RESUMO
Chronic kidney disease (CKD) is a disorder frequently suffered by cirrhotic patients, and therefore it is crucial to perform an accurate renal assessment in this population. This assessment should be based on the integral evaluation of the clinical exam, glomerular filtration rate (GFR), serum electrolytes, hemoglobin, and parathyroid hormone values, as well as urinalyses and renal imaging. GFR assessment can be performed by different methods, such as serum creatinine, serum cystatin C, GFR equations (based on creatinine, cystatin C or both), endogenous and exogenous markers clearance, and renal functional imaging. All these evaluating methods have their particular characteristics, advantages and disadvantages. Even though Cr-51 EDTA clearance seems to be the best gold standard method, creatinine-based equation (RFH cirrhosis) and cystatin C based-equations (CKD-EPI and Stevens) seem to be the most inexpensive and accurate equations, respectively, for evaluating GFR in this population. In conclusion, renal assessment in cirrhotic patients is a complex task that should not be based on a single renal functional marker.
Assuntos
Testes de Função Renal/métodos , Cirrose Hepática/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Biomarcadores , Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Humanos , Inulina/urina , Lipocalina-2/urina , Insuficiência Renal Crônica/diagnóstico por imagemRESUMO
INTRODUCTION: The glomerular filtration rate (GFR) is considered an especially important tool for the measurement of renal function. Inulin clearance (InCl) is the classic reference method for this purpose, although it is associated with a number of disadvantages; thus, other markers have been proposed, including iohexol. Determination of iohexol clearance (IoCl) has been established for clinical use; however, its application as a GFR marker in experimental rat models has not been reported. OBJECTIVES: This study aims to standardize a methodology for the measurement of iohexol clearance and to evaluate its applicability as a marker of GFR in rats with induced toxic acute renal failure (ARF), using InCl as the gold standard. MATERIALS AND METHODS: Twenty-six Wistar male rats (200-300 g) were divided into the following two groups: a control group (n=7) and an ARF group (n=19). ARF was induced by the subcutaneous administration of cisplatin (5 mg/kg); IoCl and InCl were determined simultaneously, and plasma creatinine (pCreat) dosage was measured colorimetrically. RESULTS: The pCreat, InCl and IoCl levels were consistent with the expected values for the renal function ranges of the evaluated animals, and the IoCl and InCl levels were significantly correlated (r=0.792). An inverse moderate linear correlation between the IoCl and pCreat measurements (r=-0.587) and between the InCl and pCreat measurements (r=-0.722) were observed. CONCLUSION: These results confirm a correlation between IoCl and the gold standard of GFR, InCl measurement. IoCl offers a relevant advantage over InCl because determination of the former allows the animal to live after the procedure.
Assuntos
Injúria Renal Aguda/urina , Taxa de Filtração Glomerular , Iohexol/farmacocinética , Animais , Biomarcadores/sangue , Biomarcadores/urina , Cisplatino/química , Creatinina/sangue , Inulina/urina , Testes de Função Renal/métodos , Masculino , Ratos , Ratos WistarRESUMO
The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks, a mechanism to which NF-κB activation is central. Downregulation of endothelial nitric oxide synthase (eNOS) contributes to sepsis-induced endothelial dysfunction. Erythropoietin (EPO) has emerged as a major tissue-protective cytokine in the setting of stress. We investigated the role of EPO in sepsis-related acute kidney injury using a cecal ligation and puncture (CLP) model. Wistar rats were divided into three primary groups: control (sham-operated); CLP; and CLP+EPO. EPO (4,000 IU/kg body wt ip) was administered 24 and 1 h before CLP. Another group of rats received N-nitro-l-arginine methyl ester (l-NAME) simultaneously with EPO administration (CLP+EPO+l-NAME). A fifth group (CLP+EPOtreat) received EPO at 1 and 4 h after CLP. At 48 h postprocedure, CLP+EPO rats presented significantly higher inulin clearance than did CLP and CLP+EPO+l-NAME rats; hematocrit levels, mean arterial pressure, and metabolic balance remained unchanged in the CLP+EPO rats; and inulin clearance was significantly higher in CLP+EPOtreat rats than in CLP rats. At 48 h after CLP, creatinine clearance was significantly higher in the CLP+EPO rats than in the CLP rats. In renal tissue, pre-CLP EPO administration prevented the sepsis-induced increase in macrophage infiltration, as well as preserving eNOS expression, EPO receptor (EpoR) expression, IKK-α activation, NF-κB activation, and inflammatory cytokine levels, thereby increasing survival. We conclude that this protection, which appears to be dependent on EpoR activation and on eNOS expression, is attributable, in part, to inhibition of the inflammatory response via NF-κB downregulation.
Assuntos
Injúria Renal Aguda/prevenção & controle , Eritropoetina/antagonistas & inibidores , NF-kappa B/biossíntese , Óxido Nítrico Sintase Tipo III/biossíntese , Sepse/tratamento farmacológico , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Creatinina/urina , Citocinas/análise , Regulação para Baixo , Quimioterapia Combinada , Inibidores Enzimáticos/farmacologia , Quinase I-kappa B/metabolismo , Inflamação/metabolismo , Inulina/urina , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Ratos Wistar , Receptores da Eritropoetina/biossíntese , Sepse/metabolismo , Regulação para CimaRESUMO
We studied prospectively the perioperative changes of renal function in nine children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with inulin and (131)I-hippuran clearances before CPB, during hypo and normothermic CPB, following sternal closure and 1 h postoperatively. Urinary alpha glutathione S-transferase (alpha GS-T) was measured pre- and postoperatively as a marker for tubular cellular damage. Plasma and urine creatinine and electrolytes were measured. Free water, osmolal and creatinine clearances, as well as fractional excretion of sodium (FeNa) and potassium transtubular gradient (TTKG) were calculated. GFR was normal before and after surgery. ERPF was low before and after surgery; it increased significantly immediately after CPB. Filtration fraction (FF) was abnormally elevated before and after surgery; however, a significant decrease during normothermic CPB and sternal closure was found. Alpha GS-T presented a moderate, but nonsignificant increase postoperatively. FeNa also increased in this period, but not significantly. Creatinine, osmolal, free water clearances, as well as TTKG, were normal in all patients pre- and postoperatively. We conclude that there is no evidence of clinically significant deterioration of renal function in children undergoing repair of cardiac lesions under CPB. Minor increases of alpha GS-T in urine postoperatively did not confirm cellular tubular damage. There was no tubular dysfunction at that time.
Assuntos
Ponte Cardiopulmonar , Túbulos Renais/patologia , Túbulos Renais/fisiologia , Creatinina/urina , Feminino , Taxa de Filtração Glomerular/fisiologia , Glutationa Transferase/urina , Humanos , Lactente , Inulina/urina , Ácido Iodoipúrico/metabolismo , Isoenzimas/urina , Testes de Função Renal , Masculino , Estudos Prospectivos , Fluxo Plasmático Renal/fisiologiaRESUMO
The management of the preterm infant often requires rapid assessment of glomerular filtration rate (GFR). We sought to develop a screening test using GFR = kL/Pcr, where GFR is expressed as ml/min/1.73 m2, L is body length in centimeters, Pcr is plasma creatinine concentration, and k is a constant that depends on muscle mass. The value for k in 118 appropriate for gestational age preterm infants (0.34 +/- 0.01 SE) was significantly less than that of full-term infants (0.43 +/- 0.02, P less than 0.001). There was no difference between 12- to 24-hour single-injection inulin clearance and either 0.33 L/Pcr or creatinine clearance in preterm infants. We compared the body habitus of preterm and full-term infants using the assessment of muscle mass from urinary creatinine excretion (UcrV) and from upper arm muscle area (AMA) and volume (AMV), and that of fatness from the sum of five skinfold thickness measurements. During the first year of life, premature infants were found to have a lower percentage of muscle mass than term infants did. On the other hand, they took on a relatively greater amount of subcutaneous fat. There was a very good correlation between AMA or AMV and urinary creatinine excretion (r = 0.91 and 0.94, respectively) in 68 infants with heterogeneous body composition during the first year, indicating the validity of the urinary creatinine measurement. Absolute GFR (ml/min) was also well estimated from AMA or AMV factored by Pcr. We conclude that GFR can be well estimated from 0.33 L/Pcr in preterm infants. The lower value for k reflects the smaller percentage of muscle mass in preterm versus term infants. As a screening test, 1.5 X k or 0.05 L/Pcr predicted low values of GFR with an efficiency of 73%, specificity of 67%, and sensitivity of 88%.
Assuntos
Composição Corporal , Taxa de Filtração Glomerular , Recém-Nascido de Baixo Peso/fisiologia , Estatura , Creatinina/sangue , Humanos , Recém-Nascido de Baixo Peso/crescimento & desenvolvimento , Recém-Nascido , Inulina/urina , Dobras CutâneasRESUMO
Because of its effects on the cardiovascular and renin-angiotensin systems and on fluid and electrolyte homeostasis, maternal administration of ritodrine to inhibit preterm labor may cause significant alterations in renal function in the newborn infant. We determined inulin clearance, plasma renin activity, urinary arginine vasopressin excretion, and serum and urine electrolyte concentrations and osmolalities at 12 to 36 hours of life and at 6 days of life in 15 infants whose mothers had received ritodrine and in 15 infants whose mothers did not (control infants). At the time of each study, plasma ritodrine concentrations were obtained in the infants whose mothers received ritodrine. The infants whose mothers had received ritodrine had significantly lower inulin clearances and higher plasma renin activity and urinary arginine vasopressin excretion on day 1 but not on day 6. Gestational age was inversely correlated with plasma ritodrine concentration, plasma renin activity, and urinary arginine vasopressin excretion. There were no overt clinical signs of renal failure in any of the infants, and no differences in serum and urine electrolyte values, osmolality, fractional sodium excretion, or urine flow rate were observed between the groups.