Urinary IL-6 Levels Research Articles

Quercetin ameliorates diabetic kidney injury in rats by inhibiting the HMGB1/RAGE/NF-κB signaling pathway

To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms. Twenty-four adult male SD rats were randomized equally into normal control group, high-glucose and high-fat feeding group, streptozotocin (STZ) -induced diabetic model group, and quercetin treatment (daily dose 100 mg/kg) group. Pathological changes of the renal tissues of the rats were observed with HE staining, serum inflammatory factor levels were determined with ELISA, and renal expression of NF‑κB was observed by immunohistochemistry. Fast blood glucose (FBG), serum levels of triglyceride (TG), BUN, and Scr, and 24-h urine protein content of the rats were measured, and renal expressions of HMGB1, RAGE, NF‑κB, Bax, Bcl-2, and caspase-3 were detected with Western blotting. The diabetic rats showed significantly increased levels of FBG, TG, BUN, and Scr, renal hypertrophy index, 24-h urinary protein content, serum IL-1β, IL-6 and TNF-α levels and renal expressions HMGB1, RAGE, NF‑κB, Bax, and caspase-3 with decreased renal expression of Bcl-2. All these changes were significantly alleviated by quercetin treatment of the rats. Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Activation of the inflammasome and pyroptosis cascade in podocytes of patients with minimal change disease.

In contrast to childhood minimal change disease (MCD), adult-onset MCD frequently recurs and requires prolonged immunosuppressive therapy. Accordingly, an investigation of the pathogenesis of adult MCD is required. MCD is usually accompanied by severe dyslipidaemia. Oxidized low-density lipoprotein (ox-LDL) is known to function in a damage-associated molecular pattern (DAMP) through CD36, triggering the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome and programmed cell death called pyroptosis. However, the relationship between MCD pathogenesis and NLRP3 inflammasome/pyroptosis activation via CD36 is not fully understood. We conducted comprehensive histological and clinical evaluations by analysing renal biopsy (RBx) specimens and urine samples obtained from 26 patients with MCD. These samples were compared with control kidneys from 15 transplant donors and urine samples from 15 healthy volunteers. The number of podocytes was lower in the MCD group than in the control group. Urinary ox-LDL levels were higher in the MCD group than in the control group. Immunofluorescence staining revealed that NLRP3 and CD36 were upregulated in MCD podocytes. Urinary interleukin (IL)-18 levels increased in patients with MCD. Steroid therapy performed before RBx appeared to maintain the podocyte number and reduce urinary ox-LDL and IL-18 levels. In MCD, the NLRP3 inflammasome and pyroptosis cascade seem to be activated via upregulation of CD36 in podocytes, associated with increased urinary ox-LDL. Elevated urinary IL-18 levels suggest that pyroptosis may occur in MCD. Further research is required to confirm the significance of the podocyte NLRP3 inflammasome/pyroptosis in MCD.

Urinary markers of pain in children in neonatal intensive care units: a cross-section study

Introduction: Repetitive exposition to pain negatively affects newborns development. Procedural pain in newborn in Neonatal Intensive Care Unit (NICU) triggers a series of physiological, behavioral and hormonal disorders that may set off the impairment of the neurological development in preterm infants, who undergo long periods of hospitalization at a moment of physiological immaturity and fast brain development. Objective: This study aimed not only to observe the pain score in newborns and infants when undergoing painful procedures in neonatal intensive care units but also to analyse urinary IL-8 and cortisol levels at such stressful moments. Methods: Patients were submitted to venipuncture and to other methods of blood collection. Cortisol and IL-8 levels were measured by immunometric assay and chemiluminescence detection. For the collection of data regarding observation of neonatal pain, the Neonatal Infant Pain Scale was used with immediate results. To describe the qualitative variables, absolute and relative frequencies were used. For the quantitative variables with normal distribution, mean, standard deviation, minimum and maximum were used. Results: A total of 81 patients were included: 47 were submitted to venipuncture and 36 to other methods of blood collection. Significance for cortisol can be seen (p=0.04); however, IL-8 levels, when associated with the pain scale, were not sensitive enough (p=0.11). Conclusion: The results showed that cortisol is a better marker for pain than IL-8, and its accumulation in urine may help the detection and interpretation of pain. Conclusion: Based on this information, nurses can step in to reduce the discomfort brought by painful procedures, and thus highlight humanistic practices in nursing assistance.

Phytotherapy (BNO 1045) of Acute Lower Uncomplicated Urinary Tract Infection in Women Normalizes Local Host Responses

Introduction: Acute lower uncomplicated urinary tract infection (uUTI) affects a large proportion of women. Increased antimicrobial resistance has created an urgent need for novel therapeutics and the phytotherapeutic drug BNO 1045 (Canephron^® N) has previously been shown to be noninferior to standard antimicrobial stewardship. This sub-analysis from a randomized, double-blind, controlled phase III noninferiority clinical trial using BNO 1045 versus fosfomycin to treat uUTI aimed to determine how urine cytokine levels are altered by the two different treatments. Methods: Urine samples from a predefined subset of women diagnosed with uUTI (18–70 years) and treated with BNO 1045 (n = 58) or fosfomycin (n = 69) were analyzed for urine levels of IL-6 and IL-8, using analyte-to-creatinine ratios. Results: BNO 1045 treatment showed similar effects to fosfomycin treatment in reducing both urine IL-6 and IL-8 levels. Mean IL-6 and IL-8 levels were markedly reduced in all patients regardless of treatment. BNO 1045 treatment decreased urine IL-8 significantly (p = 0.0142) and showed a trend toward reduction of urine IL-6 (p = 0.0551). Fosfomycin treatment reduced both IL-6 and IL-8 levels significantly (p = 0.0038, <0.0001 respectively). Conclusion: BNO 1045 is, in addition to reducing symptoms, comparable to fosfomycin treatment in reducing the local inflammatory response associated with uUTI.

#3564 DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF INTERLEUKIN-6 IN LUPUS NEPHRITIS

Abstract Background and Aims Lupus nephritis is a frequent and potentially serious complication of SLE. The present study is aimed to evaluate the usefulness of urinary IL-6 as a non-invasive diagnostic &amp; prognostic biomarkers of disease activity in LN. Method The study was done in IMS and Sum hospital, Bhubaneswar, India from January, 2018 to July 2022. The study included 20 healthy controls and 32 patients of SLE diagnosed based of Systemic Lupus International Collaborating Clinic (SLICC) criteria, who presented with renal involvement. The exclusion criteria was inability to obtain informed consent and SLE patients without renal involvement. Urinary IL-6 levels were assessed in patients before initiation of therapy and in controls by quantitative sandwich EASIA technique using human IL-6 EASIA kit (DIA Source Belgium). All patients underwent ultrasound guided renal biopsy and the results were classified according to the ISN/RPS classification of LN. Treatment was started in all patients according to class of LN as per KDIGO guidelines. Urinary IL-6 levels were again assessed in all patients after 6 months of induction phase treatment. Results In our 32 patients, female to male ratio was 7:1 with a mean age of 28.68 ± 9.28 years. In our study, ANA was positive in 96.8%, anti-dsDNA Ab in 78%, C3 was low in 78% &amp; C4 was low in 72% of LN patients. Based on renal biopsy findings, there were 2 cases of Class II LN, 6 cases of Class III LN, 19 cases of Class IV LN and 5 cases of Class V LN. In our study, patients with LN have significantly higher urinary IL-6 levels (301.58 ± 483.96 pg/ml) as compared to 20 healthy controls (4.7±2.282 pg/ml) with a p-value = 0.001. The mean urinary IL-6 levels in different ISN/RPS classes of LN patients based on renal biopsy showed a statistically significant difference between different classes (p-value = 0.005). Highest values of urinary IL-6 (475.126 ± 580.90 pg/ml) was seen in Class-IV LN which is most active form of LN and lowest values (28.28 ±7.30pg/ml) were seen in Class-II LN. In our study, a significant correlation was found between serum creatinine &amp; presence of active urinary sediment with urinary IL-6 levels but there was no correlation between 24 hour urinary protein with urinary IL-6 levels in patients of LN (p value = 0.799). In our study 2 patients (6.25%) died, 3 patients (9.37%) lost follow up, 16 patients (50%) achieved complete remission, 8 patients (25%) achieved partial remission and 3 patients (9.37%) did not show any improvement after 6 months treatment. Urinary IL-6 levels were near normal among 12 patients (75%) out of 16 patients who achieved remission after 6 months of induction treatment (p-value = 0.001). Urinary IL-6 levels remained elevated in all 8 patients (100%) who achieved partial remission (p-value = 0.028, and also remained elevated in all 3 patients who had no remission at all (p-value = 0.109). Conclusion Urinary IL-6 may provide a simple non-invasive potential biomarker of disease activity of renal involvement in patients with SLE and may be used to monitor therapy.

Degree of kidney injury due to artificial pelvic-ureteric junction obstruction with level of neutrophil gelatinase-associated lipocalin, interleukin 18, and histopathological descriptions in Wistar: experimental research.

A total of thirty male Wistar rats, 200-250g, were divided into three groups: (1) control, (2) sham, (3) PUJO (4th, 7th, 14th, and 21st days). Urine NGAL, IL-18 levels, and renal histopathology were observed on day 0, 4, 7, 14, and 21. Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney test with P less than 0.05 considered significant. There was no significant difference in urine NGAL levels between groups, while IL-18 levels were significantly different based on the Kruskal-Wallis test (P 0.031). The results of the Mann-Whitney test showed a significant difference in IL-18 levels between the control group and the PUJO group on day 4 (P=0.028); the Sham surgery group with the PUJO group on day 4 (P=0.014); the PUJO group on day 4 with the PUJO group on the 7th day (P=0.008); and the PUJO group on the 7th day with the PUJO group on the 14th day (P=0.033). Urinary IL-18 levels can be used as a predictor of kidney damage in acute-subacute PUJO cases.

Shionone Relieves Urinary Tract Infections by Removing Bacteria from Bladder Epithelial Cells

In clinical practice, urinary tract infections (UTIs) are second only to respiratory infections in terms of infectious diseases. In recent years, drug resistance of Escherichia coli (E. coli) has increased significantly. The therapeutic effects of Shionone on UTI were assessed by modelling UTI in SD rats and SV-HUC-1 cells with E. coli solution. After treatment of Shionone, the UTI rat model showed a decrease in wet weight/body weight of bladder, as well as a reduction in cellular inflammatory infiltration of bladder tissue and a decrease in urinary levels of IL-6, IL-1β, and TNF-α. In addition, the levels of proinflammatory factors were significantly reduced in a dose-dependent manner in UTI cell model treated with different doses of Shionone (5, 10, and 20 μg/kg). The results of immunofluorescence analysis in both in vivo and in vitro experiments revealed that Shionone reduced bacterial load and the number of E. coli colonies growing on the plates was greatly reduced. These results suggested that Shionone has a good therapeutic effect on UTI, achieved by reducing bacterial load in bladder epithelial cells. The data presented here provide a basis for further research into the treatment of UTI.

Heart Failure (HF): Recent innovations in clinical therapy and critical profiles of acute and chronic forms

Background and objectives: Heart failure is a pathological condition characterized by the inability of the heart to pump (cardiac output) an adequate amount of blood to meet the metabolic needs of the body or, at any rate, to be able to do so only at the expense of increased filling pressures in one or more cardiac chambers and the upstream venous circulation. The research group states here the primary objective of expanding the indications contained in the ESC 2021 with the results of the last year on the subject of treatment profiles, to facilitate a better understanding of the overall clinical picture and contribute to the next edition of the guidelines. Materials and methods: Systematic literature review in the English language from January 1, 2021, to September 30, 2022, on PubMed/MedLine, Web on Science, and Cochrane archive. Our search strategy retrieved 8,317 articles. We excluded books and papers, meta-analyses, reviews, and systematic reviews and selected only 46 studies most significant about the clinical trial and randomized controlled trial. Results: The recent ESC 2021 guidelines are accurate and timely, and have confirmed their usefulness from a functional perspective, including concerning certain aspects that were represented as a “grey area”. Early risk prediction plays a key role in the subsequent management of patients, and to optimize risk prediction and intensity of management, one should take into account that: a) biomarkers have improved the understanding of the pathophysiology of heart failure and may therefore help to adjust the intensity of management in AHF; b) among the wide variety of biomarkers currently available, NT-proBNP and cTn seem the most promising in this indication; c) among the risk scores described, those combining demographic and clinical parameters with biomarkers in a model with routinely available rapid variables seem the most promising tools; d) in addition to biomarkers, age, systolic blood pressure, respiratory rate, oxygen saturation, creatinine, electrolytes, and blood urea nitrogen are the most commonly used predictor variables in the risk scores described; e) among the models selected, the MEESSI-AHF risk score appears to be currently the most promising tool for predicting the risk of AHF; f) during the management of decompensated patients (and in later stages), the psychological aspect is completely ignored, thus promoting the worsening of psychological symptoms (the need is as evident during the acute episode as it is in the daily management of chronic heart failure). Conclusions: The scientific literature search enriched the structure of ESC 2021, suggesting its implementation, with other findings related to new drug therapies such as Sotagliflozin, Hydrochlorothiazide Apabetalone, Alprostadil, Empagliflozin, Sacubitril/Valsartan, Dapagliflozin, Sodium-glucose co-transporter-2 inhibitors, and biomarkers such as Urinary sodium (UNa+), IL-6 levels and rh-brain natriuretic peptide (rhBNP), as well as the use of mindful breathing session, osteopathic manipulative treatment, electrical muscle stimulation, low-level tragus stimulation, venoarterial extracorporeal membrane oxygenation, oral nutritional supplements, and the correlative hypothesis between heart failure and intestinal dysbiosis, also concerning the psychological profile. However, these clinical studies suffer from some limitations that will necessarily have to be taken into account, such as the limited size of the population sample selected or the conflict of interest determined by the fact that some research is funded by the same pharmaceutical company producing the drug used that do not necessarily represent a negative limitation on the results obtained from studies.

Kidney injury molecule type-1, interleukin-18, and insulin-like growth factor binding protein 7 levels in urine to predict acute kidney injury in pediatric sepsis.

This study aimed to observe the role of urinary kidney injury molecule (KIM-1), interleukin (IL-18), and insulin-like growth factor-binding protein 7 (IGFBP-7) levels in predicting acute kidney injury (AKI) in children with sepsis. This prospective cohort observational study was conducted at Dr. RSUP. Wahidin Sudirohusodo, Makassar, South Sulawesi, from January to December 2021. Inclusion criteria were septic patients treated in the pediatric intensive care unit (PICU) aged 1 month to 18 years with normal serum creatinine or normal urine output (>5 ml/kg/body weight (BW)/h in 6-12 h). Patients with a history of kidney disease, prior urinary tract infection, or history of using nephrotoxic drugs were excluded. There was a significant difference in urinary KIM-1, IL-18, and IGFBP-7 levels between septic patients with and without AKI. The cut-off point for urinary KIM-1 level in sepsis with and without AKI was 1.666 ng/ml, with sensitivity of 82.5%, specificity of 82.2%, and a relative risk (RR) [95% confidence interval (CI)] of 6.866 (95% CI, 3.329-14.165). The cut-off point for urinary IL-18 levels was 3.868 ng/ml, with sensitivity of 92.50%, specificity of 91.78%, and RR of 20.078 (95%CI, 6.593-61.142). The cut-off point for urinary IGFBP-7 levels was ≥0.906 ng/ml with a sensitivity of 75.00%, specificity of 75.34%, and RR of 4.063 (95% CI, 2.206-7.483). Urinary KIM-1, IL-8, and IGFBP-7 levels could be used to predict AKI in septic patients. Urinary IL-8 has a higher sensitivity and specificity as a predictor of AKI in patients with sepsis.

Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice.

Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL-18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL-18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg-Ay /TaJcl (KK-Ay) mice against DKD progression. Suramin or saline was administered i.p. to KK-Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin. Suramin treatment significantly suppressed the increase in the urinary albumin-to-creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK-Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome-related genes and proteins in the renal cortex of KK-Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK-Ay mice and mainly distributed in the glomerular mesangial cells of KK-Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP-induced NLRP3 complex formation and the downstream expression of caspase-1 and IL-18 in MMCs. These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD.

Exploring Urinary Extracellular Vesicles and Immune Mediators as Biomarkers of Kidney Injury in COVID-19 Hospitalized Patients.

Kidney injury is an important outcome associated with COVID-19 severity. In this regard, alterations in urinary extracellular vesicles (uEVs) could be detected in the early phases of renal injury and may be reflective of the inflammatory process. This is an observational study performed with a case series of COVID-19 hospitalized patients presenting mild-to-critical disease. Total and podocyte-derived uEVs were identified by nanoscale flow cytometry, and urinary immune mediators were assessed by a multiplex assay. We studied 36 patients, where 24 (66.7%) were considered as mild/moderate and 12 (33.3%) as severe/critical. Increased levels of total uEVs were observed (p = 0.0001). Importantly, total uEVs were significantly higher in severe/critical patients who underwent hemodialysis (p = 0.03) and were able to predict this clinical outcome (AUC 0.93, p = 0.02). Severe/critical patients also presented elevated urinary levels (p &lt; 0.05) of IL-1β, IL-4, IL-6, IL-7, IL-16, IL-17A, LIF, CCL-2, CCL-3, CCL-11, CXCL-10, FGFb, M-CSF, and CTAcK. Lastly, we observed that total uEVs were associated with urinary immune mediators. In conclusion, our results show that early alterations in urinary EVs could identify patients at higher risk of developing renal dysfunction in COVID-19. This could also be relevant in different scenarios of systemic and/or infectious disease.

Usefulness of Urinary Biomarkers for Assessing Bladder Condition and Histopathology in Patients with Interstitial Cystitis/Bladder Pain Syndrome.

This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic characteristics (visual analog scale (VAS) score and bladder capacity) and cystoscopic hydrodistention findings (Hunner’s lesion, glomerulation grade, and maximal bladder capacity (MBC)) were recorded. Urine samples were utilized to assay inflammatory, neurogenic, and oxidative stress biomarkers, including interleukin (IL)-8, C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-isoproatane, and total antioxidant capacity. Further, specific histopathological findings were identified via bladder biopsy. The associations between urinary biomarker levels and bladder conditions and histopathological findings were evaluated. The results reveal that patients with IC/BPS had significantly higher urinary MCP-1, eotaxin, TNF-α, PGE2, 8-OHdG, and 8-isoprostane levels than controls. Patients with Hunner’s IC (HIC) had significantly higher IL-8, CXCL10, BDNF, eotaxin, IL-6, MIP-1β, and RANTES levels than those with non-Hunner’s IC (NHIC). Patients with NHIC who had an MBC of ≤760 mL had significantly high urinary CXCL10, MCP-1, eotaxin, IL-6, MIP-1β, RANTES, PGE2, and 8-isoprostane levels and total antioxidant capacity. Patients with NHIC who had a higher glomerulation grade had significantly high urinary MCP-1, IL-6, RANTES, 8-OHdG, and 8-isoprostane levels. A significant association was observed between urinary biomarkers and glomerulation grade, MBC, VAS score, and bladder sensation. However, bladder-specific histopathological findings were not well correlated with urinary biomarker levels. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. Most urinary biomarkers are not correlated with specific bladder histopathological findings; nevertheless, they are more important in the assessment of bladder condition than bladder histopathology.

Immune cell profiles of patients with interstitial cystitis/bladder pain syndrome

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder characterized by bladder pain upon filling which severely affects quality of life. Clinical presentation can vary. Local inflammatory events typify the clinical presentation of IC/BPS patients with Hunner lesions (IC/BPS-HL). It has previously been proposed that B cells are more prevalent in HL, but understanding their exact role in this environment requires a more complete immunological profile of HL. We characterized immunological dysfunction specifically in HL using immunohistochemistry. We detected significantly more plasma cells (50× increase, p < 0.0001), B cells (28× increase, p < 0.0001), T cells (3× increase, p < 0.0001), monocytes/macrophages (6× increase, p < 0.0001), granulocytes (4× increase, p < 0.0001), and natural killer cells (2× increase, p = 0.0249) in IC/BPS patients with HL than in unaffected controls (UC). Patients with IC/BPS-HL also had significantly elevated urinary levels of IL-6 (p = 0.0054), TNF-α (p = 0.0064) and IL-13 (p = 0.0304) compared to patients with IC/BPS without HL (IC/BPS-NHL). In contrast, IL-12p70 levels were significantly lower in the patients with HL than in those without these lesions (p = 0.0422). Different cytokines were elevated in the urine of IC/BPS patients with and without HL, indicating that different disease processes are active in IC/BPS patients with and without HL. Elevated levels of CD138+, CD20+, and CD3+ cells in HL are consistent B and T-cell involvement in disease processes within HL.

The association of rs187238, rs19465518 and rs1946519 IL-8 polymorphisms with acute kidney injury in preterm infants.

BackgroundInterleukin 18 (IL-18) promoter polymorphisms (−656G > T, −607C > A, and −137G > C) affect serum IL- 18 (sIL-18) levels and are associated with renal injury.PurposeThis study aimed to determine the diagnostic utility of sIL-18 and urine IL-18 (uIL-18) as biomarkers for acute kidney injury (AKI) and analyse the association of IL-18 polymorphisms to AKI in preterm infants.MethodsBlood and urine samples were collected from 56 preterm infants with AKI and 56 without AKI to measure serum creatinine (SCr), sIL-18, and uIL-18. Genotyping of polymorphisms was performed and analysed, with AUC-ROCs analysis used to evaluate the diagnostic utility of s-/uIL-18 levels.ResultsThe median sIL-18 and uIL-18 levels were significantly higher than those without AKI. For a cutoff of >132 pg/mL, the sIL-18 expression had sensitivity and specificity of 80.36% and 60.71%, respectively, while for uIL-18, a cutoff of >900.7 pg/mL had sensitivity and specificity of 51.79% and 78.57%, respectively. The odds ratio of sIL-18 and uIL-18 to predict AKI in preterm infants was 5.89 (95%CI:2.31–15.02) and 4.15 (95%CI:1.58–10.89), respectively. The polymorphisms −137G > C and −656G > T were significantly associated with sIL-18 expression.ConclusionSerum and urine IL-18 levels are risk factors for and a moderate predictor of AKI in preterm infants.

The IL-8-CXCR1/2 axis contributes to diabetic kidney disease

Aims/hypothesisInflammation has a major role in diabetic kidney disease. We thus investigated the role of the IL-8-CXCR1/2 axis in favoring kidney damage in diabetes. MethodsUrinary IL-8 levels were measured in 1247 patients of the Joslin Kidney Study in type 2 diabetes (T2D). The expression of IL-8 and of its membrane receptors CXCR1/CXCR2 was quantified in kidney tissues in patients with T2D and in controls. The effect of CXCR1/2 blockade on diabetic kidney disease was evaluated in db/db mice. ResultsIL-8 urinary levels were increased in patients with T2D and diabetic kidney disease, with the highest urinary IL-8 levels found in the patients with the largest decline in glomerular filtration rate, with an increased albumin/creatine ratio and the worst renal outcome. Moreover, glomerular IL-8 renal expression was increased in patients with T2D, as compared to controls. High glucose elicits abundant IL-8 secretion in cultured human immortalized podocytes in vitro. Finally, in diabetic db/db mice and in podocytes in vitro, CXCR1/2 blockade mitigated albuminuria, reduced mesangial expansion, decreased podocyte apoptosis and reduced DNA damage. Conclusions/interpretationThe IL-8- CXCR1/2 axis may have a role in diabetic kidney disease by inducing podocyte damage. Indeed, targeting the IL-8-CXCR1/2 axis may reduce the burden of diabetic kidney disease.

Exploring molecular pathology of chronic kidney disease in systemic sclerosis by analysis of urinary and serum proteins.

Objective.Renal involvement is common in systemic sclerosis (scleroderma; SSc) and includes chronic kidney disease (CKD). We have performed analysis of urinary proteins to gain insight into local molecular pathology of CKD in SSc and identify candidate markers for use in clinical trials.Methods.To evaluate urinary proteins that might specifically reflect SSc-related CKD, patients were recruited with confirmed SSc and stratified for the presence or absence of CKD. Controls included patients with CKD and no SSc, in addition to healthy volunteers. Candidate markers were measured in serum and urine by multiplex immunoassay testing for IL6, IL18, TNF-α, monocyte chemoattractant protein 1 (MCP1), monocyte chemoattractant protein 3 (MCP3), VEGF and the soluble adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Results.One hundred and two subjects were examined, including patients with SSc with no evidence of CKD (n = 40), SSc with CKD (n = 39), non-SSc CKD (n = 11) and healthy volunteers (n = 12). Urinary levels of IL6, MCP1, TNF-α, MCP3, IL18 and ICAM-1 were elevated in SSc patients compared with healthy controls. The most significant differences were for MCP1 and ICAM-1 (both P < 0.0001), and these analytes also showed the most significant differences between groups overall (P = 0.003 for MCP1 and P < 0.0001 for ICAM-1). These markers showed a trend (MCP1, P = 0.0868) or a significant difference (ICAM-1, P = 0.0134) between SSc–CKD and SSc with normal renal function.Conclusion.Urinary levels of candidate molecular markers appear to reflect SSc–CKD more than serum markers. MCP1 and ICAM-1 are promising molecular markers for SSc–CKD and might be potential biomarkers of SSc renal involvement. This might be explored in future prospective analyses.

Serum and Urine Interleukin-6 and Interleukin-8 Levels Do Not Differentiate Acute Pyelonephritis from Lower Urinary Tract Infections in Children.

BackgroundUrinary tract infection (UTI) is common in pediatrics. Infection of the upper urinary tract may cause renal scarring, and subsequently renal failure and hypertension. Permanent renal damage has been suggested to be caused by the host inflammatory response. Therefore, it is crucial to understand the host defense mechanisms against such infection in order to make timely diagnosis. The aim of this study was to evaluate interleukin-6 (IL-6) and IL-8 as potential biomarkers in differentiating acute pyelonephritis (AP) from cystitis (Cys) in children.MethodsForty-three children (21 with AP and 22 with Cys) were included. Serum and urinary IL-6 and IL-8 were measured during the acute phase (within 12 hours of presentation) and the convalescent phase (8 weeks post-infection). Thirty-eight healthy children were included as controls.ResultsDuring the acute phase, the mean urinary IL-6 level in the Cys group was significantly higher than that in the controls (17.8 pg/mL vs 14.8 pg/mL, P=0.03), while the serum levels were significantly higher in both the Cys and AP groups than in the controls (19.5 pg/mL, 19.4 pg/mL, 15 pg/mL, P=0.005 and 0.02, respectively). During the convalescent phase, serum and urinary IL-6 levels were higher in patients than in controls. Urinary IL-8 levels were significantly higher in both the AP and Cys groups compared to controls (206.5 pg/mL, 291.8 pg/mL, 89.4 pg/mL, P=0.05 and 0.02, respectively) during the acute phase. Serum IL-8 was not significantly different between the 3 groups. Nonetheless, no significant differences were found between the AP and Cys groups, in urinary or serum levels of IL-6 or IL-8, during both phases.ConclusionIL-6 and IL-8 levels are elevated in patients with UTI. However, the levels did not differentiate between AP and cystitis. Further studies are warranted to evaluate their roles as indicators of the site of UTIs.

Renal Protection Against Ischemia Reperfusion Injury: Hemoglobin-based Oxygen Carrier-201 Versus Blood as an Oxygen Carrier in Ex Vivo Subnormothermic Machine Perfusion.

The optimal method of oxygen delivery to donor kidneys during ex vivo machine perfusion has not been established. We have recently reported the beneficial effects of subnormothermic (22°C) blood perfusion in the preservation of porcine donation after circulatory death kidneys. Since using blood as a clinical perfusate has limitations, including matching availability and potential presence of pathogen, we sought to assess hemoglobin-based oxygen carrier (HBOC-201) in oxygen delivery to the kidney for renal protection. Pig kidneys (n = 5) were procured after 30 minutes of warm in situ ischemia by cross-clamping the renal arteries. Organs were flushed with histidine tryptophan ketoglutarate solution and subjected to static cold storage or pulsatile perfusion with an RM3 pump at 22°C for 4 hours with HBOC-201 and blood. Thereafter, kidneys were reperfused with normothermic (37°C) oxygenated blood for 4 hours. Blood and urine were subjected to biochemical analysis. Total urine output, urinary protein, albumin/creatinine ratio, flow rate, resistance were measured. Acute tubular necrosis, apoptosis, urinary kidney damage markers, neutrophil gelatinase-associated lipocalin 1, and interleukin 6 were also assessed. HBOC-201 achieved tissues oxygen saturation equivalent to blood. Furthermore, upon reperfusion, HBOC-201 treated kidneys had similar renal blood flow and function compared with blood-treated kidneys. Histologically, HBOC-201 and blood-perfused kidneys had vastly reduced acute tubular necrosis scores and degrees of terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining versus kidneys treated with cold storage. Urinary damage markers and IL6 levels were similarly reduced by both blood and HBOC-201. HBOC-201 is an excellent alternative to blood as an oxygen-carrying molecule in an ex vivo subnormothermic machine perfusion platform in kidneys.

Effect Of L-Carnitine On Urinary Il-18 And Gfr In Patient Receiving Cisplatin-Based Regimen

Background: Nephrotoxicity is a major dose-limiting side effect facing cisplatin-based chemotherapy of a wide variety of cancers. Acute kidney injury occurs after cisplatin chemotherapy in approximately 30% of patients where severe and lifelong nephrotoxicity can result regardless of the use of powerful hydration with normal saline.In spite of scientific efforts to find relatively less toxic but equally effective substitutes, cisplatin continues to be widely involved in chemotherapy as first line antitumor agent. Apoptosis and necrosis, due to DNA damage response pathways, oxidative stress in association with severe inflammatory response and caspase activation, are the major sources of acute kidney injury due to cisplatin. L-carnitine with their antioxidant, anti-inflammatory and to some extent antiapoptotic effects may have ameliorative effect on nephrotoxicity. Aim: To assess the effects of L-carnitine in protection from cisplatin–induced nephrotoxicity in cancer patients. Patients and methods:28 patients were participated in the study and successfully completed their treatment cycles. They were randomized into two groups (N=14 in each). In group I, patients received six cycles of cisplatin based regimen with 21 days-intervals. In group II, patients received L-carnitine(500 mg oral tablet twice daily) plus cisplatin based regimen. GFR (Modification of Diet in renal Diseases formula) was measured at base line and 21 days after 1, 2, 4 and 6 cycles but IL-18 was measured at base line and 1 day after 1, 2, 4 and 6 cycles of cisplatin based regimen. Results:In patients of group I, cisplatin-based regimen caused significant (P&lt;0.05) increment in serum creatinine and urea levels, highly significant (P&lt;0.01) increment in serum urinary IL-18 levels, and significant (P&lt;0.05) decrement in GFR in comparison to base line levels. Conclusions:Each of L-carnitine significantly ameliorated nephrotoxicity in patients that received cisplatin.

Spontaneous Aneurysmal Subarachnoid Hemorrhage and Related Cortisol and Immunologic Alterations: Impact on Patients' Health-related Quality of Life

To highlight the impact of aneurysmal subarachnoid hemorrhage (SAH) on surviving patients' health-related quality of life (HRQoL) with respect to cortisol and interleukin (IL)-6 alterations and also to identify possible clinical predictors for a better HRQoL. Fifty surviving patients treated in our hospital for aneurysmal SAH in a 2-year period with sufficient HRQoL data were enrolled. A good clinical outcome was represented by the modified Rankin Scale (mRS) 0 to 2. The patient's HRQoL was assessed using the Short Form health survey questionnaire, the Beck Depression Inventory, and the Daily Fatigue Impact Scale at 6 and 12 months. The results were analyzed regarding possible correlation to 24-hour urinary free cortisol, serum, and cerebrospinal fluid IL-6 levels. A reduction of HRQoL in up to 35% of survivors was observed at 6 months and in a high proportion of patients (47.2%) with an assumable good outcome (mRS 0-2). Reduced HRQoL in survivors was found in terms of SF-36 (34.9%), depression (26.8%), and fatigue (14%) at 6 months and 18.4%, 39.4%, and 18.9% at 12 months, respectively. Improvement was recorded at 12 months, mainly in SF-36. Early elevated 24-hour urinary free cortisol and IL-6 levels showed a significant positive impact on HRQoL. Early cortisol and IL-6 levels may predict patients' HRQoL after SAH. Twelve months after SAH, a considerable percentage of patients with a presumably good outcome (mRS 0-2) had a lower HRQoL compared with the general population. Implementing corresponding tests at discharge and 12-month follow-up is recommended.