RESUMO
BACKGROUND: Acyclovir is one of the most common prescribed antiviral drugs. Acyclovir nephrotoxicity occurs in approximately 12-48% of cases. It can present in clinical practice as acute kidney injury (AKI), crystal-induced nephropathy, acute tubulointerstitial nephritis, and rarely, as tubular dysfunction. Electrolytes abnormalities like hypokalemia, were previously described only when given intravenously. CASE PRESENTATION: A 54 year-old female presented with weakness and lower extremities paresis, nausea and vomiting after receiving oral acyclovir. Physical examination disclosed a decrease in the patellar osteotendinous reflexes (++ / ++++). Laboratory data showed a serum creatinine level of 2.1 mg/dL; serum potassium 2.1 mmol/L. Kidney biopsy was obtained; histological findings were consistent with acute tubular necrosis and acute tubulointerstitial nephritis. The patient was advised to stop the medications and to start with oral and intravenous potassium supplement, symptoms improved and continued until serum potassium levels were > 3.5 meq/L. CONCLUSIONS: The case reported in this vignette is unique since it is the first one to describe hypokalemia associated to acute tubular necrosis induced by oral acyclovir.
Assuntos
Aciclovir/efeitos adversos , Antivirais/efeitos adversos , Hipopotassemia/induzido quimicamente , Hipopotassemia/patologia , Necrose Tubular Aguda/induzido quimicamente , Necrose Tubular Aguda/patologia , Aciclovir/administração & dosagem , Administração Oral , Antivirais/administração & dosagem , Feminino , Humanos , Hipopotassemia/sangue , Necrose Tubular Aguda/sangue , Pessoa de Meia-IdadeRESUMO
We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.
Assuntos
Rejeição de Enxerto/patologia , Transplante de Rim/efeitos adversos , Necrose Tubular Aguda/patologia , MicroRNAs/sangue , MicroRNAs/urina , Regulação para Cima/fisiologia , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Expressão Gênica , Rejeição de Enxerto/sangue , Rejeição de Enxerto/urina , Humanos , Biópsia Guiada por Imagem , Rim/patologia , Necrose Tubular Aguda/sangue , Necrose Tubular Aguda/urina , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/sangue , Disfunção Primária do Enxerto/patologia , Disfunção Primária do Enxerto/urina , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Transplantados , Resultado do TratamentoRESUMO
We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Rejeição de Enxerto/patologia , Transplante de Rim/efeitos adversos , Necrose Tubular Aguda/patologia , MicroRNAs/sangue , MicroRNAs/urina , Regulação para Cima/fisiologia , Biomarcadores/sangue , Biomarcadores/urina , Expressão Gênica , Rejeição de Enxerto/sangue , Rejeição de Enxerto/urina , Biópsia Guiada por Imagem , Necrose Tubular Aguda/sangue , Necrose Tubular Aguda/urina , Rim/patologia , Disfunção Primária do Enxerto/sangue , Disfunção Primária do Enxerto/patologia , Disfunção Primária do Enxerto/urina , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Transplantados , Resultado do TratamentoRESUMO
Reperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia-reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twenty-four hours after transplant, the kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen and creatinine compared with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine: P < 0·001 versus control]. A further decrease was observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was decreased significantly in donors treated with immunosuppressants compared with the control group (P < 0·001 versus control). Moreover, the number of apoptotic nuclei in the control group was higher compared with the treated groups (P < 0·001 versus control). Surprisingly, only rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, showed lower levels in the graft of those animals that had been pretreated with rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.
Assuntos
Imunossupressores/administração & dosagem , Transplante de Rim , Complicações Pós-Operatórias/prevenção & controle , Pré-Medicação , Traumatismo por Reperfusão/prevenção & controle , Sirolimo/administração & dosagem , Tacrolimo/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Complemento C3/análise , Creatinina/sangue , Citocinas/sangue , Avaliação de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Imunossupressores/uso terapêutico , Necrose Tubular Aguda/sangue , Necrose Tubular Aguda/etiologia , Necrose Tubular Aguda/imunologia , Necrose Tubular Aguda/prevenção & controle , Masculino , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/imunologia , Sirolimo/uso terapêutico , Tacrolimo/uso terapêuticoRESUMO
There are few studies on the relationship between the morphology of acute tubular necrosis (ATN) in native kidneys and late functional recovery. Eighteen patients with acute renal failure (ARF) who had undergone renal biopsy were studied. All had the histological diagnosis of ATN and were followed for at least six months. Clinical characteristics of ARF were analyzed, and histological features were semi-quantitatively evaluated (tubular atrophy, interstitial inflammatory infiltrate, interstitial fibrosis, and ATN). According to the maximal GFR achieved during the follow-up, patients were divided into two groups: complete recovery (GFR >or= 90 mL/min/1.73 m(2)) and partial recovery (GFR < 90 mL/min/1.73 m(2)). Only 39% of the patients achieved complete recovery. Patients with partial recovery achieved their maximal GFR (63 +/- 9 mL/min/1.73 m(2)) 37 +/- 14 months after ARF, a period of time similar to those patients with complete recovery (i.e., 54 +/- 22 months). Patients with partial recovery had more severe ARF: oliguria was more frequent (90 versus 17%, p < 0.01), and they had higher peak creatinine (13.85 +/- 1.12 versus 8.95 +/- 1.30 mg/dL, p = 0.01), and longer hospitalization (45 +/- 7 versus 20 +/- 4 days, p = 0.03). No single histological parameter was associated with partial recovery, but the sum of all was when expressed as an injury index [4.00 (2.73-5.45) versus 2.00 (1.25-3.31), p < 0.05]. In conclusion, among patients with atypical ATN course, those with more severe ARF and tubule-interstitial lesions are more prone to partial recovery.