Pub Date : 2026-01-01DOI: 10.1016/j.nefro.2025.501411
Sonia Sharma , Ankur Gupta
Kidney transplantation (KT) is the most effective treatment for end-stage kidney disease. With advancements in modern immunosuppression, graft survival rates for standard-risk recipients have significantly improved, reaching approximately 95% in the first year, 85% at five years, and 65% at 10 years. However, long-term outcomes remain challenging due to chronic graft loss and drug-related toxicities. Immunosuppressive drugs, with narrow therapeutic range of safety and efficacy, require drug-monitoring strategies to optimize outcomes. In KT, the standard triple maintenance regimen of tacrolimus, mycophenolate mofetil (MMF), and prednisolone is practiced and MMF is typically administered as a fixed-dose drug. However, evidence suggests that dosage adjustments based on concentration monitoring yield superior clinical outcomes. MMF, an ester prodrug of mycophenolic acid (MPA), necessitates area under the concentration curve (AUC) monitoring due to its complex pharmacokinetics and an exposure level of 30–60 mg/L h is considered adequate for transplant recipients. However, fixed dosing practices continued, due to controversial evidence and lack of familiarity with AUC and monitoring techniques. AUC monitoring has also been proposed for tacrolimus, a calcineurin inhibitor (CNI), instead of routinely used trough concentration, particularly in “rapid metabolizers” who may experience higher peak concentrations and toxicities. To enhance transplant outcomes, a comprehensive understanding of AUC and relevance to immunosuppressant exposure is critical. This review will primarily focus on MPA AUC exposure in post-kidney transplant patients, explore and explain methods for AUC monitoring, and highlight recent developments in tacrolimus AUC monitoring.
{"title":"Rationalized immunosuppressant dosing in kidney transplantation: Mycophenolate mofetil AUC monitoring and key updates on tacrolimus exposure","authors":"Sonia Sharma , Ankur Gupta","doi":"10.1016/j.nefro.2025.501411","DOIUrl":"10.1016/j.nefro.2025.501411","url":null,"abstract":"<div><div>Kidney transplantation (KT) is the most effective treatment for end-stage kidney disease. With advancements in modern immunosuppression, graft survival rates for standard-risk recipients have significantly improved, reaching approximately 95% in the first year, 85% at five years, and 65% at 10 years. However, long-term outcomes remain challenging due to chronic graft loss and drug-related toxicities. Immunosuppressive drugs, with narrow therapeutic range of safety and efficacy, require drug-monitoring strategies to optimize outcomes. In KT, the standard triple maintenance regimen of tacrolimus, mycophenolate mofetil (MMF), and prednisolone is practiced and MMF is typically administered as a fixed-dose drug. However, evidence suggests that dosage adjustments based on concentration monitoring yield superior clinical outcomes. MMF, an ester prodrug of mycophenolic acid (MPA), necessitates area under the concentration curve (AUC) monitoring due to its complex pharmacokinetics and an exposure level of 30–60<!--> <!-->mg/L<!--> <!-->h is considered adequate for transplant recipients. However, fixed dosing practices continued, due to controversial evidence and lack of familiarity with AUC and monitoring techniques. AUC monitoring has also been proposed for tacrolimus, a calcineurin inhibitor (CNI), instead of routinely used trough concentration, particularly in “rapid metabolizers” who may experience higher peak concentrations and toxicities. To enhance transplant outcomes, a comprehensive understanding of AUC and relevance to immunosuppressant exposure is critical. This review will primarily focus on MPA AUC exposure in post-kidney transplant patients, explore and explain methods for AUC monitoring, and highlight recent developments in tacrolimus AUC monitoring.</div></div>","PeriodicalId":18997,"journal":{"name":"Nefrologia","volume":"46 1","pages":"Article 501411"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963288","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 : 2026-01-01DOI: 10.1016/j.nefro.2025.501396
Marina Almenara-Tejederas , Águeda López-de la Torre Molina , María Jesús Moyano Franco , Marina de Cueto-López , Jesús Rodríguez-Baño , Mercedes Salgueira-Lazo
<div><h3>Background and objective</h3><div>Tunneled catheters (TC) have become an essential vascular access for hemodialysis, despite their association with increased morbidity and mortality, particularly due to infections. Existing studies assessing the optimal combination of prophylactic measures to prevent TC-related infections are limited by small sample sizes and short follow-up periods. The objectives of this study were to describe the clinical and demographic characteristics of patients with TC in our healthcare area, determine the incidence and etiology of TC-related bloodstream infections (TC-BSI), and analyze the impact of pre-implantation prophylactic measures and patient survival over a long-term follow-up.</div></div><div><h3>Material and method</h3><div>We conducted a retrospective study including all patients with a TC implanted between 2005 and 2019 in a tertiary care hospital. Catheter implantation was performed by nephrologists following a protocol developed in collaboration with the Infectious Diseases Department. The protocol emphasized 3 main measures: screening and treatment of <em>Staphylococcus aureus</em> carriers, chlorhexidine bathing prior to the procedure, and antibiotic prophylaxis. We collected clinical-demographic variables, catheter-related data, and details of TC-BSI episodes. Patients were followed from the time of TC insertion until the end of the study (December 31, 2020), loss to follow-up, or death.</div></div><div><h3>Results</h3><div>Over the 14-year study period, 462 TCs were implanted in 381 patients (179 [55.1%] male; median age 67 [IQR 55-74] years; 154 [47.4%] with diabetes mellitus, 292 [89.9%] with hypertension, and 135 [41.5%] with cardiovascular disease). The internal jugular vein was the most common site of insertion (275; 84.6%). Two types of catheters were predominantly used: Palindrome® (192; 59.1%) and Hemoglyde® (102; 31.4%). A total of 85 TC-BSI episodes were recorded (0.36 per 1000 TC-days). The majority (71; 83.4%) were caused by Gram-positive organisms: <em>Staphylococcus epidermidis</em> (36; 42.4%) and <em>S. aureus</em> (24; 28.0%), including 3 methicillin-resistant strains. Over 80% of infections occurred after 6 months of catheter placement. Only four (4.7%) infections occurred within the first 30 days. During follow-up, 177 patients (54.4%) died. The most frequent cause of death was infection (55; 31.1%), although only 7 deaths occurred following a TC-BSI (2.1% of the study population).</div></div><div><h3>Conclusions</h3><div>The implementation of a dedicated protocol for TC implantation was associated with a low incidence of TC-BSI. These infections tended to present late and were predominantly caused by <em>S. epidermidis,</em> a less virulent organism than <em>S. aureus.</em> Among the preventive measures, systematic screening and decolonization of nasal <em>S. aureus</em> carriers significantly reduced the incidence of TC-BSI caused by this pathogen, with no observed increase
{"title":"Bacteriemias asociadas a catéter tunelizado: un enfoque basado en resultados a largo plazo","authors":"Marina Almenara-Tejederas , Águeda López-de la Torre Molina , María Jesús Moyano Franco , Marina de Cueto-López , Jesús Rodríguez-Baño , Mercedes Salgueira-Lazo","doi":"10.1016/j.nefro.2025.501396","DOIUrl":"10.1016/j.nefro.2025.501396","url":null,"abstract":"<div><h3>Background and objective</h3><div>Tunneled catheters (TC) have become an essential vascular access for hemodialysis, despite their association with increased morbidity and mortality, particularly due to infections. Existing studies assessing the optimal combination of prophylactic measures to prevent TC-related infections are limited by small sample sizes and short follow-up periods. The objectives of this study were to describe the clinical and demographic characteristics of patients with TC in our healthcare area, determine the incidence and etiology of TC-related bloodstream infections (TC-BSI), and analyze the impact of pre-implantation prophylactic measures and patient survival over a long-term follow-up.</div></div><div><h3>Material and method</h3><div>We conducted a retrospective study including all patients with a TC implanted between 2005 and 2019 in a tertiary care hospital. Catheter implantation was performed by nephrologists following a protocol developed in collaboration with the Infectious Diseases Department. The protocol emphasized 3 main measures: screening and treatment of <em>Staphylococcus aureus</em> carriers, chlorhexidine bathing prior to the procedure, and antibiotic prophylaxis. We collected clinical-demographic variables, catheter-related data, and details of TC-BSI episodes. Patients were followed from the time of TC insertion until the end of the study (December 31, 2020), loss to follow-up, or death.</div></div><div><h3>Results</h3><div>Over the 14-year study period, 462 TCs were implanted in 381 patients (179 [55.1%] male; median age 67 [IQR 55-74] years; 154 [47.4%] with diabetes mellitus, 292 [89.9%] with hypertension, and 135 [41.5%] with cardiovascular disease). The internal jugular vein was the most common site of insertion (275; 84.6%). Two types of catheters were predominantly used: Palindrome® (192; 59.1%) and Hemoglyde® (102; 31.4%). A total of 85 TC-BSI episodes were recorded (0.36 per 1000 TC-days). The majority (71; 83.4%) were caused by Gram-positive organisms: <em>Staphylococcus epidermidis</em> (36; 42.4%) and <em>S. aureus</em> (24; 28.0%), including 3 methicillin-resistant strains. Over 80% of infections occurred after 6 months of catheter placement. Only four (4.7%) infections occurred within the first 30 days. During follow-up, 177 patients (54.4%) died. The most frequent cause of death was infection (55; 31.1%), although only 7 deaths occurred following a TC-BSI (2.1% of the study population).</div></div><div><h3>Conclusions</h3><div>The implementation of a dedicated protocol for TC implantation was associated with a low incidence of TC-BSI. These infections tended to present late and were predominantly caused by <em>S. epidermidis,</em> a less virulent organism than <em>S. aureus.</em> Among the preventive measures, systematic screening and decolonization of nasal <em>S. aureus</em> carriers significantly reduced the incidence of TC-BSI caused by this pathogen, with no observed increase ","PeriodicalId":18997,"journal":{"name":"Nefrologia","volume":"46 1","pages":"Article 501396"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963320","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 : 2026-01-01DOI: 10.1016/j.nefro.2025.501362
Susana Enrique Madrid, Jesús Lucas García
The thick ascending limb of the loop of Henle (TAL) reabsorbs approximately 30% of filtered NaCl through two mechanisms: transepithelial and paracellular reabsorption. The latter is carried out through a class of tight junction proteins known as claudins. A mutation in the gene encoding claudin-10 causes a rare salt-wasting tubular disorder with hypokalemic metabolic alkalosis. However, unlike Bartter syndrome and Gitelman disease, it usually presents with hypermagnesemia and extrarenal manifestations such as xerostomia, alacrima, and hypohidrosis with ichthyosis, known by the acronym HELIX syndrome.
{"title":"Síndrome de HELIX en la infancia. Una claudinopatía con fenotipo de tubulopatía pierde sal con hipermagnesemia","authors":"Susana Enrique Madrid, Jesús Lucas García","doi":"10.1016/j.nefro.2025.501362","DOIUrl":"10.1016/j.nefro.2025.501362","url":null,"abstract":"<div><div>The thick ascending limb of the loop of Henle (TAL) reabsorbs approximately 30% of filtered NaCl through two mechanisms: transepithelial and paracellular reabsorption. The latter is carried out through a class of tight junction proteins known as claudins. A mutation in the gene encoding claudin-10 causes a rare salt-wasting tubular disorder with hypokalemic metabolic alkalosis. However, unlike Bartter syndrome and Gitelman disease, it usually presents with hypermagnesemia and extrarenal manifestations such as xerostomia, alacrima, and hypohidrosis with ichthyosis, known by the acronym HELIX syndrome.</div></div>","PeriodicalId":18997,"journal":{"name":"Nefrologia","volume":"46 1","pages":"Article 501362"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963282","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 : 2025-10-01DOI: 10.1016/j.nefro.2025.501351
Verónica López , Juan Pablo Gámez , Myriam León , Juana Alonso-Titos , Cristina Gutiérrez , Carolina Polo , Teresa Vázquez , Pedro Ruiz-Esteban , Domingo Hernández
{"title":"Tacrolimus formulations in de novo kidney transplantation: Evidence from a paired kidney study","authors":"Verónica López , Juan Pablo Gámez , Myriam León , Juana Alonso-Titos , Cristina Gutiérrez , Carolina Polo , Teresa Vázquez , Pedro Ruiz-Esteban , Domingo Hernández","doi":"10.1016/j.nefro.2025.501351","DOIUrl":"10.1016/j.nefro.2025.501351","url":null,"abstract":"","PeriodicalId":18997,"journal":{"name":"Nefrologia","volume":"45 8","pages":"Article 501351"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183735","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 : 2025-10-01DOI: 10.1016/j.nefro.2025.501347
Alberto López-Lera , Fernando Corvillo , Laura González-Sánchez , Marta Melgosa , Pilar Sánchez-Corral
The complement system is a network of soluble and cell surface proteins primarily involved in innate immune responses. Complement signalling is essential for pathogen defence and homeostasis, but an activation-regulation imbalance can lead to tissue damage. This phenomenon has been implicated in kidney diseases such as atypical Haemolytic Uraemic Syndrome (aHUS), frequently associated with dysfunction of the complement regulator Factor H (FH). Physiologically, complement interacts with the coagulation, fibrinolysis, renin-angiotensin and kallikrein-kinin systems (KKS). The KKS is a proinflammatory and procoagulant cascade comprised of the protease prekallikrein, the coagulation factors XI (FXI) and XII (FXII), and the cofactor/substrate high-molecular-weight kininogen. KKS can be activated conformationally or proteolytically. KKS activation in vitro triggers a number of biochemical interactions between FXI, FXII, FH and other complement proteins that result in direct or secondary complement activation. These functional links point to an overall complement pro-activating role for the KKS that has implications for coagulation and immunity, but whose physiological consequences in vivo remain largely unexplored. This review aims to summarize the main physiopathological events of KKS activation in the context of complement-mediated kidney disease, with particular emphasis in aHUS.
{"title":"Relevancia de las interacciones entre el complemento y el sistema de contacto de la coagulación en la enfermedad renal","authors":"Alberto López-Lera , Fernando Corvillo , Laura González-Sánchez , Marta Melgosa , Pilar Sánchez-Corral","doi":"10.1016/j.nefro.2025.501347","DOIUrl":"10.1016/j.nefro.2025.501347","url":null,"abstract":"<div><div>The complement system is a network of soluble and cell surface proteins primarily involved in innate immune responses. Complement signalling is essential for pathogen defence and homeostasis, but an activation-regulation imbalance can lead to tissue damage. This phenomenon has been implicated in kidney diseases such as atypical Haemolytic Uraemic Syndrome (aHUS), frequently associated with dysfunction of the complement regulator Factor H (FH). Physiologically, complement interacts with the coagulation, fibrinolysis, renin-angiotensin and kallikrein-kinin systems (KKS). The KKS is a proinflammatory and procoagulant cascade comprised of the protease prekallikrein, the coagulation factors XI (FXI) and XII (FXII), and the cofactor/substrate high-molecular-weight kininogen. KKS can be activated conformationally or proteolytically. KKS activation <em>in vitro</em> triggers a number of biochemical interactions between FXI, FXII, FH and other complement proteins that result in direct or secondary complement activation. These functional links point to an overall complement pro-activating role for the KKS that has implications for coagulation and immunity, but whose physiological consequences <em>in vivo</em> remain largely unexplored. This review aims to summarize the main physiopathological events of KKS activation in the context of complement-mediated kidney disease, with particular emphasis in aHUS.</div></div>","PeriodicalId":18997,"journal":{"name":"Nefrologia","volume":"45 8","pages":"Article 501347"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183777","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 : 2025-10-01DOI: 10.1016/j.nefro.2025.501339
Eman A.E. Badr , Safwa O. Toulan , Yasser A. El Ghobashy , Ahmed Mostafa Nofal , Mohamed F.A. Assar
Background
Diabetic nephropathy (DN) is a major cause of chronic kidney disease, influenced by genetic and inflammatory factors. SNPs in NLRP1 and NLRP3 genes, key regulators of inflammation, may contribute to DN susceptibility, offering insights into its pathogenesis and potential therapeutic targets. This study aims to investigate the association between single nucleotide polymorphisms (SNPs) in NLRP1 and NLRP3 genes and the susceptibility to diabetic nephropathy.
Methods
This cross-sectional study was conducted on 192 subjects, comprising 96 DN patients and 96 healthy controls. Diabetic nephropathy was diagnosed with albumin creatinine ratio in urine. Genotyping of SNPs rs878329 in NLRP1 and rs10754558 in NLRP3 was performed using the TaqMan® Allelic Discrimination assay.
Results
Significant differences were found in the distribution of both rs878329 and rs10754558 genotypes between cases and controls. The GG genotype of rs878329 and the CG genotype of rs10754558 were significantly more prevalent among DN patients (p = 0.002 and p = 0.005, respectively). Allelic analysis revealed a higher frequency of the G allele in both SNPs among DN cases (p = 0.001 and p = 0.002, respectively).
Conclusion
Our study supports the involvement of NLRP gene polymorphisms in the pathogenesis of DN, potentially offering new insights into genetic predispositions to this condition.
{"title":"The association between single nucleotide polymorphisms in NLRP gene and diabetic nephropathy","authors":"Eman A.E. Badr , Safwa O. Toulan , Yasser A. El Ghobashy , Ahmed Mostafa Nofal , Mohamed F.A. Assar","doi":"10.1016/j.nefro.2025.501339","DOIUrl":"10.1016/j.nefro.2025.501339","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy (DN) is a major cause of chronic kidney disease, influenced by genetic and inflammatory factors. SNPs in NLRP1 and NLRP3 genes, key regulators of inflammation, may contribute to DN susceptibility, offering insights into its pathogenesis and potential therapeutic targets. This study aims to investigate the association between single nucleotide polymorphisms (SNPs) in NLRP1 and NLRP3 genes and the susceptibility to diabetic nephropathy.</div></div><div><h3>Methods</h3><div>This cross-sectional study was conducted on 192 subjects, comprising 96 DN patients and 96 healthy controls. Diabetic nephropathy was diagnosed with albumin creatinine ratio in urine. Genotyping of SNPs rs878329 in NLRP1 and rs10754558 in NLRP3 was performed using the TaqMan® Allelic Discrimination assay.</div></div><div><h3>Results</h3><div>Significant differences were found in the distribution of both rs878329 and rs10754558 genotypes between cases and controls. The GG genotype of rs878329 and the CG genotype of rs10754558 were significantly more prevalent among DN patients (<em>p</em> <!-->=<!--> <!-->0.002 and <em>p</em> <!-->=<!--> <!-->0.005, respectively). Allelic analysis revealed a higher frequency of the G allele in both SNPs among DN cases (<em>p</em> <!-->=<!--> <!-->0.001 and <em>p</em> <!-->=<!--> <!-->0.002, respectively).</div></div><div><h3>Conclusion</h3><div>Our study supports the involvement of NLRP gene polymorphisms in the pathogenesis of DN, potentially offering new insights into genetic predispositions to this condition.</div></div>","PeriodicalId":18997,"journal":{"name":"Nefrologia","volume":"45 8","pages":"Article 501339"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183778","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 : 2025-10-01DOI: 10.1016/j.nefro.2025.501361
Juan A. Martín Navarro , Ana S. Pareja Martínez , M. Angeles Matías de la Mano , M. Teresa Navío Marco , Eva M. Chavarría Mur , Elena Conde Montero , Santos Esteban Casado , Laura Medina Zahonero , Fabio L. Procaccini , Patricia Muñoz Ramos , Roberto Alcázar Arroyo , Patricia de Sequera Ortiz
{"title":"Dos casos de remisión de nefritis lúpica refractaria con voclosporina","authors":"Juan A. Martín Navarro , Ana S. Pareja Martínez , M. Angeles Matías de la Mano , M. Teresa Navío Marco , Eva M. Chavarría Mur , Elena Conde Montero , Santos Esteban Casado , Laura Medina Zahonero , Fabio L. Procaccini , Patricia Muñoz Ramos , Roberto Alcázar Arroyo , Patricia de Sequera Ortiz","doi":"10.1016/j.nefro.2025.501361","DOIUrl":"10.1016/j.nefro.2025.501361","url":null,"abstract":"","PeriodicalId":18997,"journal":{"name":"Nefrologia","volume":"45 8","pages":"Article 501361"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183863","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}
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