Commenced in January 2007
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Edition: International
Paper Count: 12

Diabetic Nephropathy Related Abstracts

12 Paeonol Prevents Diabetic Nephropathy Progression in STZ-Induced Diabetic Rats

Authors: Xuan Li, Xiaobing Cui, Nan Meng, Shuangshuang Guo, Lingling Wang

Abstract:

Objective: To investigate the influence of Paeonol on diabetic nephropathy progression in streptozocin (STZ) -induced diabetic rats. Method Male Wistar rats were injected STZ 30mg.kg-1 combined with Freund's complete adjuvant (CFA) 0.1mL/rat once a week for three weeks. The diabetic rats were treated with Paenol for 13 weeks. At the end of the experiments, the rats were anesthetized. Serum and the kidney were collected. Serum superoxide dismutase (SOD) activity, malondialdehyde (MDA), blood urea nitrogen (BUN), creatinine (Cr) and total cholesterol (Chol) level were detected; kidney paraffin sections were prepared and HE and PAS staining sections were used to evaluate the pathology changes of the kidney. Immunohistochemical analysis was used to observe the expression of VEGF and fibernectin expression in the kidney. Result The blood glucose level remained over 16mmol. L-1 for 13 weeks and the ECM accumulated in the diabetic kidney apparently. Paeonol treatment increased serum SOD activity, however, MDA, BUN, Cr, and Chol level was decreased by paeonol treatment. VEGF and fibernectin expression were increased significantly in the DN rats and paeonol treatment ameliorated the overexpression. Conclusion: paeonol prevented the progression of DN.

Keywords: Diabetic Nephropathy, paeonol, STZ, fibernectin expression, kidney paraffin sections

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11 AGEs-Aggravating Renal Lesions in C57BL/6J Mice, STZ-Induced Diabetes Nephropathy Model

Authors: Xing Lv, Hui-Qin Xu

Abstract:

The present study aimed to reveal the mechanism in aggravating STZ induced diabetic nephropathy (DN) by AGEs (advanced glycation end products). At the eighth day, 20 diabetic mice were randomly divided into STZ group and combination (combine AGEs with STZ) group. Simultaneously, AGEs group and normal group were set. Only mice in AGEs group, combination group were fed with high-AGEs diets. Mice diabetic conventional indicators, biochemical analysis were measured. Among the indictors, food consumptions, water intake, urine output, blood glucose, urine protein, urine creatinine, serum urea nitrogen were increased significantly in STZ, combination groups. The AGEs levels in combination group increased significantly when compared with STZ group. Weights and insulin levels in the STZ, combination groups were decreased significantly when compared with normal group, and the difference was significantly between AGEs group and STZ group. As a conclusion, AGEs play an important role in the DN development, inducing kidney damages.

Keywords: Diabetic Nephropathy, AGEs, serum urea nitrogen, urine protein

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10 Morroniside Intervention Mechanism of Renal Lesions, a Combination Model of AGEs Exacerbation of STZ-Induced Diabetes Mellitus

Authors: Xing Lv, Hui-Qin Xu, Yu-Han Tao

Abstract:

The depth study aimed on the mechanism of morroniside in protecting diabetic nephropathy. The diabetic mice models with blood glucose above 15mmol/L were divided into model, aminoguanidine, metformin, captopril, morroniside low-dose, and morroniside high-dose groups. And normal group was set simultaneously. All groups were fed with high AGEs food except normal group. Each group was intragastric administration of the corresponding medicine except model and normal groups. After 12 weeks, all the indictors were measured. It showed that the morroniside could reduce blood glucose significantly, urinary protein, serum urea nitrogen, creatine, pathological changes, AGEs levels, renal cortex RAGE mRNA and RAGE protein expression levels; increase food consumption, water intake, urine volume, insulin secretion. As a conclusion, morroniside from cornus officinalis can protect renal in diabetic mice, its mechanism may be related to the proliferation of islet cells, rectify glycometabolism, reduce serum and kidney AGEs content, and descend renal RAGEmRNA and RAGE protein expression levels.

Keywords: Diabetic Nephropathy, cornus officinalis, morroniside, RAGE protein

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9 Prevalence of Microalbuminuria and Its Relation with Various Risk Factors in Type 1 Diabetes Mellitus

Authors: Singh Baljinder, Sharma Navneet

Abstract:

Microalbuminuria is the earliest detectable marker of diabetic nephropathy. We planned to evaluate the prevalence of microalbuminuria in type 1 diabetics and correlate with various risk factor. We randomly selected 100 type 1 diabetic patients after inclusion and exclusion criteria from DCRC, S. P. Medical College, Bikaner. Clinical examinations for anthropometeric parameters, hypertension, retinopathy, glycaemic status, lipid profile were done and microalbuminuria was estimated by micral test. Microalbuminuria was seen in 38% patients. The mean urinary albumin concentration was 96.61 mg/l in microalbuminuria positive cases, 134 mg/L in hypertensive patients while 74.5 mg/L in normal patients. Mean diabetic duration was 6.43 years in microalbuminurics. Albumin excretion increased significantly with age at onset of 10-18 years and declined thereafter. Microalbuminuria cases exhibited mean cholesterol 181.63 mg%, TG 130.94 mg%, LDL 109.87 mg%, HDL 57.5 mg% and VLDL 30.64 mg%. Mean urinary albumin concentration in patients with retinopathy was 160.52 mg/L while 78.66 mg/L without retinopathy. In multiple stepwise logistic regression analysis, a strong positive association was seen between microalbuminuria and hypertension (OR=5.087, CI=2.1319-12.101), fasting blood sugar (OR=3. 491, CI=1.138-10.70), duration of diabetes (OR=3.41, CI=1.360-8.55) and HbA1c (OR=2.381, CI-=1.1-5.64). The present study indicates that microalbuminuria is a common complication of type 1 diabetes mellitus and can be prevented by careful management of risk factors.

Keywords: retinopathy, Hypertension, Diabetic Nephropathy, microalbuminuria, type 1 diabetes

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8 Angiotensin Converting Enzyme (ACE) and Angiotensinogen (AGT) Gene Variants in Pakistani Patients of Diabetes Mellitus and Diabetic Nephropathy

Authors: Muhammad Ismail, Rozeena Shaikh, Abid Azhar, Jamil Ahmad, Syed M Shahid, Qaisar Mansoor

Abstract:

Introduction: Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. In most high-income countries as well as middle-income and low- income countries. DM is among the top causes of deaths. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy, and foot. Diabetic nephropathy (DN) characterized by persistent albuminuria is a leading cause of end stage renal failure (ESRF). Pathogenesis of diabetic nephropathy is implicated by the polymorphisms in genes encoding the components of reninangiotensin- aldosteron system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and particularly angiotensin converting enzyme (ACE) gene. Method: Study subjects include 110 control, 110 patients with DM without hypertension, 110 patients with DM with hypertension and 110 patients with DN. Blood samples were collected for Biochemical analysis and PCR and sequencing for the specific region of both genes. Results: The frequency of DD genotype and D allele of ACE (I/D) was significantly (p<0.05) high in DM normotensive, DM hypertensive and DN patients when compared to control. The ACE G2350A genotypes and allele frequencies were significantly different (p<0.05) in DM hypertensive patients as compared to control and DN, while no difference was observed between DM normotensive and DN when compared to control. The genotypes and alleles of AGT (M268T) polymorphism were significantly different (p<0.05) in DM normotensive, DM hypertensive and DN when compared to control. Conclusion: The DD genotype and D allele of ACE (I/D), GG genotype and G allele of ACE (G2350A) and the TT genotype and T allele of AGT (M268T) polymorphism have shown a significant difference in genotype and allele frequencies between controls and patients.

Keywords: Pakistan, diabetes mellitus, Diabetic Nephropathy, Genetic Variations, ACE, AGT

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7 Molecular Modeling a Tool for Postulating the Mechanism of Drug Interaction: Glimepiride Alters the Pharmacokinetics of Sildenafil Citrate in Diabetic Nephropathy Animals

Authors: Anil Chandewar, Alok Shiomurti Tripathi, Ajay Kumar Timiri, Papiya Mitra Mazumder

Abstract:

The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: Pharmacokinetics, Homology Modeling, Diabetic Nephropathy, glimepiride, sildenafil citrate, schrodinger

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6 Effect of Erythropoietin Hormone Supplementation on Hypoxia-Inducible Factor1-Alpha in Rat Kidneys with Experimental Diabetic Nephropathy

Authors: Maha Deif, Alaa Eldin Hassan, Eman Shaat, Nesrine Elazhary, Eman Magdy

Abstract:

Background: Erythropoietin (EPO) is a hematopoietic factor with multiple protective effects. The aim of the present study was to investigate the potential effect of EPO administration on renal functions and hypoxia inducible factor 1-alpha (HIF-1a) in diabetic rat kidneys. Methodology: The current study was carried out on 40 male albino rats divided into four groups (n= 10 in each). Group I served as normal control, group II was the diabetic control, group III rats received EPO on the same day of diagnosis of diabetes mellitus (DM), while group IV received the first dose of EPO 2 weeks after the diagnosis of DM. Results: The results showed that EPO supplementation leads to a significant decrease in serum urea, urinary protein and creatinine clearance as well as a significant increase in renal HIF-1a in group III and IV rats compared to the diabetic control group (group II). However, fasting blood glucose was significantly decreased in group III as compared to the diabetic control group in the third week, but no significant difference was reported in the fourth week among groups II, III and IV. Conclusion: EPO administration leads to the improvement of renal functions and increased levels of HIF-1a in diabetic rats.

Keywords: Diabetic Nephropathy, Erythropoietin, hypoxia-inducible factor1-alpha, renal functions

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5 Anti-Apoptotic Effect of Pueraria tuberosa in Rats with Streptozotocin Induced Diabetic Nephropathy

Authors: Rashmi Shukla, Yamini Bhusan Tripathi

Abstract:

Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Diabetic Nephropathy, Pueraria tuberosa, anti-apoptosis, nephrin

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4 Mitochondrial DNA Defect and Mitochondrial Dysfunction in Diabetic Nephropathy: The Role of Hyperglycemia-Induced Reactive Oxygen Species

Authors: Ghada Al-Kafaji, Mohamed Sabry

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Mitochondria are the site of cellular respiration and produce energy in the form of adenosine triphosphate (ATP) via oxidative phosphorylation. They are the major source of intracellular reactive oxygen species (ROS) and are also direct target to ROS attack. Oxidative stress and ROS-mediated disruptions of mitochondrial function are major components involved in the pathogenicity of diabetic complications. In this work, the changes in mitochondrial DNA (mtDNA) copy number, biogenesis, gene expression of mtDNA-encoded subunits of electron transport chain (ETC) complexes, and mitochondrial function in response to hyperglycemia-induced ROS and the effect of direct inhibition of ROS on mitochondria were investigated in an in vitro model of diabetic nephropathy using human renal mesangial cells. The cells were exposed to normoglycemic and hyperglycemic conditions in the presence and absence of Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) or catalase for 1, 4 and 7 days. ROS production was assessed by the confocal microscope and flow cytometry. mtDNA copy number and PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 transcripts, were all analyzed by real-time PCR. PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 proteins, were analyzed by Western blotting. Mitochondrial function was determined by assessing mitochondrial membrane potential and adenosine triphosphate (ATP) levels. Hyperglycemia-induced a significant increase in the production of mitochondrial superoxide and hydrogen peroxide at day 1 (P < 0.05), and this increase remained significantly elevated at days 4 and 7 (P < 0.05). The copy number of mtDNA and expression of PGC-1a, NRF-1, and TFAM as well as ND2, CYTB, CO1 and ATPase 6 increased after one day of hyperglycemia (P < 0.05), with a significant reduction in all those parameters at 4 and 7 days (P < 0.05). The mitochondrial membrane potential decreased progressively at 1 to 7 days of hyperglycemia with the parallel progressive reduction in ATP levels over time (P < 0.05). MnTBAP and catalase treatment of cells cultured under hyperglycemic conditions attenuated ROS production reversed renal mitochondrial oxidative stress and improved mtDNA, mitochondrial biogenesis, and function. These results show that hyperglycemia-induced ROS caused an early increase in mtDNA copy number, mitochondrial biogenesis and mtDNA-encoded gene expression of the ETC subunits in human mesangial cells as a compensatory response to the decline in mitochondrial function, which precede the mtDNA defect and mitochondrial dysfunction with a progressive oxidative response. Protection from ROS-mediated damage to renal mitochondria induced by hyperglycemia may be a novel therapeutic approach for the prevention/treatment of DN.

Keywords: Oxidative Stress, Diabetic Nephropathy, Mitochondrial dysfunction, catalase, reactive oxygen species, hyperglycemia, mtDNA, manganese superoxide dismutase

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3 Lessons Learned in Implementing Programs to Delay Diabetic Nephropathy Management in Primary Health Care: Case Study in Sakon Nakhon Province

Authors: Sumattana Glangkarn, Sasiwan Tassana-iem

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Diabetic nephropathy is a major complication in diabetic patients whom as the glomerular filtration rate falls. The affects their quality of life and results in loss of money for kidney replacement therapy costs. There is an existing intervention, but the prevalence remains high, thus this research aims to study lessons learned in implementing programs to delay diabetic nephropathy management in primary health care. Method: The target settings are, 24 sub-district health promoting hospital in Sakon Nakhon province. Participants included the health care professionals, head of the sub-district health promoting hospital and the person responsible for managing diabetic nephropathy in each hospital (n= 50). There are 400 patients with diabetes mellitus in an area. Data were collected using questionnaires, patient records data, interviews and focus groups and analyzed by statistics and content analysis. Result: Reflection of participants that the interventions to delay diabetic nephropathy management in each area, the Ministry of Public Health has a policy to screen and manage this disease. The implementing programs aimed to provide health education, innovative teaching media used in communication to educate. Patients and caregivers had misunderstanding about the actual causes and prevention of this disease and how to apply knowledge suitable for daily life. Conclusion: The obstacles to the success of the implementing programs to delay diabetic nephropathy management in primary health care were most importantly, the patient needs self-care and should be evaluated for health literacy. This is crucial to promote health literacy; to access and understand health information as well to decide their health-related choices based on health information which will promote and maintain a good health. This preliminary research confirms that situation of diabetic nephropathy still exists. The results of this study will lead to the development of delay in diabetic nephropathy implementation among patients in the province studied.

Keywords: Implementation, Chronic kidney disease, Diabetic Nephropathy, primary health care

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2 Caring for a Spinal Cord Injury Patient with Diabetic Nephropathy Receiving Hospice Palliative Care

Authors: Li-Ting Kung, Hui-Zhu Chen, Hsin-Tzu Lee, Wan-Yin Hsu

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Patients with spinal cord injury combined with diabetic nephropathy may under a lot of painful conditions due to complications related to the illness itself or treatments, such as recurrent pressure ulcers, autonomic and peripheral neuropathy, as well as dialysis, for long term. This case report illustrated the nursing experience of transferring a spine cord injure patient who received hemodialysis due to adverse lifestyle-induced diabetic nephropathy to the hospice ward. Nursing care was provided in this patient from July 25th to August 30th, 2015. The tool of 'Gordon’s 11-item functional health assessment' and clinical observation, interviews as well as physical examination were used as data collections. Based on results of health assessment as above, the patient’s health problems were identified as the following: impaired skin integrity, chronic pain, and hopeless. Besides to relieve the symptom of pain due to disease or the treatment of hemodialysis and provide wound care, the first author also played a role to assist the patient to achieve his goal of receiving the hospice palliative care. Finally, with much effort of nurses to communicate with medical teams between the surgical and hospice wards, the patient was transferred to the hospice ward to have fulfilled his last wish of having a good death. We hope this nursing experience can be applied to other similar cases in the future.

Keywords: palliative care, Spinal Cord Injury, Diabetic Nephropathy, hospice care

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1 Separation of Urinary Proteins with Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis in Patients with Secondary Nephropathies

Authors: Ognen Kostovski, Irena Kostovska, Katerina Tosheska Trajkovska, Svetlana Cekovska, Julijana Brezovska Kavrakova, Hristina Ampova, Sonja Topuzovska, Goce Spasovski, Danica Labudovic

Abstract:

Background: Proteinuria is an important feature of secondary nephropathies. The quantitative and qualitative analysis of proteinuria plays an important role in determining the types of proteinuria (glomerular, tubular and mixed), in the diagnosis and prognosis of secondary nephropathies. The damage of the glomerular basement membrane is responsible for a proteinuria characterized by the presence of large amounts of protein with high molecular weights such as albumin (69 kilo Daltons-kD), transferrin (78 kD) and immunoglobulin G (150 kD). An insufficiency of proximal tubular function is the cause of a proteinuria characterized by the presence of proteins with low molecular weight (LMW), such as retinol binding protein (21 kD) and α1-microglobulin (31 kD). In some renal diseases, a mixed glomerular and tubular proteinuria is frequently seen. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) is the most widely used method of analyzing urine proteins for clinical purposes. The main aim of the study is to determine the type of proteinuria in the most common secondary nephropathies such as diabetic, hypertensive nephropathy and preeclampsia. Material and methods: In this study were included 90 subjects: subjects with diabetic nephropathy (n=30), subjects with hypertensive nephropahty (n=30) and pregnant women with preeclampsia (n=30). We divided all subjects according to UM/CR into three subgroups: macroalbuminuric (UM/CR >300 mg/g), microalbuminuric (UM/CR 30-300 mg/g) and normolabuminuric (UM/CR<30 mg/g). In all subjects, we measured microalbumin and creatinine in urine with standard biochemical methods. Separation of urinary proteins was performed by SDS-PAGE, in several stages: linear gel preparation (4-22%), treatment of urinary samples before their application on the gel, electrophoresis, gel fixation, coloring with Coomassie blue, and identification of the separated protein fractions based on standards with exactly known molecular weight. Results: According to urinary microalbumin/creatinin ratio in group of subject with diabetic nephropathy, nine patients were macroalbuminuric, while 21 subject were microalbuminuric. In group of subjects with hypertensive nephropathy, we found macroalbuminuria (n=4), microalbuminuria (n=20) and normoalbuminuria (n=6). All pregnant women with preeclampsia were macroalbuminuric. Electrophoretic separation of urinary proteins showed that in macroalbuminric patients with diabetic nephropathy 56% have mixed proteinuria, 22% have glomerular proteinuria and 22% have tubular proteinuria. In subgroup of subjects with diabetic nephropathy and microalbuminuria, 52% have glomerular proteinuria, 8% have tubular proteinuria, and 40% of subjects have normal electrophoretic findings. All patients with maroalbuminuria and hypertensive nephropathy have mixed proteinuria. In subgroup of patients with microalbuminuria and hypertensive nephropathy, we found: 32% with mixed proteinuria, 27% with normal findings, 23% with tubular, and 18% with glomerular proteinuria. In all normoalbuminruic patiens with hypertensive nephropathy, we detected normal electrophoretic findings. In group of subjects pregnant women with preeclampsia, we found: 81% with mixed proteinuria, 13% with glomerular, and 8% with tubular proteinuria. Conclusion: By SDS PAGE method, we detected that in patients with secondary nephropathies the most common type of proteinuria is mixed proteinuria, indicating both loss of glomerular permeability and tubular function. We can conclude that SDS PAGE is high sensitive method for detection of renal impairment in patients with secondary nephropathies.

Keywords: Diabetic Nephropathy, SDS PAGE, preeclampsia, hypertensive nephropathy

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