RESUMEN
Lysinuric protein intolerance (LPI) is a rare metabolic disorder with reduced renal and intestinal reabsorption of ornithine, lysine, and arginine. It is due to variants in SLC7A7, the gene encoding y+L amino acid transporter 1 (y+LAT1), which lead to urea cycle defects with protein intolerance. Chronic kidney disease in lysinuric protein intolerance is common and can progress to kidney failure and initiation of kidney replacement therapy. Kidney transplantation could in theory improve urine levels and, consequently, plasma levels of these amino acids and therefore improve clinical symptoms, as well as protein intolerance, in patients with lysinuric protein intolerance. However, data on kidney transplantation in patients with lysinuric protein intolerance are limited, and up until now no data on clinical and biochemical improvement after kidney transplantation have been reported. In this case report we describe a rare case of kidney transplantation in a lysinuric protein intolerance patient with substantial improvement in protein tolerance; in plasma and urine levels of ornithine, lysine, and arginine; and in lysinuric protein intolerance symptoms.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Trasplante de Riñón , Enfermedades Metabólicas , Humanos , Lisina/orina , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Arginina/uso terapéutico , Arginina/metabolismo , Ornitina/uso terapéutico , Sistema de Transporte de Aminoácidos y+LRESUMEN
Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.
Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/complicaciones , Fibrosis , Humanos , Riñón , Organoides/patología , Síndrome Post Agudo de COVID-19RESUMEN
BACKGROUND: Sampling error is a common problem in muscle biopsies. MRI-guided biopsy allows verification of biopsy site during the procedure, which may reduce sampling error in patients with focal disease. OBJECTIVES: To describe the technique for MRI-guided muscle biopsy and discuss potential applications. METHODS: Axial MRI images were acquired to determine the target site for muscle biopsy. Needle trajectory was planned on 3D T1 weighted imaging and a MRI-guided biopsy of the vastus lateralis was performed in 13 FSHD patients. RESULTS: An adequate amount of muscle tissue was obtained in all participants, and MRI-guided biopsy succeeded in reaching focal target sites. However, symptomatic hematomas were observed in 2/13 patientsDiscussion:MRI-guided biopsy has a higher complication rate compared to traditional needle biopsy, most likely due to proximity to blood vessels in combination with the vacuum-assisted suction of the MRI-guided technique. We recommend that this technique is reserved for select diagnostic cases and research questions, with careful assessment of vasculature and reduced suction levels.