RESUMO
Kidney iron deposition measured by R2* (magnetic resonance imaging) MRI is posited to result from tubular reabsorption of filtered haemoglobin due to intravascular haemolysis. In chronically transfused sickle cell disease (SCD), R2* is elevated and positively correlated with lactate dehydrogenase (LDH). To account for contributions to renal iron from systemic iron overload, we evaluated kidney R2*, urinary iron and haemolysis markers in 62 non-transfused SCD patients. On multivariate analysis, kidney R2* was associated with urinary iron and LDH (R2 = 0·55, P < 0·0001). Our study confirms that kidney R2* is associated with intravascular haemolysis and raises important questions regarding the role of iron in SCD nephropathy.
Assuntos
Anemia Falciforme , Hemólise , Ferro/urina , Nefropatias , Rim , Imageamento por Ressonância Magnética , Adolescente , Adulto , Idoso , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/urina , Biomarcadores/urina , Criança , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/metabolismo , Nefropatias/diagnóstico por imagem , Nefropatias/urina , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: There is no reliable marker for detecting early renal disease in early children with sickle cell disease (SCD). Estimation of glomerular filtration rate (eGFR) as derived from the height/plasma creatinine formula is dependent on the accuracy of the creatinine analytical method used. The aim of this study was to evaluate different equations for eGFR. METHODS: Children aged 5-16 years recruited. mGFR was obtained using plasma disappearance of Inutest/Iohexol, serum creatinine (SCr) was measured either by standard laboratory method or by tandem mass spectrometry (MSMS). Estimated GFR was then calculated either by "Bedside Schwartz method" or by the full-age spectrum (FAS) equation. FINDINGS: A total of 79 patients (mean age 9.8 ± 4.0 years). A revised eGFR constant was calculated for Schwartz equation from the slope of the plot of height/plasma creatinine versus mGFR. Mean values for mGFR (132.7 ± 32.1 ml/min/1.73m2) and eGFR methods compared: eGFR from standard SCr was significantly higher (144.2 ± 37.3 ml/min/1.73m2, p = 0.008). The MSMS eGFR showed the lowest SD (SD = 27.5), while both FAS eGFR and FAS-height eGFR showed the highest correlation coefficient (r = 0.67). INTERPRETATION: eGFR calculation based on height and SCr determined with MSMS traceable creatinine is more reliable than Schwartz formula using jaffe/enzymatic methods in SCD children.
Assuntos
Anemia Falciforme/fisiopatologia , Taxa de Filtração Glomerular , Rim/fisiopatologia , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/urina , Criança , Pré-Escolar , Feminino , Humanos , Testes de Função Renal , Masculino , Projetos Piloto , Reprodutibilidade dos TestesRESUMO
Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.
Assuntos
Injúria Renal Aguda/sangue , Anemia Falciforme/sangue , Lipocalina-2/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Lipocalina-2/urina , Masculino , Curva ROCRESUMO
INTRODUCTION: Sickle cell anaemia is characterized by defective haemoglobin synthesis and is associated with both endocrine and metabolic alterations. The effects of this clinical condition on kidney function are multifactorial and often begin early in childhood. This study aims to assess renal function in children with sickle cell anaemia using urine albumin:creatinine ratio (ACR) and urine human neutrophil gelatinase-associated lipocalin (NGAL). METHODS: This case-control study was conducted on 200 children aged 5-15 years in 2 tertiary hospitals in South West Nigeria: 150 were of haemoglobin S genotype and 50 were of haemoglobin A genotype. Serum urea, creatinine, urine albumin, and NGAL were assayed by known standard methods. eGFR, urine ACR, and urine NGAL/creatinine ratio (urine NCR) were calculated. RESULTS: The weight, height, BMI, systolic blood pressure, plasma urea, plasma creatinine, and spot urine creatinine of the HbS genotype children were significantly lower compared to that of the HbA genotype children. The eGFR, spot urine albumin, and urine ACR were significantly higher in the HbS group compared to the HbA group. There was no significant difference in the spot urine NGAL and urine NCR between the 2 groups, though both were higher in the HbS group compared to the HbA group. CONCLUSIONS: Kidney injury probably starts early in childhood in sickle cell individuals as indicated by the higher urine ACR detected in them. We infer that urine NGAL and uNCR are not sensitive markers of kidney disease especially in young sickle cell individuals possibly because of the hyperfiltration present at this age.
Assuntos
Albuminúria , Anemia Falciforme/sangue , Anemia Falciforme/urina , Creatinina , Rim/metabolismo , Lipocalina-2/urina , Ureia/sangue , Adolescente , Albuminas , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Creatinina/sangue , Creatinina/urina , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , NigériaRESUMO
People with sickle cell disease often report severe bone pain with repeated bouts of vaso-occlusive crises, but the extent of skeletal injury incurred during these painful episodes remain unclear. We sought to quantify bone degradation by comparing urinary concentrations of carboxyterminal cross-linked telopeptide of type I collagen (CTX-1), a well-described marker of bone resorption, in a prospective cohort of 52 adults with sickle cell disease enrolled in the Sickle Cell Pain Markers Study. We also questioned if changes in urinary CTX-1 concentrations correlated with changes in hemolysis and inflammatory markers measured both during and after resolution of a painful vaso-occlusive episode. Thirty-one of the 52 adults enrolled in the study had paired urine samples for CTX-1 analysis. Urinary CTX-1, corrected for urine creatinine, significantly decreased from a mean of 3.45⯵g/mmol during vaso-occlusive crises to 2.62⯵g/mmol at recovery (pâ¯=â¯0.01). Thus, increased bone loss appears to correlate with acute vaso-occlusive crises in sickle cell disease. Our finding that urinary CTX-1 can be used to probe bone degradation in sickle cell disease provides an important new tool for diagnosing and monitoring response to therapy for people with sickle cell-related bone loss.
Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/urina , Biomarcadores , Reabsorção Óssea/etiologia , Reabsorção Óssea/urina , Colágeno Tipo I/urina , Dor/etiologia , Peptídeos/urina , Adulto , Anemia Falciforme/diagnóstico , Feminino , Humanos , MasculinoRESUMO
In the present study, the possible activation of cellular immunity in SCD patients was investigated. As immune activation parameters, neopterin concentrations and kynurenine/tryptophan ratio for tryptophan degradation in 35 pediatric patients with sickle cell disease (31 HbSS and 4 HbSß) were determined. Our results have shown that neopterin levels (both urinary and serum) are increased in pediatric patients with sickle cell disease. The increase in neopterin concentration was accompanied by significantly increased biopterin, kynurenine concentration and kynurenine/tryptophan ratio. The mechanism of immune activation and the effects of inflammatory mediators in sickle cell disease are poorly understood, especially in terms of cell-mediated immunity. Further in-vivo and in-vitro studies are required to illuminate the association between neopterin levels and neutrophil activation in sickle cell disease.
Assuntos
Anemia Falciforme/sangue , Anemia Falciforme/urina , Neopterina/sangue , Neopterina/urina , Adolescente , Anemia Falciforme/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/urina , Masculino , Neopterina/imunologia , Ativação de Neutrófilo , Neutrófilos/imunologia , Neutrófilos/metabolismoRESUMO
BACKGROUND: Sickle cell nephropathy (SCN) is a progressive disease that contributes significant morbidity and mortality in sickle cell disease (SCD), yet it remains poorly understood. Hyperuricemia negatively impacts renal function in the non-sickle cell population but is understudied in SCD. METHODS: We performed a cross-sectional analysis of the first 78 pediatric SCD patients enrolled in a cohort study. The mechanism of development of hyperuricemia (defined, serum uric acid (UA) ≥ 5.5 mg/dL) was characterized as a result of either UA overproduction or inefficient renal excretion by the Simkin index and fractional clearance of urate (FCU) equations. Associations between hyperuricemia and albuminuria or estimated glomerular filtration rate (eGFR) were determined by linear regression. RESULTS: The prevalence of hyperuricemia in this young population (mean age 11.6 ± 3.77 years) was 34.2%. Only 1 hyperuricemic participant overproduced UA by Simkin index, while 62.5% were inefficient renal excretors of UA (FCU < 4%). Hyperuricemia was associated with a significant decrease in average eGFR, -27 ml/min/1.73m2 below normouricemia (mean eGFR 151.6 ± 40.32), p = 0.0122. Notably, the previously accepted association between decline of eGFR with age is significantly modified by hyperuricemia stratification, where hyperuricemia explains 44% of the variance in eGFR by age (R2 = 0.44, p = 0.0004) and is nonsignificant in normouricemia (R2 = 0.07, p = 0.0775). CONCLUSION: These findings indicate that hyperuricemia may be associated with early eGFR decline in SCN. This association must be further characterized in prospective cohort studies in SCN, and hyperuricemia must be investigated as a potential therapeutic target for SCN.
Assuntos
Albuminúria/epidemiologia , Anemia Falciforme/complicações , Hiperuricemia/epidemiologia , Nefropatias/fisiopatologia , Ácido Úrico/metabolismo , Adolescente , Albuminúria/sangue , Albuminúria/fisiopatologia , Anemia Falciforme/sangue , Anemia Falciforme/terapia , Anemia Falciforme/urina , Transfusão de Sangue , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/sangue , Hiperuricemia/diagnóstico , Hiperuricemia/tratamento farmacológico , Nefropatias/sangue , Nefropatias/etiologia , Nefropatias/urina , Masculino , Prevalência , Eliminação Renal/fisiologia , Fatores de Risco , Ácido Úrico/sangueRESUMO
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
Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence of hypertension underlies nephropathy, and its downregulation by losartan, an angiotensin-II-receptor-1 blocker, reduced albuminuria and progression of nephropathy. Therefore, we performed a phase-2 trial of oral losartan, given for 6 months, to explore whether it reduced albuminuria in children and adults with SCA. Participants were allocated to groups defined by class of baseline urinary albumin-to-creatinine ratio (UACR): no albuminuria (NoA), microalbuminuria (MicroA), and macroalbuminuria (MacroA). The primary endpoint was a ≥25% reduction UACR from baseline. There were 32 evaluable participants (mean age 24 years; NoA = 14, MicroA = 12, MacroA = 6). The primary endpoint was met in 83% of the MacroA group (P < 0.0001) and 58% of the MicroA group (P < 0.0001). Median fold-change in UACR was -0.74 for MacroA and -0.46 for MicroA. In MacroA and MicroA, UACR classification improved in 50% but worsened in 11%. Urine osmolality and estimated glomerular filtration rate (eGFR) did not change significantly. Losartan was discontinued in three participants [leg cramps, N = 1; decline in eGFR >25% (142â104 mL/minute/1.73 m2 ), N = 1; rise in serum creatinine >50% (0.2â0.3 mg/dL), N = 1]. Albuminuria was associated with diastolic dysfunction and impaired functional capacity, although cardiopulmonary status was unchanged after 6 months of losartan therapy. In summary, losartan decreased urinary albumin excretion in most participants with albuminuria. Those with macroalbuminuria had the greatest benefit. This study forms the basis for a phase-3, randomized, placebo-controlled trial of losartan for the nephropathy of SCA.
Assuntos
Albuminúria , Anemia Falciforme , Losartan/administração & dosagem , Adolescente , Adulto , Fatores Etários , Albuminúria/tratamento farmacológico , Albuminúria/etiologia , Albuminúria/fisiopatologia , Albuminúria/urina , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/fisiopatologia , Anemia Falciforme/urina , Criança , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Renal damage is a progressive complication of sickle cell disease (SCD) that begins in childhood and may progress to renal failure and early mortality in 12% of adults with hemoglobin SS (HbSS) SCD. Early sickle nephropathy is characterized by hyperfiltration and microalbuminuria; therefore, urine albumin to creatinine ratio (ACR) is an effective screening tool for its detection. PROCEDURE: This study investigated the effect of hydroxyurea (HU) therapy on urine ACR levels among children with SCD. A retrospective review was conducted to identify all patients with HbSS or HbSß0 thalassemia of age 7-18 years who began HU therapy in 2011-2013; a control group of patients not on HU were matched by age and baseline hemoglobin. All urine ACR measurements ≤24 months prior to and ≥24 months after HU initiation were recorded. RESULTS: There were 63 eligible patients on HU and 13 (25%) with albuminuria prior to HU initiation. Among those with baseline albuminuria, the median ACR was 96 mg/g prior to HU, 39 mg/g at 1 year (P = 0.02), and 25 mg/g at 2 years (P = 0.03). Albuminuria normalized in 37.5% (6/16) after 1 year and 61% (8/13) after 2 years of HU therapy. Among those without albuminuria prior to HU, 13% (6/47) developed albuminuria during HU therapy. Sixteen percent (13/80) of control patients had albuminuria in the beginning of study period, which normalized in 15% (two of 13) of patients at 1-year follow up. CONCLUSION: Introduction of HU is associated with significant decreases in urine ACR in children with SCD and albuminuria.
Assuntos
Albuminúria/urina , Anemia Falciforme/tratamento farmacológico , Creatinina/urina , Hidroxiureia/uso terapêutico , Adolescente , Anemia Falciforme/urina , Criança , Feminino , Humanos , Masculino , Estudos RetrospectivosAssuntos
Anemia Falciforme/sangue , Anemia Falciforme/urina , Orosomucoide/metabolismo , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Orosomucoide/urina , Adulto JovemRESUMO
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: Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects. SEARCH METHODS: The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 03 June 2015. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen. DATA COLLECTION AND ANALYSIS: Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments. MAIN RESULTS: Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure. AUTHORS' CONCLUSIONS: There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study.
Assuntos
Albuminúria/tratamento farmacológico , Anemia Falciforme/complicações , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/uso terapêutico , Proteinúria/tratamento farmacológico , Anemia Falciforme/urina , Creatinina/sangue , Feminino , Humanos , Masculino , Potássio/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal/prevenção & controleRESUMO
OBJECTIVES: Renal involvement is common in sickle cell disease (SCD). Early demonstration of renal injury and commencement of appropriate treatment will increase survival and quality of life in these patients. We investigated renal manifestations in our pediatric and adult SCD patients and evaluated the role of cystatin C, Beta2 microglobulin (B2M), retinol-binding protein (RBP), N-acetyl-beta-D-glucosaminidase (NAG), and endothelin-1 (ET-1) to indicate renal damage. METHODS: The study involved 45 pediatric and 10 adult patients with SCD and 20 healthy children and 10 healthy adults as a control. All the patients were questioned for possible renal manifestations. 24-hour urine samples were collected and glomerular filtration rates (GFRs) were calculated by using creatinine (GFR(creatinine)), Schwartz formula (GFR(Schwartz)), and cystatin C (GFR(cystatin C)). Blood and urine samples were collected and serum cystatin C, urine B2M, RBP, NAG, and ET-1 levels were measured. RESULTS: Nocturnal enuresis and proteinuria were the most common renal manifestations in SCD patients. When the groups were compared in terms of GFR, GFR(creatinine) and GFR(Schwartz) levels were higher in group 1 and 2 patients than in control 1 and 2 patients (P < .05). Cystatin C, B2M, RBP, NAG, and ET-1 values were normal in both the patient and the control groups. However, B2M/creatinine levels were higher than 160 µg/mg creatinine levels in 10 patients. CONCLUSIONS: Serum cystatin C, urine NAG, RBP, and ET-1 levels were found to be insufficient for the evaluation of SCD nephropathy. Increased B2M/creatinie levels can be valuable in estimating possible glomerular and tubular damage in SCD.
Assuntos
Acetilglucosaminidase , Anemia Falciforme , Cistatina C , Endotelina-1 , Nefropatias , Proteínas Celulares de Ligação ao Retinol , Microglobulina beta-2 , Acetilglucosaminidase/sangue , Acetilglucosaminidase/urina , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/urina , Criança , Pré-Escolar , Creatinina/sangue , Cistatina C/sangue , Cistatina C/urina , Endotelina-1/sangue , Endotelina-1/urina , Feminino , Humanos , Lactente , Nefropatias/sangue , Nefropatias/complicações , Nefropatias/urina , Masculino , Pessoa de Meia-Idade , Proteínas Celulares de Ligação ao Retinol/sangue , Proteínas Celulares de Ligação ao Retinol/urina , Microglobulina beta-2/sangue , Microglobulina beta-2/urinaAssuntos
Anemia Falciforme/urina , Indicã/urina , Anemia Ferropriva/urina , Animais , Feminino , Humanos , MasculinoRESUMO
Sickle cell disease (SCD) produces many structural and functional abnormalities in the kidney, including glomerular abnormalities. Albuminuria is the most common manifestation of glomerular damage, with a prevalence between 26 and 68% in adult patients. The pathophysiology of albuminuria in SCD is likely multifactorial, with contributions from hyperfiltration, glomerular hypertension, ischemia-reperfusion injury, oxidative stress, decreased nitric oxide (NO) bioavailability, and endothelial dysfunction. Although its natural history in SCD remains inadequately defined, albuminuria is associated with increased echocardiography-derived tricuspid regurgitant jet velocity, systemic blood pressure, and hypertension, as well as history of stroke, suggesting a shared vasculopathic pathophysiology. While most patients with albuminuria are treated with angiotensin converting enzyme inhibitors/angiotensin receptor blockers, there are no published long-term data on the efficacy of these agents. With the improved patient survival following kidney transplantation, SCD patients with end-stage renal disease should be considered for this treatment modality. Given the high prevalence of albuminuria and its association with multiple SCD-related clinical complications, additional studies are needed to answer several clinically important questions in a bid to adequately elucidate its pathophysiology, natural history, and treatment.
Assuntos
Albuminúria/etiologia , Anemia Falciforme/complicações , Glomerulonefrite/etiologia , Falência Renal Crônica/etiologia , Albuminúria/tratamento farmacológico , Albuminúria/patologia , Albuminúria/urina , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/patologia , Anemia Falciforme/urina , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/patologia , Glomerulonefrite/urina , Humanos , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/patologia , Falência Renal Crônica/urina , Transplante de RimRESUMO
BACKGROUND: Although hyperfiltration and albuminuria are common pathological conditions, kidney injury (KI) biomarkers have been seldom studied in individuals with sickle cell anemia (SCA). METHODS: We undertook a cross-sectional assessment of urine KI biomarkers in children and adults with SCA with and without albuminuria and a normal estimated glomerular filtration rate (eGFR). Albumin, KI molecule 1 (KIM-1), N-acetyl-ß-D-glucosaminidase (NAG), endothelin-1 and transforming growth factor-ß1 (TGF-ß1) were measured. Assays were normalized by urine creatinine. Urine intracellular hemosiderin and serum lactate dehydrogenase (LDH) were assessed as markers of hemolysis. Albuminuria was associated to the biomarkers by Pearson and Spearman correlation coefficients. Differences between the albuminuria (yes, no) groups were assessed by the t test. RESULTS: Nineteen patients with albuminuria (mean urine albumin/creatinine 527.14 ± 1070 mg/g, range 38.3--190 mg/g) and 19 patients without albuminuria (mean urine albumin/creatinine 15.93 ± 5.17 mg/g, range 7.9-28.4 mg/g) were studied. The age range for the whole group was 11-48 years, and 47 % were males. Patients with albuminuria were older, had lower hematocrit, were more likely to test positive for urine hemosiderin and had a higher KIM-1 (P = 0.0035) and NAG/ creatinine ratios (P = 0.0062). Urine hemosiderin strongly correlated to a higher LDH level (P < 0.001). CONCLUSIONS: Despite a normal or increased eGFR, KI biomarkers were detected in the urine of individuals with SCA. NAG, KIM-1 and urine hemosiderin correlated with the presence of albuminuria.
Assuntos
Injúria Renal Aguda/etiologia , Albuminúria/etiologia , Anemia Falciforme/complicações , Biomarcadores/análise , Hemólise , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/urina , Criança , Estudos Transversais , Feminino , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Masculino , Glicoproteínas de Membrana/urina , Pessoa de Meia-Idade , Proteínas de Neoplasias/urina , Receptores Virais , Adulto JovemRESUMO
Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Our objective was to investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by (99m)Tc-DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Hydroxyurea study of long-term effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Twenty-three children with SCA (median age 7.5 years, range, 2.5-14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range, 15.3-30.6 mg/kg/day). After 3 years of treatment, GFR measured by (99m)Tc-DTPA decreased significantly from 167 ± 46 mL/min/1.73 m² to 145 ± 27 mL/min/1.73 m² (P = 0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin (P = 0.042) and decrease in lactate dehydrogenase levels (P = 0.035). Urine microalbumin and cystatin C levels did not change significantly. Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA.
Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Glomerulonefrite/prevenção & controle , Hidroxiureia/uso terapêutico , Glomérulos Renais/efeitos dos fármacos , Adolescente , Albuminúria/etiologia , Albuminúria/prevenção & controle , Anemia Falciforme/sangue , Anemia Falciforme/fisiopatologia , Anemia Falciforme/urina , Antidrepanocíticos/administração & dosagem , Antidrepanocíticos/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Cistatina C/sangue , Monitoramento de Medicamentos , Feminino , Hemoglobina Fetal/análise , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulonefrite/etiologia , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Glomérulos Renais/fisiopatologia , Masculino , Pentetato de Tecnécio Tc 99m , Fatores de TempoRESUMO
BACKGROUND/AIMS: Kidney abnormalities are one of the main chronic complications of sickle cell disease (SCD). The aim of this study is to investigate the occurrence of renal tubular abnormalities among patients with SCD. METHODS: This is a prospective study with 26 SCD adult patients in Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl2), after a 12h period of water and food deprivation. Fractional excretion of sodium (FENa), transtubular potassium gradient (TTKG) and solute free water reabsorption (TcH2O) were calculated. The SCD group was compared to a group of 15 healthy volunteers (control group). RESULTS: Patient`s average age and gender were similar to controls. Urinary acidification deficit was found in 10 SCD patients (38.4%), who presented urinary pH >5.3 after CaCl2 test. Urinary osmolality was significantly lower in SCD patients (355 ± 60 vs. 818 ± 202 mOsm/kg, p=0.0001, after 12h period water deprivation). Urinary concentration deficit was found in all SCD patients (100%). FENa was higher among SCD patients (0.75 ± 0.3 vs. 0.55 ± 0.2%, p=0.02). The TTKG was higher in SCD patients (5.5 ± 2.5 vs. 3.0 ± 1.5, p=0.001), and TcH2O was lower (0.22 ± 0.3 vs. 1.1 ± 0.3L/day, p=0.0001). CONCLUSIONS: SCD is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating and incomplete distal acidification defect. There was also an increase in the potassium transport and decrease in water reabsorption, evidencing the occurrence of distal tubular dysfunction. .