RESUMO
Aim: The aim of this study was to compare novel kidney injury biomarkers in sickle cell anemia (SCA) children with and without albuminuria or glomerular hyperfiltration. Materials & methods: A total of 358 Brazilian children with SCA were studied. Fifteen kidney injury biomarkers in urine were measured. Albuminuria was defined as urine albumin/creatinine ratio >100 mg/g. Glomerular hyperfiltration was defined as estimated glomerular filtration rate ≥140 ml/min/1.73 m2. Results: After adjustment for age, sex and modifying therapies in use, EGF and collagen IV urinary levels were associated with albuminuria. Renin and clusterin levels were associated with hyperfiltration. Conclusion: Levels of novel kidney injury biomarkers were associated with albuminuria and hyperfiltration in Brazilian children with SCA, suggesting concomitant structural and functional abnormalities.
Assuntos
Albuminúria/urina , Anemia Falciforme/urina , Biomarcadores/urina , Nefropatias/urina , Adolescente , Albuminúria/complicações , Albuminúria/diagnóstico , Anemia Falciforme/complicações , Brasil , Criança , Estudos de Coortes , Estudos Transversais , Taxa de Filtração Glomerular , Humanos , Rim/patologia , Rim/fisiopatologia , Nefropatias/complicações , Nefropatias/diagnóstico , Testes de Função Renal/métodos , MasculinoRESUMO
Sickle cell disease (SCD) is a hereditary condition characterized by homozygosis of the hemoglobin S (HbS) gene. Marked morbimortality is observed due to chronic hemolysis, endothelial injury, and episodes of vaso-occlusion, which leads to multi-organ damage. Renal impairment is common and may have different presentations, such as deficiency in urinary acidification or concentration, glomerulopathies, proteinuria, and hematuria, frequently resulting in end-stage renal disease (ESRD). Novel biomarkers of renal function, such as kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein 1 (MCP-1) are being studied in order to enable early diagnosis of kidney damage in SCD.
Assuntos
Anemia Falciforme/urina , Quimiocina CCL2/urina , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Falência Renal Crônica/urina , Rim/metabolismo , Lipocalina-2/urina , Anemia Falciforme/complicações , Biomarcadores/urina , Humanos , Falência Renal Crônica/etiologiaRESUMO
Sickle cell disease (SCD) is an autosomal recessive disease in which homozygosity for a single point mutation in the gene encoding the ß-globin chain produces hemoglobin S molecules that polymerize within the erythrocyte during deoxygenation; the result is sustained hemolytic anemia and vaso-occlusive events. As patients live to adulthood, the chronic impact of sustained hemolytic anemia and episodic vaso-occlusive episodes leads to progressive end-organ complications. This scenario culminates in the development of 1 or more major cardiovascular complications of SCD for which there are no approved or consensus therapies. These complications include elevated pulmonary artery systolic pressure, pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, sudden death, and chronic kidney disease with associated proteinuria, microalbuminuria, and hemoglobinuria. In patients with advancing age, cardiopulmonary organ dysfunction and chronic kidney injury have significant effects on morbidity and premature mortality. Over the last 15 years, a number of tests have been validated in multiple replicate cohort studies that identify patients with SCD at the highest risk of experiencing pulmonary and systemic vasculopathy and death, providing for screening strategies tied to targeted, more aggressive diagnostic and therapeutic interventions.
Assuntos
Anemia Falciforme , Doenças Cardiovasculares , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Anemia Falciforme/urina , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/urina , Humanos , Proteinúria/etiologia , Proteinúria/terapia , Proteinúria/urina , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/urinaRESUMO
OBJECTIVES: As populations with sickle cell disease (SCD) live longer, it is likely that the burden of renal dysfunction will be an increasing challenge for patients. In this study, we aim to determine the prevalence of renal dysfunction and its possible predictors in persons with SCD. METHODS: Ninety-eight patients with the homozygous SCD (SS disease;55 females, 43 males; mean age 34 ± 2.3 years) in their steady state had measurements of glomerular filtration rate (GFR) using 99mTc-DTPA nuclear renal scan, serum creatinine, and urinary albumin: creatinine ratio. Other haematological and biochemical measurements and data on clinical events were completed for each individual. RESULTS: Chronic kidney disease (CKD) stages 3 and above was present in 6% of the study population, and 65.3% had albuminuria. Hyperfiltration occurred in 24.5% patients with two-thirds having albuminuria as well. Serum creatinine was an insensitive marker of renal dysfunction as started rising after measured GFR fell below 50 mls/min/1.73 m(2). Multiple regression modelling showed serum creatinine and height to be significantly associated with GFR. Serum creatinine was also significantly associated with albuminuria, and age was not a predictor in any of the models. There was no association with markers of haemolysis. CONCLUSION: We conclude that the burden of renal dysfunction is quite high in this young cohort with SS disease. Serum creatinine is a late and insensitive marker of worsening glomerular function, and screening for albuminuria could begin early in life. Longitudinal studies will continue to increase our understanding of pathophysiological mechanisms that lead to CKD in this specific population.
Assuntos
Albuminúria , Anemia Falciforme , Taxa de Filtração Glomerular , Nefropatias , Rim , Albuminúria/sangue , Albuminúria/diagnóstico por imagem , Albuminúria/etiologia , Albuminúria/fisiopatologia , Albuminúria/urina , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/fisiopatologia , Anemia Falciforme/urina , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/sangue , Creatinina/urina , Estudos Transversais , Feminino , Humanos , Jamaica , Rim/diagnóstico por imagem , Rim/metabolismo , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/diagnóstico por imagem , Nefropatias/etiologia , Nefropatias/fisiopatologia , Nefropatias/urina , Masculino , Prevalência , RadiografiaRESUMO
BACKGROUND: The aim of this study was to evaluate the monocyte chemoatractant protein-1 (MCP-1) as a novel biomarker of renal lesion in sickle cell disease (SCD) and correlate it with oxidative stress. METHODS: This is a prospective study with SCD patients followed at a tertiary center in Brazil. Urine samples were collected to dosage of protein, MCP-1, malondialdehyde (MDA) and urinary creatinine. Patients taking hydroxyurea (SSHU) were compared to those not taking the drug (SS). Patients' data were also compared to a control group of 15 healthy blood donors. RESULTS: MCP-1 dosage was increased in SCD patients (Control: 42.12±27.6; SSHU: 168.2±90.1 and SS: 231.4±123.7 p<0.0001). SS patients presented higher levels of MCP-1 in comparison to SSHU group (SSHU: 168.2±90.10 and SS: 231.4±123.7; p=0.023). The same results were observed for MDA (Control: 2:29±1:13; SSHU: 5.60±2.39 and SS: 7.23±2.64, p<0.0001) and NO (control: 2.25±1.9; SSHU: 56.54±9.1 and SS: 39.1±9.02, p<0.0001). A positive correlation was obtained between MCP-1 and MDA (r=0.34, p=0.01); albuminuria (r=0.5, p=0.03); NO (r=0.39, p=0.005). CONCLUSION: The outcomes of the study suggest that MCP-1 is a predictive biomarker of renal lesion that can also reflect damage caused by oxidative stress present in SCD.
Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/urina , Quimiocina CCL2/urina , Nefropatias/etiologia , Estresse Oxidativo , Adulto , Albuminúria/etiologia , Albuminúria/metabolismo , Anemia Falciforme/epidemiologia , Anemia Falciforme/metabolismo , Brasil/epidemiologia , Feminino , Humanos , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/urina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Renal abnormalities are often seen in sickle cell disease (SCD). OBJECTIVE: To investigate the role of hydroxycarbamide as a protective agent in sickle cell nephropathy. SETTING: Patients with SCD followed at a Hematology outpatients clinic. METHODS: Prospective study with 26 SCD patients. Renal function evaluation was performed and a comparison between patients and control group was done. Patients using hydroxycarbamide were compared to those not taking this drug. MAIN OUTCOME MEASURE: Effect of hydroxycarbamide on renal function. RESULTS: Patients mean age was 32.1 ± 9.9 years, and 16 (61 %) were males. Glomerular hyperfiltration was found in nine patients with SCD (34.6 %). GFR < 60 mL/min/1.73 m² was observed in three cases (11.5 %). Microalbuminuria (30-300 mg/day) was found in seven cases (27 %) and macroalbuminuria (>300 mg/dia) in one patient (3.8 %). All patients had urinary concentrating deficit, and inability to acidify urine was found in ten cases (38.4 %). The comparison of patients according to the use of hydroxycarbamide showed lower levels of serum creatinine in those using the drug (0.6 ± 0.1 vs. 0.8 ± 0.3 mg/dL, p = 0.03), as well as lower levels of 24 h-proteinuria (226 ± 16 vs. 414 ± 76 mg/dL, p = 0.0001), but not microalbuminuria (79 ± 15 vs. 55 ± 86 mg/dL, p = 0.35). CONCLUSION: SCD is associated with important renal abnormalities. Hydroxycarbamide seems to protect kidney function in SCD by decreasing proteinuria but not microalbuminuria.
Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Hidroxiureia/uso terapêutico , Rim/efeitos dos fármacos , Proteinúria/prevenção & controle , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/fisiopatologia , Anemia Falciforme/urina , Brasil , Estudos de Coortes , Feminino , Barreira de Filtração Glomerular/efeitos dos fármacos , Barreira de Filtração Glomerular/fisiopatologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Hospitais Universitários , Humanos , Concentração de Íons de Hidrogênio , Rim/fisiopatologia , Capacidade de Concentração Renal/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Proteinúria/etiologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: The increase of urinary albumin excretion could be associated with morbidity in patients with sickle cell disease. The objective of this study was to evaluate the relation between blood pressure and urinary albumin excretion, and to estimate the prevalence of hypertension according to the level of urinary albumin excretion. METHODS: A cross-sectional study was carried in 77 patients with sickle cell disease (48 patients with haemoglobin SS, 29 with haemoglobin SC) et 30 controls with haemoglobin AA. The patients with sickle cell disease were divided into 3 groups according to urinary albumin excretion: less than 30 mg daily (group I: normoalbuminuria); from 30 to 300 mg daily (group II: microalbuminuria); above 300 mg daily (group III: macroalbuminuria). All AA selected controls had normoalbuminuria (group IV). RESULTS: In normoalbuminuric patients, the average of blood pressure was significantly lower in patients with sickle cell disease than in controls (respectively 115.0 +/- 8.1 vs 132.1 +/- 15.1, p = 4.10(-6) for systolic pressure and 67.2 +/- 8.0 vs 78.8 +/- 9.8 mmHg, p = 10(-4) for diastolic pressure). There was a positive relation between urinary albumin excretion, even moderate (values < or = 300 mg daily) and blood pressure in SS patients (r = 0.40, p < 0.02 for systolic and r = 0.54, p < 0.01 for diastolic pressure) and in SC patients (r = 0.74, p < 0.001 and r = 0.58, p < 0.01). The prevalence of hypertension was 0% in group I, 25% in group II and 66% in group III. CONCLUSION: The positive association between blood pressure and urinary albumin excretion suggests that the latter should be taken into account in sickle cell disease's follow up.
Assuntos
Albuminúria/complicações , Anemia Falciforme/complicações , Hipertensão/etiologia , Adolescente , Adulto , Albuminúria/urina , Anemia Falciforme/urina , Determinação da Pressão Arterial , Criança , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Valores de Referência , Índias Ocidentais/epidemiologiaRESUMO
Urea kinetics were measured on two separate occasions in five adults with normal haemoglobin genotype (HbAA) and in four who were homozygous for sickle cell disease (HbSS). Prime/intermittent doses of [15N15N]urea were given orally on one occasion and intravenously on the other. In three of the nine individuals there appeared to be significant hydrolysis of the oral dose of urea before absorption, leading to spurious results for the urea kinetics. When only the studies in which isotope was given intravenously were considered, there was a difference in the rate at which urea-N was salvaged, with more urea-N being salvaged by HbSS subjects than HbAA. It is concluded that the oral presentation of isotope can be used to measure urea kinetics provided care is taken to exclude those subjects who are likely to display upper intestinal hydrolysis, and that there are differences in aspects of urea kinetics between HbAA and HbSS which may be of metabolic importance.
Assuntos
Anemia Falciforme/tratamento farmacológico , Ureia/farmacocinética , Absorção , Administração Oral , Adolescente , Adulto , Anemia Falciforme/urina , Estudos de Avaliação como Assunto , Feminino , Humanos , Hidrólise , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Isótopos de Nitrogênio , Ureia/administração & dosagem , Ureia/urinaRESUMO
Urea kinetics were measured on two seperate occasions in five adults with normal haemoglobin genotype (HbAA) and in four who were homozygous for sickle cell disease (HbSS). Prime/intermittent dose of {15N15N} urea were given orally on one occasion and intravenously on the other. In three of the nine individuals there appeared to be significant hydrolysis of the oral dose of urea before absorption, leading to spurious results for the urea kientics. When only the studies in which the isotope was given intravenously were considered, there was a difference in the rate at which urea-N was salvaged, with more urea-N being salvaged by HbSS subjects than HbAA. It is concluded that the oral presentation of isotope can be used to measure urea kinetics provided care is taken to exclude those subjects who are kikely to display upper intestinal hydeolysis, and that there are differences in aspects of urea kinetics between HbAA and HbSS which may be of metabolic importance. (Au)
Assuntos
Humanos , Masculino , Feminino , Adulto , Anemia Falciforme/tratamento farmacológico , Ureia/farmacocinética , Administração Oral , Anemia Falciforme/urina , Hidrólise , Isótopos de Nitrogênio , Estudo de AvaliaçãoRESUMO
The determinants of nocturnal enuresis in homozygous sickle cell (SS) disease have been investigated in 16 enuretic and 16 age and sex matched non-enuretic children. Overnight fluid deprivation tests (8pm-8am) demonstrated no significant difference in maximum urine osmolality or urine volumes, although the latter tended to be higher in the enuretic children. Maximum functional bladder capacity, estimated by maximum voided volume during oral fluid loading, was lower and the ratio of overnight urine volume to maximum functional bladder capacity higher in the enuretic than the non-enuretic group. Enuretic children were more likely than non-enuretics to be considered deep sleepers by their family. High urine volumes may contribute to nocturnal enuresis in SS disease, although the similar values in enuretic and non-enuretic children implies that additional factors determine the presence of enuresis. Low maximum functional bladder capacity, and a high ratio of overnight urine volume to maximum functional bladder capacity, appear to be important determinants.