Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, ...COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS).
Retrospective cohort study.
82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected.
A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P=0.8), causative genes (P=0.6), or type of variant (P=0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was−1.46 (−1.66 to−1.26) mL/min/1.73m2 per year for the overall group, with no significant differences between ADAS genes (P=0.2).
The relatively small size of this series from a single country, potentially limiting generalizability.
Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.
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Fabry disease or also called Anderson-Fabry disease (FD) is a rare disease caused by pathogenic variants in the GLA gene, located on the X chromosome. This gene is involved in the metabolism of ...glycosphingolipids and its pathogenic variants cause a deficit or absence of α-galactosidase A causing the deposition of globotriaosylceramide throughout the body. Females have a variable phenotypic expression and a better prognosis than males. This is due to the X chromosome inactivation phenomenon. We present a clinical case of Fabry disease in a female with predominantly renal involvement and demonstrate how the X chromosome inactivation phenomenon is tissue dependent, showing preferential inactivation of the mutated allele at the renal level.
La enfermedad de Fabry o también llamada de Anderson-Fabry (EF) es una enfermedad rara, causada por variantes patogénicas en el gen GLA, localizado en el cromosoma X. Este gen interviene en el metabolismo de los glucoesfingolípidos y variantes patogénicas en el mismo causan déficit o ausencia de la α-galactosidasa A ocasionando el depósito de globotriaosilceramida en todo el organismo. Las mujeres presentan una expresión fenotípica variable y de mejor pronóstico que los varones. Esto es debido al fenómeno de inactivación del cromosoma X. Presentamos un caso clínico de enfermedad de Fabry en una mujer con afectación predominantemente renal y demostramos cómo el fenómeno de la inactivación del cromosoma X es tejido dependiente, mostrando una inactivación preferencial del alelo mutado a nivel renal.
La enfermedad de Fabry o también llamada de Anderson-Fabry (EF) es una enfermedad rara, causada por variantes patogénicas en el gen GLA, localizado en el cromosoma X. Este gen interviene en el ...metabolismo de los glucoesfingolípidos y variantes patogénicas en el mismo causan déficit o ausencia de la α-galactosidasa A, ocasionando el depósito de globotriaosilceramida en todo el organismo. Las mujeres presentan una expresión fenotípica variable y de mejor pronóstico que los varones. Esto es debido al fenómeno de inactivación del cromosoma X. Presentamos un caso clínico de enfermedad de Fabry en una mujer con afectación predominantemente renal y demostramos cómo el fenómeno de la inactivación del cromosoma X es tejido dependiente, mostrando una inactivación preferencial del alelo mutado a nivel renal.
Fabry disease or also called Anderson–Fabry disease (FD) is a rare disease caused by pathogenic variants in the GLA gene, located on the X chromosome. This gene is involved in the metabolism of glycosphingolipids and its pathogenic variants cause a deficit or absence of α-galactosidase A causing the deposition of globotriaosylceramide throughout the body. Females have a variable phenotypic expression and a better prognosis than males. This is due to the X chromosome inactivation phenomenon. We present a clinical case of Fabry disease in a female with predominantly renal involvement and demonstrate how the X chromosome inactivation phenomenon is tissue dependent, showing preferential inactivation of the mutated allele at the renal level.
La gammapatía monoclonal de significado renal incluye todas las enfermedades renales causadas por una inmunoglobulina monoclonal secretada por un clon de célula B no maligno. Por definición, los ...pacientes con gammapatía monoclonal de significado renal no cumplen criterios de mieloma múltiple y la alteración hematológica es generalmente considerada gammapatía monoclonal de significado incierto. No obstante, la dolencia que pueden causar a nivel renal puede ser importante, requiriendo un tratamiento específico. El espectro de la gammapatía monoclonal de significado renal es amplio, incluyendo una entidad reciente como la nefropatía C3. El desarrollo de una nefropatía C3 en el contexto de una gammapatía monoclonal de significado renal tras el trasplante renal no es frecuente y hasta el momento ha sido poco descrita. A continuación presentamos 3 casos de nefropatía C3 asociados a una gammapatía monoclonal de aparición de novo tras el trasplante renal.
Monoclonal gammopathy of renal significance includes all renal disorders caused by a monoclonal immunoglobulin secreted by a non-malignant B-cell clone. Patients with MGRS do not, by definition, meet criteria for multiple myeloma, with haematological disorders generally considered to be monoclonal gammopathy of undetermined significance. Nevertheless, the renal involvement can be serious and require specific treatment. Monoclonal gammopathy of renal significance is associated with a wide spectrum of disorders, including the recently discovered C3 glomerulopathy. Development of C3 glomerulopathy in the context of monoclonal gammopathy of renal significance after kidney transplantation is uncommon and very few cases have been published to date. We report on three cases of C3 glomerulopathy in the context of de novo monoclonal gammopathy after kidney transplantation.
A nine months old girl with prenatal diagnosis of bilateral hydronephrosis underwent serious studies and in view of the presumed diagnosis of right functional annulment, a right laparoscopic ...nephroureterectomy was performed. The anatomopatological result was suggestive of tuberculosis without previous contact with the disease. Postoperatively, the child received antituberculosis therapy (ATT) for a full 8 months (isoniazid, rifampin, pyrazinamide and ethambutol for 2 months and isoniazid and rifampin for 6 months) and the follow-up tests revealed improvement of ureterohydronephrosis in left kidney.
Monoclonal gammopathy of renal significance includes all renal disorders caused by a monoclonal immunoglobulin secreted by a non-malignant B-cell clone. Patients with MGRS do not, by definition, meet ...criteria for multiple myeloma, with haematological disorders generally considered to be monoclonal gammopathy of undetermined significance. Nevertheless, the renal involvement can be serious and require specific treatment. Monoclonal gammopathy of renal significance is associated with a wide spectrum of disorders, including the recently discovered C3 glomerulopathy. Development of C3 glomerulopathy in the context of monoclonal gammopathy of renal significance after kidney transplantation is uncommon and very few cases have been published to date. We report on three cases of C3 glomerulopathy in the context of de novo monoclonal gammopathy after kidney transplantation. Resumen: La gammapatía monoclonal de significado renal incluye todas las enfermedades renales causadas por una inmunoglobulina monoclonal secretada por un clon de célula B no maligno. Por definición, los pacientes con gammapatía monoclonal de significado renal no cumplen criterios de mieloma múltiple y la alteración hematológica es generalmente considerada gammapatía monoclonal de significado incierto. No obstante, la dolencia que pueden causar a nivel renal puede ser importante, requiriendo un tratamiento específico. El espectro de la gammapatía monoclonal de significado renal es amplio, incluyendo una entidad reciente como la nefropatía C3. El desarrollo de una nefropatía C3 en el contexto de una gammapatía monoclonal de significado renal tras el trasplante renal no es frecuente y hasta el momento ha sido poco descrita. A continuación presentamos 3 casos de nefropatía C3 asociados a una gammapatía monoclonal de aparición de novo tras el trasplante renal. Keywords: Monoclonal gammopathy, Kidney transplant, C3 glomerulopathy, Palabras clave: Gammapatía monoclonal, Trasplante renal, Nefropatía C3
Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis characterized by inflammation of small blood vessels, with the kidney ...being one of the most affected organs. Its pathogenesis is a complex, multifactorial process involving inflammation and fibrosis in which macrophages play a crucial role. Macrophages are plastic cells that can change their phenotype in response to their environment. Infiltration of CD163+ macrophages (anti-inflammatory) in the interstitium and glomeruli is observed in AAV patients. Clinical and demographic differences between PR3-AAV and MPO-AAV were observed. We observed that interstitial fibrosis (IFTA) is more pronounced in MPO-AAV than in PR3-AAV. We aimed to investigate the differences in CD163+ macrophage infiltration and interstitial fibrosis between PR3-AAV and MPO-AAV. Method Retrospective single-center study of 80 AAV patients (66 MPO-AAV and 14 PR3-AAV) diagnosed by renal biopsy with at least 1 year of follow-up. Clinical and laboratory variables, ANCA type and renal/patient survival were evaluated. 26 human kidney tissue samples (13 MPO-AAV and 13 PR3-AAV) were stained for CD163+ by immunohistochemistry and immunofluorescence, and trichrome-stained biopsy slides were used to measure the degree of fibrosis. Histomorphometric quantification was performed using MetaMorph® software in both cases. Data analysis was performed under standard conditions. Statistical significance was defined as P values less than 0.05. All P values were 2-sided. Results CD163+ macrophages infiltration in the interstitial space was greater in MPO-AAV than PR3-AAV with statistical significance (p < 0.001), observing an average infiltration area of 0.333% in MPO-AAV than 0.116% in PR3-AAV. Furthermore, IFTA was higher at diagnosis in MPO-AAV (35.35%) than in PR3-AAV (31.21%) at the diagnosis with a p = 0.03. However, a correlation between IF and CD163+ macrophages infiltration was not possible to stablish. Conclusion We have observed an increased macrophage infiltrate with an anti-inflammatory and reparative phenotype that is higher at diagnosis in ANCAS-MPO compared to ANCAS-PR3, the same difference occurs with respect to interstitial fibrosis. Since the study population is small, no correlations between fibrosis and CD163 macrophage infiltration have yet been found.
Is there a CD4+ and CD8+ immunity alteration in patients with pulmonary tuberculosis (TB) and diabetes (DM) that does not recover after antituberculosis treatment? This prospective comparative study ...evaluated CD4+ and CD8+ lymphocytic subpopulations and antituberculosis antibodies in patients with diabetes and tuberculosis (TB-DM), before and after antituberculosis treatment. CD4+ T cell counts were lower in patients with TB-DM compared to those with only TB or only DM, and these levels remained low even after two months of anti-TB treatment. Regarding the CD8+ T cell analysis, we identified higher blood values in the DM-only group, which may be explained by the high prevalence of latent tuberculosis (LTBI) in patients with DM. IgM antituberculosis antibodies levels were elevated in patients with only TB at baseline, and 2 months post-anti-TB treatment, IgG did not express any relevant alterations. Our results suggest an alteration in CD4+ immunity in patients with TB-DM that did not normalize after antituberculosis treatment.
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