Potential Urine and Serum Biomarkers in Patients with Bladder Pain Syndrome/Interstitial Cystitis.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common chronic disease, and its aetiology and pathogenesis remain unclear. This study aimed to identify potential urine and serum biomarkers in patients with IC/BPS to further understand the pathogenesis and diagnosis of the disease. METHODS: Patients with IC/BPS diagnosed and treated in the First Hospital of Hebei Medical University from 1 July 2021 to 30 July 2023 were selected. The urine and serum biomarkers of 50 patients with IC/BPS were investigated and compared with the urine and serum samples of 50 healthy controls. IBM SPSS Statistics 26.0 was used for statistical analysis of the recorded data by using chi-square test, T-test and logistic regression analysis. RESULTS: Overall, 50 patients with IC/BPS (mean age, 54.20 ± 8.15 years) were included in the study. Those with history of urinary diseases, anxiety or depression were susceptible to IC/BPS. Levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), nerve growth factor, and prostaglandin E2 (PGE2) in urine, as well as IL-8, TNF-α, and PGE2 in serum, were found to significantly increase in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). These differences were statistically significant (p < 0.05). Multifactor analysis showed that anxiety, depression, IL-6, IL-8, TNF-α and PEG2 are risk factors for patients with IC/BPS. CONCLUSIONS: Multiple biomarkers were identified in the urine and serum of patients with IC/BPS, suggesting a potential close relationship to the pathogenesis of IC/BPS.

Valor de los niveles urinarios de interleucina 6, factor de crecimiento epidérmico, proteína quimioatractante de monocitos de tipo 1 y factor de crecimiento transformante Beta1 para la predicción de la extensión de las lesiones de fibrosis en biopsias de enfermos con nefropatía IgA / Value of urinary levels of interleukin-6, epidermal growth factor, monocyte chemoattractant protein type1 and transforming growth factor Beta1 in predicting the extent of fibrosis lesions in kidney biopsies of patients with IgA nephropathy

Objetivo: Analizar las asociaciones entre el nivel urinario de IL-6, EGF, MCP-1 y TGFβ1 y las características clínicas, bioquímicas y anatomopatológicas en enfermos con nefropatía IgA primaria y determinar su capacidad para realizar una estimación de la extensión de las lesiones de esclerosis glomerular e intersticial. Pacientes y métodos: Se estudió a 58 enfermos con nefropatía IgA. Se determinaron los niveles urinarios de IL-6, EGF, MCP-1 y TGFβ1 en el momento del diagnóstico. Tras realizar un análisis de la extensión de las lesiones renales mediante morfometría cuantitativa y mediante los criterios de Oxford, se analizó la capacidad de dichas moléculas para estimar la extensión de las lesiones glomerulares e intersticiales de fibrosis. Resultados: La IL-6, MCP-1 y TGF-β1 se asociaron a glomeruloesclerosis focal y a la extensión de la fibrosis intersticial, pero no a la presencia de proliferación mesangial, intracapilar o extracapilar. EGF presentó una asociación negativa con la fibrosis intersticial. Al categorizar a los enfermos según la clasificación de Oxford, los enfermos con scores T1 y T2 presentaron niveles significativamente superiores de IL-6, MCP-1 y TGFβ1, y niveles de EGF significativamente inferiores que los enfermos con T0. Tanto mediante regresión múltiple como mediante regresión logística, los niveles de MCP-1, IL-6 y EGF fueron predictores independientes de la superficie de fibrosis, tras ajustar por edad y FGe. Conclusión: La determinación de la concentración urinaria de IL-6, EGF y MCP-1 proporciona una información adicional que mejora de forma significativa la estimación de la superficie de fibrosis intersticial (AU)

Objective: To analyse the associations between urinary levels of IL-6 EGF, MCP-1 and TGFβ1 and clinical, biochemical and histopathological characteristics in patients with primary IgA nephropathy and their ability to predict the extent of lesions of glomerular and/or interstitial sclerosis. Patients and methods: A total of 58 patients with IgA nephropathy were studied. We determined the urine levels of IL-6, EGF, MCP-1, and TGFβ1 at the time of diagnosis. The extent of glomerular and interstitial fibrosis was analyzed by quantitative morphometry and kidney biopsies were classified according to the Oxford criteria. We analysed the ability of these molecules to predict the extent of glomerular and interstitial fibrosis lesions. Results: IL-6, TGFβ1 and MCP-1 were associated with focal glomerulosclerosis and interstitial fibrosis extension but not with the presence of mesangial, extracapillary or endocapillary proliferation. EGF showed a negative association with interstitial fibrosis. By categorising patients according to the Oxford classification, patients with T1 and T2 scores had significantly higher levels of IL-6, MCP-1, TGF-β1 and significantly lower levels of EGF than patients with T0 scores. By multiple regression and logistic regression analyses, the levels of MCP-1, IL-6 and EGF were independent predictors of the fibrosis surface, after adjusting for age and eGFR. Conclusion: The urinary concentration of IL-6, EGF and MCP-1 provides additional information that significantly improves the estimation of the surface of interstitial fibrosis in patients with IgA nephropathy (AU)

The combination of urinary IL - 6 and renal biometry as useful diagnostic tools to differentiate acute pyelonephritis from lower urinary tract infection

ABSTRACT Objective: To evaluate the role of renal ultrasound (RUS) and urinary IL-6 in the differentiation between acute pyelonephritis (APN) and lower urinary tract infection (LUTI). Patients and methods: This prospective study was carried out at the Pediatric and urology outpatient and inpatient departments of Cairo University Children's Hospital as well as October 6 University Hospital and it included 155 children between one month and fourteen years old with positive culture UTI. Patients were categorized into APN and LUTI based on their clinical features and laboratory parameters. Thirty healthy children, age and sex matched constituted the control group. Children with positive urine cultures were treated with appropriate antibiotics. Before treatment, urinary IL-6 was measured by enzyme immunoassay technique (ELISA), and renal ultrasound (RUS) was done. CRP (C-reactive protein), IL-6 and RUS were repeated on the 14th day of antibiotic treatment to evaluate the changes in their levels in response to treatment. Results: UIL-6 levels were more significantly higher in patients with APN than in patients with LUTI (24.3±19.3pg/mL for APN vs. 7.3±2.7pg/mL in LUTI (95% CI: 2.6-27.4; p<0.01). Similarly, serum CRP was more significantly higher in patients with APN than in children with LUTI (19.7±9.1μg/mL vs. 5.5±2.3μg/mL (p<0.01). IL-6 levels >20pg/mL and serum CRP >20μg/mL were highly reliable markers of APN. Mean renal volume and mean volume difference between the two kidneys in the APN group were more than that of the LUTI and control groups (P<0.001). Renal volume between 120-130% of normal was the best for differentiating APN from LUTI. Conclusions: RUS and urinary IL-6 levels have a highly dependable role in the differentiation between APN and LUTI especially in places where other investigations are not available and/ or affordable.

La excreción urinaria de interleucina 6 refleja la presión arterial sistólica media durante 24 h en pacientes con diabetes mellitus tipo 2 / Urinary interleukin-6 excretion reflects mean 24-hour systolic blood pressure in type 2 diabetes

Objetivo: Debido a la necesidad de investigar nuevos marcadores de riesgo de nefropatía diabética, en este estudio se decidió evaluar la excreción en orina de 24 h de interleucina 6 (uIL-6) en pacientes con diabetes mellitus tipo 2 (DM2) y su relación con el daño tisular inducido por el aumento de presión arterial. Métodos: La uIL-6, la excreción de albúmina y la presión arterial medida durante 24 h fueron evaluadas en 49 pacientes con DM2 y función renal normal. Comparamos a los sujetos con presión arterial sistólica (PAS)media de 24 h correcta, definida por PAS 130 mmHg, con los pacientes con PAS no controlada (PAS > 130 mmHg). Se calculó mediante estudio de regresión múltiple qué factores contribuían de manera significativa ala uIL-6.Resultados: La tasa de excreción de albúmina (AER) y la uIL-6 se asociaron de manera significativa (r = 0,63; p < 0,0001). Los pacientes con una PAS media de 24 h > 130 mmHg (n = 27) tenían una media de uIL-6superior a la de los pacientes con PAS media de 24 h 130 mmHg (n =22) (p = 0,009). La fuerza de la asociación de la uIL-6 con la presión diastólica diurna y con la media (PAD) fue superior a la que presentaba con la AER. La PAS media (p < 0,0001) contribuyó al 25% de la variancia de la AER tras ajustar por el índice de masa corporal, el sexo, la edad, la PAS media, la PAD media, la HbA1c y el tabaquismo. La PAS media de 24h (p = 0,005) y el tabaquismo (p = 0,03) contribuyeron al 15 y el 9% de la variancia de la uIL-6, respectivamente. Conclusiones: El aumento de uIL-6, quizá reflejando el daño y el remodelado tisular, podría ser un marcador de la elevación de la PAS en sujetos con DM2 (AU)

Aims: Research into new risk markers for diabetic kidney disease is required. We aimed to study 24-hour urinary interleukin-6 excretion (uIL-6) in type 2 diabetic patients in relation to organ damage induced by increased blood pressure. Methods: 24-hour uIL-6 and albumin excretion and 24-hour blood pressure recording were evaluated in 49 patients with type 2 diabetes and normal renal function. Patients with optimized mean 24-hour systolic blood pressure (SBP), defined as SBP 130 mmHg, and those with uncontrolled SBP (SBP > 130 mmHg) were compared. Multiple linear regression analysis was performed to study significant contributors to variance in the24-hour uIL-6 excretion rate. Results: Albumin excretion rate (AER) anduIL-6 were significantly correlated (r = 0.63;p < 0.0001). Patients with mean 24-hourSBP above 130 mmHg (n = 27) had significantly higher mean uIL-6 excretion than those with a mean 24-hour SBP equal to or below 130 mmHg (n = 22) (p = 0.009).The strength of the association of uIL-6with diurnal and mean diastolic blood pressure (DBP) was significantly greater than that with AER. Mean SBP (p < 0.0001)contributed to 25% of AER variance after body mass index, age, sex, mean SBP, mean DBP, HbA1c and smoking status were accounted for. Mean 24-hour SBP (p =0.005) and smoking (p = 0.03) contributed to 15% and 9%, respectively, of uIL-6variance.Conclusions: Increased uIL-6, perhaps by reflecting significant tissue damage and remodeling, could be a marker for increased mean SBP in type 2 diabetes (AU)

Niveles normales de interleucinas 6 y 8 en suero y orina de niños sanos asintomáticos / Normal levels of interleukin 6 and 8 in serum and urine in asymptomatic healthy children

Introducción: La infección urinaria es una patología muy frecuente en niños, y su diagnóstico y tratamiento precoces dependen de la sospecha clínica y la aplicación de parámetros analíticos. Algunas citocinas han despertado un gran interés en este terreno. Objetivo: Conocer los niveles de las interleucinas (IL) 6 y 8 en sangre y orina en niños sanos, y establecer el rango de normalidad de nuestro laboratorio. Material y métodos: Estudio observacional transversal, descriptivo y analítico, en niños sanos sin infección urinaria. Se analizan las variables sexo, edad, niño mayor o menor de 1 año, y nivel de IL 6 y 8 en sangre y orina (mediante ELISA). Se calcula la estadística básica de las variables cuantitativas. La comparación entre muestras independientes se llevó a cabo con el test U de Mann-Whitney, y la correlación entre las mismas con el test de Pearson. Se consideró un error alfa del 5% (SPSS 9.0). El límite superior de normalidad de las IL se estableció en la media más 2 desviaciones estándar (95% de la población). Resultados: Estudiamos 52 niños (40 varones, 76,92%) con una edad media de 51,31 + 47,98 meses (1-149 meses), sin diferencias en su distribución por sexo y grupos de edad inferior o superior a un año. Los niveles medios de IL (e intervalo de confianza IC: 95%), y el límite superior de la normalidad, fueron respectivamente, para IL-6 suero: 0,49 (IC: 0-1,05), y 3,95 pg/mL; IL-6 orina: 0,17 (IC: 0-0,51), 1,83 pg/mL; IL-8 suero: 136,66 (IC: 0,74-272,58), 974,58 pg/mL; IL-8 orina: 47,23 (14,71-79,75), 242,39 pg/mL. No hubo diferencias entre ambos sexos ni grupos de edad, salvo niveles medios de IL-8 urinaria más elevados en menores de 1 año, con una correlación negativa entre dicha variable y edad (p<0,05). Asimismo, existe una correlación positiva y muy significativa de IL-6 y 8 en orina (p<0,001) y de IL-8 entre suero y orina (p<0,01). Conclusiones: En niños sanos, no se observaron diferencias según sexos en los niveles de IL-6 y 8, pero la producción de IL-8 en orina es mayor en niños más pequeños. Adiferencia de la IL-6, se detectan niveles significativos de IL-8 en suero y orina de niños sanos, cuestionando su validez en el diagnóstico de infección. Finalmente, existe en condiciones normales una excelente correlación entre IL-6 y 8 en orina

Objective: To determine the interleukins (IL) 6 and 8 levels in serum and urine in the healthy pediatric population, and to establish our laboratory reference values, whit the purpose of subsequently to apply this determination to diagnosis of urinary tract infection. Material and methods: Observational, transversal, descriptive and analytical study, in healthy children without urinary tract infection. We analyse the following variables: sex, age, to be oldest or youngest than 1 year, and IL-6 and IL-8 levels in serum and urine (ELISA). We evaluate the basic statistics for quantitative variables. It compare the independent samples by means of Mann-Whitney U test, and its correlation with the Pearson test. We consider an alpha-error of 5% (SPSS 9.0). The upper limit of normality was established in two standard deviation more than the mean (95% of population). Results:We have studied 52 children (40 males, 76.92%). The mean of age was 51.31 + 47.98 months (1-149 months), and it didn’t have differences according to sex, or to be oldest and youngest than 1 year of age. The mean values of IL (and confidence interval IC: 95%), and the upper limit of normality, respectively were for serum IL-6: 0.49 (IC: 0-1,05), and 3.95 pg/mL; urine IL-6: 0,17 (IC: 0-0,51), 1,83 pg/mL; serum IL-8: 136,66 (IC: 0,74-272,58), 974,58 pg/mL; and urine IL-8: 47,23 (14,71-79,75), 242,39 pg/mL. It didn’t have differences neither between both sex nor age groups, except urine IL-8 mean levels greater in youngest of 1 year of age, with a negative correlation between this variable and age (p<0,05). Moreover, it exist a positive and very significant correlation of urine IL-6 and 8 (p<0,001), and serum and urine IL-8 (p<0,01). Conclusions: In healthy pediatric population, it didn’t observe differences according to sex in IL-6 and IL-8 levels, but the urine IL-8 production is greater in more little children. It observe significant serum and urine IL-8 levels in healthy children, making questionable its validity in urinary tract infection diagnosis. Finally, it exist an excellent correlation between urinary IL-6 and IL-8 in normal conditions