Urinary Interleukin-6 Research Articles

An NLRP3-specific inflammasome inhibitor attenuates crystal-induced kidney fibrosis in mice

Intrarenal crystal formation activates the Nlrp3 inflammasome in myeloid cells and triggers a profound inflammatory response. Here, we studied whether a specific inhibitor of the Nlrp3 inflammasome, CP-456,773, can prevent kidney fibrosis in a murine model of crystal nephropathy induced by diets rich in oxalate or adenine. Inflammasome activation in renal dendritic cells and the resulting interleukin (IL)-1β and IL-18 production were markedly reduced by CP-456,773 treatment both exvivo and invivo. We directly visualized intrarenal inflammasome activation and its inhibition by CP-456,773 invivo by adoptive transfer of bone marrow cells transduced with interleukin-1β-Gaussia luciferase, a proteolytic luciferase-based reporter for inflammasome activation, into irradiated mice. CP-456,773 treatment strongly attenuated kidney fibrosis when given early in the genesis of crystal nephropathy, but was unable to reverse established crystal-induced fibrosis. The urinary IL-18 concentration appeared to be a useful noninvasive biomarker for renal inflammasome activation. Finally, NLRP3 inhibition did not compromise adaptive immune responses as previously reported for the global inhibition of IL-1 signaling. Thus, early NLRP3 inhibition by CP-456,773 may be an effective treatment for crystal nephropathy. Use of iGLuc transfected cells introduces a novel imaging technique for inflammasome activation in mice.

NON-SPECIFIC PROTECTION FACTORS AND INFLAMMATORY MEDIATORS IN URINE OF CHILDREN WITH GLOMERULONEPHRITIS IN THE PRESENCE OF HERPESVIRAL INFECTION NOTICE 2. DETERMINATION OF THE LEVEL OF IL-8 AND SLPI

The aim of this work was the study of indicators characterizing the local immunity in patients with various forms of glomerulonephritis by presence of herpesviral infection.
 Materials and methods. A quantitative estimation of the content of IL-8 and SLPI in urine of 47 patients with glomerulonephritis and 10 apparently healthy individuals was conducted.
 Results. A insignificant increase of IL-8 level in urine was showed in patients with glomerulonephritis. The level of urinary SLPI was reliably higher than the control value, at the same time the majority ofpatients (74,0 %) did not exceed the upper limit of the physiological norm. The essential increase ofIL-8 level in urine was observed in 13 sick children, and of SLPI – in 12 patients. The increase of IL-8 and SLPI levels was observed more frequently in patients with hematuric form of glomerulonephritis, with nephrotic steroidoresistant variant of nephrotic form, in the absence of remission, and in the case of IL-8 - with severe course of the disease. More such changes were found in children with active (reactivated) herpesviral infections.
 Conclusion. There has been confirmed the importance of the study of immunologic parameters in the urine of patients with glomerulonephritis to characterize immunopathological process in the kidney and prognosis of the disease.

Cholinergic Stimulation of Immune Cells with Nicotine Induces Renal Inflammation and Pre‐mature Development of Hypertension in Young SHR

We have shown that nicotinic cholinergic stimulation of immune cells in vitro and in vivo exaggerates pro‐inflammatory innate immune responses and increases proliferation of a CD161a+/CD68+ macrophage population in isolated bone marrow cells and splenocytes in young pre‐hypertensive Spontaneously Hypertensive Rat (SHR). In vivo administration of nicotine also led to renal infiltration of macrophages within 24 hours, without any increase in arterial pressure and independent of renal sympathetic innervation. We also found that 2 week subcutaneous infusion of nicotine not only leads to continued CD161a+/CD68+ macrophage infiltration, but also the development of premature hypertension in young SHR. We hypothesized 1) that the nicotine induced CD161a+/CD68+ macrophage infiltration is caused by increased renal expression of Vascular Cell Adhesion Molecule‐1 (VCAM‐1) and 2) this renal macrophage infiltration results in renal damage/toxicity. Nicotine (15mg/kg/day) was infused subcutaneously for 2 weeks. Systolic blood pressures (SBP) were measured twice weekly by tail cuff and urine, serum, and kidney tissue were collected at the end of nicotine infusion. Tissues and fluid were analyzed by luminex assay. Renal lysates were also analyzed by Western blot for the presence of VCAM‐1. Nicotine infusion led to the pre‐mature development of hypertension in SHR (153.2 ± 3 mmHg vs 138.6 ± 3 mmHg in saline infused SHR, respectively, n=10, p <0.001). There was no significant increase in SBP in control Wistar Kyoto (WKY) rats infused with nicotine, compared to saline. There was a greater infiltration of the kidney with CD161a+/CD68+ macrophages with nicotine infusion (16±2 cells per 400× field), compared to saline infusion (9±1 cells per 400× field) (n=6, p<0.001). In contrast, there was no significant renal macrophage infiltration in nicotine infused WKY, compared to saline (1±1 cells vs 1±1 cells per 400× field) (n=6, p>0.05). CD161a+/CD68+ renal macrophage infiltration in the young SHR was not associated with an increase in VCAM‐1 expression. However, nicotine induced renal CD161a+/CD68+ macrophage infiltration was associated with renal damage/toxicity, as measured by an increase in urinary Interleukin −18 (IL‐18) (283±42 pg/mL vs 101±10 pg/mL, n=4, p<0.001) and Monocyte Chemoattracatant Protein‐1 (MCP‐1) (241±22 pg/mL vs 145±23 pg/mL, n=4, p<0.05). We conclude that cholinergic stimulation with nicotine leads to renal infiltration with a CD161a+/CD68+ macrophage population that is not explained by renal expression of VCAM‐1, but is associated with renal damage, as well as the pre‐mature development of hypertension. Thus, renal damage from infiltration of this CD161a+/CD68+ macrophage population is one of the mechanisms involved in nicotine induced hypertension in the young pre‐hypertensive SHR.Support or Funding InformationNIH K08 HL11958NIH PPG HL014388

A Decline in Intraoperative Renal Near-Infrared Spectroscopy Is Associated With Adverse Outcomes in Children Following Cardiac Surgery.

Renal near-infrared spectroscopy is known to be predictive of acute kidney injury in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a greater than or equal to 20% reduction in renal near-infrared spectroscopy for 20 consecutive minutes intraoperatively or within the first 24 postoperative hours is associated with 1) acute kidney injury, 2) increased acute kidney injury biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery. Prospective single center observational study. Pediatric cardiac ICU. Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011-July 2012). None. A reduction in near-infrared spectroscopy was not associated with acute kidney injury. Nine of 12 patients (75%) with a reduction in renal near-infrared spectroscopy did not develop acute kidney injury. The remaining three patients had mild acute kidney injury (pediatric Risk, Injury, Failure, Loss, End stage-Risk). A reduction in renal near-infrared spectroscopy was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p < 0.01). A decline in renal near-infrared spectroscopy in combination with an increase in serum interleukin-6 and serum interleukin-8 was associated with a longer intensive care length of stay, and the addition of urine interleukin-18 to this was associated with a longer hospital length of stay. In this cohort, the rate of acute kidney injury was much lower than anticipated thereby limiting the evaluation of a reduction in renal near-infrared spectroscopy as a predictor of acute kidney injury. A greater than or equal to 20% reduction in renal near-infrared spectroscopy was significantly associated with adverse outcomes in children following cardiac surgery. The addition of specific biomarkers to the model was predictive of worse outcomes in these patients. Thus, real-time evaluation of renal near-infrared spectroscopy using the specific levels of change of a 20% reduction for 20 minutes may be useful in predicting prolonged mechanical ventilation and other adverse outcomes in children undergoing cardiac surgery.

Effects of Minocycline on Urine Albumin, Interleukin-6, and Osteoprotegerin in Patients with Diabetic Nephropathy: A Randomized Controlled Pilot Trial.

BackgroundWe tested minocycline as an anti-proteinuric adjunct to renin-angiotensin-aldosterone system inhibitors (RAASi) in diabetic nephropathy (DN) and measured urinary biomarkers to evaluate minocycline’s biological effects.MethodsDesign: Prospective, single center, randomized, placebo-controlled, intention-to-treat pilot trial. Inclusion. Type 2 diabetes/DN; Baseline creatinine clearance > 30 mL/min; proteinuria ≥ 1.0 g/day; Age ≥30 years; BP <150/95 mm Hg; intolerant of/at maximum RAASi dose. Protocol. 3-wk screening; Baseline randomization; Urine and blood measures at months 1, 2, 4, and Month 6 study completion. Urine interleukin-6 (IL-6) and osteoprotegerin were measured in a subset. Primary outcome. Natural log of urine protein/creatinine (ln U P:Cr) ratio at Month 6 vs Baseline.Results30 patients completed the study. The 15% decline in U P: Cr in minocycline patients (6 month P:Cr ÷ Baseline P:Cr, 0.85 vs. 0.92) was not significant (p = 0.27). Creatinine clearance did not differ in the 2 groups. Urine IL-6:Cr (p = 0.03) and osteoprotegerin/Cr (p = 0.046) decrements were significant. Minocycline modified the relationship between urine IL-6 and proteinuria, suggesting a protective biological effect.ConclusionsAlthough the decline in U P:Cr in minocycline patients was not statistically significant, the significant differences in urine IL-6 and osteoprotegerin suggest that minocycline may confer cytoprotection in patients with DN, providing a rationale for further study.Trial RegistrationClinicaltrials.gov NCT01779089

Distinguishing asymptomatic bacteriuria from urinary tract infection in the elderly – the use of urine levels of heparin-binding protein and interleukin-6

Asymptomatic bacteriuria (ABU) is highly prevalent among elderly patients. It can be difficult to distinguish ABU from symptomatic urinary tract infection (UTI) in this population, which leads to unnecessary antibiotic treatment. Urinary heparin-binding protein (U-HBP) and urinary interleukin-6 (U-IL-6) have previously been studied as diagnostic markers for UTI. In this study, biomarkers were measured in the urine of 134 nursing home residents. The prevalence of ABU in this population, excluding patients with urinary catheter, was 32.8%. Levels of U-HBP and IL-6 were significantly lower among residents with ABU when compared to 49 patients with verified UTI. When previously defined cut-off limits were used, U-HBP had a high negative predictive value for UTI (93%), however, the specificity for differentiating patients with UTI and ABU was low. Discriminatory values were better for U-IL-6 with a sensitivity of 80% and specificity of 82% for the differentiation between the subgroup of pyelonephritis and ABU.

Hepcidin as a Biomarker of Impaired Renal Function in Rat Models for Chronic Allograft Nephropathy.

BackgroundTo explore the use of hepcidin as a marker of impaired renal function in a rat model for chronic allograft nephropathy (CAN).Material/MethodsTwenty-four models were developed and 20 models were included in this study, using Fisher (F344) rats (donors) and Lewis rats (recipients). Renal function tests were performed preoperatively and postoperatively. Hepcidin, interleukin-6 (IL-6), and erythropoietin levels in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA). To observe pathological changes in the kidneys, 10 rats each were sacrificed at 2 months and 4 months after surgery.ResultsAfter transplantation, the serum hepcidin and IL-6 levels increased, while urine hepcidin levels decreased. Erythropoietin levels showed a similar trend; all P<0.05. Serum creatinine (SCr) and blood urea nitrogen significantly increased post-operatively, with SCr positively correlating with serum hepcidin. Serum hepcidin positively correlated with IL-6 and negatively correlated with EPO. Histopathological results were consistent with CAN, after transplantation.ConclusionsHepcidin may be considered as a potential marker of impaired renal function.

Serum and Urinary Interleukin-6 in Assessment of Renal Activity in Egyptian Patients with Systemic Lupus Erythematosus.

AIM OF THE WORKThis study investigates whether serum and urinary interleukin-6 (IL-6) represent an early marker of kidney involvement and assesses the difference between them and renal biopsy in lupus nephritis (LN).PATIENTS AND METHODSA total of 60 systemic lupus erythematosus (SLE) patients were compared to 20 healthy controls. Urinary and serum IL-6 were measured in both patients and controls. In addition, renal biopsy was done prior or shortly after urine and blood sampling; the results were classified according to the International Society of Nephrology/Renal Pathology Society classification of LN by recording the activity score and chronicity score for each sample.RESULTSThere was a significant higher level of urinary IL-6 in the SLE patients with biopsy-proven LN than in those without LN and those of the control group. However, no significant difference was reported between the three groups as regards serum IL-6. A strong positive correlation was found between urinary IL-6 and renal disease activity based on the renal SLE disease activity index (SLEDAI) score with no significant correlation regarding the extra renal SLEDAI. Urinary IL-6 was positively correlated with renal biopsy results and with its activity scores but weakly correlated with the chronicity scores.CONCLUSIONUrinary IL-6 may provide a simple noninvasive potential marker of disease activity of renal involvement in adult patients with SLE.

Inflammatory Cytokines as Risk Factors for Mortality After Acute Cardiac Events.

Introduction:Inflammatory markers have been identified as potential indicators of future adverse outcome after acute cardiac events.Aim:This study aimed to analyze baseline inflammatory cytokines levels in patients with acute heart failure (AHF) and/or acute coronary syndrome (ACS) according to survival. The main objective was to identify risk factors for mortality after an episode of AHF and/or ACS.Methods:In this prospective longitudinal study 75 patients with the diagnosis of AHF and/or ACS were enrolled. Baseline laboratory and clinical data were retrieved. Serum and urine interleukin-6 (IL-6) and interleukin-18 (IL-18) levels, plasma B-type natriuretic peptide (BNP) and serum cystatin C values were determined. The primary outcome was in-hospital mortality while secondary outcome was six-month mortality.Results:Median serum and urine IL-6 levels, serum and urine IL-18 levels, as well as median concentrations of plasma BNP and serum cystatin C, were significantly increased in deceased in comparison to surviving AHF and/or ACS patients. Univariate Cox regression analysis identified serum IL-6, serum IL-18, urine IL-6, urine IL-18 as well as serum cystatin C and Acute Physiology and Chronic Health Evaluation (APACHE) II score as risk factors for mortality after an episode of AHF and/or ACS. Multivariate Cox regression analysis revealed that only serum IL-6 is the independent risk factor for mortality after acute cardiac events (HR 61.7, 95% CI 2.1-1851.0; p=0.018).Conclusion:Present study demonstrated the strong prognostic value of serum IL-6 in predicting mortality of patients with AHF and/or ACS.

Urine interleukin-6, interleukin-8 and transforming growth factor β1 in infants with urinary tract infection and asymptomatic bacteriuria.

IntroductionUrinary tract infection (UTI) occurs in 1.1% of girls and 1.4% of boys during the first year of life. Asymptomatic bacteriuria (ABU) is usually detected incidentally in 0.9% of girls and 2.5% of boys at this age. The aim of the study was to assess the usefulness of measurement of pro-inflammatory urine interleukin (IL)-6 and IL-8 concentrations and anti-inflammatory transforming growth factor β1 (TGF-β1) level in infants with febrile UTI, non-febrile UTI and ABU.Material and methodsA total of 35 children, mean age 6.14 ±3.47 months, were divided into three groups: group I – febrile UTI (n = 13), group II – non-febrile UTI (n = 13) and group III – ABU (n = 9). At the time of enrollment urine IL-6, IL-8, TGF-β1 and serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) were measured. Renal ultrasound was performed in all children, 99mTc-dimercaptosuccinic acid scintigraphy (DMSA) and voiding cystourethrography in children with UTI.ResultsUrine concentrations of IL-6 and IL-8 were significantly higher in febrile UTI compared to those with non-febrile UTI and ABU (p < 0.5, p < 0.01) and positively correlated with CRP, ESR and WBC (p < 0.01). Urine levels of TGF-β1 were significantly higher in children with febrile UTI compared to those with ABU (p < 0.05) and positively correlated with WBC (p < 0.01). Inflammatory changes in the DMSA scan were detected in 66.6% of children with UTI. No significant difference in frequency of an abnormal DMSA scan compared to a normal scan was found in groups with febrile and non-febrile UTI. No relations between urine cytokines, systemic inflammatory markers and changes in DMSA scan were observed. The cutoff value for detection of inflammatory changes in the DMSA scan for IL-8 was 120 pg/mg creatinine (Cr) and 40 pg/mg Cr for TGF-β1. Based on this value, the sensitivity for IL-8 was 58.3%, specificity 100% and for TGF-β1 66.7% and 83.7%, respectively.ConclusionsWe found significant differences in children with febrile UTI and ABU regarding urine IL-6, IL-8 and TGF-β1 levels. Urine cytokines and systemic inflammatory markers do not differentiate between upper and lower UTI in infants.

Early Diagnosis of Renal Tubular Dysfunction in HIV-Infected Patients; a Case of Interleukin (IL)-18 and other Common Indicators of Renal Toxicity

Background: At present renal dysfunction in clinical practice is measured using serum creatinine values to calculate eGFR (estimated glomerular filtration rate) but creatinine is a late marker of renal dysfunction and is only raised when up to 30-50% of renal function is lost. Methods: Serial urine samples were analyzed by enzyme-linked immunosorbent assay for IL-18. Urinary IL-18 together with other common indicators of renal damage was assessed in 325 HIV patients; of which 66 developed renal dysfunction after 12 weeks of follow-up. Result: Marked increase in IL-18 (p=0.000) was observed at an earlier stage in the renal disease group compared to a delayed elevation of eGFR, serum creatinine, fractional excretion of phosphate and fractional excretion of uric acid which was evident only after 4 weeks. Conclusion: This finding seems to suggest that IL-18 can be used as an early marker of subclinical renal tubular dysfunction in HIV-infected patients, owing to the fact that IL-18 increases in urine only under conditions of marked tubular damage, apoptotic tubular cell shedding, and cell necrosis, associated with deterioration of renal function.

Effects of Yishen Pinggan Recipe on Renal Protection and NF-κB Signaling Pathway in Spontaneously Hypertensive Rats.

Inflammation is an important etiological factor of hypertensive renal damage. The effects of Yishen Pinggan Recipe (YPR) on urine microalbumin, histology, and NF-κB/P65, IκB-α, IL-1β, IL-6, and TNF-α in renal tissues were evaluated in SHR to explore the mechanism of its renal protection in hypertensive renal damage. The SBP of 12-week-old SHR was 192.41 ± 3.93 mmHg and DBP was 142.38 ± 5.79 mmHg. Without treatment, the 24-week-old SHRs' SBP was 196.96 ± 3.77 mmHg and DBP was 146.08 ± 4.82 mmHg. After the 12-week-old SHR were administered YPR for 12 weeks, the rats' SBP was 161.45 ± 7.57 mmHg and DBP was 117.21 ± 5.17 mmHg; YPR could lower blood pressure in SHR. And renal function damage was observed in 24-week-old SHR without treatment, manifested as urine protein and morphological changes which could be inhibited by YPR. In addition, YPR could reduce the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in kidneys. It could also inhibit the nuclear translocation of NF-κB p65 and degradation of IκB-α in renal cells, indicating that the NF-κB signaling pathway was inhibited by YPR. Finally, the study suggests that YPR could significantly improve the renal function in SHR. The mechanism could be attributed to its inhibition of renal NF-κB signaling pathway and inflammation.

Assessment of Urinary Interleukin-18 and Serum Amyloid A Efficacies against C-Reactive Protein in Diagnosis and Follow-up of Neonatal Sepsis

Objective: infection is a leading cause of morbidity and mortality in neonates. The aim of this study was to evaluate the diagnostic and prognostic performances of urinary interleukin-18 (uIL-18) and serum amyloid A (SAA) in neonatal sepsis parallel to C- reactive protein (CRP). Subjects and methods: A total of 275 neonates were included in this case-control study. This study was conducted in neonatal intensive care unit at both Minia University Hospital for obstetric and pediatrics as well as Qena University hospital (Egypt). Among those 275 neonates, 150 non septic neonates - who had neither clinical signs nor laboratory findings suggestive of sepsis - were involved as a non-septic control group (Group II) and 125 septic neonates were classified as a septic group (group I). Blood and urine samples were obtained before initiation of antibiotic therapy. Full sepsis screen was performed at the time of sepsis onset plus measurement of SAA and uIL-18 by Enzyme Immune Assay (EIA). A second blood and urine samples were collected 72 hours later. The effectiveness of these 3 biomarkers as diagnostic ones was determined by using receiver operating characteristic (ROC) curve analysis. We also calculated the sensitivity, specificity, and positive, and negative predictive values. Results: The levels of uIL-18 and SAA were significantly elevated in septic neonates than in control group. The two markers showed significant decrease in their levels after 72 hours which matched with clinical improvement but not CRP. Moreover, very high levels of these markers were observed in neonates who died later on. The area under ROC curve (AUC) was used to evaluate the diagnostic efficacies of these markers. The superiority of SAA over both uIL-18 and CRP was obvious in the diagnosis of neonatal sepsis [AUC: 0.995] versus [AUC: 0.934 (uIL-18) and 0.871 (CRP)]. However in discriminating late onset sepsis (LOS), both uIL-18 and SAA have equal diagnostic capacities [AUC: 44 0.991] which are better than that of CRP [AUC: 0.866]. As to EOS, SAA has the most efficient performance as well but CRP is advanced than uIL-18. The specificities and sensitivities of either SAA or uIL-18 were higher than that of CRP in differentiating neonatal sepsis mainly LOS from controls. Conclusion: Both uIL-18 and SAA have enhanced performance over CRP for distinguishing neonatal sepsis mostly for LOS. Thus, they could be promising biomarkers for the screening and follow up of neonatal sepsis. This warrants further assessment of their prognostic values.

Dexmedetomidine for heart rate control and renal protection in patients undergoing mitral valve replacement for tight mitral stenosis

Background Dexmedetomidine (DXM) is an α2 adrenoceptor agonist that reduces the sympathetic outflow from the central nervous system resulting in bradycardia and hypotension. We used this drug in this randomized controlled double-blind study to test its efficacy in controlling the heart rate and its safety regarding renal function in patients undergoing mitral valve replacement surgery. Patients and methods A total of 70 patients scheduled for mitral valve replacement were randomly allocated into two groups: in group D, 35 patients received DXM 1 μg/kg bolus dose over 10 min followed by an infusion of 0.5 μg/kg/h. In group C, 35 patients received saline bolus and infusion by the same method instead of DXM. The heart rate was measured at induction of anesthesia, after the end of bolus infusion, at skin incision, and every 10 min till the start of the cardiopulmonary bypass. We also measured the urine interleukin-18 level during the first 12 h of surgery and serum creatinine and blood urea for 3 days postoperatively. Results The mean heart rate was significantly lower after bolus infusion, at skin incision, at 10 and 30 min, and just before bypass in the DXM group. Also, the urine output was higher in the DXM group during surgery and on the first postoperative day of surgery. No significant difference was found regarding other parameters of renal functions. Conclusion DXM can be used effectively in reducing the heart rate in patients undergoing mitral valve replacement surgery and was associated with an increase in the urinary output, and it did not alter the renal function in this cohort of patients.

Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents.

OBJECTIVEThe aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function.METHODSWe measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration.RESULTSBaseline serum creatinine was 57.8 ± 34.5 µmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels.CONCLUSIONSUrinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function.

Evaluating engrailed-2 and cytokines in urine with serum PSA as potential biomarkers in patients with prostatism at Moi Teaching and Referral Hospital, Eldoret, Kenya

Background: Prostatism is a clinical syndrome, occurring mostly in older men, usually caused by enlargement of the prostate gland and manifested by irritative and obstructive symptoms. Prostate cancer (CaP) is the most common non-cutaneous and the second leading cause of cancer related death in men. It is a disease in which cells in the prostate gland become abnormal and start to grow uncontrollably, forming tumours. The prostate specific antigen (PSA) test has been shown to be of low specificity and low sensitive and unable to differentiate the various forms of prostatism. Engrailed 2 and pro-inflammatory cytokines may be able to distinguish and stage protatism.Objective: To evaluate EN-2 and Cytokines in urine with serum PSA as potential biomarkers in patients with prostatism.Design: Cross sectional studySetting: Moi Teaching and Referral Hospital, Eldoret, Kenya.Subjects: Thirty nine (39) respondents were recruited in to the study. Thirteen (13) cases of prostate cancer and twenty six (26) controls were matched by age.Results: The mean age of cases was 73.1years and controls 71.1 years. Over 92.3% of the cases and 73.1% of controls had PSA values >4.0ng/ml. Both groups had elevated levels of urinary EN-2, which were statistically not significant. IL-6 and TNF-α expressions were higher in cases compared to controls with p-values of 0.0001 and 0.04 respectively. There was a good correlation between urinary IL-6 levels and urinary TNF-α levels (r=0.49)Conclusion: EN-2 expression in urine was not a predictive marker, however, IL-6 and TNF-α levels were elevated in urine of CaP patients. The potential for using these cytokines as urinary biomarkers to distinguish prostatism should be further explored.

Pro-inflammatory cytokines in determining of the activi phase severity of chronic pyelonephritis

Diagnosis of exacerbation of active phase of chronic pyelonephritis in accordance with the concept of the role of the immune system in forming and further aggravation of the inflammatory process is an important task. The aim of this study was to determine the severity of exacerbation of chronic pyelonephritis by examining changes in the level of proinflammatory and anti-inflammatory cytokines. Presents results of a study of the content of proinflammatory and anti-inflammatory cytokines in the urine collected from the ureter, bladder, and in blood plasma in patients with exacerbation of chronic pyelonephritis. Proven to be highly informative of the level of iL-8 in urine from the ureter and the safety of catheterization of the ureter during exacerbation of chronic pyelonephritis, which allowed for a differentiated therapy depending on the severity of the inflammatory process, to improve the results of treatment.

Prognostic Value of Levels of Urine Neutrophil Gelatinase-associated Lipocalin and Interleukin-18 in Patients With Delayed Graft Function After Kidney Transplantation

ObjectiveThe aim of our study was to examine how serial urine neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin (IL)-18 concentrations change over time after kidney transplantation and whether we can use them to predict delayed graft function (DGF). MethodsSpot urine samples for the NGAL and IL-18 tests were taken at 4, 12, 24, 48, and 72 hours after transplantation from every patient at hospital presentation. Urine samples were tested for NGAL by a chemiluminescence assay kit on the ARCHITECT I2000 immunology analyzer. IL-18 were measured by a quantitative immunoenzymatic assay kit. Serum samples for the creatinine measurement were taken at 24, 48, and 72 hours after kidney transplantation. Serum samples were tested for creatinine on the Olympus analyzer 5821 by alkaline picric acid method. The patients were divided into 2 groups: DGF group and non-DGF group. ResultsThe urine NGAL levels were increased in DGF group at all points over the follow-up period. There are differences (P < .05) in NGAL concentrations between DGF (n = 21) and non-DGF groups (n = 102). However, urine samples from the DGF group (n = 21) had increased IL-18 concentrations at 4, 12, 24, and 48 hours postoperatively compared with non-DGF group samples (n = 102) (P < .05). There were obvious distinctions (P < .05) of serum creatinine (SCr) levels in 24 hours between the DGF (n = 21) and non-DGF groups (n = 102). The specificity and positive predictive value of NGAL in the DGF diagnosis increased with time, but the sensitivity and negative predictive value do not change. The specificity, sensitivity, positive predictive, value and negative predictive value of IL-18 in the DGF diagnosis changed irregularly at multiple time points after transplant. The positive predictive value and negative predictive value of 24-hour SCr were 47.4% and 95.7%, respectively. The positive predictive value and negative predictive value of combination of NGAL, IL-18, and SCr (area under the receiver–operating characteristic curve = 0.984; 95% CI, 0.887–0.994) were 90.9% and 100%, respectively. Overall, the combination of NGAL, IL-18, and SCr was found to have a significantly better positive predictive value than all the other combination assays (P < .05). In addition, there were obvious distinction of the negative predictive value of NGAL and IL-18 combination compared with those of other combinations (P < .05). ConclusionsThe combination of NGAL, IL-18, and SCr measurements after initiation of treatment may be highly effective for risk stratification in patients with DGF. The combination may be useful to cover the complete diagnostic window of patients presenting with DGF.

Predictive Value of Urine Interleukin-18 in the Evolution and Outcome of Acute Kidney Injury in Critically Ill Adult Patients

Nisula, S.*; Yang, R.†; Poukkanen, M.‡; Vaara, S. T.*; Kakounen, K. M.*; Tallgren, M.§; Haapio, M.∥; Tenhunen, J.¶; Korhonen, A. M.*; Pettilä, V.* for The FINNAKI (Finnish Acute Kidney Injury) Study Group Author Information

Predictive value of urinary interleukin-6 for symptomatic urinary tract infections in a nursing home population.

To study urinary interleukin-6, interleukin-8 and pyuria during episodes of asymptomatic bacteriuria and symptomatic urinary tract infection in the institutionalized elderly, and to investigate the role of interleukin-6 as a biomarker for differential diagnosis. Levels of interleukin-6, interleukin-8 and pyuria were assessed in 35 older adults with asymptomatic bacteriuria and symptomatic urinary tract infection to define possible diagnostic thresholds. In a two-phase intervention study, the antibiotic treatment for urinary tract infection before and after introduction of urinary interleukin-6 as a biomarker was then assessed. Asymptomatic bacteriuria patients had no or low levels of interleukin-6, and low levels of interleukin-8 and pyuria. Women had lower interleukin-6 and interleukin-8 than men (P = 0.05). Interleukin-6 was the only marker showing significant increases during urinary tract infection episodes in patients with both asymptomatic bacteriuria and urinary tract infection, in pooled (P = 0.042) and in paired intra-individual (P = 0.017) comparisons. In the intervention study lectures, the increased use of urine cultures and the introduction of interleukin-6 as a biomarker reduced antibiotic treatments by 20%. Antibiotic-treated urinary tract infection episodes had increased interleukin-6 as compared with urinary tract infection episodes not treated (P = 0.02), and as compared with asymptomatic bacteriuria patients (P < 0.0001). The sensitivity and specificity of interleukin-6 (cut-off 25 pg/mL) differentiating asymptomatic bacteriuria from urinary tract infection was 57% and 80%, respectively. Urinary interleukin-6 shows promise as a biomarker to detect the transition from asymptomatic bacteriuria to symptomatic urinary tract infection in older adults. Further larger studies with robust methodology are warranted to determine whether development for near to patient testing would be worthwhile.