adjusted hazard ratio (aHR) 0.83 (0.76-0.92)], hip [aHR 0.81 (0.74-0.89)] and distal radius [aHR 0.88 (0.78-0.99)] fractures compared with non-users. This relationship presented in a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months [aHR 0.9 (0.83-0.99)] and ≥6 months [aHR 0.83 (0.78-0.89)], compared with those using CBPB for <3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared with non-users.</p><p><strong>Conclusions: </strong>Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared with non-users.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"329-340"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved prenatal assessment of kidney disease using multiple ultrasound features.","authors":"Bénédicte Buffin-Meyer, Julie Klein, Jacqueline Aziza, Manon Fernandez, Guylène Feuillet, Mouhamed Seye, Marie Buléon, Camille Fédou, Mylène Camus, Odile Burlet-Schiltz, Jelena Martinovic, Jean-Sébastien Saulnier-Blache, Stéphane Decramer, Joost P Schanstra","doi":"10.1093/ndt/gfae145","DOIUrl":"10.1093/ndt/gfae145","url":null,"abstract":"<p><strong>Background: </strong>Congenital anomalies of the kidney and urinary tract (CAKUT), often discovered in utero, cover a wide spectrum of outcomes ranging from normal postnatal kidney function to foetal death. The current ultrasound workup does not allow for an accurate assessment of the outcome. The present study aimed to significantly improve the ultrasound-based prediction of postnatal kidney survival in CAKUT.</p><p><strong>Methods: </strong>Histological analysis of kidneys of 15 CAKUT foetuses was performed to better standardize the ultrasound interpretation of dysplasia and cysts. Ultrasound images of 140 CAKUT foetuses with 2-year postnatal follow-up were annotated for amniotic fluid volume and kidney number, size, dysplasia and/or cysts using a standardized ultrasound readout. Association of ultrasound features and clinical data (sex and age at diagnosis) with postnatal kidney function was studied using logistic regression. Amniotic fluid proteome related to kidney dysplasia or cysts was characterized by mass spectrometry.</p><p><strong>Results: </strong>Histologically, poor ultrasound corticomedullary differentiation was associated with dysplastic lesions and ultrasound hyperechogenicity was associated with the presence of microcysts. Of all ultrasound and clinical parameters, reduced amniotic volume, dysplasia and cysts were the best predictors of poor outcome (odds ratio 57 [95% confidence interval (CI) 11-481], 20 [3-225] and 7 [1-100], respectively). Their combination into an algorithm improved prediction of postnatal kidney function compared with amniotic volume alone (area under the receiver operating characteristics curve 0.92 [95% CI 0.86-0.98] in a 10-fold cross-validation). Dysplasia and cysts were correlated (Cramer's V coefficient = 0.44, P < .0001), but amniotic fluid proteome analysis revealed that they had a distinct molecular origin (extracellular matrix and cell contacts versus cellular death, respectively), probably explaining the additivity of their predictive performances.</p><p><strong>Conclusion: </strong>Antenatal clinical advice for CAKUT pregnancies can be improved by a more standardized and combined interpretation of ultrasound data.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"341-351"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}