RESUMEN
BACKGROUND: Sotagliflozin is a dual sodium-glucose co-transporter 1 and 2 inhibitor that increases glucosuria and natriuresis in patients with type 2 diabetes mellitus (T2DM). However, the safety and efficacy in patients with concomitant chronic kidney disease (CKD) remains unclear. Therefore, we aimed to conduct a meta-analysis to evaluate the current evidence in this regard. METHODS: We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled clinical trials on the safety and efficacy of Sotagliflozin in patients with T2DM and CKD compared with placebo. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I2 statistics. The study was recorded in PROSPERO registry (CRD42023449631). RESULTS : We included three studies totaling 11,648 patients followed for 15.7 ± 5.9 months. Reduction in HbA1C (mean difference - 0.33%; 95% CI [- 0.54, - 0.11]; p = 0.003; I2 = 100%) and weight (mean difference - 1.01 kg; 95% CI [- 1.17, - 0.86]; p < 0.00001; I2 = 96%) were significantly higher in the Sotagliflozin group compared with placebo. All-cause mortality (RR 0.98; 95% CI [0.81, 1.20]; p = 0.87; I2 = 0%) and major adverse cardiovascular events (RR 0.70; 95% CI [0.40, 1.21]; p = 0.20; I2 = 39%) were not significantly different between groups. However, estimated glomerular filtration rate reduction (mean difference - 0.95; 95% CI [- 1.32, - 0.58]; p < 0.00001; I2 = 98%), genital mycotic infections (RR 2.73; 95% CI [1.96, 3.79]; p < 0.00001; I2 = 0%), diarrhea (RR 1.42; 95% CI [1.24. 1.63]; p < 0.00001; I2 = 0%) and volume depletion (RR 1.31; 95% CI [1.11, 1.56]; p = 0.002; I2 = 0%) were more common with Sotagliflozin. CONCLUSIONS: In patients with T2DM and CKD, Sotagliflozin appears to be effective for glycemic control and weight loss. Although the medication seemed safe concerning mortality and cardiovascular events, it induced estimated glomerular filtration rate reduction, and was associated with a higher risk of genital mycotic infections, diarrhea, and volume depletion.
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Diabetes Mellitus Tipo 2 , Glicósidos , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Glicósidos/uso terapéutico , Glicósidos/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/fisiopatología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Resultado del Tratamiento , Tasa de Filtración Glomerular/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversosRESUMEN
Introducción: la amiloidosis AA puede ser una complicación de ciertos trastornos inflamatorios crónicos, aunque entre el 21% y 50% puede ser idiopática. No existe un tratamiento específico. El tocilizumab, dirigido contra el receptor de IL-6 y orientado a disminuir la producción de SAA, podría ser eficaz. Métodos: en este estudio informamos datos de 6 pacientes con amiloidosis AA tratados con tocilizumab monoterapia subcutáneo en el período 2011-2018. Los criterios de valoración principales fueron la mejora clínica y bioquímica de los órganos afectados y los parámetros bioquímicos marcadores de inflamación. Resultados: el riñón estaba afectado en todos los pacientes, manifestándose con caída del filtrado glomerular y síndrome nefrótico. La hemorragia digestiva se presentó en un paciente y otro tenía afectación pulmonar en la biopsia. Luego del posterior al tratamiento, todos mejoraron el hematocrito, la albúmina sérica y el índice de masa corporal. El SAA disminuyó en 5 pacientes. Un paciente mejoró su función renal, mientras 4 se mantuvieron estables. Tres pacientes disminuyeron los valores de proteinuria. Conclusión: el tratamiento con tocilizumab podría ser eficaz en el tratamiento de los pacientes con amiloidosis AA. (AU)
Introduction: AA amyloidosis can be a complication of certain chronic inflammatory disorders, although between 21% and 50% can be idiopathic. There is no specific treatment. Tocilizumab, directed against the IL-6 receptor and aimed at decreasing SAA production, could be effective. Methods: in this study, we report data from 6 patients with AA amyloidosis treated with subcutaneous tocilizumab monotherapy between the period 2011-2018. The main endpoints were the clinical and biochemical improvement of the affected organs and the biochemical parameters markers of inflammation. Results: the kidney was affected in all patients, manifesting with a fall in glomerular filtration rate and nephrotic syndrome. Gastrointestinal bleeding occurred in one patient and another had lung involvement on biopsy. After treatment, all improved hematocrit, serum albumin, and body mass index. SAA decreased in 5 patients. One patient improved his kidney function, while 4 remained stable. Three patients decreased proteinuria values. Conclusion: treatment with tocilizumab could be effective in the treatment of patients with AA amyloidosis. (AU)
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Proteína Amiloide A Sérica/efectos de los fármacos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Amiloidosis/tratamiento farmacológico , Índice de Masa Corporal , Receptores de Interleucina-6/efectos de los fármacos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Tasa de Filtración Glomerular/efectos de los fármacos , Hemorragia Gastrointestinal/complicaciones , Amiloidosis/sangre , Inflamación/complicaciones , Enfermedades Pulmonares/complicaciones , Síndrome Nefrótico/complicacionesRESUMEN
Metabolic syndrome (MS) is the association of three or more pathologies among which obesity, hypertension, insulin resistance, dyslipidemia, and diabetes are included. It causes oxidative stress (OS) and renal dysfunction. Hibiscus sabdariffa L. (HSL) is a source of natural antioxidants that may control the renal damage caused by the MS. The objective of this work was to evaluate the effect of a 2% HSL infusion on renal function in a MS rat model induced by the administration of 30% sucrose in drinking water. 24 male Wistar rats were divided into 3 groups: Control rats, MS rats and MS + HSL rats. MS rats had increased body weight, systolic blood pressure, triglycerides, insulin, HOMA index, and leptin (p ≤ 0.04). Renal function was impaired by an increase in perfusion pressure in the isolated and perfused kidney, albuminuria (p ≤ 0.03), and by a decrease in clearance of creatinine (p ≤ 0.04). The activity of some antioxidant enzymes including the superoxide dismutase isoforms, peroxidases, glutathione peroxidase, glutathione-S-transferase was decreased (p ≤ 0.05). Lipoperoxidation and carbonylation were increased (p ≤ 0.001). The nitrates/nitrites ratio, total antioxidant capacity, glutathione levels and vitamin C were decreased (p ≤ 0.03). The treatment with 2% HSL reversed these alterations. The results suggest that the treatment with 2% HSL infusion protects renal function through its natural antioxidants which favor an improved renal vascular response. The infusion contributes to the increase in the glomerular filtration rate, by promoting an increase in the enzymatic and non-enzymatic antioxidant systems leading to a decrease in OS and reestablishing the normal renal function.
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Albuminuria/tratamiento farmacológico , Fármacos Antiobesidad/farmacología , Antioxidantes/farmacología , Hibiscus/química , Hipolipemiantes/farmacología , Riñón/efectos de los fármacos , Síndrome Metabólico/tratamiento farmacológico , Albuminuria/sangre , Albuminuria/patología , Animales , Fármacos Antiobesidad/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Ácido Ascórbico/sangre , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Creatinina/sangre , Tasa de Filtración Glomerular/efectos de los fármacos , Glutatión/sangre , Glutatión Peroxidasa/sangre , Glutatión Transferasa/sangre , Hipolipemiantes/aislamiento & purificación , Insulina/sangre , Riñón/metabolismo , Riñón/fisiopatología , Leptina/sangre , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/patología , Extractos Vegetales/química , Ratas , Ratas Wistar , Superóxido Dismutasa/sangre , Triglicéridos/sangreRESUMEN
In this report, we aim to provide an updated meta-analysis of the sodium-glucose cotransporter 2 (SGLT2) inhibitors trial data with the new trial data on sotagliflozin, a first-in-class dual SGLT1 and SGLT2 inhibitor. We searched Medline, Cochrane library, and Embase databases for randomized clinical trials comparing cardiovascular and kidney outcomes between SGLT2 and dual SGLT1/2 inhibitors and placebo. Nine randomized clinical trials with a total of 60,914 patients with type 2 diabetes were included. In patients with type 2 diabetes, the use of SGLT2 and dual SGLT1/2 inhibitors improves the cardiovascular and kidney outcome.
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Sistema Cardiovascular/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glicósidos/farmacología , Riñón/efectos de los fármacos , Transportador 1 de Sodio-Glucosa/antagonistas & inhibidores , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Compuestos de Bencidrilo/farmacología , Causas de Muerte , Tasa de Filtración Glomerular/efectos de los fármacos , Glucósidos/farmacología , Hospitalización , Humanos , Enfermedades Renales/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To describe discrepancies in calculated and measured glomerular filtration rate in patients using PARP (poly ADP ribose polymerase) inhibitors who had an elevation in serum creatinine levels. METHODS: Retrospective cohort, single center study. Patients included were those with ovarian or endometrial cancer taking olaparib, rucaparib or niraparib, and in in whom an increased serum creatinine was identified. The study cohort included those who also underwent technetium-99m radioisotope renography (glomerular filtration rate (GFR) scan). The main objective is to describe the discrepancies in calculated glomerular filtration rate using the Cockcroft-Gault method and measured glomerular filtration rate using a GFR scan. RESULTS: 211 patients were included in the study; 64 (30%) had on-treatment elevated serum creatinine, and 23 (36%) underwent a GFR scan. 32 GFR scans were performed (six patients had more than one scan). Using a clinical cut-off ≥50 mL/min as normal renal function, both calculated and estimated glomerular filtration rates were below normal in 6 of 32 GFR scans. In those patients undergoing a GFR scan, serum creatinine had risen a median 49% (IQR 20-66%, range 0-144%) above baseline. Discordance between a calculated low glomerular filtration rate and an estimated normal glomerular filtration rate occurred in 63% (range of glomerular filtration rate discrepancy: -46% to +237%). Despite increases in serum creatinine on therapy and a subsequent significant decline in the per patient calculated creatinine clearance (mean 65.6 mL/min vs 43.4 mL/min; p<0.0001), the estimated glomerular filtration rate from the renal scan was nearly identical to the patient's baseline (65.6 mL/min vs 66.1 mL/min; p=0.89). CONCLUSIONS: Serum creatinine elevation in patients taking PARP inhibitors may not be associated with a true decrease in glomerular filtration rate. A high index of suspicion should be maintained for alternative causes of elevated serum creatinine in patients treated with PARP inhibitors who lack other sources of renal injury.
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Neoplasias Endometriales/tratamiento farmacológico , Tasa de Filtración Glomerular/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Anciano , Ensayos Clínicos Fase III como Asunto , Estudios de Cohortes , Creatinina/sangre , Neoplasias Endometriales/sangre , Femenino , Humanos , Indoles/administración & dosificación , Persona de Mediana Edad , Neoplasias Ováricas/sangre , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Renografía por Radioisótopo , Estudios RetrospectivosRESUMEN
BACKGROUND: Case studies and reviews have shown that creatine supplementation can affect kidney function. The objective of this study is to verify the effects of 8 weeks of creatine supplementation on renal function (creatinine clearance: primary outcome) in patients with symptomatic peripheral arterial disease. METHODS: Twenty-nine patients, of both genders, were randomized (1:1) in a double-blind manner for administration of Placebo (PLA; n = 15) or creatine monohydrate (Cr; n = 14). The supplementation protocol consisted of 20 g/day for 1 week divided into 4 equal doses (loading phase), followed by single daily doses of 5 g in the subsequent 7 weeks (maintenance phase). Before and after the supplementation period, markers of renal function, serum creatinine, creatinine excretion rate, and creatinine clearance were evaluated. The Generalized Estimation Equation Model was used for comparison between groups. The level of significance was P < 0.05. RESULTS: No significant differences were found between groups before and after the intervention for serum creatinine (Cr: pre 1.00 ± 0.15 mL/dL vs. post 1.07 ± 0.16 mL/dL; PLA: pre 1.30 ± 0.53 mL/dL vs. post 1.36 ± 0.47 mL/dL, P = 0.590), creatinine excretion rate (Cr: pre 81.73 ± 43.80 mg/dL vs. post 102.92 ± 59.57 mg/dL; PLA: pre 74.37 ± 38.90 mg/dL vs. post 86.22 ± 39.94 mg/dL, P = 0.560), or creatinine clearance (Cr; pre 108 ± 59 mL/min/1.73 m2 vs. post 117 ± 52 mL/min/1.73 m2; PLA: pre 88 ± 49 mL/min/1.73 m2 vs. post 82 ± 47 mL/min/1.73 m2, P = 0.366). CONCLUSIONS: Eight weeks of creatine supplementation is safe and does not compromise the renal function of patients with peripheral arterial disease.
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Creatina/administración & dosificación , Suplementos Dietéticos , Tasa de Filtración Glomerular/efectos de los fármacos , Riñón/efectos de los fármacos , Enfermedad Arterial Periférica/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Creatina/efectos adversos , Creatinina/sangre , Creatinina/orina , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Eliminación Renal/efectos de los fármacos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Renal proximal tubular sodium and glucose reabsorption are regulated by the sodium-glucose cotransporter (SGLT2). Changes in this transporter can play a role in hyperglycaemia and reactive oxygen species (ROS) production. We demonstrated increased glucose absorption in proximal tubule membrane vesicles and increased expression of SGLT2 in hypertensive rats. Here we investigated Angiotensin II (Ang II) -dependent SGLT2 expression induction and the role of SGLT2 induction in the development of Ang II-dependent kidney damage. The aim of this study was to determine whether SGLT2 induction by Ang II is associated with Ang II-dependent kidney damage. We propose the following objectives a) to demonstrate that Ang II induces SGLT2 expression and b) to demonstrate that prevention of SGLT2 expression and activity prevent Ang II-induced kidney damage. METHODS: We used chronic Ang II infusion as a model of kidney damage in male Wistar rats and evaluated systolic blood pressure by telemetric methods. SGLT2 mRNA and protein expression were evaluated by PCR and immunoblotting. SGLT2 activity was evaluated in brush border membrane vesicles by measuring glucose uptake. ROS production was measured by confocal microscopy. The glomerular filtration rate (GFR) was evaluated by the inulin excretion method, and urinary protein excretion was evaluated by the Bradford method. Biological parameter evaluations were performed, after two weeks of infusion of Ang II. We compared the effects of Angiotensin II (AT1) receptor blockade by Losartan and SGLT2 inhibition by Empagliflozin both as monotherapy treatments and in combination on the development of kidney damage. RESULTS: Chronic Ang II infusion led to a blood pressure elevation and increased SGLT2 mRNA expression and activity as well as kidney damage, as reflected by increased ROS production, decreased GFR and increased urinary protein excretion. AT1 receptor blockade prevented all these changes. By contrast, SGLT2 inhibition did not affect blood pressure and had a small effect on kidney damage. However, the combination of both drugs resulted in the potentiation of the effects observed by AT1 receptor blockade alone. CONCLUSIONS: We suggest that Ang II-dependent increased SGLT2 induction is one mechanism by which Ang II induces kidney damage.
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Lesión Renal Aguda/prevención & control , Angiotensina II/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Transportador 2 de Sodio-Glucosa/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Compuestos de Bencidrilo/farmacología , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Tasa de Filtración Glomerular/efectos de los fármacos , Glucosa/metabolismo , Glucósidos/farmacología , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Losartán/farmacología , Masculino , Microvellosidades/metabolismo , Proteinuria/diagnóstico , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Transportador 1 de Sodio-Glucosa/metabolismo , Transportador 2 de Sodio-Glucosa/efectos de los fármacos , Transportador 2 de Sodio-Glucosa/genéticaRESUMEN
INTRODUCTION: The complex interaction between cytomegalovirus (CMV) infection and acute rejection after kidney transplantation is well recognized. METHODS: This single center retrospective cohort analysis investigated the incidence and risk factors associated with CMV infection after treatment for acute rejection (tAR) in kidney transplant recipients receiving only CMV preemptive therapy. Of the 938 kidney transplants performed between 04/30/2014 and 04/30/2015 we identified 87 (9.3%) that were treated for acute rejection within the first year. RESULTS: Most patients (64%) received rATG induction therapy followed by tacrolimus in combination with azathioprine (67%) or mycophenolate (33%) and corticosteroids. The incidence of CMV infection/disease after tAR was 47%, of which 73% occurred within 30 days. Using multivariable logistic regression analysis, eGFR at 1 month (OR = 0.98; 95% CI, 0.97-0.99; P = 0.007) and timing of tAR (OR = 0.98; 95% CI, 0.96-0.99; P = 0.021) were independently associated with CMV infection/disease after tAR. CONCLUSION: In this cohort of kidney transplant recipients receiving tacrolimus-based immunosuppressive and preemptive CMV therapy, almost 50% developed CMV infection/disease after tARin the first year of transplantation. Early rejection and poor initial renal function were risk factors associated with CMV infection or disease.
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Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/inmunología , Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Aloinjertos/efectos de los fármacos , Aloinjertos/inmunología , Aloinjertos/fisiopatología , Profilaxis Antibiótica/métodos , Suero Antilinfocítico/administración & dosificación , Suero Antilinfocítico/efectos adversos , Antivirales/uso terapéutico , Azatioprina/administración & dosificación , Azatioprina/efectos adversos , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Quimioterapia Combinada/métodos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Rechazo de Injerto/inmunología , Humanos , Inmunosupresores/administración & dosificación , Incidencia , Riñón/efectos de los fármacos , Riñón/inmunología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Adulto JovenRESUMEN
Glycerol injection in rats can lead to rhabdomyolysis, with the release of the intracellular muscle content to the extracellular compartment and acute kidney injury (AKI). Oxidative stress and the inflammatory processes contribute to the disturbances in renal function and structure observed in this model. This study evaluated the effect of calcitriol administration in AKI induced by rhabdomyolysis and its relationship with oxidative damage and inflammatory process. Male Wistar Hannover rats were treated with calcitriol (6 ng/day) or vehicle (0.9% NaCl) for 7 days and were injected with 50% glycerol or saline 3 days after the beginning of calcitriol or saline administration. Four days after glycerol or saline injection, urine, plasma and renal tissue samples were collected for renal function and structural analysis. The oxidative stress and the inflammatory processes were also evaluated. Glycerol-injected rats presented increased sodium fractional excretion and decreased glomerular filtration rates. These alterations were associated with tubular injury in the renal cortex. These animals also presented increased oxidative damage, apoptosis, inflammation, higher urinary excretion of vitamin D-binding protein and decreased cubilin expression in renal tissue. All these alterations were less intense in calcitriol-treated animals. This effect was associated with decreases in oxidative damage and inflammation.
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Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Calcitriol/uso terapéutico , Glicerol/farmacología , Sustancias Protectoras/uso terapéutico , Rabdomiólisis/inducido químicamente , Rabdomiólisis/complicaciones , Lesión Renal Aguda/sangre , Lesión Renal Aguda/orina , Animales , Apoptosis/efectos de los fármacos , Calcitriol/farmacología , Calcio/sangre , Creatina Quinasa/sangre , Tasa de Filtración Glomerular/efectos de los fármacos , Inflamación/tratamiento farmacológico , Pruebas de Función Renal , Masculino , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Proteína de Unión a Vitamina D/orinaRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is a public health problem worldwide, and proteinuria is a well-established marker of disease progression in CKD patients. Propolis, a natural resin produced by bees from plant materials, has anti-inflammatory, immunomodulatory, and anti-oxidant properties, as well as having been shown to have an antiproteinuric effect in experimental CKD. The aim of this study was to evaluate the impact of Brazilian green propolis extract on proteinuria reduction and the changes in the estimated glomerular filtration rate (eGFR). METHODS: This was a randomized, double-blind, placebo-controlled study including patients with CKD caused by diabetes or of another etiology, 18-90 years of age, with an eGFR of 25-70 ml/min per 1.73 m2 and proteinuria (urinary protein excretion > 300 mg/day) or micro- or macro-albuminuria (urinary albumin-to-creatinine ratio > 30 mg/g or > 300 mg/g, respectively). We screened 148 patients and selected 32, randomly assigning them to receive 12 months of Brazilian green propolis extract at a dose of 500 mg/day (n = 18) or 12 months of a placebo (n = 14). RESULTS: At the end of treatment, proteinuria was significantly lower in the propolis group than in the placebo group-695 mg/24 h (95% CI, 483 to 999) vs. 1403 mg/24 h (95% CI, 1031 to 1909); P = 0.004-independent of variations in eGFR and blood pressure, which did not differ between the groups during follow-up. Urinary monocyte chemoattractant protein-1 was also significantly lower in the propolis group than in the placebo group-58 pg/mg creatinine (95% CI, 36 to 95) vs. 98 pg/mg creatinine (95% CI, 62 to 155); P = 0.038. CONCLUSIONS: Brazilian green propolis extract was found to be safe and well tolerated, as well as to reduce proteinuria significantly in patients with diabetic and non-diabetic CKD. TRIAL REGISTRATION: ( ClinicalTrials.gov number NCT02766036. Registered: May 9, 2016).
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Própolis , Proteinuria , Insuficiencia Renal Crónica , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Antioxidantes/administración & dosificación , Antioxidantes/efectos adversos , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Exudados de Plantas/administración & dosificación , Exudados de Plantas/efectos adversos , Própolis/administración & dosificación , Própolis/efectos adversos , Proteinuria/diagnóstico , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , Eliminación Renal/efectos de los fármacos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/orina , Resultado del TratamientoRESUMEN
Estradiol may antagonize the adverse cardiovascular effects of angiotensin II (Ang II). We investigated the effects of 2-methoxyestradiol (2-ME), a nonestrogenic estradiol metabolite, on Ang II-induced cardiovascular and renal injury in male rats. First, we determined the effects of 2-ME on Ang II-induced acute changes in blood pressure, renal hemodynamics, and excretory function. Next, we investigated the effects of 2-ME and 2-hydroxyestardiol (2-HE) on hypertension and cardiovascular and renal injury induced by chronic infusion of Ang II. Furthermore, the effects of 2-ME on blood pressure and cardiovascular remodeling in the constricted aorta (CA) rat model and on isoproterenol-induced (ISO) cardiac hypertrophy and fibrosis were examined. 2-ME had no effects on Ang II-induced acute changes in blood pressure, renal hemodynamics, or glomerular filtration rate. Both 2-ME and 2-HE reduced hypertension, cardiac hypertrophy, proteinuria, and mesangial expansion induced by chronic Ang II infusions. In CA rats, 2-ME attenuated cardiac hypertrophy and fibrosis and reduced elevated blood pressure above the constriction. Notably, 2-ME reduced both pressure-dependent (above constriction) and pressure-independent (below constriction) vascular remodeling. 2-ME had no effects on ISO-induced renin release yet reduced ISO-induced cardiac hypertrophy and fibrosis. This study shows that 2-ME protects against cardiovascular and renal injury due to chronic activation of the renin-angiotensin system. This study reports for the first time that in vivo 2-ME reduces trophic (pressure-independent) effects of Ang II and related cardiac and vascular remodeling.
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2-Metoxiestradiol/farmacología , Presión Sanguínea/efectos de los fármacos , Hipertensión/prevención & control , Hipertrofia Ventricular Izquierda/prevención & control , Enfermedades Renales/prevención & control , Riñón/efectos de los fármacos , Remodelación Vascular/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Angiotensina II , Animales , Fibrosis , Tasa de Filtración Glomerular/efectos de los fármacos , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/inducido químicamente , Hipertrofia Ventricular Izquierda/fisiopatología , Isoproterenol , Riñón/patología , Riñón/fisiopatología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/fisiopatología , Masculino , Ratas Sprague-Dawley , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
BACKGROUND: Belatacept could be the treatment of choice in renal-transplant recipients with renal dysfunction attributed to calcineurin inhibitor (CNI) nephrotoxicity. Few studies have described its use in patients with donor-specific antibody (DSA). METHODS: We retrospectively evaluated conversion from CNIs to belatacept in 29 human leukocyte antigen-immunized renal-transplant recipients. Data about acute rejection, DSA, and renal function were collected. These patients were compared with 42 nonimmunized patients treated with belatacept. RESULTS: Patients were converted from CNIs to belatacept a median of 444 days (interquartile range, 85-1200) after transplantation and were followed up after belatacept conversion, for a median of 308 days (interquartile range, 125-511). At conversion, 16 patients had DSA. Nineteen DSA were observed in these 16 patients, of which 11/19 were <1000 mean fluorescence intensity (MFI), 7/19 were between 1000 and 3000 MFI, and one was >3000 MFI. At last follow-up, preexisting DSA had decreased or stabilized. Seven patients still had DSA with a mean MFI of 1298 ± 930 at the last follow-up. No patient developed a de novo DSA in the DSA-positive group. In the nonimmunized group, one patient developed de novo DSA (A24-MFI 970; biopsy for cause did not show biopsy-proven acute rejection or microinflammation score). After belatacept conversion, one antibody-mediated rejection was diagnosed. The mean estimated glomerular filtration rate improved from 31.7 ± 14.2 mL/min/1.73 m to 40.7 ± 12.3 mL/min/1.73 m (P < 0.0001) at 12 months after conversion. We did not find any significant difference between groups in terms of renal function, proteinuria, or biopsy-proven acute rejection. CONCLUSIONS: We report on a safe conversion to belatacept in human leukocyte antigen-immunized patients with low DSA levels.
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Abatacept/administración & dosificación , Inhibidores de la Calcineurina/efectos adversos , Rechazo de Injerto/tratamiento farmacológico , Isoanticuerpos/sangre , Trasplante de Riñón/efectos adversos , Insuficiencia Renal/prevención & control , Adulto , Anciano , Aloinjertos/efectos de los fármacos , Aloinjertos/inmunología , Aloinjertos/patología , Biopsia , Inhibidores de la Calcineurina/administración & dosificación , Sustitución de Medicamentos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/inmunología , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Antígenos HLA/inmunología , Humanos , Isoanticuerpos/inmunología , Isoantígenos/inmunología , Riñón/efectos de los fármacos , Riñón/inmunología , Riñón/patología , Masculino , Persona de Mediana Edad , Insuficiencia Renal/inducido químicamente , Resultado del TratamientoRESUMEN
Long-term lithium treatment was associated with chronic kidney disease and renal failure although the underlying pathogenic mechanisms are not certainty known. The aim of this study was to evaluate changes in oxidative stress measures as well as renal functional and structural alterations associated with chronic use of lithium in rats. Forty Wistar male rats were randomized into four groups: control groups fed ad libitum powered standard diet for 1 and 3 months and experimental groups fed ad libitum the same diet supplemented with 60 mmol/kg diet for 1 and 3 months. Histopathological changes, laboratory parameters, and oxidative stress measurements were assessed at months 1 and 3. The experimental animals showed alteration of the cortical tubules from the first month of lithium-treatment and a decrease in the glomerular filtration rate and in the glomerular area at the third month. There was an increase in thiobarbituric acid reactive substances and carbonyls, as well as an increase in reduced glutathione, in the kidney of rats exposed to lithium. These changes were evident from the first month of treatment and remained throughout the experiment. Our results suggest that, oxidative stress could be one of the pathogenic mechanisms involved in the structural and functional alterations of the kidney associated with prolonged use of lithium. The study of the pathogenic mechanisms involved in lithium-induced nephropathy is a critical issue for the development of new strategies for prevention and/or early detection.
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Enfermedades Renales/sangre , Enfermedades Renales/inducido químicamente , Litio/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Tasa de Filtración Glomerular/efectos de los fármacos , Glutatión/metabolismo , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/metabolismo , Masculino , Ratas , Ratas Wistar , Insuficiencia Renal/sangre , Insuficiencia Renal/inducido químicamente , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoAsunto(s)
Hipertensión/tratamiento farmacológico , Proteinuria/prevención & control , Insuficiencia Renal Crónica/tratamiento farmacológico , Negro o Afroamericano/etnología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Comorbilidad , Quimioterapia Combinada , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Hipertensión Maligna/complicaciones , Hipertensión Maligna/epidemiología , Guías de Práctica Clínica como Asunto/normas , Prevalencia , Proteinuria/tratamiento farmacológico , Proteinuria/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
The indirect effects of cytomegalovirus (CMV) viremia can be related to chronic changes in renal allograft structure, but its real impact in early and late graft function remains speculative. A total of 159 patients undergoing renal transplantation using a preemptive therapeutic strategy to prevent CMV disease were included in the present study. The patients were prospectively followed, with serial measurements of urinary retinol-binding protein (uRBP), a marker of proximal tubule injury. uRBP levels and their dynamic performance were compared according to CMV viremia and the 5-year estimated glomerular filtration rate (eGFR), as measured with the modification of diet in renal disease (MDRD) equation. CMV viremia was detected in 79.9% of the patients, with high uRBP levels being detected in 76.0% of these patients (compared with 40.7% in CMV-, P=0.005). High uRBP was associated with male recipients (P=0.02), the number of mismatches (P=0.02) and CMV infection (P=0.001). Five-year eGFR was worse in patients with high uRBP levels (50.3 ± 25.8 compared with 59.8 ± 26.4 ml/min, P=0.04). In a multivariate model, eGFR <60 ml/min was associated with donor age (P<0.001), the number of mismatches (P=0.04), thymoglobulin dose (P=0.02), the presence of and time with delayed graft function (DGF) (P=0.005 and P=0.04), 1-month tacrolimus levels (P=0.03), and uRBP levels after CMV treatment (P=0.01). Patients with CMV viremia in whom uRBP levels were normalized up to 3 months after treatment showed significantly better 5-year eGFR than those in whom uRBP remained high: 61.0 ± 24.2 compared with 42.3 ± 23.9 ml/min, P<0.001. CMV viremia was associated with high uRBP levels, which represent a profile of proximal tubule injury, and the dynamic performance of uRBP after treatment was associated with long-term kidney graft function.
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Infecciones por Citomegalovirus/orina , Trasplante de Riñón/métodos , Proteínas de Unión al Retinol/orina , Viremia/orina , Adulto , Antivirales/uso terapéutico , Biomarcadores/orina , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/virología , Femenino , Ganciclovir/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Supervivencia de Injerto/efectos de los fármacos , Humanos , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/patología , Masculino , Persona de Mediana Edad , Factores de Tiempo , Viremia/prevención & control , Viremia/virologíaRESUMEN
Curcumin exhibits several therapeutic properties. Potassium dichromate (K2Cr2O7)-induced nephropathy is associated with oxidative stress. Reactive oxygen species production affects renal oxygenation that may participate in the progression of renal damage. The aim of the present work was to elucidate whether K2Cr2O7-induced nephropathy is associated to partial O2 pressure (pO2) impairment and if curcumin is able to prevent it. Four groups of rats were studied: control group; K2Cr2O7 group (12.5 mg/kg, s.c.); curcumin + K2Cr2O7 group, in which animals were treated with curcumin (400â¯mg/kg/day, p.o.) for 10 days before K2Cr2O7 injection; and curcumin group. All animals were sacrificed 48â¯h after the end of the treatments. K2Cr2O7 administration increased renal function markers and decreased glomerular filtration rate, pO2 and renal perfusion. Concerning hemodynamic parameters, K2Cr2O7 increased mean arterial pressure and renal vascular resistance and reduced renal blood flow. The hemodynamic changes were attributed to decreased availability of nitric oxide and increased 3-nitrotyrosine levels. Moreover, increased superoxide anion production and vascular endothelial growth factor levels were observed after K2Cr2O7 administration. Curcumin attenuated all the above-described alterations. Our results suggest that the protective effects of curcumin in K2Cr2O7-induced nephropathy are associated with its ability to prevent O2 supply reduction.
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Curcumina/farmacología , Riñón/efectos de los fármacos , Oxígeno/metabolismo , Dicromato de Potasio/toxicidad , Animales , Tasa de Filtración Glomerular/efectos de los fármacos , Hemodinámica , Masculino , Nitratos/orina , Óxido Nítrico Sintasa/metabolismo , Dióxido de Nitrógeno/orina , Fitoterapia , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Factor A de Crecimiento Endotelial VascularRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Sofosbuvir(SOF)-based regimens have been administrated with excellent efficacy in chronic hepatitis C. Few uncontrolled ("real-life") studies consider the assessment of renal function when evaluating their post-treatment outcomes. This study aims to evaluate renal biomarkers in a "real-life" experience with chronic hepatitis C patients treated with SOF therapy in a long-term follow-up. METHODS: Serum and urinary biomarkers were analysed before, at the end of therapy (EoT), after 12 weeks (sustained virological response-SVR) and one year (1y) post-treatment. Patients were categorized according to baseline glomerular filtration rate (GFR-cut-off 45 mL/min/1.73 m2 ). RESULTS: Ninety-four patients with a mean age of 59.9 ± 8.5 years were included; 98.9% of patients reached SVR. Significant improvement in renal biomarkers was observed in patients with GFR ≥45 mL/min/1.73 m2 , as indicated by a progressive increase in mean GFR values until 1y. No evidence of tubular dysfunction was identified. Patients with baseline GFR <45 mL/min/1.73 m2 did not experience alterations in renal biomarkers; however, a mean change of +10.7 in GFR values was observed. We noticed significant upper stage transition in the CKD classification, and 58.7% of patients achieved G1 stage at 1y (P < .0001). WHAT IS NEW AND CONCLUSION: In a "real-life experience" of a Brazilian centre, SOF therapy appears to guarantee renal safety for patients with chronic hepatitis C followed until one year after treatment.
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Antivirales/efectos adversos , Tasa de Filtración Glomerular/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Riñón/efectos de los fármacos , Sofosbuvir/efectos adversos , Biomarcadores/metabolismo , Brasil , Femenino , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/metabolismo , Humanos , Riñón/metabolismo , Masculino , Persona de Mediana Edad , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
Fluoride (F) is a toxicant widely distributed in the environment. Experimental studies have shown kidney toxicity from F exposure. However, co-exposure to arsenic (As) has not been considered, and epidemiological information remains limited. We evaluated the association between F exposure and urinary kidney injury biomarkers and assessed As co-exposure interactions. A cross-sectional study was conducted in 239 adults (18-77â¯years old) from three communities in Chihuahua, Mexico. Exposure to F was assessed in urine and drinking water, and As in urine samples. We evaluated the urinary concentrations of albumin (ALB), cystatin-C (Cys-C), kidney injury molecule 1 (KIM-1), clusterin (CLU), osteopontin (OPN), and trefoil factor 3 (TFF-3). The estimated glomerular filtration rate (eGFR) was calculated using serum creatinine (Creat) levels. We observed a positive correlation between water and urine F concentrations (ρâ¯=â¯0.7419, pâ¯<â¯0.0001), with median values of 1.5â¯mg/L and 2⯵g/mL, respectively, suggesting that drinking water was the main source of F exposure. The geometric mean of urinary As was 18.55â¯ng/mL, approximately 39% of the urine samples had As concentrations above the human biomonitoring value (15â¯ng/mL). Multiple linear regression models demonstrated a positive association between urinary F and ALB (ßâ¯=â¯0.56, pâ¯<â¯0.001), Cys-C (ßâ¯=â¯0.022, pâ¯=â¯0.001), KIM-1 (ßâ¯=â¯0.048, pâ¯=â¯0.008), OPN (ßâ¯=â¯0.38, pâ¯=â¯0.041), and eGFR (ßâ¯=â¯0.49, pâ¯=â¯0.03); however, CLU (ßâ¯=â¯0.07, pâ¯=â¯0.100) and TFF-3 (ßâ¯=â¯1.14, pâ¯=â¯0.115) did not show significant associations. No interaction with As exposure was observed. In conclusion, F exposure was related to the urinary excretion of early kidney injury biomarkers, supporting the hypothesis of the nephrotoxic role of F exposure.
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Arsénico/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Fluoruros/efectos adversos , Enfermedades Renales/inducido químicamente , Riñón/efectos de los fármacos , Contaminantes Químicos del Agua/efectos adversos , Adolescente , Adulto , Anciano , Albuminuria/inducido químicamente , Albuminuria/diagnóstico , Albuminuria/orina , Arsénico/orina , Biomarcadores/orina , Clusterina/orina , Estudios Transversales , Cistatina C/orina , Monitoreo del Ambiente/métodos , Femenino , Fluoruros/orina , Tasa de Filtración Glomerular/efectos de los fármacos , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Humanos , Riñón/metabolismo , Riñón/fisiopatología , Enfermedades Renales/diagnóstico , Enfermedades Renales/fisiopatología , Enfermedades Renales/orina , Masculino , México , Persona de Mediana Edad , Osteopontina/orina , Valor Predictivo de las Pruebas , Medición de Riesgo , Factor Trefoil-3/orina , Contaminantes Químicos del Agua/orina , Adulto JovenRESUMEN
OBJECTIVE: Acute kidney injury (AKI) occurs frequently after cardiac surgery. Levosimendan might reduce the incidence of AKI in patients undergoing cardiac surgery. The authors investigated whether levosimendan administration could reduce AKI incidence in a high-risk cardiac surgical population. DESIGN: Post hoc analysis of a multicenter randomized trial. SETTING: Cardiac surgery operating rooms and intensive care units of 14 centers in 3 countries. PARTICIPANTS: The study comprised 90 patients who underwent mitral valve surgery with an estimated glomerular filtration rate <60 mL/min/1.73 m2 and perioperative myocardial dysfunction. INTERVENTIONS: Patients were assigned randomly to receive levosimendan (0.025-0.2 µg/kg/min) or placebo in addition to standard inotropic treatment. MEASUREMENTS AND MAIN RESULTS: Forty-six patients were assigned to receive levosimendan and 44 to receive placebo. Postoperative AKI occurred in 14 (30%) patients in the levosimendan group versus 23 (52%) in the placebo group (absolute difference -21.8; 95% confidence interval -41.7 to -1.97; p = 0.035). The incidence of major complications also was lower (18 [39%]) in the levosimendan group versus that in the placebo group (29 [66%]) (absolute difference -26.8 [-46.7 to -6.90]; p = 0.011). A trend toward lower serum creatinine at intensive care unit discharge was observed in the levosimendan group (1.18 [0.99-1.49] mg/dL) versus that in the placebo group (1.39 [1.05-1.76] mg/dL) (95% confidence interval -0.23 [-0.49 to 0.01]; p = 0.07). CONCLUSIONS: Levosimendan may improve renal outcome in cardiac surgery patients with chronic kidney disease undergoing mitral valve surgery who develop perioperative myocardial dysfunction. Results of this exploratory analysis should be investigated in future properly designed randomized controlled trials.
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Lesión Renal Aguda/prevención & control , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Enfermedades de las Válvulas Cardíacas/cirugía , Complicaciones Posoperatorias/prevención & control , Simendán/administración & dosificación , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Anciano , Brasil/epidemiología , Cardiotónicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Enfermedades de las Válvulas Cardíacas/complicaciones , Humanos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Válvula Mitral/cirugía , Periodo Perioperatorio , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Insuficiencia Renal Crónica , Federación de Rusia/epidemiología , Resultado del TratamientoRESUMEN
The klotho gene, which encodes a single-pass transmembrane protein and a secreted protein, is expressed predominantly by the distal renal tubules and is related to calcium phosphorus metabolism, ion channel regulation, intracellular signaling pathways, and longevity. Klotho deficiency aggravates acute kidney injury and renal fibrosis. Exposure to nicotine also worsens kidney injury. Here, we investigated renal Klotho protein expression in a mouse model of chronic (28-day) nicotine exposure, in which mice received nicotine or vehicle (saccharine) in drinking water, comparing wild-type (WT) mice, klotho-haploinsufficient ( kl/+) mice, and their respective controls, in terms of the effects of that exposure. Nicotine exposure was associated with a significant decline in renal Klotho expression in WT and kl/+ mice as well as a reduction in the glomerular filtration rate in WT mice. Although plasma electrolytes were similar among the groups, fractional excretion of sodium was reduced in both nicotine-exposed groups. The nicotine-WT mice presented augmented baroreflex sensitivity to nitroprusside and augmented sympathetic cardiac modulation. However, nicotine- kl/+ mice presented higher plasma levels of urea and aldosterone together with a higher α-index (spontaneous baroreflex) and higher peripheral sympathetic modulation, as evaluated by spectral analysis. We can conclude that nicotine downregulates Klotho expression as well as that renal and autonomic responses to nicotine exposure are modified in kl/+ mice.