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1.
Kidney Int ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38844295

RESUMEN

Uncontrolled complement activation can cause or contribute to glomerular injury in multiple kidney diseases. Although complement activation plays a causal role in atypical hemolytic uremic syndrome and C3 glomerulopathy, over the past decade, a rapidly accumulating body of evidence has shown a role for complement activation in multiple other kidney diseases, including diabetic nephropathy and several glomerulonephritides. The number of available complement inhibitor therapies has also increased during the same period. In 2022, Kidney Diseases: Improving Global Outcomes (KDIGO) convened a Controversies Conference, "The Role of Complement in Kidney Disease," to address the expanding role of complement dysregulation in the pathophysiology, diagnosis, and management of various glomerular diseases, diabetic nephropathy, and other forms of hemolytic uremic syndrome. Conference participants reviewed the evidence for complement playing a primary causal or secondary role in progression for several disease states and considered how evidence of complement involvement might inform management. Participating patients with various complement-mediated diseases and caregivers described concerns related to life planning, implications surrounding genetic testing, and the need for inclusive implementation of effective novel therapies into clinical practice. The value of biomarkers in monitoring disease course and the role of the glomerular microenvironment in complement response were examined, and key gaps in knowledge and research priorities were identified.

2.
Am J Kidney Dis ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621632

RESUMEN

Erythrocytosis or polycythemia is defined as an increase in red blood cell concentration above the age- and sex-specific normal levels. Unlike anemia, which is very common in patients with chronic kidney disease (CKD), erythrocytosis is less frequent but requires specific understanding by health care professionals in order to provide the best care. Erythrocytosis, especially when undiagnosed and untreated, can lead to serious thrombotic events and higher mortality. Classic causes of erythrocytosis associated with CKD include cystic kidney diseases, kidney or other erythropoietin-secreting neoplasms, high-altitude renal syndrome, overdosage of erythropoietin-stimulating agents, androgen therapy, heavy smoking, chronic lung disease, obstructive sleep apnea, IgA nephropathy, post-kidney transplant erythrocytosis, renal artery stenosis, and congenital etiologies. After ruling out the common acquired causes of erythrocytosis and/or in the presence of suggestive parameters, primary erythrocytosis or polycythemia vera (PV) should be considered, and patients should be screened for JAK2V617F somatic mutation. The newest entity inducing erythrocytosis is linked to the use of sodium/glucose cotransporter 2 (SGLT2) inhibitors that hypothetically activate hypoxia-inducible factor 2α (HIF-2α) and in some cases unmask PV. This Review focuses on the pathogenesis, renal manifestations and management of PV, the pathophysiology of erythrocytosis induced by SGLT2 inhibitors and the relevance of timely JAK2 mutation screening in these patients.

3.
BMC Nephrol ; 25(1): 106, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500054

RESUMEN

A 75-year-old male developed acute kidney injury KDIGO stage 3 a few weeks after Whipple surgery was performed for a distal cholangiocarcinoma. Kidney biopsy revealed oxalate nephropathy. This was attributed to post-Whipple malabsorption, poor compliance with pancreatic enzyme replacement therapy, and daily intake of vitamin C supplements. Pancreatic enzyme replacement therapy was resumed and calcium carbonate initiated, with an improvement in glomerular filtration rate. Unfortunately, due to oncological progression, best supportive care was initiated.We review the pathophysiology and conditions predisposing to secondary hyperoxaluria and oxalate nephropathy. This diagnosis should be considered among the main causes of acute kidney injury following pancreatectomy, with important therapeutic implications.


Asunto(s)
Lesión Renal Aguda , Hiperoxaluria , Masculino , Humanos , Anciano , Pancreaticoduodenectomía/efectos adversos , Hiperoxaluria/complicaciones , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Oxalatos
4.
Ann Intern Med ; 176(12): 1648-1655, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38079642

RESUMEN

DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Insuficiencia Renal Crónica , Humanos , Hepacivirus , Antivirales/uso terapéutico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Hepatitis C/tratamiento farmacológico , Riñón
5.
Kidney Int ; 103(5): 842-858, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36731611

RESUMEN

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.


Asunto(s)
Fallo Renal Crónico , Diálisis Peritoneal , Insuficiencia Renal , Humanos , Hemodiálisis en el Domicilio , Calidad de Vida , Diálisis Renal , Fallo Renal Crónico/terapia
6.
Kidney Int ; 104(4): 655-680, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37236424

RESUMEN

Anemia is common in patients with chronic kidney disease and is associated with a high burden of morbidity and adverse clinical outcomes. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline for the diagnosis and management of anemia in chronic kidney disease. Since then, new data from studies assessing established and emerging therapies for the treatment of anemia and iron deficiency have become available. Beginning in 2019, KDIGO planned 2 Controversies Conferences to review the new evidence and its potential impact on the management of anemia in clinical practice. Here, we report on the second of these conferences held virtually in December 2021, which focused on a new class of agents-the hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs). This report provides a review of the consensus points and controversies from this second conference and highlights areas that warrant prioritization for future research.


Asunto(s)
Anemia , Inhibidores de Prolil-Hidroxilasa , Insuficiencia Renal Crónica , Humanos , Anemia/diagnóstico , Anemia/etiología , Anemia/terapia , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/tratamiento farmacológico , Prolina Dioxigenasas del Factor Inducible por Hipoxia , Prolil Hidroxilasas , Inhibidores de Prolil-Hidroxilasa/uso terapéutico
7.
Kidney Int ; 104(6): 1076-1091, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37236423

RESUMEN

In March 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a virtual Controversies Conference to address the important but rarely examined phase during which the kidney transplant is failing or has failed. In addition to discussing the definition of a failing allograft, 4 broad areas were considered in the context of a declining functioning graft: prognosis and kidney failure trajectory; immunosuppression strategies; management of medical and psychological complications, and patient factors; and choice of kidney replacement therapy or supportive care following graft loss. Identifying and paying special attention to individuals with failing allografts was felt to be important in order to prepare patients psychologically, manage immunosuppression, address complications, prepare for dialysis and/or retransplantation, and transition to supportive care. Accurate prognostication tools, although not yet widely available, were embraced as necessary to define allograft survival trajectories and the likelihood of allograft failure. The decision of whether to withdraw or continue immunosuppression after allograft failure was deemed to be based most appropriately on risk-benefit analysis and likelihood of retransplantation within a few months. Psychological preparation and support was identified as a critical factor in patient adjustment to graft failure, as was early communication. Several models of care were noted that enabled a medically supportive transition back to dialysis or retransplantation. Emphasis was placed on the importance of dialysis-access readiness before initiation of dialysis, in order to avoid use of central venous catheters. The centrality of the patient to all management decisions and discussions was deemed to be paramount. Patient "activation," which can be defined as engaged agency, was seen as the most effective way to achieve success. Unresolved controversies, gaps in knowledge, and areas for research were also stressed in the conference deliberations.


Asunto(s)
Enfermedades Renales , Riñón , Humanos , Trasplante Homólogo , Diálisis Renal , Aloinjertos
8.
Kidney Int ; 104(3): 441-454, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37290600

RESUMEN

Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has been related primarily to numerical targets for laboratory measures, and outcomes such as cardiovascular disease and mortality. Routine symptom assessment is not universal or standardized in dialysis care. Even when symptoms are identified, treatment options are limited and are initiated infrequently, in part because of a paucity of evidence in the dialysis population and the complexities of medication interactions in kidney failure. In May of 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference-Symptom-Based Complications in Dialysis-to identify the optimal means for diagnosing and managing symptom-based complications in patients undergoing maintenance dialysis. Participants included patients, physicians, behavioral therapists, nurses, pharmacists, and clinical researchers. They outlined foundational principles and consensus points related to identifying and addressing symptoms experienced by patients undergoing dialysis and described gaps in the knowledge base and priorities for research. Healthcare delivery and education systems have a responsibility to provide individualized symptom assessment and management. Nephrology teams should take the lead in symptom management, although this does not necessarily mean taking ownership of all aspects of care. Even when options for clinical response are limited, clinicians should focus on acknowledging, prioritizing, and managing symptoms that are most important to individual patients. A recognized factor in the initiation and implementation of improvements in symptom assessment and management is that they will be based on locally existing needs and resources.


Asunto(s)
Enfermedades Renales , Nefrología , Diálisis Renal , Humanos , Riñón , Enfermedades Renales/etiología , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos
9.
Kidney Int ; 104(5): 888-903, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37245565

RESUMEN

Chronic kidney disease (CKD) affects over 850 million people globally, and the need to prevent its development and progression is urgent. During the past decade, new perspectives have arisen related to the quality and precision of care for CKD, owing to the development of new tools and interventions for CKD diagnosis and management. New biomarkers, imaging methods, artificial intelligence techniques, and approaches to organizing and delivering healthcare may help clinicians recognize CKD, determine its etiology, assess the dominant mechanisms at given time points, and identify patients at high risk for progression or related events. As opportunities to apply the concepts of precision medicine for CKD identification and management continue to be developed, an ongoing discussion of the potential implications for care delivery is required. The 2022 KDIGO Controversies Conference on Improving CKD Quality of Care: Trends and Perspectives examined and discussed best practices for improving the precision of CKD diagnosis and prognosis, managing the complications of CKD, enhancing the safety of care, and maximizing patient quality of life. Existing tools and interventions currently available for the diagnosis and treatment of CKD were identified, with discussion of current barriers to their implementation and strategies for improving the quality of care delivered for CKD. Key knowledge gaps and areas for research were also identified.


Asunto(s)
Inteligencia Artificial , Insuficiencia Renal Crónica , Humanos , Calidad de Vida , Riñón , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Pronóstico
10.
Am J Kidney Dis ; 82(4): 410-418, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37061019

RESUMEN

RATIONALE & OBJECTIVE: Direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) has made transplantation of kidneys from HCV-infected donors to uninfected recipients (D+/R-) feasible. To facilitate an update to the 2018 KDIGO guideline for patients with CKD and HCV, we conducted a systematic review of HCV D+/R-kidney transplantation coupled with DAA treatment. STUDY DESIGN: Systematic review and meta-analysis. SETTING & STUDY POPULATIONS: We included studies of HCV D+/R-kidney transplantations that used any DAA protocol. SELECTION CRITERIA FOR STUDIES: Based on a search of PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, conferences from 2019 to 2021, and the 2018 KDIGO HCV guideline we identified single-group (D+/R-) or comparative studies of D+/R-versus D-/R-kidney transplantation. DATA EXTRACTION: Conducted in SRDR-Plus with review by a second researcher. ANALYTICAL APPROACH: Maximum likelihood meta-analyses; the certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We identified 16 studies (N=557). A sustained viral response at 12 weeks after treatment (SVR12) was observed in 97.7% (95% CI, 96.3%-98.8%). Ultrashort duration treatment (≤8 days) resulted in viremia requiring standard-course DAA treatment in some patients, all of whom achieved SVR12 after 1 or rarely 2 DAA courses. Serious adverse events from DAA treatment were rare after D+/R-transplantation (0.4% [95% CI, 0.1%-2.8%]). At≥1 year after D+/R-transplantation, recipient death occurred in 2.1% (95% CI, 0.9-3.7) and allograft survival was 97.6% (95% CI, 95.7%-98.9%). Estimated glomerular filtration rate 1 year after transplantation ranged from 46 to 74mL/min/1.73m2. LIMITATIONS: Analyses were generally based on low-certainty evidence. Uncertainty exists about the long-term safety and efficacy of D+/R-transplantation. Few studies investigated ultrashort treatment courses. CONCLUSIONS: Kidney transplantation from HCV-infected donors to uninfected recipients followed by DAA treatment appears to be safe and associated with excellent 1-year clinical outcomes. PLAIN-LANGUAGE SUMMARY: Due to the high efficacy of direct-acting antivirals (DAA), the use of kidneys from HCV-infected deceased donors may increase rates of kidney transplantation. We conducted a systematic review for the 2022 KDIGO Clinical Practice Guideline on Hepatitis C to evaluate the safety and efficacy of kidney transplantation from HCV-infected donors to uninfected recipients (D+/R-) followed by DAA therapy. Sixteen studies comprising 557 patients revealed high rates of sustained viral response, low rates of adverse events, and excellent patient and allograft survival 1 year after transplantation. Kidney transplantation from HCV-infected deceased donors to uninfected recipients treated with DAA appears safe and effective. Future studies should investigate shorter treatment durations, monitor safety, and obtain longer-term efficacy data.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Trasplante de Riñón , Insuficiencia Renal Crónica , Humanos , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C/complicaciones , Insuficiencia Renal Crónica/complicaciones , Donantes de Tejidos
11.
Artículo en Inglés | MEDLINE | ID: mdl-37873684

RESUMEN

BACKGROUND AND HYPOTHESIS: Buttonhole cannulation of native arteriovenous fistulas (AVFs) appears associated with an increased infectious risk. We previously reported a dramatic increase in the incidence of infectious events after shift to buttonhole in an in-center hemodialysis unit, largely reduced after staff (re)education regarding strict respect of the procedure. We assessed the evolution over the following 12-years period in our center. METHODS: In this prospective follow-up of a previous, pre (rope-ladder)-post (buttonhole) comparison (2001-2010), all in-center hemodialysis patients with a native AVF were included from July 1st, 2010 to December 31st, 2022. Primary and secondary outcomes were infectious events (unexplained bacteraemia due to skin bacteria and/or local AVF infection) and complicated infectious events (metastatic infection, AVF surgery, death). Overall, the impact of several quality improvement strategies was tested according to the events rate over 6 periods: 1: Rope-ladder in all; 2: switch to buttonhole; 3: buttonhole in all, before workshops; 4: buttonhole in all, after workshops; 5: buttonhole withdrawal in problematic AVFs; 6: additional procedural changes. RESULTS: This extended observation period allowed adding 195,180 AVF-days to our previous report. Overall, 381,661 AVF-days (366 AVFs, 345 patients) were analysed. After an increase of the infectious events rate in 2012, the shift to rope-ladder in problematic AVFs during Period 5 did not have a significant impact. The incidence of infectious events decrease significantly during Period 6 compared to Periods 3, 4 and 5 [IRR 0.24 (95%CI 0.09-0.52) p=0.0001, IRR 0.22 (95%CI 0.09-0.47) p<0.0001, and IRR 0.29 (95%CI 0.11-0.66) p=0.001, respectively] and became eventually for the first time comparable to Period 1 [IRR 0.59 (95%CI 0.21-1.62) p=0.27]. CONCLUSION: The constant observance of reinforced hygiene protocols by trained staff and central coordination succeeded in significantly mitigating the infectious risk associated with buttonhole.

12.
Kidney Int ; 102(6): 1228-1237, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36411019

RESUMEN

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.


Asunto(s)
Hepatitis C , Insuficiencia Renal Crónica , Humanos , Hepacivirus , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Hepatitis C/tratamiento farmacológico , Tasa de Filtración Glomerular , Riñón
13.
Am J Kidney Dis ; 79(5): 717-727, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34508834

RESUMEN

Hyperoxaluria results from either inherited disorders of glyoxylate metabolism leading to hepatic oxalate overproduction (primary hyperoxaluria), or increased intestinal oxalate absorption (secondary hyperoxaluria). Hyperoxaluria may lead to urinary supersaturation of calcium oxalate and crystal formation, causing urolithiasis and deposition of calcium oxalate crystals in the kidney parenchyma, a condition termed oxalate nephropathy. Considerable progress has been made in the understanding of pathophysiological mechanisms leading to hyperoxaluria and oxalate nephropathy, whose diagnosis is frequently delayed and prognosis too often poor. Fortunately, novel promising targeted therapeutic approaches are on the horizon in patients with primary hyperoxaluria. Patients with secondary hyperoxaluria frequently have long-standing hyperoxaluria-enabling conditions, a fact suggesting the role of triggers of acute kidney injury such as dehydration. Current standard of care in these patients includes management of the underlying cause, high fluid intake, and use of calcium supplements. Overall, prompt recognition of hyperoxaluria and associated oxalate nephropathy is crucial because optimal management may improve outcomes.


Asunto(s)
Lesión Renal Aguda , Hiperoxaluria Primaria , Hiperoxaluria , Lesión Renal Aguda/complicaciones , Oxalato de Calcio , Femenino , Humanos , Hiperoxaluria/complicaciones , Hiperoxaluria/terapia , Hiperoxaluria Primaria/complicaciones , Hiperoxaluria Primaria/diagnóstico , Hiperoxaluria Primaria/terapia , Masculino , Oxalatos
14.
J Med Virol ; 94(4): 1481-1487, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34811754

RESUMEN

In-center maintenance hemodialysis (HD) patients are at high risk of acquiring coronavirus disease 2019 (COVID-19) by cross-contamination inside the unit. The aim of this study was to assess retrospectively the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the very first pandemic phase (March-July 2020) in a cohort of in-center maintenance HD patients and in nurses the same HD facility, using a phylogenetic approach. All SARS-CoV-2 quantitative reverse-transcription polymerase chain reaction positive patients and nurses from our HD unit-respectively 10 out of 98, and 8 out of 58- and two other positive patients dialyzed in our self-care unit were included. Whole-genome viral sequencing and phylogenetic analysis supported the cluster investigation. Five positive patients were usually dialyzed in the same room and same shift before their COVID-19 diagnosis was made. Viral sequencing performed on 4/5 patients' swabs showed no phylogenetic link between their viruses. The fifth patient (whose virus could not be sequenced) was dialyzed at the end of the dialysis room and was treated by a different nurse than the one in charge of the other patients. Three nurses shared the same virus detected in both self-care patients (one of them had been transferred to our in-center facility). The epidemiologically strongly suspected intra-unit cluster could be ruled out by viral genome sequencing. The infection control policy did not allow inter-patient contamination within the HD facility, in contrast to evidence of moderate dissemination within the nursing staff and in the satellite unit. Epidemiologic data without phylogenetic confirmation might mislead the interpretation of the dynamics of viral spreading within congregate settings.


Asunto(s)
COVID-19/prevención & control , COVID-19/transmisión , Control de Infecciones/métodos , Diálisis Renal , Anciano , Bélgica , COVID-19/epidemiología , Prueba de COVID-19 , Femenino , Genoma Viral , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Filogenia , Estudios Retrospectivos , SARS-CoV-2/genética
15.
J Am Soc Nephrol ; 32(5): 1249-1261, 2021 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-33833079

RESUMEN

BACKGROUND: Membranous nephropathy (MN) results from deposition of antigen-antibody complexes along the glomerular basement membrane (GBM). PLA2R, THSD7A, NELL1, and SEMA3B account for 80%-90% of target antigens in MN. METHODS: We performed laser microdissection and mass spectrometry (MS/MS) in kidney biopsies from 135 individuals with PLA2R-negative MN, and used immunohistochemistry/immunofluorescence and confocal microscopy to confirm the MS/MS finding, detect additional cases, and localize the novel protein. We also performed MS/MS and immunohistochemistry on 116 controls and used immunofluorescence microscopy to screen biopsy samples from two validation cohorts. Western blot and elution studies were performed to detect antibodies in serum and biopsy tissue. RESULTS: MS/MS studies detected a unique protein, protocadherin 7 (PCDH7), in glomeruli of ten (5.7%) PLA2R-negative MN cases, which also were negative for PLA2R, THSD7A, EXT1/EXT2, NELL1, and SEMA3B. Spectral counts ranged from six to 24 (average 13.2 [SD 6.6]). MS/MS did not detect PCDH7 in controls (which included 28 PLA2R-positive cases). In all ten PCDH7-positive cases, immunohistochemistry showed bright granular staining along the GBM, which was absent in the remaining cases of PLA2R-negative MN and control cases. Four of 69 (5.8%) cases in the validation cohorts (all of which were negative for PLA2R, THSD7A, EXT1, NELL1, and SEMA3B) were PCDH7-positive MN. Kidney biopsy showed minimal complement deposition in 12 of the 14 PCDH7-associated cases. Confocal microscopy showed colocalization of PCDH7 and IgG along the GBM. Western blot analysis using sera from six patients showed antibodies to nonreduced PCDH7. Elution of IgG from frozen tissue of PCDH7-associated MN showed reactivity against PCDH7. CONCLUSIONS: MN associated with the protocadherin PCDH7 appears to be a distinct, previously unidentified type of MN.


Asunto(s)
Cadherinas/metabolismo , Glomerulonefritis Membranosa/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Glomerulonefritis Membranosa/patología , Humanos , Captura por Microdisección con Láser , Masculino , Espectrometría de Masas , Microscopía Confocal , Persona de Mediana Edad , Protocadherinas
16.
Kidney Int ; 100(3): 516-526, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34252450

RESUMEN

Kidney disease is an important public health problem. Both acute kidney injury (AKI) and chronic kidney disease have been well defined and classified, leading to improved research efforts and subsequent management strategies and recommendations. For those patients with abnormalities in kidney function and/or structure who meet neither the definition of AKI nor chronic kidney disease, there remains a gap in research, care, and guidance. The term acute kidney diseases and disorders, abbreviated to acute kidney disease (AKD), has been introduced as an important construct to address this. To expand and harmonize existing definitions and to ultimately better inform research and clinical care, Kidney Disease: Improving Global Outcomes (KDIGO) organized a consensus workshop. Multiple invitees from around the globe, representing both acute and chronic kidney disease researchers and experts, met virtually to examine existing data, and discuss key concepts related to AKD. Despite some remaining unresolved questions, conference attendees reached general consensus on the definition and classification of AKD, management strategies, and research priorities. AKD is defined by abnormalities of kidney function and/or structure with implications for health and with a duration of ≤3 months. AKD may include AKI, but, more importantly, also includes abnormalities in kidney function that are not as severe as AKI or that develop over a period of >7 days. The cause(s) of AKD should be sought, and classification includes functional and structural parameters. Management of AKD is currently based on empirical considerations. A robust research agenda to enable refinement and validation of definitions and classification systems, and thus testing of interventions and strategies, is proposed.


Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Enfermedad Aguda , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Consenso , Humanos , Riñón , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia
17.
Kidney Int ; 99(1): 34-47, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33127436

RESUMEN

Chronic kidney disease (CKD) causes substantial global morbidity and increases cardiovascular and all-cause mortality. Unlike other chronic diseases with established strategies for screening, there has been no consensus on whether health systems and governments should prioritize early identification and intervention for CKD. Guidelines on evaluating and managing early CKD are available but have not been universally adopted in the absence of incentives or quality measures for prioritizing CKD care. The burden of CKD falls disproportionately upon persons with lower socioeconomic status, who have a higher prevalence of CKD, limited access to treatment, and poorer outcomes. Therefore, identifying and treating CKD at the earliest stages is an equity imperative. In 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a controversies conference entitled "Early Identification and Intervention in CKD." Participants identified strategies for screening, risk stratification, and treatment for early CKD and the key health system and economic factors for implementing these processes. A consensus emerged that CKD screening coupled with risk stratification and treatment should be implemented immediately for high-risk persons and that this should ideally occur in primary or community care settings with tailoring to the local context.


Asunto(s)
Insuficiencia Renal Crónica , Tasa de Filtración Glomerular , Humanos , Riñón , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Medición de Riesgo , Factores de Riesgo
18.
Kidney Int ; 100(1): 35-48, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33961868

RESUMEN

Chronic kidney disease (CKD) affects about 10% of all populations worldwide, with about 2 million people requiring dialysis. Although patients with CKD are at high risk of cardiovascular disease and events, they are often underrepresented or excluded in clinical trials, leading to important knowledge gaps about how to treat these patients. KDIGO (Kidney Disease: Improving Global Outcomes) convened the fourth clinical Controversies Conference on the heart, kidney and vasculature in Dublin, Ireland, in February 2020, entitled Central and Peripheral Arterial Diseases in Chronic Kidney Disease. A global panel of multidisciplinary experts from the fields of nephrology, cardiology, neurology, surgery, radiology, vascular biology, epidemiology, and health economics attended. The objective was to identify key issues related to the optimal detection, management, and treatment of cerebrovascular diseases, central aortic disease, renovascular disease, and peripheral artery disease in the setting of CKD. This report outlines the common pathophysiology of these vascular processes in the setting of CKD, describes best practices for their diagnosis and management, summarizes areas of uncertainty, addresses ongoing controversial issues, and proposes a research agenda to address key gaps in knowledge that, when addressed, could improve patient care and outcomes.


Asunto(s)
Nefrología , Enfermedad Arterial Periférica , Insuficiencia Renal Crónica , Humanos , Irlanda , Riñón , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/epidemiología , Enfermedad Arterial Periférica/terapia , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia
19.
Kidney Int ; 99(6): 1280-1295, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33839163

RESUMEN

In chronic kidney disease, anemia and disordered iron homeostasis are prevalent and associated with significant adverse consequences. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) issued an anemia guideline for managing the diagnosis, evaluation, and treatment of anemia in chronic kidney disease. Since then, new data have accrued from basic research, epidemiological studies, and randomized trials that warrant a re-examination of previous recommendations. Therefore, in 2019, KDIGO decided to convene 2 Controversies Conferences to review the latest evidence, explore new and ongoing controversies, assess change implications for the current KDIGO anemia guideline, and propose a research agenda. The first conference, described here, focused mainly on iron-related issues, including the contribution of disordered iron homeostasis to the anemia of chronic kidney disease, diagnostic challenges, available and emerging iron therapies, treatment targets, and patient outcomes. The second conference will discuss issues more specifically related to erythropoiesis-stimulating agents, including epoetins, and hypoxia-inducible factor-prolyl hydroxylase inhibitors. Here we provide a concise overview of the consensus points and controversies resulting from the first conference and prioritize key questions that need to be answered by future research.


Asunto(s)
Anemia , Hematínicos , Inhibidores de Prolil-Hidroxilasa , Insuficiencia Renal Crónica , Anemia/diagnóstico , Anemia/epidemiología , Anemia/etiología , Hematínicos/uso terapéutico , Humanos , Hierro , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia
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