RESUMEN
BACKGROUND: COVID-19 infection in kidney transplant recipients often lead to allograft dysfunction. The allograft injury has various histopathological manifestations. Our case illustrates the unusual combination of allograft rejection, acute kidney injury secondary to oxalate nephropathy and SARS CoV-2 nephropathy as the cause of irreversible allograft failure. CASE PRESENTATION: A 56 year old renal allograft recipient presented with a history of fever and diarrhoea for the preceding 4 weeks, tested positive for Sars-CoV2 on nasal swab and was found to have severe allograft dysfunction, necessitating haemodialysis. He subsequently underwent an allograft biopsy, which demonstrated antibody mediated rejection along with the presence of extensive oxalate deposition in the tubules. Ultrastructural examination demonstrated spherical spiked particles in the glomerular capillary endothelium and the presence of tubulo-reticular inclusions suggestive of an active COVID-19 infection within the kidney. The intra-tubular oxalate deposition was considered to be the result of high dose, supplemental Vitamin C used as an immune booster in many patients with COVID - 19 infection in India. CONCLUSIONS: This case highlights the complex pathology that may be seen in following COVID-19 disease and the need for kidney biopsies in these patients to better understand the aetiology of disease.
Asunto(s)
Ácido Ascórbico/efectos adversos , COVID-19/complicaciones , Rechazo de Injerto/etiología , Hiperoxaluria/complicaciones , Trasplante de Riñón , Disfunción Primaria del Injerto/etiología , Lesión Renal Aguda/etiología , Ácido Ascórbico/administración & dosificación , COVID-19/diagnóstico , Resultado Fatal , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Disfunción Primaria del Injerto/patología , Disfunción Primaria del Injerto/virologíaAsunto(s)
Rechazo de Injerto/inducido químicamente , Trasplante de Hígado/efectos adversos , Fósforo/envenenamiento , Rodenticidas/envenenamiento , Adolescente , Adulto , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Femenino , Humanos , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Disfunción Primaria del Injerto/inducido químicamente , Disfunción Primaria del Injerto/patología , Adulto JovenRESUMEN
BACKGROUND: Maintenance of cell viability during cold storage is a key issue in organ transplantation. Methane (CH4) bioactivity has recently been recognized in ischemia/reperfusion conditions; we therefore hypothesized that cold storage in CH4-enriched preservation solution can provide an increased defense against organ dysfunction during experimental heart transplantation (HTX). METHODS: The hearts of donor Lewis rats were stored for 60 minutes in cold histidine-tryptophan-ketoglutarate (Custodiol [CS]) or CH4-saturated CS solution (CS-CH4) (nâ¯=â¯12 each). Standard heterotopic HTX was performed, and 60 minutes later, the left ventricular (LV) pressure-volume relationships LV systolic pressure (LVSP), systolic pressure increment (dP/dtmax), diastolic pressure decrement, and coronary blood flow (CBF) were measured. Tissue samples were taken to detect proinflammatory parameters, structural damage (by light microscopy), endoplasmic reticulum (ER) stress, and apoptosis markers (CCAAT/enhancer binding protein [C/EBP] homologous protein, GRP78, glycogen synthase kinase-3ß, very low-density lipoprotein receptor, caspase 3 and 9, B-cell lymphoma 2, and bcl-2-like protein 4), whereas mitochondrial functional changes were analyzed by high-resolution respirometry. RESULTS: LVSP and dP/dtmax increased significantly at the largest pre-load volumes in CS-CH4 grafts as compared with the CS group (114.5 ± 16.6 mm Hg vs 82.8 ± 4.6 mm Hg and 3,133 ± 430 mm Hg/s vs 1,739 ± 169 mm Hg/s, respectively); the diastolic function and CBF (2.4 ± 0.4 ml/min/g vs 1.3 ± 0.3 ml/min/g) also improved. Mitochondrial oxidative phosphorylation capacity was more preserved (58.5 ± 9.4 pmol/s/ml vs 27.7 ± 6.6 pmol/s/ml), and cytochrome c release was reduced in CS-CH4 storage. Signs of HTX-caused myocardial damage, level of ER stress, and the transcription of proapoptotic proteins were significantly lower in CS-CH4 grafts. CONCLUSION: The addition of CH4 during 1 hour of cold storage improved early in vitro graft function and reduced mitochondrial dysfunction and activation of inflammation. Evidence shows that CH4 reduced ER stress-linked proapoptotic signaling.
Asunto(s)
Trasplante de Corazón/métodos , Metano/administración & dosificación , Disfunción Primaria del Injerto/prevención & control , Animales , Suplementos Dietéticos , Modelos Animales de Enfermedad , Masculino , Preservación de Órganos , Disfunción Primaria del Injerto/patología , Disfunción Primaria del Injerto/fisiopatología , Ratas , Ratas Endogámicas LewRESUMEN
BACKGROUND: Adenine phosphoribosyl transferase (APRT) deficiency is a rare genetic form of kidney stones and/or kidney failure characterized by intratubular precipitation of 2,8 dihydroxyadenine crystals. Early diagnosis and prompt management can completely reverse the kidney injury. CASE PRESENTATION: 44 year old Indian male, renal transplant recipient got admitted with acute graft dysfunction. Graft biopsy showed light brown refractile intratubular crystals with surrounding giant cell reaction, consistent with APRT deficiency. Patient improved after receiving allopurinol and hydration. CONCLUSION: APRT forms a reversible cause of crystalline nephropathy. High index of suspicion is required for the correct diagnosis as timely diagnosis has therapeutic implications.
Asunto(s)
Adenina Fosforribosiltransferasa/deficiencia , Adenina/análogos & derivados , Trasplante de Riñón , Errores Innatos del Metabolismo/complicaciones , Disfunción Primaria del Injerto/etiología , Urolitiasis/complicaciones , Adenina/metabolismo , Adulto , Alopurinol/uso terapéutico , Antimetabolitos/uso terapéutico , Biopsia , Cristalización , Humanos , Hidroterapia , Masculino , Errores Innatos del Metabolismo/patología , Errores Innatos del Metabolismo/terapia , Disfunción Primaria del Injerto/patología , Disfunción Primaria del Injerto/terapia , Urolitiasis/patología , Urolitiasis/terapiaRESUMEN
BACKGROUND: Free radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction. We therefore assessed the efficacy of the mitochondria-targeted anti-oxidant MitoQ in reducing IR injury in a murine heterotopic cardiac transplant model. METHODS: Hearts from C57BL/6 donor mice were flushed with storage solution alone, solution containing the anti-oxidant MitoQ, or solution containing the non-anti-oxidant decyltriphenylphosphonium control and exposed to short (30 minutes) or prolonged (4 hour) cold preservation before transplantation. Grafts were transplanted into C57BL/6 recipients and analyzed for mitochondrial reactive oxygen species production, oxidative damage, serum troponin, beating score, and inflammatory markers 120 minutes or 24 hours post-transplant. RESULTS: MitoQ was taken up by the heart during cold storage. Prolonged cold preservation of donor hearts before IR increased IR injury (troponin I, beating score) and mitochondrial reactive oxygen species, mitochondrial DNA damage, protein carbonyls, and pro-inflammatory cytokine release 24 hours after transplant. Administration of MitoQ to the donor heart in the storage solution protected against this IR injury by blocking graft oxidative damage and dampening the early pro-inflammatory response in the recipient. CONCLUSIONS: IR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury.
Asunto(s)
Antioxidantes/uso terapéutico , Trasplante de Corazón , Mitocondrias Cardíacas/metabolismo , Compuestos Organofosforados/uso terapéutico , Disfunción Primaria del Injerto/etiología , Daño por Reperfusión/prevención & control , Ubiquinona/análogos & derivados , Animales , Modelos Animales de Enfermedad , Femenino , Depuradores de Radicales Libres/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Micronutrientes/uso terapéutico , Mitocondrias Cardíacas/patología , Preservación de Órganos , Estrés Oxidativo , Disfunción Primaria del Injerto/metabolismo , Disfunción Primaria del Injerto/patología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismo , Ubiquinona/uso terapéuticoRESUMEN
Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive inborn error of the glyoxylate metabolism that is based on absence, deficiency or mislocalization of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase. Hyperoxaluria leads to recurrent formation of calculi and/or nephrocalcinosis and often early end-stage renal disease (ESRD) accompanied by systemic calcium oxalate crystal deposition. In this report, we describe an adult female patient with only one stone passage before development of ESRD. With unknown diagnosis of PH, the patient received an isolated kidney graft and developed an early onset of graft failure. Although initially presumed as an acute rejection, the biopsy revealed calcium oxalate crystals, which then raised a suspicion of primary hyperoxaluria. The diagnosis was later confirmed by hyperoxaluria, elevated plasma oxalate levels and mutation of the AGXT gene, showing the patient to be compound heterozygous for the c.33_34InsC and c.508G > A mutations. Plasma oxalate levels did not decrease after high-dose pyridoxine treatment. Based on this case report, we would recommend in all patients even with a minor history of nephrolithiasis but progression to chronic renal failure to exclude primary hyperoxaluria before isolated kidney transplantation is considered.