Urinary Monocyte Research Articles

Preliminary Study for New Markers of Early Tubuloglomerular Injury and Renal Inflammation in Patients with Visceral Leishmaniasis Receiving Liposomal Amphotericin B Treatment.

Visceral leishmaniasis is treated with liposomal amphotericin B (L-AMB), which is associated with nephrotoxicity. Thus, we aimed to investigate nephrotoxicity through novel renal biomarkers in patients with visceral leishmaniasis during L-AMB use. Ours was a prospective study with 17 patients with visceral leishmaniasis treated with L-AMB during their hospital stay. Laboratory tests, renal parameters, urinary biomarkers (urinary kidney injury molecule 1, urinary monocyte chemoattractant protein 1 [uMCP-1], sodium-potassium-2 chloride cotransporter, sodium-hydrogen exchanger 3), and serum inflammatory biomarkers (MCP-1, interferon-γ, and IL-6) were evaluated in two periods: before and during L-AMB use. Glomerular filtration rate, creatinine, proteinuria, and albuminuria were similar before and during L-AMB use. IL-6 levels, aquaporin 2, and sodium-hydrogen exchanger 3 expression decreased, whereas uMCP-1 and urinary kidney injury molecule 1 levels increased during L-AMB treatment. In patients who developed acute kidney injury, uMCP-1 showed higher levels. L-AMB aggravated tubuloglomerular lesions, inflammation, and renal tubular disorders. Thus, patients treated with L-AMB need to be monitored for inflammatory and electrolyte disturbances to prevent acute kidney injury, longer length of hospital stay, higher public costs, and mortality.

C5a receptor inhibitor avacopan in immunoglobulin A nephropathy-an open-label pilot study.

ABSTRACTBackgroundImprovement of proteinuria as a marker for disease activity is associated with a better renal outcome in immunoglobulin A nephropathy (IgAN). Complement is an effector pathway in IgA-mediated kidney injury. Avacopan, a selective C5a receptor inhibitor, has previously shown efficacy in anti-neutrophil cytoplasmic antibody–associated vasculitis. The aim of this study was to evaluate the safety and efficacy of avacopan in patients with IgAN with persistent proteinuria despite a maximally tolerated dose of renin–angiotensin–aldosterone system blockade. The efficacy evaluation was based on the change in proteinuria.MethodsThis open-label pilot trial enrolled adult patients with biopsy-proven IgAN, urinary protein:creatinine ratio (UPCR) >1 g/g creatinine and an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 or >45 mL/min/1.73 m2 if eGFR has not declined >10 mL/min/1.73 m2 over the previous 24 weeks. If the UPCR remained at >1 g/g creatinine after an 8-week run-in period, patients started avacopan 30 mg twice daily. The primary efficacy endpoint was the change in the slope of the UPCR from the 8-week run-in period to the slope in the 12-week avacopan dosing period.ResultsA total of 10 of 15 screened patients entered the run-in period. Seven patients with a UPCR >1 g/g creatinine received avacopan. Six of seven patients had numerical improvement in the UPCR during the avacopan treatment period, three of whom had a numerical improvement of ∼50% at week 12. At week 24, five of seven patients still showed numerical improvement in the UPCR compared with baseline. The urinary monocyte chemoattractant protein-1:creatinine ratio decreased numerically 30% by week 8, possibly reflecting the anti-inflammatory activity of avacopan. Avacopan was well tolerated. There was one serious adverse event of unstable angina, which was deemed to be unrelated to avacopan.ConclusionsThis short-term pilot study showed an improvement in the slope of the UPCR, with ∼50% improvement in three of seven patients with IgAN. Longer avacopan treatment duration may be indicated for maximal benefit.

Steroid Responsiveness and Urinary Monocyte Chemotactic Protein-1 in Children with Nephrotic Syndrome.

Steroid Responsiveness and Urinary Monocyte Chemotactic Protein-1 in Children with Nephrotic Syndrome.

Urinary monocyte chemotactic protein 1 as a predictive marker of steroid responsiveness in children with idiopathic nephrotic syndrome

Urinary monocyte chemotactic protein 1 as a predictive marker of steroid responsiveness in children with idiopathic nephrotic syndrome

Prognostic and Diagnostic Values of Novel Serum and Urine Biomarkers in Lupus Nephritis: A Systematic Review

Introduction: While renal biopsy remains the gold standard for diagnosing lupus nephritis (LN), the prognostic and diagnostic role of non-invasive biomarkers for LN is currently debated. Methods: Available studies published in last 5 years (2015–2020) assessing the diagnostic and prognostic value of urinary and/or serological biomarkers in subjects with LN were analyzed in this systematic review. Results: Eighty-five studies were included (comprehending 13,496 patients with systemic lupus erythematosus [SLE], 8,872 LN, 487 pediatric LN, 3,977 SLE but no LN, 160 pediatric SLE but no LN and 7,679 controls). Most of the studies were cross-sectional (62; 73%), while 14 (17%) were prospective. In sixty studies (71%), the diagnosis of LN was biopsy-confirmed. Forty-four out of 85 (52%) investigated only serological biomarkers, 29 studies (34%) tested their population only with urinary biomarkers, and 12 (14%) investigated the presence of both. Outcome measures to assess the clinical utility of the analyzed biomarkers were heterogeneous, including up to 21 different activity scores, with the SLEDAI (in 60%) being the most used. Despite some heterogeneity, promising results have been shown for biomarkers such as urinary monocyte chemoattractant protein, urinary adiponectin, and urinary vascular cell adhesion protein 1. Discussion/Conclusion: While serum and urine biomarkers have the potential to improve diagnostic and prognostic pathways in patients with LN, the vast heterogeneity across studies severely limits their applicability in current clinical practice. With the kidney biopsy still representing the gold standard, future efforts should focus on harmonizing study inclusion criteria and outcomes, particularly in clinical trials, in order to improve comparability and facilitate the implementations of available biomarkers into the daily practice.

FC 032THE EFFECT OF AVACOPAN, A COMPLEMENT C5A RECEPTOR INHIBITOR, ON KIDNEY FUNCTION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS WITH RENAL DISEASE

Abstract Background and Aims Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a life- or organ-threatening condition in which patients experience severe inflammation of small arteries. Renal involvement is common in ANCA-associated vasculitis and is correlated with high morbidity and mortality. Current treatment regimens have limited efficacy for renal disease in patients presenting with organ- or life-threatening ANCA-associated vasculitis. Avacopan, a novel orally-administered antagonist of the complement fragment C5a receptor (C5aR), was evaluated through a Phase 3 trial in patients with ANCA vasculitis. Efficacy and safety results have been previously reported; this abstract provides details of the effects on renal function in patients with renal involvement. Method The ADVOCATE trial was a randomized, double-blind, active controlled, double-dummy, 52-week treatment Phase 3 trial of 331 patients with ANCA-associated vasculitis. Patients were randomized 1:1 and received either a standard daily prednisone dosing with taper (i.e., starting at 60 mg / day tapered to 0 mg by Week 21), or daily avacopan. Background therapy included either: a) cyclophosphamide (oral or IV) followed by azathioprine, or, b) rituximab (four IV infusions). Patients with active glomerulonephritis at baseline were included in this analysis. Kidney function was analyzed based on the following parameters, which were assessed at pre-specified time-points: changes in the urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and Urinary Monocyte Chemoattractant Protein-1 (MCP-1):Creatinine ratio. Results At the baseline visit, 265 patients had renal disease. eGFR improved more in the avacopan group (n=131) compared to the prednisone group (n=134). At Week 26, eGFR increased 5.8 mL/min/1.73 m2 (from a baseline of 44.6 mL/min/1.73 m2), compared to 2.9 mL/min/1.73 m2 in the prednisone group (from a baseline of 45.6 mL/min/m2), P=0.046. At Week 52, the increases in eGFR were 7.3 mL/min/1.73 m2 and 4.1 mL/min/1.73 m2, respectively, P=0.029. The improvement was most prominent in subjects with Stage 4 kidney disease at baseline (eGFR < 30 mL/min/1.73 m2), in whom eGFR improved 13.7 mL/min/1.73 m2 at Week 52 in the avacopan group (from a baseline of 21.1 mL/min/1.73 m2) compared to 8.2 mL/min/1.73 m2 in the prednisone group (from a baseline of 21.6 mL/min/1.73 m2), P=0.005. In addition to the differences in eGFR, a more rapid decrease in UACR was observed with avacopan; by Week 3 this difference was statistically significant, and at Week 4, a 40% decrease from baseline occurred in the avacopan group vs no change from baseline in the prednisone group (P<0.0001). By Week 52, both groups showed a similar decrease in UACR from baseline. The urinary MCP-1:creatinine ratio decreased 59% in the avacopan group by Week 13 vs 52% in the prednisone group, P=0.03, but there was a similar decrease in the two treatment groups by Week 52. Conclusion Treatment with avacopan in patients with ANCA-associated vasculitis with renal disease led to greater recovery in eGFR when compared to standard prednisone therapy, especially in patients with Stage 4 kidney disease (eGFR <30 mL/min/1.73 m2). Avacopan also led to more rapid improvement in the UACR and urinary MCP-1:creatinine ratio than prednisone. Since albuminuria is an independent risk factor for progression of renal disease (in addition to eGFR decline), the more rapid improvement in albuminuria with avacopan may also provide long-term benefit. These findings have important implications for the health of patients with ANCA-associated vasculitis.

Serum interferon-γ and urinary monocyte chemoattractant peptide-1 are important factors in the pathogenesis of immunoglobulin A nephropathy.

BackgroundImbalance of T helper (Th) 1/2 cells has been shown to contribute to the development of immunoglobulin A nephropathy (IgAN). To address the inconsistent results on the role of Th1/Th2 polarization, we evaluated the levels of Th1/Th2 cytokines in various samples from patients with IgAN.MethodsThirty-one patients with biopsy-proven IgAN (age, 34.48 ± 12.10 years) and 25 healthy controls (age, 44.84 ± 13.72 years) were enrolled. We evaluated the relationship between the levels of Th1/Th2 cytokines and the response to glucocorticoid treatment.ResultsThe levels of serum interferon-gamma (IFNγ) and urinary monocyte chemoattractant peptide (MCP)-1 were higher in the IgAN group than in the control group. The levels of MCP-1 in urine and secreted by peripheral blood mononuclear cells (PBMCs) were significantly different among three groups categorized based on daily proteinuria. The level of urinary MCP-1 was significantly correlated with proteinuria. The levels of urinary MCP-1, serum interleukin (IL)-4, IFNγ, and IL-2 secreted by PBMCs and intrarenal IL-1 messenger RNA (mRNA) were significantly correlated with the ratio of proteinuria at 6 months to baseline proteinuria in patients undergoing glucocorticoid treatment. MCP-1 mRNA and protein levels were significantly upregulated in mesangial cells stimulated with IFNγ among representative Th1/Th2 cytokines.ConclusionIFNγ was shown to be a key cytokine in the pathogenic processes underlying IgAN, and its upregulation induced an increase in urinary MCP-1 production. These findings suggest that Th1 cytokines may play an important role in the development of IgAN.

Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa.

Treatment of patients with lupus nephritis (LN) requires judicious use of immunosuppression. Novel biomarkers may be useful for monitoring disease activity and treatment response. We assessed the utility of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tumour necrosis factor-like weak inducer of apoptosis (uTWEAK) for disease activity and treatment response monitoring in South Africans with LN. We recruited consenting patients with active LN confirmed on kidney biopsy. Urinary levels of MCP-1 and TWEAK were assayed at baseline and after completion of induction therapy using ELISA methods. We also collected relevant demographic, clinical and biochemical data for patients included in this study. The mean age of patients in this study was 29.8 ± 10.7years, 60% were patients of mixed ancestry, 70% had proliferative LN and mean spot urine proteinuria at baseline was 0.37 (0.18-0.59) g/mmolCr. At completion of induction therapy, the level of uMCP-1 had reduced to 314.5 (IQR: 197.0-622) pg/mgCr from a baseline of 1092.7 (IQR 578.6-1848) pg/mgCr (P = 0.06) while uTWEAK had reduced to 36.0 (IQR 17.0-88.0) pg/mgCr from 159.0 (IQR: 88.5-295.5) pg/mgCr (P = 0.03). For patients reaching early complete or partial remission (n = 17), both biomarkers had significantly declined in their urine: uMCP-1 (P = 0.018) and uTWEAK (P = 0.015). There was no reduction of both biomarkers in patients not achieving remission and no association between uMCP-1 or uTWEAK with renal histological features. Our study shows that uMCP-1 and uTWEAK are elevated in patients with active LN, correlated with the remission status (response to treatment) at the end of induction therapy and can, therefore, be useful for monitoring disease activity and treatment response.

Urinary Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (uTWEAK) and Urinary Monocyte Chemo-attractant Protein-1 (uMCP-1): Promising Biomarkers of Lupus Nephritis Activity?

There is no single biomarker to detect lupus nephritis (LN) activity. Renal biopsy is still the gold standard method but it is invasive and mainly used in the initial assessment of the patients. Urinary tumor necrosis factor-like weak inducer of apoptosis (uTWEAK) and urinary monocyte chemo-attractant protein-1 (uMCP-1) can be secreted in the urine of active LN. The aim of the study is to assess the potential role of uTWEAK and uMCP-1 in lupus patients and to determine their correlation with disease activity. This is a case-control study conducted on a total of 114 subjects; 92 systemic lupus erythematosus (SLE) patients and 22 healthy volunteers. The patients were recruited from the rheumatology unit at the internal medicine department, Tanta University Hospital, Tanta, Egypt. The patients and controls were subjected to full history taking, complete clinical examination, routine laboratory tests, uTWEAK and uMCP-1 measurement, assessment of the disease activity using SLE Disease Activity Index (SLEDAI), and renal SLEDAI (rSLEDAI) scores. uTWEAK and uMCP-1 levels were higher in SLE with active nephritis group than those of other SLE groups and controls. There was a significant positive correlation between uTWEAK and uMCP-1 levels in lupus patients with proteinuria, anti-dsDNA, SLEDAI and r-SLEDAI and a negative correlation with C3 and C4. TWEAK showed a sensitivity of 80.43% and 100% and specificity of 50% and 100% in detecting lupus activity and LN activity, respectively. Furthermore, uMCP-1 showed a sensitivity of 82.6% and 100% and specificity of 50% and 100% in detecting lupus activity and LN activity, respectively. uTWEAK and uMCP-1 are new, easily obtained, accurate markers with high sensitivity and specificity in the detection of LN activity.

Diagnostic potential of urinary monocyte chemoattractant protein-1 for Alzheimer's disease and amnestic mild cognitive impairment.

The chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether urinary MCP-1 can distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects. A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age- and sex-matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP-1 levels were determined using enzyme-linked immunosorbent assays. The correlations between urinary MCP-1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. In the cohort of CN subjects of different ages, urinary MCP-1 levels increased with ageing and were correlated with age. The urinary MCP-1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age- and sex-matched CN controls, urinary MCP-1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP-1 levels between the AD group and the aMCI group. The urinary MCP-1 levels were correlated with the Mini-Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects. Urinary MCP-1 is a potential biomarker for the diagnosis of AD and aMCI.

Changes of urinary monocyte chemotactic protein 1 and epidermal growth factor and their correlations with clinicopathology in idiopathic membranous nephropathy patients

Objective: To explore the changes and clinical value of urinary monocyte chemotactic protein 1 (MCP-1), epidermal growth factor (EGF) and their ratio in patients with idiopathic membranous nephropathy (IMN). Methods: A total of 67 IMN patients were enrolled according to kidney biopsy in the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2018. The patients included 28 males and 39 females, with an average age of (47.6±14.2) years. Eighteen age-and sex-matched healthy controls were also enrolled. Clinical and pathological data, blood and urine samples of all subjects were collected. Urinary MCP-1 and EGF level were detected by enzyme-linked immunosorbent assay (ELISA). And then the levels of urinary MCP-1, EGF and the ratio of EGF/MCP-1 and their correlations with clinicopathology were analyzed. Results: There was no statistical difference of the urine EGF levels between the two groups [8.3(6.0,12.6) vs 8.4(6.5,10.2) ng/mg Cr, P=0.575]. The urine MCP-1 levels of IMN patients were 0.37 (0.21, 0.69) ng/mg Cr, which was statistical significantly higher than those of the control group [0.09 (0.02, 0.19) ng/mg Cr] (P<0.001), while the EGF/MCP-1 ratio was lower than that of the control group [22.2(15.1,36.6) vs 87.6(71.2,132.7), P<0.001]. Urine MCP-1 was negatively correlated with eGFR (r=-0.303, P=0.012), but positively correlated with the urinary ratio of albumin to creatinin (r=0.368, P=0.002). EGF was positively correlated with eGFR (r=0.722, P<0.001), but negatively correlated with the severity of interstitial fibrosis and renal tubular atrophy (IFTA) (r=-0.312, P=0.011). EGF/MCP-1 ratio was positively correlated with eGFR (r=0.693, P<0.001), but negatively correlated with the severity of the urinary ratio of albumin to creatinin and IFTA (r=-0.261, P=0.028 and r=-0.684, P<0.001, respectively). Further multivariate logistic regression analysis showed that EGF/MCP-1 was a protective factor for moderate-to-severe IFTA (OR=0.891, 95%CI: 0.844-0.949, P=0.008). Conclusion: Patients with IMN have elevated urine MCP-1 level and decreased EGF/MCP-1 ratio, which correlate with clinical indicators. In particular, EGF/MCP-1 ratio is independently related to moderate-severe IFTA, and may be a potential clinical biomarker for diagnosis of IMN.

Urinary monocyte chemoattractant protein 1 associated with calcium oxalate crystallization in patients with primary hyperoxaluria

BackgroundPatients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments.MethodsA panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24 h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and eGFR.ResultsMean (±SD) age at first visit was 19.5 ± 16.6 years with an estimated glomerular filtration rate (eGFR) of 68.4 ± 21.0 ml/min/1.73m2. After adjustment for age, sex, and eGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher eGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS.ConclusionIn PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.

Diagnostic value of urinary monocyte chemoattractant protein-1 in evaluating the activity of lupus nephritis: a meta-analysis.

ObjectiveThis study aimed to assess systematically the overall diagnostic value of urinary monocyte chemoattractant protein-1 (uMCP-1) in systemic lupus erythematosus (SLE) patients with active lupus nephritis (LN).MethodsArticles from PubMed, Web of Science, EMBASE and Cochrane Library were retrieved up to 5 November 2019. Study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, and statistical analyses were performed.ResultsA total of seven original studies with 521 participants were included in this meta-analysis. The summary estimates were: sensitivity 0.89 (95% confidence interval (CI) 0.86–0.93), specificity 0.63 (95% CI 0.55–0.69), positive likelihood ratio 2.16 (95% CI 1.66–2.80), negative likelihood ratio 0.15 (95% CI 0.08–0.30), diagnostic odds ratio 19.40 (95% CI 7.24–51.96) and area under the curve 0.9042.ConclusionAs a non-invasive biomarker, uMCP-1 has high diagnostic accuracy for active LN.

Clinical Significance of Urinary Monocyte Chemoattractant Protein-1 (uMCP-1) and TNF-Alfa in Indian Type 2 Diabetic Patients at Different Stages of Diabetic Nephropathy

Introduction: TNF alfa and Monocyte Chemoattractant Protein-1 (MCP-1) are inflammatory markers upregulated in diabetic nephropathy. This study aims to find the levels of urinary MCP-1 (uMCP-1) and serum TNF alfa levels at different stages of diabetic nephropathy and to see its correlation with UACR(Urinary Albumin Cdeatinine Ratio) in Indian type2 diabetic subjects Methods: Consecutive Patients of Type 2 Diabetes Mellitus (DM) with or without microalbuminuria attending SCB MEDICAL COLLEGE and HOSPITAL Medical OPDs in one year were recruited in this study.Patients were subjected to blood and urine investigations. Groups are Group 1 (control), Group 2 (diabetes with normoalbuminuria), Group 3 (diabetes with microalbuminuria), Group 4 (diabetes with macroalbuminuria). Diabetic Nephropathy were classified according to KIGDO staging. Anthropometric and biochemical details were recorded for all the subjects.UACR calculated by the formula which has been approved by National Kidney Disease Education Program. Urinary MCP-1 and TNF alfa levels were measured by using ELISA. Results: S.urea creatinine, Total cholesterol, TG, LDL, UACR, S.TNF alfa, UMCP1 levels are significantly high in diabetes with macroalbuminuria group (p = 0.01, 0.001, 0.013, 0.01, <0.01, <0.01, <0.01, 0.01 respectively). UACR is positively correlated with umcp1 (r= 0.413 , P=<0.01) and S.TNF alfa (r= 0.218, p=0.008). Increasing uMCP-1, S.TNF alfa levels with the progression of diabetic nephropathy indicating the extent of renal tubular and glomerular damage (p value 0.015,0.008 respectively.) Funding Statement: The authors stated: No funding has been allocated to this research work. Declaration of Interests: The authors declared: There is no conflict of interest. Ethics Approval Statement: This cross-sectional study has been approved by Ethical committee

Association of NFkB1 Gene Polymorphism with Inflammatory Markers in Patients of Type 2 Diabetes Mellitus with or without Renal Involvement in Eastern India

Aims: To evaluate the association of Nuclear factor kappa B1(NFkB1) gene polymorphism with inflammatory markers Urinary Monocyte Chemoattractant Protein 1 (UMCP1) and Tumor Necrosis Factor alfa (TNF alfa) in Patients of diabetes mellitus with or without renal involvement in Eastern India. Material and Methods: Consecutive Patients of Type 2 Diabetes Mellitus (DM) with or without microalbuminuria attending SCB MEDICAL COLLEGE and HOSPITAL Medical OPDs in between September 2018 to September 2019 were recruited in this study. Patients were subjected to blood and urine investigations. DNA extraction and Restriction fragment Length Polymorphism (RFLP) was done in Department of Biochemistry. Controls were unrelated healthy attendants with no history of Diabetes Mellitus, HTN, Chronic Kidney Disease (CKD). Results: Mean Systolic BP, Fasting Blood Glucose, Post Prandial Blood Glucose, HBA1c, Total Cholesterol were significantly higher in diabetes mellitus and diabetic nephropathy groups than control group. Estimated Glomerular Filtration Rate was significantly lower in diabetic nephropathy (p value < 0.001). UMCP1, Urinary Albumin Creatinine Ratio, TNF alfa were higher in diabetes mellitus and nephropathy with p value (<0.001, 0.006 < 0.001) respectively. In between DM and Diabetic Nephropathy groups nfkb1 gene expression, umcp1 and tnf alfa levels were significantly increased in Diabetic nephropathy with p value 0.019, <0.01, 0.001 respectively. Insertion/insertion NFkB1 gene polymorphisms were more in diabetic nephropathy group and were positively correlated with inflammatory markers UMCP1 (r = 0.517, p < 0.01) and TNF alfa (r = 0.172, p = 0.19). Conclusion: insertion/insertion NFkB1 gene polymorphism increases the risk of nephropathy by 2.52 times (OR = 2.52, 95% CI: 0.04 - 0.63, p value = 0.019) in diabetes patients in eastern India.

Evaluation of Urinary Monocyte Chemoattractant Protein-1and Serum Cystatin C as Markers for Detection of Diabetic Nephropathy in Comparison to Albumin to Creatinine Ratio (ACR)

Evaluation of Urinary Monocyte Chemoattractant Protein-1and Serum Cystatin C as Markers for Detection of Diabetic Nephropathy in Comparison to Albumin to Creatinine Ratio (ACR)

Urinary Monocyte Chemoattractant Protein -1 as A Diagnostic Marker of Lupus Nephritis

Background: Lupus nephritis accounts for significant morbidity and mortality in patients with systemic lupus erythematosus (SLE). Many biomarkers for renal involvement in SLE have been suggested in Egyptian patients; one of them is Monocyte chemoattractant protein-1 (MCP-1) which is one of the key chemokines that have chemotactic effect for monocytes and macrophages to sites of inflammation and may share in the pathogenesis of lupus nephritis (LN). Aim: The study aimed at assessing the role of MCP-1 in the early diagnosis of lupus nephritis and to explore any correlation its levels with disease activity and renal status. Subjects and Methods: The study was done as a case-control study where 60 SLE patients with lupus nephritis (30 patients with active LN and 30 patients with inactive LN) in addition to 30 healthy volunteers as control group were enrolled in the study and MCP-1 levels was determined using ELISA technique. Results: Urinary MCP-1 levels in SLE studied patients’ groups were significantly higher than their level in the control group (p = 0.0001) and it was significantly higher in active LN than in non-active LN subgroups (P-value =0.0001). Conclusion: Urinary MCP-1 can be used as a marker for LN activity. Keywords: SLE, Lupus nephritis, MCP-1

A dual role of 12/15-lipoxygenase in LPS-induced acute renal inflammation and injury

Recent studies suggest a potential role of bioactive lipids in acute kidney injury induced by lipopolysaccharide (LPS). The current study was designed to determine the profiling activities of various polyunsaturated fatty acid (PUFA) metabolizing enzymes, including lipoxygenases (LO), cyclooxygenase, and cytochrome P450 in the plasma of LPS-injected mice using LC-MS. Heat map analysis revealed that out of 126 bioactive lipids screened, only the 12/15-LO metabolite, 12-HETE, had a significant (2.24 ± 0.4) fold increase relative to control (P = 0.0001) after Bonferroni Correction (BCF α = 0.003). We then determined the role of the 12/15-LO in LPS-induced acute kidney injury using genetic and pharmacological approaches. Treatment of LPS injected mice with the 12/15-LO inhibitor, baicalein, significantly reduced levels of renal injury and inflammation markers including urinary thiobarbituric acid reactive substance (TBARs), urinary monocyte chemoattractant protein-1 (MCP-1), renal interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Similarly, knocking-out of 12/15-LO reduced levels of renal inflammation and injury markers elicited by LPS injection. Next, we tested whether exogenous supplementation with docosahexaenoic acid (DHA) as a substrate would divert the role of 12/15-LO from being pro-inflammatory to anti-inflammatory via increased production of the anti-inflammatory metabolite. DHA treatment restored the decreased in plasma level of resolvin D2 (RvD2) and reduced renal injury in LPS-injected mice whereas DHA treatment failed to provide any synergistic effects in reducing renal injury in LPS injected 12/15-LO knock-out mice. The ability of RvD2 to protect kidney against LPS-induced renal injury was further confirmed by exogenous RvD2 which significantly reduced the elevation in renal injury in LPS injected mice. These data suggest a double-edged sword role of 12/15-LO in LPS-induced acute renal inflammation and injury, depending on the type of substrate available for its activity.

Urinary Monocyte Chemotactic Protein -1 in Childhood Nephrotic Syndrome

Background Childhood nephrotic syndrome is a clinical entity characterized by massive loss of urinary protein (primarily albuminuria) leading to hypoproteinemia (hypoalbuminemia) and edema. The mechanism of development of childhood nephrotic syndrome is not yet clear. Kidney disease involves an interplay between inflammatory and biochemical changes with the development of innate immune response and accumulation and activation of leucocytes, particularly monocytes/macrophages in the kidney. The moncyte chemotactic protein-1 (MCP-1) is one of the CC chemokine family and it plays an important role in the recruitment of monocytes/macrophages into renal tubulointerstitium. Aim of the Work The aim was to measure the urinary levels of MCP-1 in children with nephrotic syndrome and compare these levels in remission and relapse as well as in steroid sensitive and steroid resistant cases. Patients and method The study included 70 patients with nephrotic syndrome following up in Pediatric Nephrology Clinic, Ain Shams University diagnosed for at least one year and 20 age and sex matched healthy children as control group. Patients with renal impairment and secondary nephrotic syndrome were excluded from the study. Patients were divided into Group A: 35 patients in remission and Group B: 35 patients in relapse. Subgrouping according to the clinical type of nephrotic syndrome was done. Patients were subjected to thorough history taking and careful clinical examination. Routine laboratory investigations were done (s. albumin, s. creatinine, s. cholesterol, complete urialysis and urinary protein/creatinine ratio) together with quantitative determination of urinary monocyte chemotactic protein-1 in cases and controls. Results We found a highly significant difference in urinary MCP-1 between group A, group B, and controls, the highest being group B. the levels in patients in remission still exceeded the controls significantly. However, in group B, no significant difference was found between clinical types of the disease in urinary MCP-1. The same was found in group A. no difference was found between males and females in group A as regards urinary MCP-1 levels yet females had significantly higher levels in group B. This difference was not seen in controls. We found no significant difference in MCP-1 levels in patients receiving different treatment modalities. Conclusion Urinary MCP-1 is a highly sensitive and specific biomarker in childhood nephrotic syndrome (98.5% and 100% respectively), being highly elevated in both remission and relapse, but is not a suitable prognostic biomarker being insignificantly different among different clinical types of nephrotic syndrome.

Association of urinary monocyte chemoattractant protein-1 (MCP-1) and kidney injury molecule-1 (KIM-1) with risk factors of diabetic kidney disease in type 2 diabetes patients.

Urinary kidney injury molecule-1 and monocyte chemoattractant protein-1 are significance factors in the diagnosis and intervention of diabetic kidney diseases. This study determined levels of these proteins in diabetic patients with varying degrees of kidney disease and assessed their relationship with risk factors associated with diabetic kidney diseases. A total of 185 patients with type 2 diabetes were divided into three groups [low risk (n = 47), moderate risk (n = 63), and high risk (n = 75)] based on the severity of diabetic kidney disease according to kidney disease: improving global outcomes guidelines. Both urinary kidney injury molecule-1 and monocyte chemoattractant protein-1 levels were measured by enzyme-linked immunosorbent assay. Student`s t test, analysis of variance, and Spearman's correlation were used for statistical analysis. The kidney injury molecule-1-to-creatinine ratio (P = 0.035) and monocyte chemoattractant protein-1-to-creatinine ratio (P < 0.001) increased significantly with the increase in kidney disease severity and varied according to different albuminuria statuses and estimated glomerular-filtration rates. The monocyte chemoattractant protein-1-to-creatinine ratio showed a significant correlation with hemoglobin A1c (P = 0.002) and inflammatory marker levels (interleukin-6, P = 0.005; tumor necrosis factor-α, P < 0.001). Urinary levels of both kidney injury molecule-1 and monocyte chemoattractant protein-1 represent distinguishing markers for the evaluation of diabetic kidney disease progression according to the associated degrees of albuminuria or/and the estimated glomerular-filtration rate. In addition, correlations between urinary monocyte chemoattractant protein-1 and glycemic and inflammatory marker levels revealed the role of hyperglycemia and chronic inflammation in the pathogenesis of diabetic kidney disease.