La acidosis tubular renal distal (ATRd) es una enfermedad minoritaria, de origen genético o adquirido, caracterizada por una incapacidad de excreción urinaria de hidrogeniones (H+), ...hipobicarbonatemia, hipercloremia, hipocitraturia y habitualmente hipokaliemia e hipercalciuria. Las formas genéticas suelen diagnosticarse en los primeros meses de vida y su tratamiento consiste en suplementos de álcali encaminados a evitar las consecuencias clínicas a largo plazo, sobre todo la enfermedad renal crónica (presente en algunas series hasta en el 82% de los pacientes) y la enfermedad ósea asociada. Se desarrolló una encuesta multirrespuesta cerrada de 10 preguntas encaminada a conocer aspectos epidemiológicos, diagnósticos, del manejo clínico y terapéutico, dentro del colectivo de nefrólogos españoles.
Encuesta distribuida a los asistentes a un foro científico sobre ATRd durante el congreso de 2019 de la Sociedad Española de Nefrología (SEN); las respuestas se recogieron a la salida del mismo. Los resultados se analizaron con un test estadístico paramétrico estableciéndose el porcentaje de cada respuesta a las 10 preguntas.
De entre los que respondieron a la encuesta, el 44,4 y el 37,7% no atendieron a ningún paciente con ATRd en el último año ni en los tres anteriores, respectivamente. Cuando se sospecha la patología, el diagnóstico genético confirmatorio se realiza solo en el 13,3% de los casos y el estudio familiar solo en el 11,1%. Solo el 26,6% afirman que el control metabólico es excelente, bueno o muy bueno, y el 69% piensan que el cumplimiento terapéutico es regular, malo o muy malo.
La encuesta ha puesto de manifiesto el relativo desconocimiento de esta patología, así como la baja satisfacción con el control metabólico y el pobre cumplimiento terapéutico, lo cual puede conllevar una mayor severidad en la enfermedad renal y ósea asociadas a la ATRd.
dRTA is a genetic or acquired rare disease, characterized by an unability to excrete hydrogens (H+) into urine, hypobicarbonatemia, hyperchloremia, and frequently hypercalciuria and hypokalaemia. Genetic forms are usually diagnosed during the first months of life and its treatment is based on providing alkali supplements in order to prevent long term clinical consequences, particularly chronic kidney disease (described in some cohorts up to 82% of dRTA patients) and the associated bone disease. A 10 queries multi choice closed response survey was designed to know more about epidemiological, diagnostics, clinical management and therapeutical issues of this disease among Spanish nephrologists.
This survey was delivered to the attendees to a scientific meeting on dRTA at the Spanish Nephrology Society congress in 2019. Surveys were collected at the end of this dRTA event. Results were analyzed by using a parametric statistical test, obtaining the percentage of each response for the 10 questions.
Among the survey responders, 44.4% and 37.7% did not visit any dRTA patient during the 1st and 3rd last year respectively. When having a suspicious diagnose, confirming genetic diagnostic test is only performed on the 13.3% of cases and pedigree studies only on 11.1%. Only a 26.6% confirms that metabolic control is excellent, good or very good, and 69% of the responders believe that treatment compliance is not bad, bad or very bad.
This survey enhances the fact that dRTA is not a well known entity, satisfaction with metabolic control is poor and compliance is low. All these factors can lead to a higher severity of renal and bone diseases associated to dRTA.
This study was designed to assess the current perception of Spanish nephrologists in the clinical management of mineral and bone metabolism disorders in chronic kidney disease (CKD-MBD). As such, we ...used a semi-structured distance professional consensus procedure via e-mail (modified Delphi method) on a representative nephrologist panel, under the direction of a coordinating committee. To analyse the group's opinion and the type of consensus reached on each issue raised, we used the median of the group's scores and the "level of agreement" reached by those surveyed. On a total of 86 issues, a consensus agreement and disagreement was achieved in 70 (81.4%), of which 60.5% (52 items) agreed with the statement and 20.9% (18 items) disagreed. In 16 items (18.6%), there was insufficient unanimity in the panel's opinion, either due to professional opinion disparity or due to the lack of opinion established in the majority of the expert committee. Accepting the study's limitations, we considered that the items for which there was a consensus reinforce some CKD-MBD concepts with their impact on daily clinical practice and allow the degree of homogeneity that we could expect in this area to be assessed. The items in which there was no consensus help us to know the areas of uncertainty and are very useful for clarifying which aspects have a greater need for further knowledge and which areas require prospective studies to be conducted to improve the management of these disorders.
Abstract Background and Aims Despite offering superior outcomes for patients with end-stage kidney disease, kidney transplantation poses significant cardiovascular risks. Recently, histopathological ...findings in chronic kidney disease patients have been associated with all-cause mortality and cardiovascular events, but there is scant data on this subject in kidney transplant recipients. This study assesses the relationship between histopathological findings in protocol biopsies of kidney grafts and cardiovascular events, graft loss, and mortality in renal transplant recipients. Method A prospective observational study included 530 renal transplant recipients at the Hospital Clínic de Barcelona from March 2015 to 2019, with follow-up until March 2023. Data included demographics, comorbidities, laboratory tests, and protocol allograft biopsies at 3 and 12 months post-transplant. Associations between histopathological findings and outcomes (cardiovascular events, graft loss, mortality) were analyzed. Results Chronic vascular lesions (CV) were significantly correlated with cardiovascular death and major adverse cardiovascular events (MACE) (OR 10.4 (1.6–66.4); p 0.002). Arteriolar hyalinosis and interstitial fibrosis were independently associated with all-cause mortality (OR 4.9 (1.1-21.4); p 0.02, and 1.2 (1.03-1.3), p 0.005; respectively) regardless of the estimated glomerular filtration rate (eGFR). Associations were also found between pre-transplant factors (diabetes, hypertension, hyperphosphatemia), active smoking, and deceased donors. Notably, post-transplant hypophosphatemia was related to MACE, suggesting a potential association with malnutrition though, this subject requires further investigation. Conclusion Histopathological findings in early protocol biopsies of kidney grafts, especially chronic vascular lesions, arteriolar hyalinosis, and interstitial fibrosis, have a potential predictive value for cardiovascular events, mortality, and graft outcomes in transplant recipients, irrespective of eGFR. These insights emphasize the importance of timely post-transplant histological assessments for risk stratification and personalized interventions. Prospective studies are imperative to validate these findings and improve customized care strategies in this population.
Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease (CKD) that is characterised by elevated parathyroid hormone (PTH) levels and a series of ...bone-mineral metabolism anomalies. In patients with SHPT, treatment with paricalcitol, a selective vitamin D receptor activator, has been shown to reduce PTH levels with minimal serum calcium and phosphorus variations. The classic effect of paricalcitol is that of a mediator in mineral and bone homeostasis. However, recent studies have suggested that the benefits of treatment with paricalcitol go beyond PTH reduction and, for instance, it has a positive effect on cardiovascular disease and survival. The objective of this study is to review the most significant studies on the so-called pleiotropic effects of paricalcitol treatment in patients with CKD.
dRTA is a genetic or acquired rare disease, characterized by an unability to excrete hydrogens (H+) into urine, hypobicarbonatemia, hyperchloremia, and frequently hypercalciuria and hypokalaemia. ...Genetic forms are usually diagnosed during the first months of life and its treatment is based on providing alkali supplements in order to prevent long term clinical consequences, particularly chronic kidney disease (described in some cohorts up to 82% of dRTA patients) and the associated bone disease. A 10 queries multi choice closed response survey was designed to know more about epidemiological, diagnostics, clinical management and therapeutical issues of this disease among Spanish nephrologists.
This survey was delivered to the attendees to a scientific meeting on dRTA at the Spanish Nephrology Society congress in 2019. Surveys were collected at the end of this dRTA event. Results were analyzed by using a parametric statistical test, obtaining the percentage of each response for the 10 questions. Results. Among the survey responders, 44.4% and 37.7% did not visit any dRTA patient during the 1st and 3rd last year respectively. When having a suspicious diagnose, confirming genetic diagnostic test is only performed on the 13.3% of cases and pedigree studies only on 11.1%. Only a 26.6% confirms that metabolic control is excellent, good or very good. 69% of the responders believe that treatment compliance is not bad, bad or very bad.
This survey enhances the fact that dRTA is not a well known entity, satisfaction with metabolic control is poor and compliance is low. All these factors can lead to a higher severity of renal and bone diseases associated to dRTA.
La ATRd es una enfermedad minoritaria de origen genético o adquirido, caracterizada por una incapacidad de excreción urinaria de hidrogeniones (H+), hipobicarbonatemia, hipercloremia, hipocitraturia y habitualmente hipokaliemia e hipercalciuria. Las formas genéticas suelen diagnosticarse en los primeros meses de vida y su tratamiento consiste en suplementos de álcali encaminados a evitar las consecuencias clínicas a largo plazo, sobre todo la enfermedad renal crónica (presente en algunas series hasta en el 82% de los pacientes) y la enfermedad ósea asociada. Se desarrolló una encuesta multirrespuesta cerrada de 10 preguntas encaminada a conocer aspectos epidemiológicos, diagnósticos, del manejo clínico y terapéutico, dentro del colectivo de nefrólogos españoles.
Encuesta distribuida a los asistentes a un foro científico sobre ATRd durante el congreso de 2019 de la Sociedad Española de Nefrología (SEN), se recogieron las respuestas a la salida del mismo. Los resultados se analizaron con un test estadístico paramétrico estableciéndose el porcentaje de cada respuesta las 10 preguntas. Resultados. De entre los que respondieron a la encuesta, un 44,4% y un 37,7% no atendió ningún paciente con ATRd en el último año ni en los 3 anteriores, respectivamente. Cuando se sospecha la patología, el diagnóstico genético confirmatorio se realiza solo en un 13,3% de los casos y el estudio familiar solo en un 11,1%. Solo un 26,6% afirma que el control metabólico es excelente, bueno o muy bueno, y el 69% piensa que el cumplimiento terapéutico es regular, malo o muy malo.
La encuesta ha puesto de manifiesto el relativo desconocimiento de esta patología, así como la baja satisfacción con el control metabólico y el pobre cumplimiento terapéutico, lo cual puede conllevar a una mayor severidad en la enfermedad renal y ósea asociadas a la ATRd.
3006 Therapeutic apheresis in Fabry disease Ugalde-Altamirano, Jessica; Juarez, Jordi Rovira; Plana, Josep Maria Campistol ...
Nephrology, dialysis, transplantation,
05/2024, Letnik:
39, Številka:
Supplement_1
Journal Article
Recenzirano
Odprti dostop
Abstract Background and Aims Fabry's disease (FD) is a rare lysosomal disorder linked to the X chromosome due to a mutation in the gene encoding alpha-galactosidase A (alpha-Gal A). This mutation ...leads to a defect in the metabolism of glycosphingolipids, causing the progressive accumulation of globotriaacylceramide (GB3) or LysoGB3 in cells, tissues, and organs. In the treatment of FD, we have enzyme replacement therapy (ERT) with Agalsidase-alfa (Replagal®), Agalsidase-beta (Fabrazyme®), and chaperones (Migalastat®). However, there are limitations such as disease progression and morbimortality. Regarding ERT, the development of circulating immunoglobulin G (IgG) antibodies against agalsidase (aGAL) in the long term appears to be associated with a loss of effectiveness. The use of Therapeutic Apheresis (TA), such as plasma exchange therapy (PE) and low-density lipoprotein apheresis (LDL-apheresis), is employed in the treatment of various pathologies due to its ability to eliminate plasma, antibodies, low-density lipoproteins, apolipoproteins, and the adaptability of therapy to the molecule to be removed. The aim was to demonstrate that LDL-apheresis and PE favor Lyso-Gb3 elimination, and PE also eliminates IgG-aGAL as an adjunctive treatment in FD and conducted a proof-of-concept study. Method Two branches of intervention were established, where patients were classified into two groups based on the presence or absence of anti-agalsidase IgG antibodies. If they have the presence of antibodies, they would be eligible for plasma exchanges with two objectives: removing pre-formed antibodies and eliminating Lyso-Gb3. Conversely, in the absence of pre-formed antibodies, LDL-apheresis is performed with the aim of eliminating Lyso-Gb3. The proof-of-concept study was done with two FD patients undergoing ERT were identified, one with IgG-aGAL and the other with very low levels. PE was performed on the first patient, and LDL-apheresis on the second. Lyso-Gb3 levels were titrated in blood before and after LDL-apheresis, and in the washout bag of the column. For antibodies, titration was done in pre and post PE blood and in the extracted plasma from PE. Results After applying TA techniques, we observed that PE reduces IgG-aGAL by 85%, and in the case of LDL-apheresis, there was a 28% reduction in IgG-aGAL. While the ability to eliminate LysoGb3 showed a reduction of 25.5% in PE and 39.7% for LDL-apheresis. To eliminate a potential confounding factor, LysoGb3 determination in albumin was within normal limits. Conclusion With these results, we confirm that PE is more efficient in removing IgG-aGAL but also eliminates LysoGb3, whereas LDL-apheresis is a very effective technique for removing Lyso-Gb3 but also contributes to antibody removal. Based on these findings, we consider TA to be an effective adjunctive tool for FD treatment, even as a standalone treatment. However, these are very preliminary results and should be reproduced with a larger number of patients.
Abstract Background and Aims Fabry's disease (FD), a hereditary condition, is linked to the X chromosome due to a mutation in the gene encoding alpha-galactosidase A (alpha-GalA). This mutation ...results in a defect in the metabolism of glycosphingolipids, leading to the deposition of globotriaosylceramide (GB3) primarily in organs such as the heart, kidneys, and nervous system. Renal injury can affect any level of the structure, with the podocytes being the most commonly affected due to their low regeneration and high contact with GB3. This leads to proteinuria, and if it exceeds 0.5 g, it is associated with a rapid deterioration of renal function. Renal assessment is carried out through blood analysis, proteinuria measurement, ultrasound, and the gold standard, renal biopsy. However, there is a growing trend towards less invasive biomarkers such as lysoGB3 titration in blood and urine, podocyturia, or renal progenitor cells (RPCs) in renal biopsy material or cell culture. RPCs possess self-renewal, clonogenicity, and multidifferentiation properties, contributing to cellular remodeling. They express specific markers like CD133/CD24 and CD106 in the parietal epithelium of Bowman's capsule. It is known that GB3 expresses CD77. The proliferative response of RPCs can become dysregulated, leading to detachment and elimination in the urine. The aim of the study was to demonstrate the presence of renal progenitor cells (RPCs) in urine as a non-invasive early marker for detecting renal damage in patients with Fabry's disease (FD) and to establish a correlation between RPC presence, GB3 deposition, and their potential association with the degree of renal injury. Method It is an open observational, case-control, single-center study on the urine of patients with Fabry's disease (FD) considered as cases, patients without a history considered as healthy controls, and patients with non-FD renal disease such as Gittelman syndrome or another biopsy-proven cause as positive controls. Renal progenitor cells (RPCs) were isolated using specific markers and flow cytometry, correlating these findings with renal function and albuminuria. Results A total of 75 recent urine samples were processed, corresponding to 59 patients: 16 with Fabry's disease (FD), 11 with Gittelman syndrome, 10 with chronic kidney disease (CKD), and 22 healthy controls. The samples were divided for sediment and microalbuminuria analysis, and separately for the isolation of renal progenitor cells (RPCs). The classification and quantification of the isolated cell types were performed, establishing positivity points using compensation panels with CD3 lymphocyte markers. This was followed by the identification of RPCs through positivity for CD133+/CD24+, CD106+, and CD106– markers. Once RPCs were identified, GB3 marking was carried out using CD77+. Differences were observed among the analyzed patient groups. In healthy controls, there was minimal or no presence of renal progenitor cells (RPCs), except in two patients where isolation was repeated in three different samples, maintaining positivity. Subsequent diagnoses revealed bilateral lithiasis and previously unknown hypertension in these cases. Patients with Gittelman syndrome showed a higher quantity of RPCs compared to healthy controls, but with P > .05. However, clear RPCs positivity was evident in patients with Fabry's disease (FD) and chronic kidney disease (CKD) confirmed by biopsy, with P < .05. Additionally, differences in the number of RPCs were noted based on the degree of renal disease when correlated with the presence of proteinuria < 0.5 g and > 0.5 g, with P < .05. Conclusion With these results, we can conclude that renal progenitor cells (RPCs) may serve as an early biomarker for silent renal injury of various etiologies. Furthermore, if we perform labeling with CD77, we can attribute it to the deposition of GB3 in Fabry's disease (FD).
El hiperparatiroidismo secundario (HPTS) es una complicación habitual en pacientes con enfermedad renal crónica que se caracteriza por unos niveles elevados de hormona paratiroidea (PTH) y una serie ...de anomalías en el metabolismo mineral-óseo. En pacientes con HPTS, el tratamiento con paricalcitol, un activador selectivo de los receptores de la vitamina D, ha demostrado reducir los niveles de PTH con mínimas variaciones del calcio y del fósforo séricos. El efecto clásico de paricalcitol es el de mediador en la homeostasis mineral y ósea. Sin embargo, estudios recientes han indicado que los beneficios del tratamiento con paricalcitol van más allá de la reducción de PTH, por ejemplo, ocasionando efectos positivos en la enfermedad cardiovascular y en la supervivencia. El objetivo del presente trabajo es revisar los estudios más significativos sobre los llamados efectos pleiotrópicos del tratamiento con paricalcitol en pacientes con ERC.
Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease (CKD) that is characterised by elevated parathyroid hormone (PTH) levels and a series of bone-mineral metabolism anomalies. In patients with SHPT, treatment with paricalcitol, a selective vitamin D receptor activator, has been shown to reduce PTH levels with minimal serum calcium and phosphorus variations. The classic effect of paricalcitol is that of a mediator in mineral and bone homeostasis. However, recent studies have suggested that the benefits of treatment with paricalcitol go beyond PTH reduction and, for instance, it has a positive effect on cardiovascular disease and survival. The objective of this study is to review the most significant studies on the so-called pleiotropic effects of paricalcitol treatment in patients with CKD.
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