scholarly journals Evaluation of kidney injury molecule-1 as a disease progression biomarker in diabetic nephropathy

2019 ◽  
Vol 35 (4) ◽  
Author(s):  
Fatima Abid Khan ◽  
Syeda Sadia Fatima ◽  
Ghulam Mustafa Khan ◽  
Sana Shahid
Keyword(s):  
Diabetic Nephropathy ◽  
Disease Progression ◽  
Kidney Function ◽  
Kidney Injury ◽  
Positive Association ◽  
Kidney Damage ◽  
Control Group ◽  
Diabetic Patients ◽  
Kidney Injury Molecule 1

Background & Objective: Kidney Injury Molecule-1 (KIM-1) is a peptide whose release into circulation is specific to tubular injury. This study aimed to estimate levels of kidney injury molecule-1 in diabetic patients with and without kidney disease. And evaluate the role of KIM-1 as an early screening marker of progressive kidney injury. Methods: This follow-up study included n=85 subjects from the diabetic clinic of Jinnah Post Graduate Medical Center (JPMC) in collaboration with Aga Khan University from November 2016 till September 2017 They were divided as: i) Group A1 (n=30) participants with diabetes for <5 years without microalbuminuria ii) Group A2 (n= 30) subjects with diabetes for 6-10 years with microalbuminuria; iii) Group B (n=25) subjects as healthy control group. All study participants were followed for 6 months and their blood glucose, urea, creatinine, electrolytes, albuminuria and serum KIM-1 were assayed. Results: High KIM-1 at baseline was present in group A2 patients as compared to controls and group A1 (p<0.001). Higher levels were seen after six months in group A1 along with the presence of micro albuminuria (p<0.001) suggesting kidney damage. Moderate positive association were seen for KIM1 with creatinine levels (r=0.530; p<0.001), and HbA1c (r=0.576; p<0.001) in all patients. While a strong positive association was seen for blood urea nitrogen as a marker for kidney function both at baseline (r= 0.728; p=0.000) and follow up (r=0.747; p=0.001). Multiple logistic regression controlling for age showed that KIM1 was independently associated with BUN (r=0.727; p<0.001), creatinine (r=0.510; p<0.001) and HbA1c (r=0.401; p=0.008) in all groups. Conclusion: Rising KIM-1 levels with progressive kidney damage with or without derangement of kidney function is reported in this study. This finding may pave a way towards identifying KIM1 as a prognostic marker for kidney injury. doi: https://doi.org/10.12669/pjms.35.4.154 How to cite this:Khan FA, Fatima SS, Khan GM, Shahid S. Evaluation of kidney injury molecule-1 as a disease progression biomarker in diabetic nephropathy. Pak J Med Sci. 2019;35(4):---------. doi: https://doi.org/10.12669/pjms.35.4.154 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Kidney Injury ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Zucker Diabetic Fatty Rats ◽  
Kidney Injury Molecule 1 ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

Searching for Perfect Marker - Differences and Dependencies in Serum Levels of Renalase, KIM-1, MCP-1, Calbindin and GST-Pi in Patients with Diabetes, Glomerulonephritis and Congenital Defects of the Kidney

2018 ◽  
Author(s):  
Natalia Maria Serwin ◽  
Magda Wiśniewska ◽  
Edyta Skwirczyńska ◽  
Karol Serwin ◽  
Oskar Wróblewski ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Function ◽  
Kidney Injury ◽  
Congenital Defects ◽  
Glutathione S Transferase ◽  
Kidney Toxicity ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Kidney Injury Molecule 1

Diagnosis of kidney diseases has recently become more comprehensive and accurate by using new renal markers. Despite the fact that creatinine and cystatin c have been sufficient in determining kidney function, they did not indicate the exact site of the damage and they were often insufficient in predicting the course of the disease. Aim of the study was to evaluate the potential correlations and differences in levels of six&nbsp; factors related to kidney function and injury: kidney injury molecule-1 (KIM-1), ncalbindin (CALB), glutathione S-transferase Pi (GST-Pi), calbindin and monocyte chemoattractant protein-1 (MCP-1), between renal patients with diabetic nephropathy (DM), congenital defects (CD) of the kidney and glomerulonephritis (GN). Study involved 75 patients: 49 with diabetic nephropathy, 12 with congenital defects and 14 with glomerulonephritis. Levels of renalase was measured using immunoenzymatic tests. Levels of other markers: calbindin, glutathione-S-transferase (GST-pi), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1), were analyzed using Kidney Toxicity-1 Panel and BioPlex system, designed for analyses in urine and optimized by us for serum.From all analyzed markers, only levels of KIM-1 differed significantly between any subgroups, and that was for CD and DM. Renalase correlated significantly negatively with creatinine and positively with all other markers, apart from MCP-1. Obtained results indicate, that serum renalase, KIM-1, calbindin and GST-pi are related to kidney function, with KIM-1 being the most exact, while MCP-1 levels are unrelated to creatinine and glucose levels, does not differ between patients with diabetic nephropathy and other subgroups, and therefore seem to be independent of diabetes. Also, serum-optimized Kidney Toxicity Panel 1 kit for determination of selected markers gave results similar to previous ones and therefore the method can be valuable in determination of analyzed factors.

scholarly journals Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years

2019 ◽  
Vol 35 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Christina-Alexandra Schulz ◽  
Gunnar Engström ◽  
Jan Nilsson ◽  
Peter Almgren ◽  
Marinka Petkovic ◽  
...  
Keyword(s):  
Kidney Function ◽  
Cystatin C ◽  
Risk Model ◽  
Kidney Injury ◽  
Predictive Marker ◽  
Population Based ◽  
Preventive Action ◽  
Net Reclassification Improvement ◽  
Kidney Injury Molecule 1

Abstract Background The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear. Methods At baseline (1991–1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine–cystatin C equation at baseline and follow-up examination (2007–2012). Incident CKD was defined as an eGFR &lt;60 mL/min/1.73 m2 at follow-up. Results During a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 −1.36 versus quartile 4 −1.54 mL/min/1.73 m2; P &lt; 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio [OR] 1.45 [95% confidence interval (CI) 1.10–1.92]} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD [OR 1.20 (95% CI 1.08–1.33) per 1 standard deviation (SD) increase in p-KIM-1] was comparable to those of age and systolic blood pressure (SBP) [OR 1.55 (95% CI 1.38–1.74) and OR 1.21 (95% CI 1.09–1.35) per 1 SD increase, respectively]. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 [hazard ratio per 1 SD 1.43; (95% CI 1.18–1.74)] during a mean follow-up time of 19.2 years. Conclusion Our results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.

scholarly journals Kidney Injury Molecule-1 and the Loss of Kidney Function in Diabetic Nephropathy: A Likely Causal Link in Patients With Type 1 Diabetes

Diabetes Care ◽  
2015 ◽  
Vol 38 (6) ◽  
pp. 1130-1137 ◽  
Author(s):  
Nicolae M. Panduru ◽  
Niina Sandholm ◽  
Carol Forsblom ◽  
Markku Saraheimo ◽  
Emma H. Dahlström ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Kidney Function ◽  
Kidney Injury ◽  
Causal Link ◽  
Kidney Injury Molecule 1

scholarly journals The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy

2008 ◽  
Vol 27 (3) ◽  
pp. 376-382 ◽  
Author(s):  
Tatjana Cvetković ◽  
Predrag Vlahović ◽  
Vidosava đorđević ◽  
Lilika Zvezdanović ◽  
Dušica Pavlović ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Urine Concentration ◽  
Control Group ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Urinary Markers ◽  
Stress Markers

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-β-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p<0.001 and P<0.05). The urine concentration of RCD shows similar results with a significant elevation in the groups with DMT2-MAA and DMT1-MIA, compared to the DMT2-MIA (p<0.001) and control group (p<0.001). Activities of NAG, APN and DPPIV were significantly higher in the urine of DMT2-MAA, compared to the control (p<0.01). The activity of PC-1 was slightly increased in that group, but not significantly. In conclusion, the level of oxidative stress markers and activities of brush border ectoenzymes in the urine may be a useful non-invasive and easily repeatable test in DN.

scholarly journals Elabela levels in patients with type 2 diabetes: can it be a marker for diabetic nephropathy?

2020 ◽  
Vol 20 (2) ◽  
pp. 833-840
Author(s):  
Erhan Onalan ◽  
Yusuf Doğan ◽  
Ebru Onalan ◽  
Nevzat Gozel ◽  
Ilay Buran ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
High Serum ◽  
Control Group ◽  
Diabetic Patients ◽  
Healthy Individuals ◽  
Urine Albumin ◽  
Healthy Control ◽  
Group 2

Backround: Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Methods: Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. Results: The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative corre- lation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=- 0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). Conclusions: The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbu- minuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients. Keywords: Elabela, diabetes, diabetic kidney disease, albuminuria.

scholarly journals Effects of physical activity on the progression of diabetic nephropathy: a meta-analysis

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Zixin Cai ◽  
Yan Yang ◽  
Jingjing Zhang
Keyword(s):  
Physical Activity ◽  
Diabetic Nephropathy ◽  
Healthy Lifestyle ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Cochrane Library ◽  
Diabetic Patients ◽  
Mean Differences

Abstract Background: Diabetic nephropathy (DN) is an important microvascular complication of diabetes. Physical activity (PA) is part of a healthy lifestyle for diabetic patients; however, the role of PA in DN has not been clarified. Our aim was to conduct a meta-analysis to explore the association between PA and DN risk. Methods: PubMed, Embase, Cochrane Library and Web of Science were systematically searched for articles examining PA in diabetic patients and its effect on renal function. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study protocol is registered with PROSPERO (CRD42020191379). Results: A total of 38991 participants were identified from 18 studies. The results indicated that PA was associated with increases in the glomerular filtration rate (SMD = 0.01, 95% CI = [0.02–0.17]) and decreases in the urinary albumin creatinine ratio (SMD = −0.53, 95% CI: −0.72 to −0.34), rate of microalbuminuria (OR = 0.61, 95% CI = [0.46–0.81]), rate of acute kidney injury (OR = 0.02, 95% CI = [0.01–0.04]), rate of renal failure (OR = 0.71, 95% CI = [0.52–0.97]) and risk of DN in patients with Type 1 diabetes (OR = 0.67, 95% CI = [0.51–0.89]). Conclusions: This meta-analysis indicated that PA is effective for improving DN and slowing its progression; however, more high-quality randomized controlled trials are required on this topic.

scholarly journals Effect of alpha-lipoic acid on antioxidant gene expression and kidney injury in alloxan-induced diabetic rats

2018 ◽  
Vol 8 (1) ◽  
pp. 6-6 ◽  
Author(s):  
Parisa Jamor ◽  
Hassan Ahmadvand ◽  
Hesam Ashoory ◽  
Esmaeel Babaeenezhad
Keyword(s):  
Gene Expression ◽  
Lipoic Acid ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Pcr Analysis ◽  
Control Group ◽  
Diabetic Patients ◽  
Alpha Lipoic Acid ◽  
The Impact ◽  
Gpx Activity

Background: Myeloperoxidase (MPO) is involved in the initiation, progression, and complications of atherosclerosis in diabetic patients. Objectives: In the current study, the impact of alpha-lipoic acid (LA), a natural antioxidant and a cofactor in the enzyme complexes on MPO, catalase (CAT) and glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) level, histopathology of kidney and expression of antioxidant enzymes, superoxide dismutase (SOD), GPx and CAT which are involved in the detoxification of reactive oxygen species (ROS), was evaluated in alloxan-induced diabetic rats. Materials and Methods: In this study, 30 male Rattus norvegicus rats randomly divided into three groups; control (C), non-treated diabetic (NTD), and LA-treated diabetics (LATD) was induced by alloxan monohydrate (100mg/kg; subcutaneous [SC]). Then treatment was performed with alphaLA (100 mg/kg intraperitoneal (i.p) daily to 6 weeks). Blood sample of animals collected to measure levels of MPO, CAT and GPx activity GSH and MDA. Kidney paraffin sections were prepared to estimate histological studies and to measure quantitative gene expression SOD, GPX and CAT in kidney. Results: Induction of diabetes led to a significant increase in MPO and MDA, reduced GSH level and GPx and CAT activities (P < 0.05). However, treatment with alpha-LA led to a significant elevation in GPx, CAT and GSH levels with a reduction in MPO activities and MDA levels (P < 0.05). Furthermore, the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis results showed increased expressions of GPx, CAT and SOD enzyme in the treatment group compared with the diabetic control group. Histopathological lesions such as increased glomerular volume and lymphocyte infiltration were attenuated in the alpha-LA treated group. Conclusions: Our findings indicated that alpha-LA supplementation is effective in preventing complications induced by oxidative stress and atherosclerosis in diabetic rats.

scholarly journals Urinary Measurement of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 Helps Diagnose Acute Pyelonephritis in a Preclinical Model

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hahn-Ey Lee ◽  
Sun Hee Lee ◽  
Minki Baek ◽  
Hwang Choi ◽  
Kwanjin Park
Keyword(s):  
Acute Pyelonephritis ◽  
Time Course ◽  
Kidney Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Preclinical Model ◽  
Urinary Ngal ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Background. The study assessed whether measurement of urinary biomarkers of acute kidney injury could be helpful in diagnosing acute pyelonephritis and subsequent scarring. Method. Escherichia coli J96 (0.3 mL inoculum containing 1×109/mL) was directly injected into the renal cortex of 3-week-old female Sprague Dawley rats (n=20), with saline substituted in a control group (n=10). Following the injection, urine was collected 2, 7, 14, 28, and 42 days after injection. Urinary neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and interleukin-18 were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The levels of the biomarkers were adjusted for creatinine. Time course changes within a group or between the groups were compared. Correlation analysis was performed to understand the relationship between urinary levels and histological scarring. Results. Significantly elevated urinary NGAL was evident at two and seven days after injection, and Kim-1 was elevated at two days after injection. Receiver operating characteristic analyses confirmed the sensitivity of these markers at these times. No urinary marker at acute stage of APN was correlated with the amount of future scarring, negating their predictive value. Conclusion. Urinary NGAL and Kim-1 could be helpful in diagnosing febrile urinary tract infection in children.

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