RESUMEN
Integrin Subunit Alpha 8 gene (ITGA8) encodes an integrin chain that is known to be critical in the early stage of the kidney development. Bi-allelic pathogenic variants in ITGA8 are associated with bilateral renal agenesis, as well as anomalies involving urogenital system. Here, we report two unrelated patients presenting with slowly progressing chronic kidney disease associated with bilateral renal hypodysplasia carrying homozygous loss of function variants in the ITGA8 gene. These results broaden the clinical and genotypic spectrum of ITGA8 defects, revealing the high and unexpected degree of phenotypic heterogeneity of this autosomal recessive disease. Our study emphasizes the usefulness of Next-Generation Sequencing in unraveling the genetic cause of chronic kidney disease of unknown etiology, and raises the question of genetic modifiers involved in the variation of the phenotypes associated with autosomal recessive ITGA8 pathogenic variants.
Asunto(s)
Cadenas alfa de Integrinas , Enfermedades Renales , Humanos , Cadenas alfa de Integrinas/genética , Enfermedades Renales/genéticaRESUMEN
Shoot architecture is a key component of the interactions between plants and their environment. We present a novel model of grass, which fully integrates shoot morphogenesis and the metabolism of carbon (C) and nitrogen (N) at organ scale, within a three-dimensional representation of plant architecture. Plant morphogenesis is seen as a self-regulated system driven by two main mechanisms. First, the rate of organ extension and the establishment of architectural traits are regulated by concentrations of C and N metabolites in the growth zones and the temperature. Second, the timing of extension is regulated by rules coordinating successive phytomers instead of a thermal time schedule. Local concentrations are calculated from a model of C and N metabolism at organ scale. The three-dimensional representation allows the accurate calculation of light and temperature distribution within the architecture. The model was calibrated for wheat (Triticum aestivum) and evaluated for early vegetative stages. This approach allowed the simulation of realistic patterns of leaf dimensions, extension dynamics, and organ mass and composition. The model simulated, as emergent properties, plant and agronomic traits. Metabolic activities of growing leaves were investigated in relation to whole-plant functioning and environmental conditions. The current model is an important step towards a better understanding of the plasticity of plant phenotype in different environments.
Asunto(s)
Modelos Biológicos , Poaceae , Simulación por Computador , Modelos Estructurales , Hojas de la PlantaRESUMEN
Background: In kidney transplant recipients, anticardiolipin (ACL) antibodies without antiphospholipid syndrome (APS) are found in up to 38% of patients and could be associated with thrombotic events (TEs). However, the prognostic role of ACL regarding kidney transplant and patients outcomes have still not been well defined. Methods: We conducted an observational, monocentric, retrospective cohort study including 446 kidney transplant recipients and standardized follow-up: 36-month allograft and patient survival, 12-month estimated glomerular filtration rate (eGFR) and 3- and 12-month screening biopsies. Results: ACL tests were run on 247 patients, 101 were positive (ACL+ group, 41%) and 146 were negative (ACL- group, 59%). Allografts and patient survival within 36 months as TE were similar between both groups [hazard ratio (HR) = 1.18 and HR = 0.98, respectively]. The 12-month eGFR was significantly lower in the ACL+ group [median (95% confidence interval) 48.5 (35.1-60.3) versus 51.9 (39.1-65.0) mL/min/1.73 m2, P= 0.042]. ACL+ was independently associated with eGFR decrease (P = 0.04). In 12-month screening biopsies, tubular atrophy was significantly more severe in the ACL+ group compared with the ACL- group (P = 0.02). Conclusions: ACL without APS before kidney transplantation is an independent risk factor of eGFR decline within the first year post-transplant without over-incidence of TEs. Specific immunosuppressive therapy including mammalian target of rapamycin inhibitors should be discussed in the future.
Asunto(s)
Anticuerpos Anticardiolipina/efectos adversos , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Supervivencia de Injerto , Enfermedades Renales/cirugía , Trasplante de Riñón/efectos adversos , Adulto , Anticuerpos Anticardiolipina/sangre , Anticuerpos Anticardiolipina/inmunología , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/patología , Humanos , Enfermedades Renales/sangre , Enfermedades Renales/inmunología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Receptores de TrasplantesRESUMEN
BACKGROUND: Pemetrexed, a multitargeted antifolate cytotoxic agent, is currently used primarily in combination with cisplatin for metastatic non-small cell lung cancer and for malignant mesothelioma. Acute renal toxicity of pemetrexed has been recently described with polychemotherapy, in which the individual responsibility of each drug is difficult to establish. Only one recent report documents renal involvement in long-term exposed patients. CASE PRESENTATION: We report on a case of rapidly progressive nephropathy leading to the cessation of platinum salts and the secondary interruption of pemetrexed and bevacizumab. Acute tubular necrosis shown on the renal biopsy could potentially be due to pemetrexed. Persistent severe renal failure after the resumption of all drugs led to new treatment lines with gemcitabine (while the glomerular filtration rate was below 30 ml/min/1.73m2), then followed by Taxol. CONCLUSIONS: The optimal strategy with regard to renal complications in cancer patients is not clear. Acute or chronic loss in renal function generally leads to a new treatment line, possibly impairing the overall success of the treatment. The use of chemotherapy in patients with a glomerular filtration rate below 30 ml/min/1.73m2 is usually associated with an increased risk of side effects when not contraindicated by renal elimination of the drug.
Asunto(s)
Lesión Renal Aguda/patología , Antineoplásicos/efectos adversos , Pemetrexed/efectos adversos , Insuficiencia Renal/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/complicaciones , Anciano , Antineoplásicos/uso terapéutico , Biopsia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Manejo de la Enfermedad , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/fisiopatología , Neoplasias Pulmonares/tratamiento farmacológico , Pemetrexed/uso terapéutico , Insuficiencia Renal/patologíaRESUMEN
Tenofovir disoproxil fumarate is currently the cornerstone of HIV treatment. Although it shows an overall good safety profile, numerous cases of nephrotoxicity have been reported. Tenofovir alafenamide is a novel tenofovir prodrug that has been developed to improve renal safety. Pharmacokinetic studies suggest a better renal tolerance of tenofovir alafenamide than tenofovir disoproxil fumarate, probably because tenofovir plasma concentrations are lower after tenofovir alafenamide administration. Consistently in clinical trials, renal tolerance seems to be improved in patients treated with tenofovir alafenamide. However, some questions remain. First, whether tenofovir can accumulate and lead to nephrotoxicity under specific circumstances after tenofovir alafenamide administration is unknown. Second, only "real-world practice" will inform us on the long-term renal safety of tenofovir alafenamide. Last, tenofovir alafenamide renal safety in patients with chronic kidney disease has not been studied in any randomized clinical trial. In conclusion, tenofovir alafenamide appears as a very promising drug and long-term safety will be an important determinant of its expanded use.
Asunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH/efectos adversos , Enfermedades Renales/inducido químicamente , Tenofovir/efectos adversos , Adenina/efectos adversos , Adenina/sangre , Adenina/farmacocinética , Alanina , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Enfermedades Renales/complicaciones , Tenofovir/sangre , Tenofovir/farmacocinéticaRESUMEN
We herein present a case of bilateral serous retinal detachment (SRD) as a presenting sign of nephrotic syndrome (NS). A 48-year-old man complained of decreased vision related to bilateral SRD. Laboratory tests revealed NS (serum albumin, 17 g/L: proteinuria, 15.40 g over 24 hours). Following treatment for edema with a diuretic, the bilateral SRD resolved completely, with a full recovery of the patient's vision. A kidney biopsy disclosed glomerular and vascular amyloid deposits; the amyloid stained strongly with anti-λ antiserum. Therefore, a diagnosis of AL amyloidosis was made. The sudden appearance of SRD should raise suspicion of a diagnosis of NS. Prompt recognition of this symptom is important for early treatment and restoration of the visual function.
Asunto(s)
Síndrome Nefrótico/complicaciones , Desprendimiento de Retina/etiología , Amiloidosis/epidemiología , Humanos , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/epidemiología , ProteinuriaRESUMEN
Tetracyclines are broad-spectrum antibiotics that interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s in the treatment of acne. More recently, their biological actions on inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism were studied. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade components of the extracellular matrix (ECM). MMPs have direct or indirect effects on the vascular endothelium and the vascular relaxation/contraction system. The therapeutic effects of tetracyclines and analogues were studied in rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis and autoimmune diseases autoimmune diseases such as rheumatoid arthritis and scleroderma. In addition, downregulation of MMP using doxycycline could be beneficial in reducing vascular dysfunction mediated by MMPs and progressive damage of the vascular wall. We review the nonantibiotic properties of doxycycline and its potential clinical applications.
Asunto(s)
Antibacterianos/farmacología , Doxiciclina/farmacología , Reposicionamiento de Medicamentos , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Metaloproteinasas de la Matriz/metabolismo , Animales , Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Doxiciclina/uso terapéutico , Humanos , Inhibidores de la Metaloproteinasa de la Matriz/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Enfermedades Periodontales/tratamiento farmacológico , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológicoRESUMEN
Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The mainstay of treatment has been management of hyperglycaemia, blood pressure and proteinuria using hypoglycemic agents, ACE inhibitors, and angiotensin receptor blockers. Since 2000, new therapeutic strategies began to emerge targeting the biochemical activity of glucose molecules on the renal tissue. Various substances have been studied with varying degrees of success, ranging from vitamin B to camel's milk. Silymarin reduces urinary excretion of albumin, tumor necrosis factor (TNF)-α, and malondialdehyde in patients with diabetic nephropathy and may be considered as a novel addition to the anti-diabetic nephropathy armamentarium. Although some results are promising, studies on a larger scale are needed to validate the utility of these molecules in the treatment of the DN.