RESUMEN
Kidney disease is an important public health problem. Both acute kidney injury (AKI) and chronic kidney disease have been well defined and classified, leading to improved research efforts and subsequent management strategies and recommendations. For those patients with abnormalities in kidney function and/or structure who meet neither the definition of AKI nor chronic kidney disease, there remains a gap in research, care, and guidance. The term acute kidney diseases and disorders, abbreviated to acute kidney disease (AKD), has been introduced as an important construct to address this. To expand and harmonize existing definitions and to ultimately better inform research and clinical care, Kidney Disease: Improving Global Outcomes (KDIGO) organized a consensus workshop. Multiple invitees from around the globe, representing both acute and chronic kidney disease researchers and experts, met virtually to examine existing data, and discuss key concepts related to AKD. Despite some remaining unresolved questions, conference attendees reached general consensus on the definition and classification of AKD, management strategies, and research priorities. AKD is defined by abnormalities of kidney function and/or structure with implications for health and with a duration of ≤3 months. AKD may include AKI, but, more importantly, also includes abnormalities in kidney function that are not as severe as AKI or that develop over a period of >7 days. The cause(s) of AKD should be sought, and classification includes functional and structural parameters. Management of AKD is currently based on empirical considerations. A robust research agenda to enable refinement and validation of definitions and classification systems, and thus testing of interventions and strategies, is proposed.
Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Enfermedad Aguda , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Consenso , Humanos , Riñón , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapiaRESUMEN
BACKGROUND: Acute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries. METHODS AND FINDINGS: Patients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27-62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily. CONCLUSIONS: This multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.
Asunto(s)
Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Lesión Renal Aguda/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Bolivia/epidemiología , Niño , Preescolar , Creatinina/sangre , Países en Desarrollo , Progresión de la Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Lactante , Malaui/epidemiología , Masculino , Persona de Mediana Edad , Nepal/epidemiología , Pruebas en el Punto de Atención , UrinálisisRESUMEN
BACKGROUND: Epidemiological data for acute kidney injury are scarce, especially in low-income countries (LICs) and lower-middle-income countries (LMICs). We aimed to assess regional differences in acute kidney injury recognition, management, and outcomes. METHODS: In this multinational cross-sectional study, 322 physicians from 289 centres in 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidney injury in hospital and non-hospital settings who met criteria for acute kidney injury. Signs and symptoms at presentation, comorbidities, risk factors for acute kidney injury, and process-of-care data were obtained at the start of acute kidney injury, and need for dialysis, renal recovery, and mortality recorded at 7 days, and at hospital discharge or death, whichever came earlier. We classified countries into high-income countries (HICs), upper-middle-income countries (UMICs), and combined LICs and LMICs (LLMICs) according to their 2014 gross national income per person. FINDINGS: Between Sept 29 and Dec 7, 2014, data were collected from 4018 patients. 2337 (58%) patients developed community-acquired acute kidney injury, with 889 (80%) of 1118 patients in LLMICs, 815 (51%) of 1594 in UMICs, and 663 (51%) of 1241 in HICs (for HICs vs UMICs p=0.33; p<0.0001 for all other comparisons). Hypotension (1615 [40%] patients) and dehydration (1536 [38%] patients) were the most common causes of acute kidney injury. Dehydration was the most frequent cause of acute kidney injury in LLMICs (526 [46%] of 1153 vs 518 [32%] of 1605 in UMICs vs 492 [39%] of 1260 in HICs) and hypotension in HICs (564 [45%] of 1260 vs 611 [38%%] of 1605 in UMICs vs 440 [38%] of 1153 LLMICs). Mortality at 7 days was 423 (11%) of 3855, and was higher in LLMICs (129 [12%] of 1076) than in HICs (125 [10%] of 1230) and UMICs (169 [11%] of 1549). INTERPRETATION: We identified common aetiological factors across all countries, which might be amenable to a standardised approach for early recognition and treatment of acute kidney injury. Study limitations include a small number of patients from outpatient settings and LICs, potentially under-representing the true burden of acute kidney injury in these areas. Additional strategies are needed to raise awareness of acute kidney injury in community health-care settings, especially in LICs. FUNDING: International Society of Nephrology.
Asunto(s)
Lesión Renal Aguda/terapia , Lesión Renal Aguda/etiología , Lesión Renal Aguda/mortalidad , Adulto , Anciano , Estudios Transversales , Femenino , Salud Global , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Despite an increasing incidence of acute kidney injury in both high-income and low-income countries and growing insight into the causes and mechanisms of disease, few preventive and therapeutic options exist. Even small acute changes in kidney function can result in short-term and long-term complications, including chronic kidney disease, end-stage renal disease, and death. Presence of more than one comorbidity results in high severity of illness scores in all medical settings. Development or progression of chronic kidney disease after one or more episode of acute kidney injury could have striking socioeconomic and public health outcomes for all countries. Concerted international action encompassing many medical disciplines is needed to aid early recognition and management of acute kidney injury.
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Lesión Renal Aguda , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Costo de Enfermedad , Costos y Análisis de Costo , Países Desarrollados/estadística & datos numéricos , Países en Desarrollo/estadística & datos numéricos , Salud Global , Humanos , Incidencia , Renta , Prevalencia , Pronóstico , Terapia de Reemplazo Renal/métodos , Factores de Riesgo , Terminología como Asunto , Clima TropicalRESUMEN
We discuss the performance of novel biomarkers in acute kidney injury (AKI). Comparison of the areas under the receiver operating characteristic curves of several biomarkers with some clinical and/or routine biochemical outcome parameters reveals that none of the biomarkers has demonstrated a clear additional value beyond the traditional approach in clinical decision making in patients with AKI. Unscrutinized use of these biomarkers may distract from adequate clinical evaluation and carries the risk of worse instead of better patient outcome.
Asunto(s)
Lesión Renal Aguda/diagnóstico , Biomarcadores/orina , Proteínas de Fase Aguda/orina , Área Bajo la Curva , Humanos , Lipocalina 2 , Lipocalinas/orina , Proteínas Proto-Oncogénicas/orinaRESUMEN
The development of clinical practice guidelines for the treatment of anemia in chronic kidney disease has been instrumental in identifying and reducing variations in the use of erythropoiesis-stimulating agents and iron replacement. Challenges to the effectiveness and safety of recommendations made in these guidelines were magnified when recent clinical trials showed no benefit or harm with respect to cardiovascular outcomes in subjects randomized to higher target hemoglobin levels. To address these concerns, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international conference to examine the problems and shortcomings of existing anemia guidelines, which are a prime example of duplication of efforts to derive recommendations from a limited evidence base. The meeting was attended by representatives of the major guideline developing organizations, who agreed to avoid future duplicative efforts and to save resources in generating a common evidence report, whose recommendations could then be prioritized and implemented locally. This is a report to the international nephrology community of the recommendations for and timeline of the next anemia guidelines. It has been reviewed by the conference participants and approved as a position statement by the KDIGO Board of Directors.
Asunto(s)
Anemia/terapia , Enfermedades Renales/complicaciones , Anemia/etiología , Enfermedad Crónica , Hemoglobinas/normas , Humanos , Hierro/uso terapéutico , Enfermedades Renales/terapia , Diálisis RenalRESUMEN
Studies have produced conflicting findings on outcomes for patients with antimicrobial-resistant infection. This study evaluated whether infection with an antimicrobial-resistant organism affects outcome in critically ill patients with acute kidney injury treated with renal replacement therapy and whose clinical course is complicated with a nosocomial bloodstream infection. We found that infection with an antimicrobial-resistant organism did not adversely affect clinical outcome in this specific cohort, which already has a high mortality rate.
Asunto(s)
Lesión Renal Aguda/complicaciones , Bacteriemia/complicaciones , Infección Hospitalaria/complicaciones , Farmacorresistencia Bacteriana Múltiple , Lesión Renal Aguda/terapia , Anciano , Bacteriemia/tratamiento farmacológico , Bacteriemia/mortalidad , Bélgica/epidemiología , Estudios de Cohortes , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/mortalidad , Femenino , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Terapia de Reemplazo RenalRESUMEN
BACKGROUND: Uraemia is associated with fibrosis of the peritoneal membrane, even prior to the start of peritoneal dialysis. Increased carbonyl stress and the resultant formation of advanced glycation end-products (AGEs) are potentially involved. The interaction of AGEs with their cell surface receptor for AGE (RAGE) induces sustained cellular activation, including the production of the fibrogenic growth factor-beta (TGF-beta). TGF-beta is pivotal in the process of epithelial-to-mesenchymal transition with the acquisition of myofibroblast characteristics. We investigated whether antagonism of RAGE prevents uraemia-induced peritoneal fibrosis. In addition, we examined whether myofibroblast transdifferentiation of mesothelial cells contributes to peritoneal fibrosis in uraemia. METHODS: Uraemia was induced in rats by subtotal nephrectomy. Uraemic and age-matched sham-operated rats were treated for 6 weeks with neutralizing monoclonal anti-RAGE antibodies or placebo. Expression of AGE, RAGE, cytokeratin and alpha-smooth muscle actin was evaluated using immunohistochemistry. TGF-beta expression was examined with immunostaining and western blotting, and Snail expression with western blotting. Fibrosis was quantified with a picro-sirius red staining and measurement of the hydroxyproline content of the tissue. RESULTS: Uraemia resulted in the accumulation of AGE, up-regulation of RAGE and TGF-beta and the development of interstitial fibrosis and vascular sclerosis in the peritoneal membrane. Prominent myofibroblast transdifferentiation of mesothelial cells was identified by colocalization of cytokeratin and alpha-smooth muscle actin in submesothelial and interstitial fibrotic tissue. The antagonism of RAGE prevented the up-regulation of TGF-beta, epithelial-to-mesenchymal transition of mesothelial cells and fibrosis in uraemia. CONCLUSION: The ligand engagement of RAGE and the subsequent up-regulation of TGF-beta induces peritoneal fibrosis in chronic uraemia. The process may be mediated by the conversion of mesothelial cells into myofibroblasts.
Asunto(s)
Diferenciación Celular , Células Epiteliales/patología , Fibroblastos/patología , Miofibrillas/patología , Peritoneo/patología , Receptores Inmunológicos/metabolismo , Uremia/patología , Animales , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Femenino , Fibrosis/etiología , Fibrosis/metabolismo , Fibrosis/patología , Productos Finales de Glicación Avanzada/metabolismo , Immunoblotting , Inmunohistoquímica , Peritoneo/metabolismo , Ratas , Ratas Wistar , Receptor para Productos Finales de Glicación Avanzada , Factor de Crecimiento Transformador beta/biosíntesis , Uremia/complicaciones , Uremia/metabolismoRESUMEN
Contrast-induced nephropathy (CIN) is a serious, but potentially preventable adverse event associated with the use of iodinated contrast media (CM). Studies suggest that the occurrence of CIN is directly related to the number of pre-existing patient risk factors such as pre-existing renal insufficiency (RI) with or without diabetes, advanced age, congestive heart failure and dehydration. Because the risk factors for CIN are common and the consequences serious or even life-threatening, it is important for physicians to implement preventive strategies. Although the optimal strategy for preventing CIN has not been fully established, it is important to first identify patients at risk. The commonly used methods for identifying patients at risk include use of patient questionnaires, review of medical history and measurement of serum creatinine levels prior to the administration of CM. Estimation of the glomerular filtration rate (GFR) before CM administration should be encouraged. To prevent the development of CIN, patients should be well-hydrated and nephrotoxic medications should be withdrawn at least 24 h prior to CM. Use of the minimal necessary CM dose is recommended, as the nephrotoxic effect of CM is dose-dependent. Furthermore, appropriate selection of CM is important. The incidence of CIN has been shown to be lower when an iso-osmolar CM rather than a low-osmolar CM (iohexol) is used in patients with RI and diabetes. Pharmacological intervention with calcium channel blockers, dopamine and N-acetylcysteine have not consistently been shown to reduce the incidence of CIN. This article will review the risk factors for the development of CIN and discuss practical strategies for its prevention in at-risk patients.
Asunto(s)
Medios de Contraste/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Humanos , Medición de Riesgo , Factores de Riesgo , Conducta de Reducción del RiesgoRESUMEN
BACKGROUND: Antagonism of vascular endothelial growth factor (VEGF) has improved the outcome in experimental nephropathies of various origins, including diabetic nephropathy in a type 1 diabetic rat model and a type 2 diabetic mouse model. Neutralizing VEGF antibodies prevented glomerular hypertrophy in these models. We examined the renal effects of VEGF blockade in an obese rat model of type 2 diabetic nephropathy and investigated the mechanism underlying the inhibition of glomerular hypertrophy. METHODS: Twenty female Zucker diabetic fatty (ZDF) rats, fed a high-fat diet and aged 10 weeks, were treated with VEGF antibodies or an irrelevant isotype-matched IgG. Ten heterozygous (fa/+) littermates served as additional non-diabetic, lean controls. Urinary albumin excretion (UAE) and creatinine clearance (CrCl) were assessed at baseline, and at 3 and 5 weeks. Kidney weight and glomerular volume were determined at the end of the study. Glomerular apoptosis was examined with anti-active caspase-3 immunohistochemistry. RESULTS: All obese animals had established diabetes, hyperlipidaemia and normal blood pressure, which were not influenced by VEGF antibody treatment. ZDF control rats had increased UAE, CrCl, kidney weights and glomerular volumes compared with non-diabetic, lean control rats. VEGF antibody treatment prevented the glomerular hypertrophy, but did not affect UAE, CrCl and kidney weight. Glomerular anti-active caspase-3 immunostaining was not different between the groups. CONCLUSIONS: Inhibition of VEGF prevented early glomerular hypertrophy in ZDF rats with established diabetes. Increased apoptosis of glomerular endothelial cells does not appear to underly the inhibition of glomerular growth.
Asunto(s)
Anticuerpos/inmunología , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/prevención & control , Modelos Animales de Enfermedad , Glomérulos Renales/inmunología , Glomérulos Renales/patología , Obesidad/complicaciones , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/inmunología , Animales , Caspasa 3 , Caspasas/fisiología , Femenino , Hipertrofia/etiología , Hipertrofia/prevención & control , Inmunohistoquímica , Ratas , Ratas ZuckerRESUMEN
BACKGROUND: Sodium bicarbonate is despite its side effects, considered the standard alkali therapy in metabolic acidosis. THAM is an alternative alkalizing agent; however, there are limited data on the use of THAM in metabolic acidosis. The aim of this study was to compare the efficacy and adverse effects of a single dose of sodium bicarbonate and THAM in intensive care unit (ICU) patients with mild metabolic acidosis. METHODS: 18 adult ICU patients with mild metabolic acidosis (serum bicarbonate < 20 mmol/L) were randomized to a single dose of either sodium bicarbonate or THAM, administered over a 1-hour period, and titrated to buffer the excess of acid load. RESULTS: Sodium bicarbonate and THAM had equivalent alkalinizing effect during the infusion period. This was still present 4 hours after start of infusion of sodium bicarbonate, and until 3 hours after start of infusion of THAM. Serum potassium levels decreased after sodium bicarbonate infusion, and remained unchanged after THAM. After sodium bicarbonate, sodium increased, and after THAM, serum sodium decreased. CONCLUSIONS: Sodium bicarbonate and THAM had a similar alkalinizing effect in patients with mild metabolic acidosis; however, the effect of sodium bicarbonate was longer lasting. Sodium bicarbonate did decrease serum potassium, and THAM did not; THAM is therefore not recommended in patient with hyperkalemia. As sodium bicarbonate leads to an increase of serum sodium and THAM to a decrease, THAM may be the alkalinizing agent of choice in patients with hypernatremia. Similarly, because sodium bicarbonate increases PaCO2 and THAM may even decrease PaCO2, sodium bicarbonate is contraindicated and THAM preferred in patients with mixed acidosis with high PaCO2 levels.
Asunto(s)
Acidosis/tratamiento farmacológico , Pacientes Internos , Unidades de Cuidados Intensivos , Bicarbonato de Sodio/uso terapéutico , Trometamina/uso terapéutico , Acidosis/sangre , Análisis de los Gases de la Sangre , Tampones (Química) , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Lactatos/sangre , Masculino , Persona de Mediana Edad , Potasio/sangre , Índice de Severidad de la Enfermedad , Sodio/sangre , Bicarbonato de Sodio/administración & dosificación , Resultado del Tratamiento , Trometamina/administración & dosificaciónRESUMEN
BACKGROUND: Subtotal renal ablation is characterized by initial glomerular hypertrophy, followed by progressive development of glomerulosclerosis and interstitial fibrosis. Vascular endothelial growth factor (VEGF) is involved in glomerular hypertrophy and dysfunction in several pathophysiological conditions. On the other hand, progressive glomerulosclerosis and tubulo-interstitial fibrosis in the remnant kidney have been associated with loss of VEGF expression. METHODS: To explore the pathophysiological role of VEGF in the development of glomerular hypertrophy and renal damage in the remnant kidney model, we examined the effect of a neutralizing VEGF antibody on glomerular volume and kidney function in rats after subtotal nephrectomy or sham operation. Erythropoietin was administered to exclude a confounding effect of anaemia. RESULTS: Six weeks after subtotal nephrectomy, plasma urea and creatinine concentrations, urinary albumin excretion, and mean glomerular volume were elevated in the placebo-treated uraemic rats as compared with the sham-operated rats. Inhibition of VEGF partially prevented the glomerular hypertrophy and largely prevented the rise in urinary albumin excretion, but did not affect creatinine clearance in uraemic rats. CONCLUSIONS: VEGF is a mediator of glomerular hypertrophy after subtotal renal ablation. In view of glomerular hypertrophy as the initial deleterious event ultimately leading to progressive glomerulosclerosis, agents that block this glomerular growth could be useful in preventing scarring in progressive renal disease.
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Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Fallo Renal Crónico/fisiopatología , Riñón/fisiología , Factor A de Crecimiento Endotelial Vascular/fisiología , Animales , Anticuerpos , Proliferación Celular , Femenino , Fibrosis , Humanos , Riñón/patología , Nefrectomía , Ratas , Ratas Wistar , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
Acute renal failure (ARF) is defined as a sudden decrease in glomerular filtration rate leading to an acute rise in blood urea nitrogen and serum creatinine levels. It is a serious complication of cancer and constitutes a major source of morbidity and mortality. Current data suggest that ARF has the potential to substantially jeopardize the chances of cancer patients receiving optimal treatment and a potential cure. The pathways leading to ARF in cancer patients are common to the development of ARF in other conditions. However, ARF may also develop due to aetiologies arising from cancer treatment or the disease itself, including: nephrotoxic chemotherapy agents, post-renal obstruction, compression and infiltration by malignancy, tumour lysis syndrome, uric acid, sepsis and contrast agent nephropathy. This review provides a comprehensive overview of the causes of ARF in patients with cancer and guidance on how to prevent and treat this condition. Ultimately, the key to managing ARF in cancer patients is to ensure that a multidisciplinary approach provides adequate assessment, appropriate preventative measures and early intervention.
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Lesión Renal Aguda/etiología , Neoplasias/complicaciones , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/prevención & control , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Humanos , Hiperuricemia/sangre , Hiperuricemia/complicaciones , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Pronóstico , Factores de Riesgo , Síndrome de Lisis Tumoral/sangre , Síndrome de Lisis Tumoral/complicaciones , Ácido Úrico/sangreRESUMEN
The development of an adequate animal model for peritoneal research remains an object of concern. In vivo peritoneal dialysis (PD) research is hampered by the large variety of available models that make interpretation of results and comparison of studies very difficult. Species and strain of experimental animals, method of peritoneal access, study duration, measures of solute transport and ultrafiltration, and sampling for histology differ substantially among the various research groups. A collective effort to discuss the shortcomings and merits of the different experimental models may lead to a consensus on a standardized animal model of PD.
Asunto(s)
Investigación Biomédica , Modelos Animales , Diálisis Peritoneal/métodos , Animales , ConsensoRESUMEN
BACKGROUND: Long-term exposure to standard peritoneal dialysis fluid (PDF) results in alterations in peritoneal morphology and function. Studies investigating the long-term effects on the peritoneum of a low-glucose degradation product (GDP) bicarbonate/lactate-buffered PDF demonstrated its superior biocompatibility. We examined the potential of the low-GDP bicarbonate/lactate-buffered solution to reverse or reduce standard PDF-induced peritoneal alterations. METHODS: Female Wistar rats received twice daily intraperitoneal infusions with either a lactate-buffered solution with 3.86% glucose at pH 5.5 (Dianeal, referred to as standard PDF), or a low-GDP bicarbonate/lactate-buffered solution with 3.86% glucose at physiologic pH (Physioneal, referred to as bicarbonate/lactate PDF) for different periods of time: (1) 12 weeks Dianeal (N= 9); (2) 12 weeks Physioneal (N= 9); (3) 20 weeks Dianeal (N= 11); (4) 20 weeks Physioneal (N= 10); (5) 12 weeks Dianeal followed by 8 weeks Physioneal (N= 10). RESULTS: Chronic standard PDF exposure resulted in loss of ultrafiltration capacity, increased VEGF expression and vascular density, higher advanced glycation end product (AGE) accumulation, up-regulation of TGF-beta expression, and development of fibrosis compared to low-GDP bicarbonate/lactate-buffered PDF. The PDF-induced alterations were time-dependent. Crossover from standard PDF to low-GDP bicarbonate/lactate PDF resulted in a less impaired ultrafiltration (UF), less pronounced VEGF expression and neoangiogenesis, and less severe AGE accumulation, TGF-beta expression, and fibrosis compared to continuous standard PDF exposure for 20 weeks. CONCLUSION: Low-GDP bicarbonate/lactate-buffered PDF has the potential to slow down standard PDF-induced peritoneal membrane damage.
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Soluciones para Diálisis/efectos adversos , Soluciones para Diálisis/farmacología , Guanosina Difosfato , Ácido Láctico , Animales , Bicarbonatos , Femenino , Infecciones/epidemiología , Modelos Animales , Cavidad Peritoneal/fisiología , Ratas , Ratas Wistar , Ultrafiltración , Vísceras/citología , Vísceras/efectos de los fármacosRESUMEN
BACKGROUND: Detection of renal dysfunction is important in critically ill patients, and in daily practice, serum creatinine is used most often. Other tools allowing the evaluation of renal function are the Cockcroft-Gault and MDRD (Modification of Diet in Renal Disease) equations. These parameters may, however, not be optimal for critically ill patients. The present study evaluated the value of a single serum creatinine measurement, within normal limits, and three commonly used prediction equations for assessment of glomerular function (Cockcroft-Gault, MDRD and the simplified MDRD formula), compared with creatinine clearance (Ccr) measured on a 1 h urine collection in an intensive care unit (ICU) population. METHODS: This was a prospective observational study. A total of 28 adult patients with a serum creatinine <1.5 mg/dl, within the first week of ICU admission, were included in the study. Renal function was assessed with serum creatinine, timed 1 h urinary Ccr, and the Cockcroft-Gault, MDRD and simplified MDRD equations. RESULTS: Serum creatinine was in the normal range in all patients. Despite this, measured urinary Ccr was <80 ml/min/1.73 m2 in 13 patients (46.4%), and <60 ml/min/1.73 m2 in seven patients (25%). Urinary creatinine levels were low, especially in patients with low Ccr, suggesting a depressed production of creatinine caused by pronounced muscle loss. Regression analysis and Bland-Altman plots revealed that neither the Cockcroft-Gault formula nor the MDRD equations were specific enough for assessment of renal function. CONCLUSIONS: In recently admitted critically ill patients with normal serum creatinine, serum creatinine had a low sensitivity for detection of renal dysfunction. Furthermore, the Cockcroft-Gault and MDRD equations were not adequate in assessing renal function.
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Creatinina/sangre , Enfermedad Crítica , Riñón/fisiopatología , Anciano , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Admisión del Paciente , Estudios Prospectivos , Factores de TiempoRESUMEN
BACKGROUND: Starting renal replacement therapy (RRT) for acute renal failure in critically ill patients with haematological malignancies is controversial because of the poor outcome and high costs. The aim of this study was to compare the outcome between critically ill medical patients with and without haematological malignancies who received RRT for acute renal failure. METHODS: We retrospectively collected data on all consecutive patients who received RRT for acute renal failure at the Medical Intensive Care Unit (ICU) of a University Hospital between 1997 and 2002, and assessed the impact of the presence of a haematological malignancy on the survival within 6 months after ICU admission by Cox proportional hazard models. RESULTS: Fifty of the 222 (22.5%) consecutive patients with haematological malignancies admitted to the ICU over the study period received RRT for acute renal failure compared with 248 of the 4293 (5.8%) patients without haematological malignancies (P<0.001). Among patients who received RRT, those with haematological malignancies had higher crude ICU (79.6 vs 55.7%, P=0.002) and in-hospital (83.7 vs 66.1%, P=0.016) mortality rates, and a higher mortality at 6 months (86 vs 72%, P=0.018) by Kaplan-Meier estimates compared with those without haematological malignancies. However, after adjustment for the severity of illness and the duration of hospitalization before ICU admission, haematological malignancy by itself was no longer associated with a higher risk of death (hazard ratio 1.04; 95% confidence interval, 0.73-1.54, P=0.78). CONCLUSIONS: Medical ICU patients with haematological malignancies have a higher rate of occurrence of acute renal failure treated with RRT and a higher mortality, compared with those without haematological malignancies. However, the presence of a haematological malignancy by itself is not a reason to withhold RRT in medical ICU patients with acute renal failure.
Asunto(s)
Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/mortalidad , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/mortalidad , Terapia de Reemplazo Renal , Lesión Renal Aguda/terapia , Adulto , Anciano , Enfermedad Crítica , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Hyperhomocysteinemia is present in the majority of chronic hemodialysis patients. Treatment with folic acid, vitamin B12, and vitamin B6 cannot fully normalize plasma homocysteine concentrations (tHcy). Previously we have demonstrated the tHcy-lowering effect of creatine supplementation in an animal model of uremia (Kidney Int 64:1331-1337, 2003). The present study investigates the effects of creatine supplementation on tHcy in a vitamin-repleted chronic hemodialysis population. METHODS: Forty-five hemodialysis patients receiving folic acid and vitamin B6 and B12 were included. Patients were treated with creatine (2 g/day) or placebo during 2 treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma tHcy, creatine, Kt/V(urea), folic acid, vitamin B12, and routine biochemistry were determined, as well as the prognostic inflammatory and nutritional index. RESULTS: All patients had elevated tHcy concentrations (21.2 +/- 5.6 micromol/L). Creatine treatment resulted in increased plasma and red blood cell creatine levels, documenting uptake of creatine. Creatine did not affect tHcy concentrations. There was no relationship between plasma creatine concentrations and tHcy concentrations. No changes in body weight, routine biochemistry, nutritional status, folic acid, or vitamin B12 were observed during the study. CONCLUSION: Creatine supplementation at a rate of 2 g/day does not further decrease tHcy concentrations in chronic dialysis patients already treated with high dose folic acid, vitamin B6, and B12 supplementation.