Urinary Interleukin-6 Research Articles

RENAL SYMPATHETIC NERVES AND INFLAMMATION IN HYPERTENSION

Objective: Renal denervation (RDN) may be an effective treatment for hypertension; however, the mechanisms remain unknown. RDN mitigates hypertension in addition to the concomitant renal inflammation in the deoxycorticosterone (DOCA)-salt rat model. Renal inflammation is hypothesized to drive the hypertension, but the timing and relationship to mean arterial pressure (MAP) remain elusive. We aimed to elucidate the temporal inflammatory and MAP response to DOCA-salt through urinary cytokine excretion, and test its responsiveness to renal denervation. We hypothesized that (a) RDN would mitigate renal and urinary cytokine content, and (b) a decrease urinary cytokine would precede changes in MAP. Design and method: 12 uninephrectomized male Sprague Dawley rats (300–325 g) received either surgical renal denervation (RDN; n = 6) or sham (Sham; n = 6). One week following, rats were administered DOCA (100 mg) and 0.9% saline for 21 days. Urine samples were collected weekly. Urinary and renal tissue cytokines (IL-1β, IL-2, IL-6, GRO/KC, MCP-1) were measured by multiplex assay. Temporal data analyzed by two-way ANOVA with Bonferroni post-hoc test (α=0.05). All other data were analyzed by Student's t-test. Data presented as mean ± SEM. Results: MAP response to DOCA-salt was attenuated (*p < .05) by RDN vs. Sham, where MAP significantly diverged at Days 14–21 (see Table). Similarly, all measured renal cytokines were markedly reduced (*p < .05) in RDN vs. Sham - a reduction of 42–70% of Sham values (see Table). Urinary cytokine excretion on day 21 mirrored this effect, where each cytokine was lower (*p < .05) in RDN vs. Sham – reduced by 44–84% Sham values (see Table). No difference was detected between RDN and Sham urinary cytokine content on Days 0–7, and only urinary IL-1β and IL-2 were reduced (*p < .05) at Day 14.Conclusions: In conclusion, these data support our hypothesis that urinary cytokines reflect renal inflammatory cytokine content, and both are abated by RDN. However, our second hypothesis was not supported, as differences in MAP appeared prior to a significant reduction of most urinary cytokines. With these findings, we hypothesize that hypertension may precede renal inflammation in this model. Further studies are necessary to elucidate the driving force for renal inflammation in this model.

Social Determinants of Health Are Associated with Markers of Renal Injury in Adolescents with Type 1 Diabetes

ObjectiveTo examine the relationship between the social determinants of health and markers of early renal injury in adolescent patients with type 1 diabetes (T1D).Study designRenal outcomes included estimated glomerular filtration rate (eGFR) and albumin–creatinine excretion ratio (ACR). Differences in urinary and serum inflammatory markers also were assessed in relation to social determinants of health. Regression analysis was used to evaluate the association between the Ontario Marginalization Index (ON-Marg) as a measure of the social determinants of health, patient characteristics, ACR, eGFR, and renal filtration status (hyperfiltration vs normofiltration).ResultsParticipants with T1D (n = 199) with a mean age of 14.4 ± 1.7 years and diabetes duration of 7.2 ± 3.1 years were studied. Mean eGFR was 122.0 ± 19.4 mL/min/1.73 m2. Increasing marginalization was positively associated with eGFR (P < .0001) but not with ACR (P = .605). Greater marginalization was associated with greater median levels of urinary interleukin (IL)-2, IL-12 (p40), macrophage-derived chemokine, monocyte chemoattractant protein-3, and tumor necrosis factor-β and serum IL-2. ON-Marg was significantly associated with eGFR after we controlled for age, sex, body mass index z score, ethnicity, serum glucose, and hemoglobin A1c in linear regression. A similar association between hyperfiltration and ON-Marg score was observed in multivariable logistic regression.ConclusionIncreasing marginalization is significantly associated with both eGFR and hyperfiltration in adolescents with T1D and is associated with significant changes in urinary inflammatory biomarkers. These findings highlight a potentially important interaction between social and biological determinants of health in adolescents with T1D.

Priming with percutaneous bacillus Calmette-Guerin (BCG) prior to intravesical BCG treatment safely improves BCG-specific response in patients with bladder cancer

Abstract Bacillus Calmette-Guérin (BCG) is the gold standard immunologic agent for patients with high-grade non-muscle invasive bladder cancer (NMIBC). Nevertheless, responses to BCG are heterogeneous and limited options exist when BCG therapy fails. Preclinical data in animal models of bladder cancer (BC) suggests that priming with percutaneous BCG vaccine prior to intravesical BCG instillation can enhance BCG-specific immunity and improve outcome. To study the safety, immunogenicity and preliminary efficacy of this approach, we administered percutaneous BCG 21 days prior to intravesical BCG instillation in “prime patients” with NMIBC (n=13) in a prospective single-arm clinical trial. Immune responses and clinical outcomes were monitored and compared to a contemporaneous cohort of “control patients” (n=9) receiving intravesical BCG without prior percutaneous BCG. Priming was well tolerated and no grade ≥3 adverse events were observed. Compared to control, prime patients had improvement in both local and systemic measures of BCG-specific immunity, scored by increased post-BCG urinary IL-8 and IL-17A and increased circulating CD4, CD8, and γδ T cell proliferation and effector function in response to BCG. Furthermore, ex vivo cytotoxicity of circulating NK and γδ T cells against RT4 BC was significantly increased in prime patient after BCG treatment and was mediated in part by NKG2D, suggesting an important role of innate effector immune mechanisms underlying BCG’s antitumor activity. Remarkably, no prime patients progressed whereas 3 out of 9 control patients progressed to muscle-invasive disease and underwent cystectomy. Thus, BCG priming safely enhances BCG-specific immunity and could improve outcome for patients with NMIBC.

Renal Sympathetic Nerves and Inflammation in Hypertension: Assessing Temporal Renal Inflammation Responses to Renal Denervation by Urinary Cytokine Excretion in the DOCA‐Salt Rat

Preclinical and clinical studies demonstrate renal sympathetic denervation (RDN) may be an effective treatment for hypertension and end stage renal disease; however, the mechanisms of this effect remain unknown. We recently reported (RDN) mitigates hypertension in addition to the concomitant renal inflammation in the deoxycorticosterone acetate (DOCA)‐salt rat model. In this model, renal inflammation is hypothesized to drive the hypertension, but the timing and relationship to arterial pressure remain elusive. In this study, we aimed to elucidate the temporal renal inflammatory and arterial pressure response to DOCA‐salt through repeated‐measurement of urinary pro‐inflammatory cytokine excretion, and test the responsiveness to renal sympathetic denervation. We hypothesize that (a) RDN would mitigate renal and urinary cytokine content, and (b) a decrease urinary cytokine content due to RDN would precede changes in arterial pressure. To test this hypothesis, 12 uninephrectomized adult male Sprague Dawley rats (300–325 g) were implanted with radiotelemeters to measure 24‐hour mean arterial pressure (MAP) weekly, and received either surgical renal denervation (RDN; n=6) or sham procedure (Sham; n=6). One week following, both groups were administered DOCA (100 mg, s.c.) and 0.9% saline for 21 days. 6‐hour urine samples were collected weekly over ice using metabolic cage housing. At day 21, rats were anesthetized, and renal tissue was collected for cytokine and histological analysis. Pro‐inflammatory cytokines (IL‐1β, IL‐2, IL‐6, GRO/KC, MCP‐1) were measured by Luminex assay in both urine and renal tissue. Renal and urinary cytokine content were normalized to total protein and creatinine, respectively. Temporal response data analyzed by two‐way repeated measured ANOVA with Bonferroni post‐hoc test (α=0.05). All other data were analyzed by Student's t‐test. Data presented as mean±SEM. MAP response over 21‐day DOCA‐salt treatment was attenuated (*p&lt;.05) by RDN vs. Sham, where MAP significantly diverged at Days 14–21 (see Data Table). Similarly, all measured pro‐inflammatory cytokines in renal parenchymal protein isolates were markedly reduced (*p&lt;.05) in RDN vs. Sham ‐ a reduction of 42–70% of Sham values (see Data Table). Interestingly, urinary cytokine excretion on day 21 mirrored this effect, where each cytokine was lower (*p&lt;.05) in RDN vs. Sham – similarly reduced by 44–84% Sham values (see Data Table). Of note, no difference was observed between RDN and Sham urinary cytokine content on Days 0–7, and only urinary IL‐1β and IL‐2 were reduced (*p&lt;.05) at Day 14 (see Data Table). Histological analysis of renal injury and immune cell (macrophage, T‐cell) infiltration is currently underway to establish the end organ damage and immune cell specificity in the reported anti‐inflammatory effects of RDN. Taken together, these data support our first hypothesis of urinary cytokines reflect renal inflammatory cytokine content, and both are abated by RDN. However, our second hypothesis was not supported by the current data, as MAP was reduced in the RDN‐treated group prior to a significant reduction of most urinary cytokines. With these findings, we hypothesize that DOCA‐salt hypertension may precede the renal inflammation in this model. Further studies are necessary to elucidate the source of renal inflammation in this model, and its relationship to arterial pressure control.Support or Funding InformationThis project was supported in part by NIH HL116476 (JWO) and AHA 17POST33661003 (CTB).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fully electronic urine dipstick probe for combinatorial detection of inflammatory biomarkers.

Aim:An electrochemical urine dipstick probe biosensor has been demonstrated using molybdenum electrodes on nanoporous polyamide substrate for the quantitative detection of two inflammatory protein biomarkers, CRP and IL-6.Materials & methods:The electrode interface was characterized using ζ-potential and Fourier transform infrared spectroscopy. Detection of biomarkers was demonstrated by measuring impedance changes associated with the dose concentrations of the two biomarkers. A proof of feasibility of point-of-care implementation of the biosensor was demonstrated using a portable electronics platform.Results & conclusion:Limit of detection of 1 pg/ml was achieved for CRP and IL-6 in human urine and synthetic urine buffers. The developed portable hardware demonstrated close correlation with benchtop equipment results.

Kidney injury biomarkers 5years after AKI due to pediatric cardiac surgery.

We previously reported that children undergoing cardiac surgery are at high risk for long-term chronic kidney disease (CKD) and hypertension, although postoperative acute kidney injury (AKI) is not a risk factor for worse long-term kidney outcomes. We report here our evaluation of renal injury biomarkers 5years after cardiac surgery to determine whether they are associated with postoperative AKI or long-term CKD and hypertension. Children aged 1month to 18years old undergoing cardiopulmonary bypass were recruited to this prospective cohort study. At 5years after cardiac surgery, we measured urine interleukin-18, kidney injury molecule-1, monocyte chemoattractant protein-1, YKL-40, and neutrophil gelatinase-associated lipocalin (NGAL). Biomarker levels were compared between patients with AKI and those without. We also performed a cross-sectional analysis of the association between these biomarkers with CKD and hypertension. Of the 305 subjects who survived hospitalization, four (1.3%) died after discharge, and 110 (36%) participated in the 5-year follow-up. Of these 110 patients, 49 (45%) had AKI. Patients with versus those without postoperative AKI did not have significantly different biomarker concentrations at 5years after cardiac surgery. None of the biomarker concentrations were associated with CKD or hypertension at 5 years of follow-up, although CKD and hypertension were associated with a higher proportion of participants with abnormal NGAL levels. Postoperative pediatric AKI is not associated with urinary kidney injury biomarkers 5years after surgery. This may represent a lack of chronic renal injury after AKI, imprecise estimation of the glomerular filtration rate, the need for longer follow-up to detect chronic renal damage, or that our studied biomarkers are inadequate for evaluating subclinical chronic renal injury.

High urinary interleukin-8 levels is associated with poor prognosis in idiopathic membranous nephropathy.

Biomarkers required to assess accurately the prognosis of idiopathic membranous nephropathy (IMN) are still unavailable. A retrospective study on 156 IMN patients showed only urinary IL-8 was associated with the achievement of initial complete remission (CR) in IMN patients. A urinary IL-8 level of less than 61.25 pg/mL was more sensitive for prediction of CR in IMN patients. Therefore, urinary IL-8 may be a potential biomarker for evaluating short-term prognosis of IMN patients.

Bio-marcatori e malattia cardio-renale: significato clinico e prognostico

La sindrome cardio-renale (SCR) è una sindrome clinica ben nota, che descrive tanto gli effetti negativi dell'insufficienza renale sull'equilibrio cardio-circolatorio quanto quelli dell'insufficienza cardiaca sulla funzione renale. Molti autori hanno studiato l'utilità di marcatori sierologici ai fini dell'identificazione e del monitoraggio ambulatoriale delle varie forme di questa sindrome. L'analisi dei livelli sierici dei peptidi natriuretici è, al momento, quella maggiormente utilizzata, in quanto essi stessi non sono solo direttamente associati alla gravità delhinsufficienza cardiaca, ma anche capaci di rilevare precocemente la disfunzione renale, certamente prima che sia possible osservare un incremento nei livelli sierici di creatinina. NGAL, cistatina C, NAG, KIM-1 e IL-18 rappresentano interessanti biomarcatori per la diagnosi precoce di danno renale acuto (AKI), e quindi per la diagnosi precoce delle forme renocardiache acute, mentre il loro utilizzo in altre forme di SCR non appare codificato. Al contrario, la valutazione di KIM-1 e IL-18 sembra più utile per cercare una diagnostica differenziale tra forme diverse di insufficienza renale acuta. (Cardionephrology)

Investigating Colorimetric Protein Array Assay Schemes for Detection of Recurrence of Bladder Cancer.

A colorimetric microarray for the multiplexed detection of recurrence of bladder cancer including protein markers interleukin-8 (IL8), decorin (DCN), and vascular endothelial growth factor (VEGF) was established to enable easy and cheap read-out by a simple office scanner paving the way for quick therapy monitoring at doctors’ offices. The chip is based on the principle of a sandwich immunoassay and was optimized prior to multiplexing using IL8 as a model marker. Six different colorimetric assay formats were evaluated using a detection antibody (dAB) labeled with (I) gold (Au) nanoparticles (NPs), (II) carbon NPs, (III) oxidized carbon NPs, and a biotinylated dAB in combination with (IV) neutravidin–carbon, (V) streptavidin (strp)–gold, and (VI) strp–horseradish peroxidase (HRP). Assay Format (III) worked best for NP-based detection and showed a low background while the enzymatic approach, using 3,3′,5,5′-tetramethylbenzidine (TMB) substrate, led to the most intense signals with good reproducibility. Both assay formats showed consistent spot morphology as well as detection limits lower than 15 ng/L IL8 and were thus applied for the multiplexed detection of IL8, DCN, and VEGF in synthetic urine. Colorimetric detection in urine (1:3) yields reaction signals and measurement ranges well comparable with detection in the assay buffer, as well as excellent data reproducibility as indicated by the coefficient of variation (CV 5–9%).

Urinary IL-8 and BLCA-4 in detection of bladder cancer and their clinical significant

Bladder cancer is a highly prevalent human disease world wide This study of bladder cancer was conducted to assess the significance of level difference in some cancer biomarkers in bladder cancer patients, like IL-8 which is an angiogenic factor associated with inflammation and carcinogenesis and Bladder cancer-associated protein (BLCA4) that is a specific nuclear matrix protein (transcription factor) found in bladder cancer functioning in the regulation of the gene expression related to cell growth. IL8and BLCA4 evaluated in urine of 48 bladder cancer patients and 40 healthy controls by ELISA test, result indicated that urine IL8 and BLCA4 shows high specificity in diagnosis bladder cancer patients, The correlation between IL-8 with BLCA4 showed a significant association in patients with recurrent bladder cancer, urine IL8 and BLCA4 have a role in discrimination between ( newly diagnosed vs recurrence, low grade vs high grade, muscle invasion vs non muscle invasion),but un related to some risk factors like smoking ,Schistosomiasis,Urinary tract infection,stones and family history of cance.

A prognostic value of early urinary biomarkers NGAL and IL-18 in critically ill children: a 10-year literature review

Introduction. Acute kidney injury (AKI) is a life-threatening syndrome caused by a sudden and rapidly progressing impair-ment of renal function. It is a common and complicated clinical entity among hospi-talized children, occurring in 2%-4.5% of children treated in a pediatric intensive care unit. Mortality among such patients remains high (from 8% to 89%) despite improving patient care and technical pos-sibilities. The stage of renal damage is a reversible process, and its timely detection would prevent the progression of renal damage and thus reduce pediatric mor-tality rates. Therefore, modern medicine necessitates the identification of novel AKI biomarkers that would correlate with renal cell damage and could be detected ear-lier than a rise in serum creatinine (sCr). Neutrophil gelatinase-associated lipocalin (NGAL) and interleukin 18 (IL-18) are one of such early markers of AKI.Aim. To carry out a literature review of studies on changes in NGAL and IL-18 lev-els in the urine of critically ill patients and to determine a prognostic value of these biomarkers in the detection of renal injury and impact on disease outcomes. Material and methods. This literature review includes the publications of bio-medical studies assessing early biomark-ers of AKI in urine (uNGAL or uIL-18) of critically ill children, published in English during the 10-year period. Search for pub-lication was performed in the PubMed da-tabase.Results. Analysis included 10 studies that investigated early biomarkers of AKI (NGAL or IL-18) in urine of critically ill children and compared them with sCr. Among the biomedical studies analyzed in our literature review, 9 measured the NGAL level in urine or both in urine and serum, while 2measured IL-18 in urine. It was determined that uNGAL and uIL-18 were good early diagnostic biomarkers of AKI, which increased 48 h earlier than Cr in serum (P<0.005). The meta-analysis carried out by Haase et al. showed that uNGAL predicted the development of AKI better in critically ill children than in adults (OR, 25.4; ROC, 0.930 vs. OR, 10.6; ROC, 0.782). Three studies reported that the uNGAL level in study populations with AKI directly depended on disease severity and AKI degree (P<0.005). Four studies found that uNGAL and one study that uIL-18 are good predictive factors of mortality (P<0.005).Conclusions. uNGAL and uIL-18 are early predictive biomarkers of AKI in critically ill children. uNGAL and uIL-18 level cor-related well with disease severity and are independent predictive biomarkers of mortality.

Nesiritide modulates inflammatory response during cardiac surgery: A pilot study

Objectives: We investigated the effects of nesiritide (NES) on inflammatory response during cardiac surgery. Materials and Methods: Twenty-nine cardiac surgery patients were randomized to an infusion of NES at 0.01 mcg/kg/min for 48 h versus placebo (Ctrl). A panel of candidate biomarkers and clinical parameters were measured at predetermined time points. Results: There were no significant differences between the groups with regard to urine neutrophil gelatinase-associated lipocalin (NES 230.3 + 71.5 ng/mL vs. Ctrl 554.4 + 263.3 ng/mL, P = 0.253) and urine interleukin (IL)-18 (NES 29.9 + 4.8 pg/mL vs. 254.5 + 118.3 pg/mL, P = 0.090), or to the incidence of acute kidney injury (NES 7.1% vs. Ctrl 13.3%, P = 0.374). A concerted biomarker kinetic pattern of time-differentiated peak concentrations was observed. IL-10, inflammatory protein (IP)-10, IL-6, IL-10, IP-10, monocyte IP (MIP)-1α, interferon (IFN)-α, IFN-α, IL-1a, IL-3, and IL-7 reached peak concentration at 0 h following the end of cardiopulmonary bypass; tumor necrosis factor (TNF)-α, endothelial growth factor (EGF), granulocyte macrophage-colony-stimulating factor (GM-CSF), IL-12p40, IL-17, MIP-1α, and monocyte chemoattractant protein-1 at 1 h; IL-18, vascular EGF (VEGF), IL-13 and IL-1ra at 2 h, TNF-α, G-CSF, IL-1b, IL-2, IL-4, IL-5, and IL-15 at 4 h; and endothelin (ET)-1 and IL-18 at 6 h. At 0 h, the NES group exhibited significant reduction of peak concentrations of IL-6 (P = 0.009), IL-10 (P = 0.009), IL-1α (P = 0.020), IP-10 (P = 0.001), and IFN-α (P = 0.032) compared to the Ctrl group. Significant reduction in peak concentrations of TNF-α (P = 0.007) and MIP1-α (P = 0.027) at 1 h and ET-1 (P = 0.020) at 6 h in the NES group compared to the Ctrl group was noted. Conclusion: NES modulated the concerted inflammatory response in cardiac surgery and also attenuated ET-1 response, thus suggesting that previously observed favorable renal effect may be linked to reduced renal vasoconstriction.

Маркеры повреждения почек в диагностике инфекционно-воспалительных у пациентов с мочекаменной болезнью после контактной уретеролитотрипсии

Currently one of the main methods of treatment of patients with ureteral stones is contact ureterolithotripsy (CULT). Despite the high effectiveness of the method, the problem of early detection and prevention of exacerbation of inflammatory complications of nephrolithiasis remains urgent. To improve the diagnosis of pyelonephritis after CULT in patients with urolithiasis, a study of the diagnostic efficacy of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, s2-microglobulin, and interleukin-18 was performed in 123 patients with ureteral stones. The greatest value in preoperative diagnostics of pyelonephritis was demonstrated for serum NGAL of blood, urine NGAL, and urine s2-microglobulin. The most significant increase during early term (2 hours) after CULT was observed for urine s2-microglobulin and IL-18. The concentration of urine NGAL among all the studied markers remained elevated for a relatively longer period.

Effects of Pioglitazone and Irbesartan on Endothelial Dysfunction on Experimentally Streptozotocin-Induced Diabetic Nephropathy in Rats

Background and Aim. Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED) that leads to the pathogenesis of diabetic nephropathy (DN). Diabetic nephropathy (DN) is a main cause of end stage renal disease. This study was designed to investigate the protective effects of irbesartan (IRB) and its combination with pioglitazone (PIO) on impaired endothelial dysfunction, oxidative stress, and inflammation beyond blood glucose control in streptozotocin- (STZ-) induced diabetic nephropathy in rats. Materials and Methods. Forty-eight male albino rats were divided equally and randomly into six groups: A (control non- diabetic non-treated) and B (diabetic non-treated) injected intraperitoneally by streptozotocin (65mg/kg) and nicotinamide (110 mg/kg) to induce diabetic nephropathy; C (diabetic treated with IRB (30mg/kg/daily) orally), D (diabetic treated with PIO (30mg/kg/daily) orally), E (diabetic treated with IRB and PIO in doses (30 mg/kg/day and 30 mg/kg/day) orally), and F (diabetic treated with IRB and PIO in doses (5mg/kg/day and 15mg/kg/day, resp.) orally for 12 weeks). Fasting blood glucose, urea, creatinine, albumin in urine levels, IL-6, nitric oxide (NO), and Malondialdehyde peroxidase (MDA) were determined in serum of the different groups at the end of the experiment; renal blood flow and aortic and renal histopathological changes were also evaluated. Results. Administration of irbesartan and pioglitazone to diabetic rats caused significant decrease in levels of urea, creatinine, albumin, serum inflammatory mediators (IL-6 and NO), and oxidative stress markers. The effects of irbesartan and/or pioglitazone were associated with improvement of renal blood flow, and they markedly reduced vascular and renal damage induced by diabetes. Conclusion. The results of the present study support the fact that the combination between irbesartan and pioglitazone was better than monotherapy on endothelial dysfunction and diabetic nephropathy through inhibition of the pro-inflammatory mediators, NO bioavailability, and oxidative stress, which are independent of their glucose-lowering properties. And there was no significant difference between the combination of pioglitazone and irbesartan in large doses and in low doses.

Repeated intravesical injections of platelet-rich plasma are effective in the treatment of interstitial cystitis: a case control pilot study.

Interstitial cystitis (IC), also known as bladder pain syndrome (BPS), is a debilitating chronic disease. There are few treatment options for IC/BPS refractory to current medical therapy. This study investigated the clinical efficacy of intravesical injections of platelet-rich plasma (PRP) in IC/BPS. Fifteen patients with IC/BPS received 4 intravesical injections, at 1-monthly intervals, of 12 mL PRP extracted from 50 mL of the patient's whole blood, followed by cystoscopic hydrodistention. The primary endpoint was the change in O'Leary-Sant symptom (OSS) index from baseline to 1 month after the 4th PRP injection. Secondary endpoints were changes in pain (measured using a visual analog scale [VAS]), daily frequency, nocturia, functional bladder capacity (FBC), maximum flow rate, voided volume, post-void residual (PVR) volume, and global response assessment (GRA). Urinary cytokine levels were measured at baseline and 1 month after the 1st PRP treatment. Of the 15 women in the study, 13 completed the 4 injections and follow-up visits (mean [± SD] age 52.9 ± 12.1 years). The OSS index and VAS pain score decreased significantly and FBC and GRA increased after the 1st PRP injection and lasted until the final endpoint. There was no change in PVR after repeated PRP injections, and all patients were free of urinary tract infections and difficulty urinating. Urinary interleukin (IL)-2 and IL-8 concentrations increased significantly after the 1st PRP injection. In patients with reductions in the VAS pain score ≥1, urinary IL-8 and vascular endothelial growth factor increased. In patients without reductions in the VAS pain score, IL-6 concentrations increased after PRP injection. Repeated intravesical PRP injections are well tolerated and appear to be safe and effective in medically refractive IC/BPS, providing significant symptom improvement.

Epidemiology of Acute Kidney Injury

The worldwide incidence of acute kidney injury (AKI) is increasing. Recent surveys demonstrated that AKI occurs in 21% of hospital admissions. In low-income countries, AKI has a bimodal presentation. In large urban centers, the pattern of AKI is very similar to that found in high and upper middle-income countries, with a predominance of hospital-acquired AKI, occurring mostly in older, critically ill, multiorgan failure patients with comorbidities. At the same time, in regional hospitals in small urban communities and rural areas, AKI is usually a community-acquired disease (related to diarrheal and infectious diseases, animal venom, and septic abortion). Although AKI mortality seems to be decreasing, it remains extremely high, varying from 23.9 to 60% in recent series. The most important risk factors for short-term mortality (in hospital or &lt; 90 days) in AKI are the primary diagnosis (sepsis) and the severity of the acute illness, expressed by the presence of nonrenal organ dysfunction. New biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, cystatin C, and interleukin-18 measurements, have been able to identify patients with AKI who are at risk for a less favorable prognosis, such as the likelihood of the need for renal replacement therapy, nonrecovery of kidney function, and higher mortality. Several studies have demonstrated an association between hospital-associated AKI and postdischarge mortality in a variety of contexts, and the most important risk factors for this late lethality are older age, preexisting comorbid disease (chronic kidney disease [CKD], cardiovascular disease, or malignancy), and incomplete organ recovery with ongoing residual disease. AKI is associated with de novo end-stage renal disease (ESRD) (CKD, progression of preexisting CKD) and the occurrence of ESRD in the long term. Herein, it is suggested that high-risk patients recovering from an AKI episode, such as those with baseline CKD, diabetes mellitus, or heart failure and those dialyzed for AKI, should likely be followed by a nephrologist.

The effect of whole-body cooling on renal function in post-cardiac arrest patients

To evaluate the incidence of Acute Kidney Injury (AKI) during therapeutic hypothermia (TH) and rewarming in comatose patients resuscitated from Cardiac Arrest (CA). We have performed a pilot study of consecutive comatose patients resuscitated from CA and admitted to our Intensive Care Unit (ICU) from January 2013 to March 2015. The surface cooling devices used were: 1) Arctic Sun® 5000; 2) Blanketrol® III. Data obtained at baseline and during TH included: temperature trend and rate, serum creatinine, interleukin 1-beta, interleukin 6 (IL-6), urinary Interleukin-18 (uIL-18), diuretic use, urine output, fluid balance (FB). AKI was defined according to Kidney Diseases Improving Global Outcomes (KDIGO) criteria. Thirty-six patients were treated with TH out of 46 ICU admissions (78%). According to KDIGO classification, 21 (58%) had no evidence of AKI while 15 (41.7%) presented AKI during TH. In particular, the incidence of AKI was 2.8% at 24 h, 33.33% at 48 h and 30.6% at 72 h from the onset of cooling. Slower rewarming (above 600 min) was associated with with a non-significant lower incidence of AKI and with a non-significant lower levels of IL-6 and IL-18u. Only two patients required renal replacement therapy during TH (7.6%). Median cumulative FB was 2441 [437–4043] ml for all patients; 3140 [1421–4347] and 1332 [−131–3772] specifically for AKI and not-AKI patients. The hypothermia treatment, if not well performed, could be a double-edged sword for kidneys: whereas hypothermia may confer protection by reducing metabolism and oxygen consumption, rapid rewarming could nullify benefits leading to a worsening of kidney function and AKI. Additional clinical studies are needed to determine the optimal rewarming rate and strategy.

Biomarkers of IgA vasculitis nephritis in children.

Henoch–Schönlein purpura is a systemic vasculitis characterized by IgA deposits, which target the skin, joints, and kidneys, among other organs. In children, prognosis is often good but little is known about biomarkers of pediatric nephritis. We hypothesized that biological markers, including cytokines, immunoglobulins, IgA-immune complexes, IgA glycosylation and neutrophil gelatinase-associated lipocalin (NGAL), may discriminate IgA vasculitis (IgAV) pediatric patients with renal involvement from those without renal involvement. Fifty children at the time of IgAV rash between 2010 and 2015 were prospectively enrolled and compared to 21 controls. All patients were assessed for clinical and biological parameters at the time of diagnosis, including the levels of cytokines, immunoglobulins, immune complexes, IgA glycosylation and NGAL in serum and urine. Among IgAV patients, 33 patients exhibited nephritis (IgAV-N) and 17 children were without nephritis (IgAV-woN). The serum level of galactose-deficient (Gd)-IgA1 (p<0.01) and the urinary concentrations of IgA, IgG, IgM, IL-6, IL-8, IL-10, IgA-IgG complexes and IgA-sCD89 complexes (p<0.001 for all) were higher in the IgAV-N patients than in the IgAV-woN patients. Among those markers, urinary IgA and IgM had the highest AUC (0.86 and 0.87 respectively, p<0.0001). This prospective cohort study furthers our understanding of the pathophysiology of IgAV. We identified biomarkers that are able to distinguish patients initially with or without nephritis. To conclude, serum Gd-IgA1 and urinary IgA, IgG, IgM, IL-6, IL-8, IL-10, and IgA-IgG and IgA-sCD89 complexes could identify IgAV pediatric patients with renal involvement at the time of diagnosis.

High urinary interleukin-2 in late post-transplant period portends a risk of decline in kidney allograft function: a preliminary study

BackgroundPredictive factors for the rate of decline in kidney allograft function beyond the first post-transplant year have not been thoroughly studied. We aimed to determine whether a single measurement of serum and urinary interleukin 2, interleukin 8 and interleukin 10 at 1–15 years after kidney transplantation could predict a decline in estimated glomerular filtration rate (eGFR) over a 2-year period.ResultsGreater serum concentrations of interleukin 8 and interleukin 10 in 30 recipients of kidney allograft at enrollment were associated with lower eGFR after 1 year (beta = − 0.616, p = 0.002 and beta = − 0.393, p = 0.035, respectively), whereas serum concentrations of interleukin 8 also demonstrated significant association with eGFR after 2 years of follow-up (beta = − 0.594, p = 0.003). Higher urinary interleukin 2 concentrations were associated with lower eGFR at baseline (rho = − 0.368, p = 0.049) and after the first (beta = − 0.481, p = 0.008) and the second year (beta = − 0.502, p = 0.006) of follow-up. Higher urinary interleukin 2 concentrations predicted certain decline in eGFR of ≥ 25% from baseline after 1 year of follow-up in logistic regression: odds ratio = 2.94, confidence interval 1.06–8.18, p = 0.038. When combined with time after transplantation, urinary interleukin 2 demonstrated good accuracy in predicting rapid decline in eGFR by > −5 mL/min/1.73 m2/year (area under the receiver-operator characteristic curve: 0.855, confidence interval 0.687–1.000, and p = 0.008).ConclusionsOur findings suggest that urinary interleukin 2 in the late period after kidney transplantation has promise in identifying patients who are at risk for progressive loss of graft function in a short-time perspective and need closer monitoring.

Value of biomarkers for predicting immunoglobulin A vasculitis nephritis outcome in an adult prospective cohort.

Henoch-Schönlein purpura, more recently renamed immunoglobulin A vasculitis (IgAV), is a systemic vasculitis characterized by IgA deposits. The current markers used to assess IgAV inaccurately evaluate the risk of nephritis occurrence and its long-term outcomes. The current study assessed biomarkers of nephritis outcomes. This French multicentre prospective study enrolled 85 adult patients at the time of disease onset. Patients were assessed for clinical and biological parameters and re-examined after 1 year. Immunoglobulins, cytokines, IgA glycosylation, IgA complexes and neutrophil gelatinase-associated lipocalin (NGAL) concentrations were assessed in blood and urine. We identified 60 patients with IgAV-related nephritis (IgAV-N) and 25 patients without nephritis (IgAV-woN). At the time of inclusion (Day 1), the serum levels of galactose-deficient IgA1 (Gd-IgA1) and urinary concentrations of IgA, IgG, IgM, NGAL, interleukin (IL)-1β, IL-6, IL-8, IL-10, IgA-IgG and IgA-sCD89 complexes were higher in the IgAV-N patients than in the IgAV-woN patients (P < 0.005 for all comparisons). After follow-up (1 year), 22 patients showed a poor outcome. Among the tested markers, urine IgA at disease onset adequately reclassified the risk of poor outcome over conventional clinical factors, including estimated glomerular filtration rate, proteinuria and age (continuous net reclassification improvement = 0.72, P = 0.001; integrated discrimination improvement = 0.13, P = 0.009) in IgAV patients. Taken together, these results showed that serum Gd-IgA1 and urinary IgA, IgG, IgM, NGAL, IL-1β, IL-6, IL-8, IL-10, IgA-IgG and IgA-sCD89 complexes were associated with nephritis in IgAV patients. Urinary IgA level may improve patient risk stratification for poor outcome.