RESUMO
Pyuria in dipstick examination serves as the most widespread screening tool for urinary tract infections (UTI). The absence of pyuria, however, does not exclude UTI. We investigated the diagnostic value of urinary calprotectin, a mediator protein of the innate immune system, which is released by leukocytes, for the detection of UTI and compared it with dipstick pyuria. Since even low numbers of leukocytes in the urine significantly increase urinary calprotectin concentrations, calprotectin might be a more sensitive marker than pyuria detected by dipstick. All 162 patients were prospectively included and underwent a urine dipstick, urine culture, quantification of proteinuria and determination of calprotectin in the urine. Urinary calprotectin was determined using an enzyme-linked immunosorbent assay (ELISA). UTI was defined as urine cultures with detection of one or a maximum of two uropathogenic bacteria with ≥ 105 colony-forming units per millilitre (CFU/ml). Exclusion criteria were acute kidney injury, chronic renal insufficiency and tumors of the urinary tract. 71 (43.8%) patients had a UTI. Of the 91 patients without UTI, 23 had a contamination and 19 had evidence of ≥ 105 CFU/ml considered to be asymptomatic bacteriuria. The median calprotectin concentration in patients with UTI and pyuria was significantly higher than in patients with UTI and without pyuria (5510.4 vs. 544.7 ng/ml). In ROC analyses, calprotectin revealed an area under the curve (AUC) of 0.70 for the detection of significant bacteriuria. Pyuria in dipstick examinations provided an AUC of 0.71. There was no significant difference between these AUCs in the DeLong test (p = 0.9). In patients with evidence of significant bacteriuria but without pyuria, a significantly higher calprotectin concentration was measured in the urine than in patients with neither pyuria nor UTI (544.7 ng/ml vs 95.6 ng/ml, p = 0.029). Urinary calprotectin is non-inferior to dipstick pyuria in the detection of UTI.
Assuntos
Bacteriúria , Biomarcadores , Complexo Antígeno L1 Leucocitário , Infecções Urinárias , Humanos , Complexo Antígeno L1 Leucocitário/urina , Masculino , Feminino , Bacteriúria/diagnóstico , Bacteriúria/urina , Pessoa de Meia-Idade , Idoso , Biomarcadores/urina , Infecções Urinárias/diagnóstico , Infecções Urinárias/urina , Adulto , Piúria/urina , Piúria/diagnóstico , Estudos Prospectivos , Urinálise/métodos , Idoso de 80 Anos ou mais , Curva ROC , Ensaio de Imunoadsorção Enzimática , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Urothelial carcinoma (UC) is the most common neoplasm of the canine lower urinary tract, affecting approximately 2% of dogs. Elderly female patients of certain breeds are predisposed, and clinical signs of UC can easily be confused with urinary tract infection or urolithiasis. Diagnosis and treatment are challenging given the lack of disease-specific markers and treatments. The S100A8/A9 complex and S100A12 protein are Ca2+-binding proteins expressed by cells of the innate immune system and have shown promise as urinary screening markers for UC. The neutrophil-to-lymphocyte ratio (NLR) can also aid in distinguishing certain neoplastic from inflammatory conditions. Our study aimed to evaluate the tissue expression of S100/calgranulins and the blood NLR in dogs with UC. Urinary bladder and/or urethral tissue samples from dogs with UC (n = 10), non-neoplastic inflammatory lesions (NNUTD; n = 6), and no histologic changes (n = 11) were evaluated using immunohistochemistry. Blood NLRs were analyzed in dogs with UC (n = 22) or NNUTD (n = 26). RESULTS: Tissue S100A12-positive cell counts were significantly higher in dogs with lower urinary tract disease than healthy controls (P = 0.0267 for UC, P = 0.0049 for NNUTD), with no significant difference between UC and NNUTD patients. Tissue S100A8/A9-positivity appeared to be higher with NNUTD than UC, but this difference did not reach statistical significance. The S100A8/A9+-to-S100A12+ ratio was significantly decreased in neoplastic and inflamed lower urinary tract tissue compared to histologically normal specimens (P = 0.0062 for UC, P = 0.0030 for NNUTD). NLRs were significantly higher in dogs with UC than in dogs with NNUTD, and a cut-off NLR of ≤ 2.83 distinguished UC from NNUTD with 41% sensitivity and 100% specificity. Higher NLRs were also associated with a poor overall survival time (P = 0.0417). CONCLUSIONS: These results confirm that the S100/calgranulins play a role in the immune response to inflammatory and neoplastic lower urinary tract diseases in dogs, but the tissue expression of these proteins appears to differ from their concentrations reported in urine samples. Further investigations of the S100/calgranulin pathways in UC and their potential as diagnostic or prognostic tools and potential therapeutic targets are warranted. The NLR as a routinely available marker might be a useful surrogate to distinguish UC from inflammatory conditions.
Assuntos
Carcinoma de Células de Transição , Doenças do Cão , Neoplasias da Bexiga Urinária , Cães , Animais , Feminino , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/veterinária , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/veterinária , Complexo Antígeno L1 Leucocitário/urina , Neutrófilos/patologia , Bexiga Urinária/patologia , Proteína S100A12 , Linfócitos , Calgranulina A , Biomarcadores , Doenças do Cão/patologiaRESUMO
Calprotectin is a protein molecule that is released from inflammatory cells. Measurement of calprotectin in various body fluids has recently gained significant importance for differentiating inflammatory and noninflammatory events. The subject has aroused interest in the field of nephrology and some renal pathologies in which urinary calprotectin levels have been studied. In this study, the measurement of urinary calprotectin level and its use for determining acute cisplatin nephrotoxicity in a group of patients with non-small cell lung cancer who received cisplatin-based oncological treatments have been investigated. The study included 41 patients who received cisplatin-based treatments for non-small cell lung cancer between January 2019 and January 2020. The patients were excluded from this study who were with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, serum creatinine (sCr) >1.5 mg/dL, a history of urinary tract infection, and nephrotoxic drug use in the past month. Baseline and 48-hour sCr values and baseline, 6-hour, 12-hour, 24-hour, and 48-hour urinary calprotectin levels of all patients were measured. Four of the 41 patients who received cisplatin treatment were excluded because their 48-hour sCr values could not be accessed. The control group included 29 patients. While there was no difference between the cisplatin group and the control group in terms of baseline sCr and eGFR values, the cisplatin group had significantly higher urinary calprotectin values. Of the 37 patients treated with cisplatin, 7 (18.9%) developed cisplatin-induced nephrotoxicity. The comparison of groups with (group 1) and without cisplatin nephrotoxicity (group 2) showed comparable mean age and male sex ratio. Baseline sCr and eGFR values were similar in both groups. The cisplatin-induced nephrotoxicity group had significantly higher 48-hour sCr and significantly lower 48-hour eGFR values. Baseline, 12-hour, 24-hour, and 48-hour urinary calprotectin levels were similar in groups with and without cisplatin nephrotoxicity. Recent studies have demonstrated that urinary calprotectin level measurement can be used to distinguish intrinsic acute kidney disease from prerenal kidney disease. However, the comparison of groups with and without cisplatin nephrotoxicity in our study showed no difference in urinary calprotectin levels. However, there is a need for large-scale studies using combined urinary biomarkers.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Complexo Antígeno L1 Leucocitário , Insuficiência Renal , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/efeitos adversos , Humanos , Complexo Antígeno L1 Leucocitário/urina , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/diagnósticoRESUMO
INTRODUCTION: It has been demonstrated that urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin are helpful biomarkers in the differentiation of intrinsic and prerenal acute kidney injury. OBJECTIVE: The present cross-sectional study investigates, whether urinary biomarkers are able to differentiate primarily inflammatory from non-inflammatory entities in chronic kidney disease (CKD). METHODS: Urinary calprotectin, NGAL, and kidney injury molecule-1 (KIM-1) concentrations were assessed in a study population of 143 patients with stable CKD and 29 healthy controls. Stable renal function was defined as an eGFR fluctuation ≤5 ml/min/1.73 m2 in the past 12 months. Pyuria, metastatic carcinoma, and renal transplantation were regarded as exclusion criteria. Diabetic nephropathy, hypertensive nephropathy, and polycystic kidney disease were categorized as 'primarily non-inflammatory renal diseases' (NIRD), whereas glomerulonephritis and vasculitis were regarded as 'primarily inflammatory renal diseases' (IRD). RESULTS: Urinary calprotectin and NGAL concentrations significantly differed between CKD and healthy controls (p < 0.05 each), whereas KIM-1 concentrations did not (p = 0.84). The three biomarkers did neither show significant differences in-between the individual entities, nor the two categories of IRD vs. NIRD (calprotectin 155.7 vs. 96.99 ng/ml; NGAL 14 896 vs. 11 977 pg/ml; KIM-1 1388 vs. 1009 pg/ml; p > 0.05 each). Albumin exceeds the diagnostic power of the investigated biomarkers by far. CONCLUSIONS: The urinary biomarkers calprotectin, NGAL, and KIM-1 have no diagnostic value in the differentiation of primarily inflammatory vs. non-inflammatory etiologies of CKD.
Assuntos
Receptor Celular 1 do Vírus da Hepatite A/análise , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Insuficiência Renal Crônica/urina , Idoso , Albuminúria/etiologia , Biomarcadores/urina , Estudos de Casos e Controles , Estudos Transversais , Diagnóstico Diferencial , Feminino , Alemanha , Taxa de Filtração Glomerular , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/patologiaRESUMO
BACKGROUND: Subjects with chronic kidney disease are at increased risk for contrast-induced acute kidney injury (CI-AKI). Risk stratification is traditionally based on glomerular filtration rate (GFR) and proteinuria. The present trial examines, whether tubular and inflammatory biomarkers are able to identify subjects at increased risk as well. METHODS: We performed a prospective study in 490 patients undergoing coronary angiography. An increase of serum creatinine concentration ≥ 0.3 mg/dl from baseline to day 2-3 was defined as primary endpoint (CI-AKI). Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and calprotectin were assessed < 24h before coronary angiography. Prognostic accuracy was assessed by receiver operating characteristics (ROC) calculations. RESULTS: 30 (6.1%) patients suffered from CI-AKI (27 AKIN stage I, 3 AKIN stage II, 0 AKIN stage III). Those subjects who developed CI-AKI had 3.1 fold higher baseline urinary NGAL/creatinine ratios than those without CI-AKI (60.8 [IQR 18.7-93.1] µg/mg vs. 19.9 [IQR 12.3-38.9] µg/mg, p = 0.001). In those subjects without clinically overt CKD (eGFR > 60 ml/min, urinary albumin creatinine ratio <30 mg/g), the NGAL/creatinine ratio was 2.6 higher in CI-AKI vs. no CI-AKI (47.8 [IQR 11.8-75.3] vs. 18.6 [IQR 11.7-36.3] µg/mg). No significant differences were obtained for KIM-1 and calprotectin (p>0.05 each). ROC analyses revealed an area under the curve (AUC) of 0.68 (95% CI 0.60-0.81) for NGAL/creatinine. An NGAL/creatinine ratio < 56.4 µg/mg has a negative predictive value of 96.5%. CONCLUSIONS: The present study is the largest investigation on the use of urinary biomarkers for CI-AKI risk stratification so far. It shows that NGAL provides prognostic information beyond the glomerular biomarkers eGFR and proteinuria.
Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Idoso , Área Sob a Curva , Biomarcadores/sangue , Angiografia Coronária/efeitos adversos , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Proteinúria , Curva ROC , Insuficiência Renal Crônica/complicaçõesRESUMO
Aim of the study is to define the diagnostic accuracy of selected urinary protein biomarkers in the non-invasive detection of primary and recurrent urothelial carcinoma of the urinary bladder. The urinary levels of calprotectin, CD147, APOA4 and protein deglycase DJ-1 were examined in 255 individuals, including 60 controls with non-malignant urological disease, 61 patients with a history of urinary bladder cancer with negative cytology and negative cystoscopy and 134 patients with urinary bladder cancer. Urinary concentrations of biomarkers were determined by Enzyme-Linked Immunosorbent Assay (ELISA). During the follow-up of patients with non-muscle invasive bladder cancer (NMIBC), a group of 44 patients with cancer recurrence was compared to the group of 61 patients with a history of NMIBC but with no evidence of disease. Urinary concentrations of the evaluated markers did not reveal any significant difference between these groups. During the primary diagnosis, a group of 90 patients with primary bladder cancer and 60 subjects with benign disease were compared. Urinary levels of CD147 were not significantly higher in patients with tumors. The greatest diagnostic accuracy was observed in APOA4 (sensitivity 55.6, specificity 83.3, AUC 0.75), and lesser in calprotectin (sensitivity 39.4, specificity 87.7, AUC 0.66) and in DJ-1 (sensitivity 61.1, specificity 66.7, AUC 0.64), respectively. Apolipoprotein A4 may be used potentially as a supplemental urinary marker in the diagnosis of primary bladder cancer.
Assuntos
Apolipoproteínas A/urina , Basigina/urina , Complexo Antígeno L1 Leucocitário/urina , Proteína Desglicase DJ-1/urina , Neoplasias da Bexiga Urinária/diagnóstico , Biomarcadores Tumorais/urina , Humanos , Recidiva Local de Neoplasia , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/urinaRESUMO
Purpose: To investigate whether measurement of urinary calprotectin can serve as a biomarker in the diagnosis of primary bladder cancer and to confirm its diagnostic role in determining high grade and stage disease. Materials and Methods: Urinary calprotectin was measured in spot urine samples from patients with primary bladder cancer and control subjects. To confirm levels in urine, tissue samples were also obtained from bladder tumor and healthy trigone of bladder by transurethral resection in both groups. Finally, calprotectin levels in tissue and urine of the patients and control subjects were compared and their diagnostic potential was investigated in high grade and stage bladder cancers. Results: Of 82 participants, 52 were patients with bladder cancer and 30 were control subjects. The two groups were comparable in terms of age, smoking status, and comorbidities. Tissue and urinary calprotectin levels were significantly higher in the bladder cancer group. In subgroup analyses, urinary calprotectin levels were significantly higher in patients with high-grade, muscle-invasive tumors. After receiver operating characteristic analyses, the sensitivity and specificity of urinary calprotectin was 100% and 96.7%, respectively, in the diagnosis of primary bladder cancer. High grade and stage bladder cancers were detected with sensitivity and specificity of 70% and 74.2%, and 80% and 84.8%, respectively. Conclusions: Urinary calprotectin may be a valuable parameter in the diagnosis of primary bladder cancer with high sensitivity and specificity. Furthermore, it may be useful in the prediction of high grade and stage disease. However, more investigations are needed.
Assuntos
Complexo Antígeno L1 Leucocitário/análise , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/urina , Complexo Antígeno L1 Leucocitário/biossíntese , Complexo Antígeno L1 Leucocitário/urina , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/metabolismoRESUMO
BACKGROUND: Urinary Calprotectin, a mediator of the innate immune system, has been identified as a biomarker in bladder cancer. Our aim was to investigate the association between sterile leukocyturia and urinary Calprotectin in low-grade and high-grade bladder cancer. MATERIALS AND METHODS: We performed a prospective cross-sectional study including 52 patients with bladder cancer and 40 healthy controls. Definition of sterile leukocyturia was > 5.0 leukocytes per visual field in absence of bacteriuria. RESULTS: The rate of sterile leukocyturia in low-grade (60.0%) and high-grade (62.0%) bladder cancer was comparable (p = 0.87). However, the median absolute urinary leukocyte count in patients with sterile leukocyturia was significantly higher in high-grade than in low-grade bladder cancer (p < 0.01). Spearman correlation revealed a significant correlation between urinary Calprotectin and leucocyte concentration (R = 0.4, p < 0.001). Median urinary Calprotectin concentration was 4.5 times higher in bladder cancer patients with than in patients without sterile leukocyturia (p = 0.03). Subgroup analysis revealed a significant difference in urinary Calprotectin regarding the presence of sterile leukocyturia in high-grade patients (596.8 [91.8-1655.5] vs. 90.4 [28.0-202.3] ng ml-1, p = 0.02). Multivariate analysis identified the leukocyte concentration to be the only significant impact factor for urinary Calprotectin (OR 3.2, 95% CI 2.5-3.8, p = 0.001). Immunohistochemistry showed Calprotectin positive neutrophils and tumour cells in high-grade bladder cancer with sterile leukocyturia. CONCLUSIONS: Urinary Calprotectin cannot be regarded as a specific tumour marker for bladder cancer, but rather as a surrogate parameter for tumour inflammation.
Assuntos
Biomarcadores Tumorais/urina , Complexo Antígeno L1 Leucocitário/urina , Leucócitos/metabolismo , Neoplasias da Bexiga Urinária/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Serum creatinine (SCr)- or urine output-based definitions of acute kidney injury (AKI) have important limitations in neonates. This study evaluates the diagnostic value of urinary biomarkers in very low-birth-weight (VLBW) infants receiving indomethacin for closure of a patent ductus arteriosus (PDA). METHODS: Prospective cohort study in 14 indomethacin-treated VLBW infants and 18 VLBW infants without indomethacin as controls. Urinary biomarkers were measured before, during, and after indomethacin administration. RESULTS: Indomethacin therapy was associated with significantly higher SCr concentrations at 36, 84, and 120 h compared to controls. At 36 h, three indomethacin-treated patients met the criteria for neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) AKI. The product of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]â¢[IGFBP7]) was significantly elevated in the AKI subgroup at 12 h (P < 0.05), hence 24 h earlier than the increase in SCr. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin were significantly increased in the indomethacin group at 12 h (P < 0.05), irrespective of fulfillment of the AKI criteria. Urinary kidney injury molecule-1 (KIM-1) was not significantly altered. CONCLUSION: While urinary [TIMP-2]â¢[IGFBP7] proves valuable for the early diagnosis of neonatal modified KDIGO-defined AKI, elevated urinary NGAL and calprotectin concentrations in indomethacin-treated VLBW infants not fulfilling the AKI criteria may indicate subclinical kidney injury.
Assuntos
Injúria Renal Aguda/urina , Fármacos Cardiovasculares/efeitos adversos , Permeabilidade do Canal Arterial/tratamento farmacológico , Indometacina/efeitos adversos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Inibidor Tecidual de Metaloproteinase-2/urina , Injúria Renal Aguda/induzido quimicamente , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Creatinina/sangue , Creatinina/urina , Estudos Transversais , Permeabilidade do Canal Arterial/complicações , Permeabilidade do Canal Arterial/urina , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: The addition of immunosuppression to supportive care reduces proteinuria in a subset of patients with IgA nephropathy (IgAN) but is associated with an increased rate of adverse events. The present work investigates whether urinary biomarkers are able to identify subjects who benefit from immunosuppression and to predict the progression of disease in a sub-cohort of the STOP-IgAN trial. METHODS: Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin, and the product of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 (TIMP2â¢IGFBP7) were measured in all available urine samples obtained at the time point of enrollment in the STOP-IgAN trial (n=113). RESULTS: Biomarker concentrations in both the overall study population and the subgroup with additional immunosuppression did not differ in subjects reaching vs. not reaching full clinical remission, eGFR loss ≥ 15, or 30 ml/min/1.73 m2 over the 3-year trial phase (p> 0.05 each). Receiver-operating characteristic curves showed a poor predictive accuracy of each biomarker for the above-mentioned parameters in the overall study population (areas under the curve ≤0.611). Accordingly, there was neither a significant correlation of any biomarker and adverse outcome in linear regression analysis, nor between biomarker concentrations at enrollment and change in the eGFR over the 3-year observation period. CONCLUSION: NGAL, KIM-1, calprotectin, and [TIMP-2]â¢[IGFBP7] had neither a prognostic value for the progression of IgAN, nor for the response to immunosuppression in the present sub-cohort of the STOP-IgAN trial. The search for appropriate biomarkers for an individualized treatment strategy in IgAN continues.
Assuntos
Biomarcadores/urina , Glomerulonefrite por IGA/diagnóstico , Adulto , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/urina , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Imunossupressores/uso terapêutico , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Indução de Remissão , Inibidor Tecidual de Metaloproteinase-2/urinaRESUMO
BACKGROUND/AIMS: Urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) do not only allow an early diagnosis of acute kidney injury, but also provide prognostic information in this setting. The present prospective study investigates, whether the urinary biomarkers NGAL, KIM-1 and calprotectin have prognostic information in chronic kidney disease (CKD) as well. METHODS: Urinary calprotectin, NGAL and KIM-1 concentrations were assessed in a study population of 143 patients with stable CKD comprising diabetic and hypertensive nephropathy, glomerulonephritis/vasculitis, and autosomal dominant polycystic kidney disease. An eGFR fluctuation > 5ml/min/1.73m2 in the past 12 months was defined as an exclusion criterion in order to exclude cases with acute on chronic kidney injury. Renal function was monitored for a median follow-up of 37 months. RESULTS: In the overall study population, all the three biomarkers failed to predict DeGFR and DACR from baseline to follow-up in linear regression analysis adjusted for age, gender, and baseline eGFR. Contrarily, baseline ACR was significantly associated with DeGFR (p< 0.001). In the subgroup of patients with vasculitis and glomerulonephritis, all the three biomarkers were significantly associated with DeGFR, with calprotectin having the highest regression coefficient. CONCLUSION: In contrast to the traditional biomarker "albuminuria", neither the inflammatory biomarker calprotectin, nor the tubular biomarkers NGAL and KIM-1, provide robust prognostic information on the loss or renal function in a heterogeneous CKD population. All of them, however, are candidate prognostic biomarkers in primarily inflammatory renal diseases.
Assuntos
Receptor Celular 1 do Vírus da Hepatite A/análise , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Insuficiência Renal Crônica/diagnóstico , Injúria Renal Aguda/diagnóstico , Idoso , Biomarcadores/urina , Feminino , Seguimentos , Humanos , Inflamação/diagnóstico , Masculino , Prognóstico , Insuficiência Renal Crônica/patologiaRESUMO
Background: Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. Methods: In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. Results: We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Conclusion: Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.
Assuntos
Doenças Inflamatórias Intestinais/complicações , Rim/patologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Adolescente , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab , Complexo Antígeno L1 Leucocitário/urina , Modelos Lineares , Lipocalina-2/urina , Masculino , Análise Multivariada , Prednisolona , Insuficiência Renal Crônica/etiologia , UltrassonografiaRESUMO
OBJECTIVES: Members of the S100 protein family, S100A8, S100A9 and their heterodimer complex known as calprotectin are thought to be involved not only in inflammatory pathways but also in tumorigenesis and cancer progression. Therefore, they have been widely studied in various types of cancer; however, there is limited knowledge about their role in bladder cancer. In this study, our aim was to determine the levels of S100A8 and S100A9 in the sera, and calprotectin levels in the sera and urines of bladder cancer patients and compare it to urinary BTA, a tumor marker that can be used in the diagnosis of bladder cancer. MATERIALS AND METHODS: The study was comprised of two major groups: 52 healthy controls and 82 patients with bladder cancer. The patient group was also divided into subgroups according to tumor stage and grade. Urine BTA levels, serum S100A8 and S100A9 levels, and serum and urine calprotectin levels in healthy controls and patients were determined using commercially available ELISA kits. RESULTS: While serum S100A8 and S100A9 levels did not differ between the controls and patients significantly, serum and urine calprotectin levels and urine BTA levels were significantly elevated in patients compared to controls. Serum calprotectin or urine BTA levels did not differ significantly among the patient subgroups. However, urine calprotectin levels were significantly elevated in muscle-invasive tumors (T2-4) compared to lower stages (Ta and T1). CONCLUSIONS: Urine calprotectin levels can be used in the diagnosis and staging of bladder cancer as a marker for muscle invasion.
Assuntos
Calgranulina A/metabolismo , Calgranulina B/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Antígenos de Neoplasias/sangue , Antígenos de Neoplasias/urina , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Calgranulina A/sangue , Calgranulina B/sangue , Calgranulina B/urina , Estudos de Casos e Controles , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/sangue , Complexo Antígeno L1 Leucocitário/urina , Masculino , Pessoa de Meia-Idade , Curva ROC , Fumar/efeitos adversos , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/urinaRESUMO
Early identification of patients with acute kidney injury (AKI) being at high risk for adverse outcome can influence medical treatment. This study compares urinary calprotectin, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) for their performance in predicting mortality and need for renal replacement therapy (RRT) in pediatric AKI patients. Urinary biomarker concentrations were assessed prospectively in 141 subjects aged 0-18 years including 55 patients with established AKI according to pediatric Risk, Injury, Failure, Loss, and End-stage kidney disease (pRIFLE) criteria, 27 patients without AKI, and 59 healthy children. Within the AKI group, receiver operating characteristic (ROC) curve analysis revealed moderate to poor performance of calprotectin and KIM-1 in the prediction of 30-day mortality (calprotectin area under the curve (AUC) 0.55; KIM-1 AUC 0.55) and 3-month mortality (calprotectin AUC 0.61; KIM-1 AUC 0.60) and fair performance in the prediction of RRT requirement (calprotectin AUC 0.72; KIM-1 AUC 0.71). Urinary NGAL showed good performance in predicting 30-day (AUC 0.79) and 3-month (AUC 0.81) mortality and moderate performance in predicting RRT (AUC 0.61). CONCLUSIONS: Whereas urinary calprotectin and KIM-1 can be useful for the prediction of RRT, urinary NGAL has a good diagnostic performance in predicting mortality in pediatric patients with AKI of heterogeneous etiology. What is known: ⢠There is increasing evidence that urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are valuable for the prediction of adverse outcome in adult acute kidney injury (AKI), whereas data on pediatric AKI is scarce. What is new: ⢠Urinary calprotectin and KIM-1 do not predict mortality in our heterogeneous pediatric AKI cohort, but they show moderate performance in the prediction of dialysis. ⢠Urinary NGAL is a good predictor of mortality performing better than pRIFLE stage, eGFR, or creatinine, but it shows moderate performance in the prediction of dialysis.
Assuntos
Injúria Renal Aguda/diagnóstico , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Injúria Renal Aguda/urina , Adolescente , Biomarcadores/urina , Criança , Pré-Escolar , Estudos Transversais , Técnicas de Apoio para a Decisão , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Prospectivos , Curva ROC , Terapia de Substituição Renal , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Onset of canine transitional cell carcinoma (TCC) and prostatic carcinoma (PCA) is usually insidious with dogs presenting at an advanced stage of the disease. A biomarker that can facilitate early detection of TCC/PCA and improve patient survival would be useful. S100A8/A9 (calgranulin A/B or calprotectin) and S100A12 (calgranulin C) are expressed by cells of the innate immune system and are associated with several inflammatory disorders. S100A8/A9 is also expressed by epithelial cells after malignant transformation and is involved in the regulation of cell proliferation and metastasis. S100A8/A9 is up-regulated in human PCA and TCC, whereas the results for S100A12 have been ambiguous. Also, the urine S100A8/A9-to-S100A12 ratio (uCalR) may have potential as a marker for canine TCC/PCA. Aim of the study was to evaluate the diagnostic accuracy of the urinary S100/calgranulins to detect TCC/PCA in dogs by using data and urine samples from 164 dogs with TCC/PCA, non-neoplastic urinary tract disease, other neoplasms, or urinary tract infections, and 75 healthy controls (nested case-control study). Urine S100A8/A9 and S100A12 (measured by species-specific radioimmunoassays and normalized against urine specific gravity [S100A8/A9USG; S100A12USG], urine creatinine concentration, and urine protein concentration and the uCalR were compared among the groups of dogs. RESULTS: S100A8/A9USG had the highest sensitivity (96%) and specificity (66%) to detect TCC/PCA, with specificity reaching 75% after excluding dogs with a urinary tract infection. The uCalR best distinguished dogs with TCC/PCA from dogs with a urinary tract infection (sensitivity: 91%, specificity: 60%). Using a S100A8/A9USG ≥ 109.9 to screen dogs ≥6 years of age for TCC/PCA yielded a negative predictive value of 100%. CONCLUSIONS: S100A8/A9USG and uCalR may have utility for diagnosing TCC/PCA in dogs, and S100A8/A9USG may be a good screening test for canine TCC/PCA.
Assuntos
Doenças do Cão/diagnóstico , Complexo Antígeno L1 Leucocitário/urina , Neoplasias Urogenitais/veterinária , Neoplasias Urológicas/veterinária , Animais , Biomarcadores/urina , Calgranulina A/análise , Calgranulina B/urina , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/urina , Carcinoma de Células de Transição/veterinária , Estudos de Casos e Controles , Creatinina/urina , Doenças do Cão/urina , Cães , Feminino , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/urina , Neoplasias da Próstata/veterinária , Proteinúria/urina , Proteinúria/veterinária , Radioimunoensaio/veterinária , Neoplasias Urogenitais/diagnóstico , Neoplasias Urogenitais/urina , Doenças Urológicas/diagnóstico , Doenças Urológicas/urina , Doenças Urológicas/veterinária , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/urinaRESUMO
AKI, a serious, common and occasionally under-recognized condition, which is a significant contributor to the growing incidence of CKD and end-stage renal disease (ESRD). To date, the diagnosis of AKI is made by serial measurement of Cr and BUN which are late and imprecise markers of kidney injury. "Calprotectin" and "endocan" are two biomarkers that could reflect renal tubular injury and glomerular/endothelial-vascular damage, respectively. Measurement of urinary calprotectin could help the physicians to diagnose tubular degradation and differentiate prerenal AKI from intrinsic AKI. Serum level of endocan could signify endothelial damage. Herein it is hypothesized that calprotectin and endocan may help the clinicians to diagnose intrinsic AKI, earlier than rise of serum creatinine, differentiate AKI from acute presentation of CKD and also discriminate tubular injury from glomerular/vascular-endothelial injury, assess the prognosis and extent of renal damage and plan for appropriate therapy which may render these biomarkers as potentially applicable equivalents of Troponin in the field of nephrology.
Assuntos
Falência Renal Crônica/diagnóstico , Complexo Antígeno L1 Leucocitário/urina , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue , Algoritmos , Biomarcadores/sangue , Biomarcadores/urina , Diferenciação Celular , Creatinina/sangue , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Inflamação , Rim/metabolismo , Rim/fisiopatologia , Modelos Teóricos , Nefrologistas , Prognóstico , Risco , Troponina/metabolismoRESUMO
BACKGROUND: Urinary calprotectin has recently been identified as a promising biomarker for the differentiation between prerenal and intrinsic acute kidney injury (AKI) in the nontransplant population. The present study investigates whether calprotectin is able to differentiate between these 2 entities in transplant recipients as well. METHODS: Urinary calprotectin was assessed by enzyme-linked immunosorbent assay in 328 subjects including 125 cases of intrinsic acute allograft failure, 27 prerenal graft failures, 118 patients with stable graft function, and 58 healthy controls. Acute graft failure was defined as AKI stages 1 to 3 (Acute Kidney Injury Network criteria), exclusion criteria were obstructive uropathy, urothelial carcinoma, and metastatic cancer. The clinical differentiation of prerenal and intrinsic graft failure was performed either by biopsy or by a clinical algorithm including response to fluid repletion, history, physical examination, and urine dipstick examination. RESULTS: Reasons for intrinsic graft failure comprised rejection, acute tubular necrosis, urinary tract infection/pyelonephritis, viral nephritis, and interstitial nephritis. Calprotectin concentrations of patients with stable graft function (50.4 ng/mL) were comparable to healthy controls (54.8 ng/mL, P = 0.70) and prerenal graft failure (53.8 ng/mL, P = 0.62). Median urinary calprotectin was 36 times higher in intrinsic AKI (1955 ng/mL) than in prerenal AKI (P < 0.001). Receiver-operating characteristic curve analysis revealed a high accuracy of calprotectin (area under the curve, 0.94) in the differentiation of intrinsic versus prerenal AKI. A cutoff level of 134.5 ng/mL provided a sensitivity of 90.4% and a specificity of 74.1%. Immunohistochemical stainings for calprotectin in renal allograft biopsy specimens confirmed the serological results. CONCLUSIONS: Urinary calprotectin is a promising biomarker for the differentiation of prerenal and intrinsic acute renal allograft failure.
Assuntos
Injúria Renal Aguda/urina , Rejeição de Enxerto/urina , Transplante de Rim/efeitos adversos , Rim/metabolismo , Complexo Antígeno L1 Leucocitário/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Idoso , Aloenxertos , Área Sob a Curva , Biomarcadores/urina , Biópsia , Estudos de Casos e Controles , Estudos Transversais , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Alemanha , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Imuno-Histoquímica , Rim/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Falha de Tratamento , UrináliseRESUMO
PURPOSE: The diagnosis of pediatric appendicitis is still a challenge, resulting in perforation and negative appendectomies. The aim of this study was to evaluate novel biomarkers in urine and to use the most promising biomarkers in conjunction with the Pediatric Appendicitis Score (PAS), to see whether this could improve the accuracy of diagnosing appendicitis. METHODS: A prospective study of children with suspected appendicitis was conducted with assessment of PAS, routine blood tests, and measurements of four novel urinary biomarkers: leucine-rich α-2-glycoprotein (LRG), calprotectin, interleukin 6 (IL-6), and substance P. The biomarkers were blindly determined with commercial ELISAs. Urine creatinine was used to adjust for dehydration. The diagnosis of appendicitis was based on histopathological analysis. RESULTS: Forty-four children with suspected appendicitis were included, of which twenty-two (50 %) had confirmed appendicitis. LRG in urine was elevated in children with appendicitis compared to children without (p < 0.001), and was higher in children with gangrenous and perforated appendicitis compared to those with phlegmonous appendicitis (p = 0.003). No statistical significances between groups were found for calprotectin, IL-6 or substance P. LRG had a receiver operating characteristic area under the curve of 0.86 (95 % CI 0.79-0.99), and a better diagnostic performance than all routine blood tests. LRG in conjunction with PAS showed 95 % sensitivity, 90 % specificity, 91 % positive predictive value, and 95 % negative predictive value. CONCLUSION: LRG, adjusted for dehydration, is a promising novel urinary biomarker for appendicitis in children. LRG in combination with PAS has a high diagnostic performance.
Assuntos
Apendicite/diagnóstico , Adolescente , Biomarcadores/urina , Criança , Pré-Escolar , Feminino , Glicoproteínas/urina , Humanos , Interleucina-6/urina , Complexo Antígeno L1 Leucocitário/urina , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Substância P/urinaRESUMO
BACKGROUND: Urinary calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) have recently been identified as promising biomarkers for the differentiation of prerenal and intrinsic acute kidney injury (AKI) in adults. In the study reported here we examined the diagnostic accuracy of calprotectin, NGAL, and kidney injury molecule 1 (KIM-1) in pediatric patients. METHODS: Urinary calprotectin, NGAL, and KIM-1 concentrations were assessed in a study population of 139 pediatric subjects including 39 patients with intrinsic AKI, 14 with prerenal AKI, and 86 non-AKI subjects. RESULTS: Median urinary calprotectin and NGAL concentrations were higher in patients with intrinsic AKI than in those with prerenal AKI (calprotectin by 22-fold, NGAL by 9-fold). Receiver operating characteristic (ROC) curve analyses for the differentiation of intrinsic and prerenal AKI resulted in an area under the curve (AUC) of 0.90 [95 % confidence interval (CI) 0.81-0.98] for calprotectin and 0.73 (95 % CI 0.58-0.87) for NGAL. Median urinary KIM-1 concentrations were not significantly different between patients with prerenal AKI and those with intrinsic disease (P = 0.98; AUC 0.50, 95 % CI, 0.35-0.65). The AUC for the fractional excretion of sodium (FENa) and proteinuria was 0.78 (95 % CI 0.63-0.92) and 0.77 (CI 0.65-0.90), respectively. CONCLUSIONS: Urinary calprotectin outperforms NGAL, KIM-1, FENa, and proteinuria as a biomarker for the differentiation of prerenal and intrinsic AKI in pediatric patients with a high diagnostic accuracy.
Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Biomarcadores/urina , Estudos de Coortes , Estudos Transversais , Diagnóstico Diferencial , Feminino , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Lactente , Recém-Nascido , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Masculino , Proteinúria/etiologia , Proteinúria/urina , Reprodutibilidade dos Testes , Sódio/urinaRESUMO
BACKGROUND: Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. METHODS: The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5-20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase-associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. RESULTS: Urinary concentrations of calprotectin and neutrophil gelatinase-associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase-associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase-associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0.049). CONCLUSION: Calprotectin and neutrophil gelatinase-associated lipocalin can be used to monitor clinical and sub-clinical tubular damage after nephron sparing surgery for kidney tumours. Urinary calprotectin concentrations start rising within 2 hours after ischaemia/reperfusion-induced kidney injury.