Diabetic Nephropathy

Published by Madridge Publishers Abstract Background: Diabetic Nephropathy (DN) is one of the complications in patients with prolonged diabetes. Among the genetic risk factors for DN, TNF-α, an anti-inflammatory cytokine is proposed to act in a paracrine/autocrine manner and is hypothesized to be associated with insulin resistance. In the current study, the relationship of the G ↆC variant of the TNF-α gene in patients, associated with other biochemical parameters with DN was investigated.

Many studies have shown that patients with type 2 diabetes mellitus are more prone to develop diabetic nephropathy.There is interrelationship between trace elements and diabetes. The patients of clinically diagnosed type 2 diabetes mellitus were divided into 2 groups, based on the presence or absence diabetic nephropathy. Patients in each group (n=50) were subjected to tests for estimation of Zinc, Magnesium and Copper concentration in serum. Decreased serum zinc levels was seen in all diabetic subjects, but the decrease in levels was more in the group with diabetic nephropathy (81.16+24.34 vs. 92.01+20.17; p<0.05). Decreased serum magnesium levels was also more significant in the group of patients with diabetic nephropathy (1.64+0.67 vs. 2.09+0.56; p<0.001). Increased serum copper levels was seen in all the patients, but the increase in levels was more significant in the group with diabetic nephropathy (140.64+33.61 vs. 116.77+26.22; p<0.001). Decreased serum zinc levels and Decreased serum magnesium levels in type 2 diabetes is said to be due to hyperglycaemia that promotes increased excretion of these trace elements in urine. The glycated proteins seen in type 2 diabetes mellitus patients have an increased affinity for copper, leading to Increased serum copper levels. This bound copper is redox active and leads to production of free radicals that cause oxidative stress which, plays some role in the development and progression of diabetic nephropathy of type 2 diabetes mellitus.

Human observational studies report no association between protein intakes less than 20% of energy intake and the development of renal disease. With protein intakes greater than 20% of energy intake there is an association between protein with increased albumin excretion rate. Once albuminuria is present, intervention studies suggest a beneficial effect on renal function with a reduction of protein to 0.8 to 1.0 g/kg/d with microalbuminuria and to 0.8 g/kg/d with macroalbuminuria. Restriction of sodium to 2400 mg/d or possibly for some to 2000 mg/d assists in the control of hypertension. In macroalbuminuria, there may be additional benefits in lowering phosphorus intake to 500 to 1000 mg/d. There is no strong evidence to suggest benefit from vegetable or plant proteins over animal protein, but there is evidence for benefit on renal function, glucose, lipids, and blood pressure from weight-maintaining diets meeting guidelines for a healthy diet.

We evaluated if a nutritional supplement containing arginine, glutamine, β-hydroxy-β-methyl butyrate commonly used to improve the healing of diabetic foot ulcers had any effect on the kidney function in the diabetic patients. We hypothesized that the action on the skin may be nonspecific and that the supplement might also act on other structural elements of the kidney. We compared the evolution of the blood creatinine and of the overnight albumin excretion in 16 diabetic subjects with mild to moderate nephropathy 6 months prior to and during the 6 months of treatment. The creatinine level remained stable during the treatment, while microalbuminuria decreased to nearly 50% of the initial value (p 

Introduction: End stage renal failure eventually develops in 40% of
patients with diabetes, the IDDM constitute the single most usual
disease leading to inadequacy in adults. Patients with type 2 diabetes
had higher HBA1c and FBS together that is distinctly reduced the
reactiveness of insulin in contrast to healthy control subjects. On
average,  death takes  place  7years  after  the  start  of  persistent
proteinuria  but  the  scale  is  wide  (2-32)  years.  Even  though
morphological bruises advance and nature in glomeruli of those that
with  diabetes  after  a  few  years  of  metabolic  deformities.Chronic
hyperglycemia as measured by mean blood glucose or HBA1c has
been  associated  with  the  development  and  advancement  of  micro
vascular diabetic complications.
Methodology: This  is  a  case  control  study  done  in  the in-patient
department of general medicine. From January to July 2014. The
patients selected has a history of diabetes for more than 3 years and
were  on  hypoglycemic  agents/insulin.  Diabetic  nephropathy  was
confirmed  by  elevated  levels  of  blood  urea  and  serum creatinine,
which  has  the  level  above  6.5  mg/dl.  All  patients  had  persistent
increase in serum creatinine examinations and controlled cases are
selected  contingent on their normal  creatinine  and urea  excretion
profile.
Results: the  mean  age  of  the  patients  with  diabetic  nephropathy  is
54.43 ± 7.99 while the mean age of patients with control profile of
diabetes were 48.37 ± 6.99. There were 22.9%, almost 23% of the
patients with diabetic nephropathy are anemic. And the mean FBS
levels in diabetic nephropathy in the current study were about180. 85
± 42.05 and the mean exhibit by control groups 81.4 ± 7.0. While the
mean HBA1C range in diabetic nephropathy patients was about 9.96
± 5.07 and 4.45 ± 0.57 is the mean of the control group. The levels of
blood  urea,  serum  creatinine  and  triglycerides  are evidently high, though  which  when  compared  to  control  group.
Conclusion:  HBA1c  and  FBS  are  the  important  predictors  of
intercapillary glomerulonephritis or diabetic nephropathy. HBA1c
is highly co-related to preceding mean blood glucose. The chief
outcome  measures  which  predicts  the  intercapillary
glomerulonephritis  or  diabetic  glomerulosclerosis  or  diabetic
nephropathy are HBA1c, triglycerides, serum creatinine and blood
urea  nitrogen.  Patients  with  progressed  nephropathy  showed
increased  levels  of  serum  triglycerides,  which  is  the  important
independent clinical attribute.

Introduction: Diabetes mellitus is increasingly common worldwide and is
expected to affect 592 million people by 2035. The kidney is often involved.
A key goal in treating diabetes is to reduce the risk of development of kidney
disease and, if kidney disease is already present, to delay the progression to
end-stage renal disease (ESRD). This represents a social and ethical issue, as a
significant proportion of patients reaching ESRD in developing countries do
not have access to renal replacement therapy.
Areas covered: The present review focuses on novel therapeutic approaches
for diabetic nephropathy (DN), implemented on the basis of recent insights
on its pathophysiology, which might complement the effects of single inhibition
of the renin-angiotensin-aldosterone system (RAAS), the cornerstone of
renoprotective interventions in diabetes, along with glycemic and blood
pressure control.
Expert opinion: Although a plethora of new treatment options has arisen
from experimental studies, the number of novel renoprotective molecules
successfully implemented in clinical practice over the last two decades is
disappointingly low. Thus, new investigational strategies and diagnostic
tools -- including the appropriate choice of relevant renal end points and
the study of urinary proteome of patients -- will be as important as new
therapeutic interventions to fight DN. Finally, in spite of huge financial interests
in replacing the less expensive ACE inhibitors and angiotensin II receptor
blockers with newer drugs, any future therapeutic approach has to be tested
on top of -- rather than instead of -- optimal RAAS blockade.

Recent years have witnessed the unprecedented development and integration of genomics, epigenetics, transcriptomics,
proteomics, and metabolomics, as well as a growing interest in novel single biomarkers and process-specific biomarker
panels in human renal diseases. In a scenario currently dominated by kidney biopsy and established biomarkers such as
serum creatinine, albuminuria, and proteinuria, novel biomarkers could potentially provide vital diagnostic and prognostic
information and help to predict response to treatment in several clinical settings, including acute kidney injury, renal
transplant, autosomal dominant polycystic kidney disease, and glomerulopathies. However, it is still uncertain whether and
to what extent novel biomarkers will succeed in this difficult task. To date, they have generally failed to provide relevant
information over and above what is already granted by established, cheap, and easily available biomarkers such as proteinuria,
while the complexity and costs of these technology platforms are an important obstacle to their wide adoption. On the
other hand, the successful implementation of anti–phospholipase A2 receptor antibodies as a diagnostic and prognostic
biomarker of membranous nephropathy, as well as the huge number of ongoing collaborative efforts worldwide, should
induce the nephrology community to be rather optimistic about a potential breakthrough in the management of kidney
diseases over the next few decades.

Background: Diabetic nephropathy is a common complication of diabetes mellitus type2. Glycated albumin level increase in states of abnormally high glucose concentration in diabetes mellitus. The increase in concentration glycated albumin plays role in diabetic nephropathy through stimulation of collagen and fibronectin expression in mesangial cell. Objective: This study aimed to evaluate the roles of the serum glycated albumin as predictor of diabetic nephropathy with type2 diabetic patients with normal albuminuria , micro albuminuria and comparing them with normal healthy subjects. Method : This study was conducted in Medical City, Baghdad Teaching Hospital during the period from December 2015 to June 2016.The study included (90) subjects with age range between (30 – 56) years, divided in to three groups , 30 healthy control, 30 type 2 diabetic mellitus patients with normal albuminuria (micro albumin < 30 µg/ml) and 30 type2 diabetic mellitus patients with micro albuminuria (micro albumin >30 µg/ml).Body mass index (BMI) was determined, Fasting blood sugar (FBS) ,serum creatinine ,blood urea ,and glycated hemoglobin (HbA1c%) were measured for each individual in addition to the concentration of albumin in urine and estimation glomerular filtration rate (eGFR) was calculated. Results : The results of the present study showed that the levels of fasting blood sugare , HbA1c %,blood urea ,and serum creatinin, were significantly higher in micro albuminuria than normal albuminuria and healthy control and Glycated Albumin(GA%) levels showed a statically significant difference (p <0.05) among the studied groups ,it was significantly higher in group micro albuminuria than group normal albuminuria when compared with healthy control group (19.0±5.7), (17.1±5.1), and (15.6±4.6) respectively. Conclusion: Diabetic patient with micro albuminuria show increase the level of serum GA % which may be considered as predictor of diabetic nephropathy. Keyword: diabetic nephropathy, micro albuminuria, serum albumin, Glycated Albumin (GA%)

In today's world, the use of sensor technology to make portable devices can help patients in detecting or monitoring diseases. One such problem is the onset of foot ulcers in diabetic patients. Diabetes often leads to improper circulation of blood to a person's feet, which results in diabetic foot ulcers. This leads to gangrene formation and loss of sensation in the patient's foot. If ignored, leads to lower leg amputation. The proposed system is a device which is developed and evaluated to identify the patients who are likely to develop diabetic foot ulcers at an early stage. This is accomplished by fixing pressure sensors in five pressure points of the foot. The foot pressure readings are converted into corresponding voltage output by the sensor. These voltage readings are amplified using an amplification unit. The voltage data are read using a data acquisition device. The output of the device decides whether the person has the probability to develop diabetic foot ulcer or not.

The purpose of this cross sectional study was to determine the frequency of under-collected 24 hours urinary samples. Diabetic patients who visited our clinic from June 2012 to November 2012 were explained the procedure for collection verbally in addition to being given written instructions. Adequacy of collection was assessed by measuring creatinine excretion rates. Out of the 112 patients enrolled, 16(14.29%) collected their samples inadequately. The education level (p< 0.001) and urine volume (p= 0.003) were lesser in these 16 patients as compared to others. Inadequate collection was common in the younger patients (22.22% patients aged less than 60 years, 6.90% aged 60 years or older ; p= 0.021). Gender (15.00% men, 12.50% women; p= 0.733) did not impact the collection of samples. Considering the high frequency of under-collections, adequacy of samples should always be checked first before proceeding further with laboratory analysis.

The objective of this study was to analyze the long-term outcome of 51 patients with brachial-jugular grafts for dialysis. Age, presence of diabetic nephropathy, complications of the angio-access, and therapeutic methods of treating complications were analyzed. All surgical procedures were performed under local anesthesia in an ambulatory surgical setting. The duration of angio-access was analyzed using the life-table method. Our results showed that brachial-jugular grafts can be performed under local anesthesia and in an ambulatory surgical setting. This procedure can be an alternative to complex intrathoracic procedures, Dacron cuff catheters, or lower limb grafts, in cases of stenosis or occlusion of the subclavian vein.

Siddha Medicine, it is clearly unique in this day and age to find a system of medicine that
is thousands of years old and still one of the Precious medical system in Southern part of India.
The system treats both the mind and the body’s equilibrium needed for its normal function.
Saint Yugi describes 21 types of Mega noigal, which includes madhu megam. Diabetes mellitus
is compared with Madhu megam in Siddha literature. Diabetes mellitus is a chronic disease
caused by inherited or acquired deficiency in production of insulin by the pancreas, or by the
ineffectiveness of the insulin produced. Such a deficiency results in increased concentrations of
glucose in the blood, which in turn damage many of the body's systems, in particular the blood
vessels and nerves. Tocopherol is a fat soluble vitamin, which prevents the non-enzymatic
oxidation of various cell components like Poly Unsaturated Fatty Acid by molecular oxygen and
free radicals. Polyphenols act as antioxidants. They protect cells and body chemicals against
damage caused by free radicals, reactive atoms (ROS, RNS) that contribute to tissue
damage. Both Tocopherols, polyphenols are the naturally available products found in most of
the herbs, it should be used as an adjuvant for treatment of diabetes patients to alleviate the
complications. Hence the Authors of this paper decided to review the concept behind the two
‘’Lifespan essential’’ Antioxidants and will be discussed later.

Diabetes mellitus occurrence has been associated to the modification of the physiological levels of glucose and is often accompanied by several long-term complications, namely neuropathy, nephropathy, retinopathy, cataract, and cardiovascular. Aldose reductase (AR) is an enzyme of aldoketo reductase super-family that catalyzes the conversion of glucose to sorbitol in the polyol pathway of glucose metabolism. In this context, aldose reductase inhibitors (ARIs) have received much attention worldwide. Decreased sorbitol flux through polyol pathway by ARIs could be an emerging target for the management of major complications of diabetes. The present review article describes a brief overview of the role of aldose reductase in the diabetic complications, advances achieved on ARIs and their potential use in the treatment and management of the major diabetic complications such as cataract, retinopathy, neuropathy, nephropathy and cardiovascular. The ARIs developed vary structurally, and representative structural classes of ARIs include i) carboxylic acid derivatives (such as Epalrestat, Alrestatin, Zopalrestat, Zenarestat, Ponalrestat, Lidorestat, and Tolrestat), ii) spirohydantoins and related cyclic amides (such as Sorbinil, Minalrestat, and Fidarestat), and iii) phenolic derivatives (related to Benzopyran-4-one and Chalcone). Among these inhibitors, Epalrestat is the only commercially available inhibitor till date. In addition, some other ARIs such as Sorbinil and Ranirestat had been advanced into late stage of clinical trials and found to be safe for human use. The role of various natural ARIs in management of diabetic complications will be discussed. Adapting ARIs could prevent sepsis complications, prevent angiogenesis, ameliorate mild or asymptomatic diabetic cardiovascular autonomic neuropathy and appear to be a promising strategy for the treatment of endotoxemia and other ROS-induced inflammatory diseases. The role of ARIs in non-diabetic diseases will also be discussed.

Diabetes mellitus is a leading cause of end-stage renal disease (ESRD) a condition which needs dialysis or kidney transplantation to sustain life. Early diagnosis of diabetic kidney disease (DKD) is important because there is strong evidence that a number of interventions if initiated at an early stage of DKD prevent or slow the progression to ESRD. The criteria for early diagnosis of DKD vary between different guidelines. The controversies in the early diagnosis of DKD will be the focus of this review article. Various international guidelines that were published through Jan 2001 to Jan 2016 were reviewed for the recommendations on early diagnosis of DKD. The issues in considering early diagnosis of DKD include (i) defining abnormal albuminuria, number of tests and duration (ii) presence or absence of impaired renal function (iii) the necessity of presence of diabetic retinopathy (iv) whether the diagnosis of DKD should be different for type 1 and type 2 diabetes and (v) whether the duration of diabetes should be taken into account. These issues need to be addressed in defining DKD. In most guidelines microalbuminuria or impaired renal function has been considered for early diagnosis of DKD.

Diabetic Nephropathy (DN) is one of the major complications of diabetes mellitus, representing the leading of cause of chronic renal disease and a major cause of
morbidity and mortality in both type 1 and type 2 diabetic patients. The Renin-Angiotensin-Aldosterone System (RAAS) has been implicated in the pathophysiology of DN, and suggests a therapeutic target for blocking this system. Therefore, inhibition of RAAS plays a crucial role in the treatment of DN and therapeutic intervention mostly involves administration of angiotensin converting enzyme (ACE) inhibitors and angiotensin AT1 receptor blockers. In
this current study, we have used computational methods to design 37 novel ACE-inhibitors and evaluated them for the interaction with the enzyme ACE through insilico analysis. The obtained results were compared with the standard drug enalapril to find out the potential inhibitors. Here we report that ligand 4 exhibited strongest inhibitory activity among all. All the analogs are also screened for their ADME & Toxicity profiles using insilico tools and ligand 9 is having better binding affinity next to ligand 4, and also having better ADMET profile when compared to that of ligand 4. Post docking calculations were also performed for the docked complexes in order to identify the individual ligand
binding energies by employing Multi-Ligand Bimolecular Association with Energetics (Embrace)

The study showed statistical significant increase in total serum sialic acid in all diabetic patients but the increase was more prominent in patients with proliferative DR. There were increase in fasting glucose level, glycosylated HB%, total cholesterol, triglycerides, LDL-C, serum urea, serum creatinine and urinary albumin/creatinine ratio with decrease in HDL-C in diabetic retinopathy patients ( mainly with proliferative retinopathy ), the increase was statistically significant.
Serum sialic acid concentrations were increased in type 2 diabetics with and without complications and this increase was strongly related to the progression of retinopathy and occurrence of nephropathy.
Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.
Diabetes mellitus is a group of metabolic disorders characterized by elevation of blood glucose concentration and is associated with increased prevalence of microvascular complications. Type 2 diabetes mellitus is the most common form of diabetes accounting for 90% of cases.
The complications of diabetes include diabetic retinopathy, nephropathy and neuropathy.
Sialic acid is a component of cell membranes and elevated levels may indicate excessive cell membrane damage, but more specifically to the cells of vascular tissue. If there is damage to vascular tissue, this leads to ischemia which is most visible in the smallest blood vessels, including those of the retina of the eyes, kidneys, heart and brain. It is this ischemia that leads to conditions including but not limited to retinopathy, nephropathy and neuropathy. In addition, sialic acid can be used as a measurement of the acute-phase response because many of the proteins of the immune response are actually glycoproteins and these glycoproteins have sialic acid the terminal sugar on their oligosaccharide chain.
The purpose of this study was mainly to determine the relationship between total serum sialic acid and occurrence and progression of diabetic retinopathy (DR). Also, the study tried to find if sialic acid was concerned with diabetic nephropathy in 30 diabetic patients with retinopathy (non-proliferative and proliferative) who were matched with 15 diabetic patients without retinopathy and 15 healthy controls.
Diabetes mellitus is a group of metabolic disorders characterized by elevation of blood glucose concentration and is associated with increased prevalence of microvascular complications. Type 2 diabetes mellitus is the most common form of diabetes accounting for 90% of cases.
The complications of diabetes include diabetic retinopathy, nephropathy and neuropathy.
Sialic acid is a component of cell membranes and elevated levels may indicate excessive cell membrane damage, but more specifically to the cells of vascular tissue. If there is damage to vascular tissue, this leads to ischemia which is most visible in the smallest blood vessels, including those of the retina of the eyes, kidneys, heart and brain. It is this ischemia that leads to conditions including but not limited to retinopathy, nephropathy and neuropathy. In addition, sialic acid can be used as a measurement of the acute-phase response because many of the proteins of the immune response are actually glycoproteins and these glycoproteins have sialic acid the terminal sugar on their oligosaccharide chain.
The purpose of this study was mainly to determine the relationship between total serum sialic acid and occurrence and progression of diabetic retinopathy (DR). Also, the study tried to find if sialic acid was concerned with diabetic nephropathy in 30 diabetic patients with retinopathy (non-proliferative and proliferative) who were matched with 15 diabetic patients without retinopathy and 15 healthy controls.
The study showed statistical significant increase in total serum sialic acid in all diabetic patients but the increase was more prominent in patients with proliferative DR. There were increase in fasting glucose level, glycosylated HB%, total cholesterol, triglycerides, LDL-C, serum urea, serum creatinine and urinary albumin/creatinine ratio with decrease in HDL-C in diabetic retinopathy patients ( mainly with proliferative retinopathy ), the increase was statistically significant.
Serum sialic acid concentrations were increased in type 2 diabetics with and without complications and this increase was strongly related to the progression of retinopathy and occurrence of nephropathy.
Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.

Nuclear factor κ B (NFκB) is an important transcription factor that together with its inhibitor (IκB) participates in the activation of genes involved in immune responses. We examined the CA repeat polymorphism of the NFKB1 gene (encoding for NFκB) and A/G point variation in the 3′UTR region of the nuclear factor kappa B inhibitor alpha (NFKBIA) gene (encoding for IκB) in Czech and German patients with type 2 diabetes. The sample consisted of 211 patients, both with and without kidney complications, and 159 controls. Additionally, 152 patients with systemic lupus erythematosus (SLE) were genotyped for NFKBIA polymorphism. We observed a significant increase in the homozygous AA genotype of the NFKBIA gene when compared with the control group (the highest value was in diabetics without diabetic nephropathy [pc* = 0.0015, odds ratio = 3.59]). No differences were seen between the SLE and control groups. With regard to the polymorphism of the NFKB1 gene, we did not observe any significant differences between the groups. Since the AA genotype of the NFKBIA gene presents a risk for type 2 diabetes development but not for diabetic nephropathy alone, we believe that the NFκB gene polymorphism can influence the pathogenesis of diabetes mellitus and affect its complications. Negative findings relative to other inflammatory autoimmune diseases, such as SLE, suggest a specific relationship between NFκB and type 2 diabetes mellitus.

Objective: To investigate protein concentration changes during venous occlusion of proteins with reported affinity for extracellular matrix (plasminogen activator inhibitor type 1, antithrombin III, fibronectin and von Willebrand factor) in comparison with proteins with no reported affinity (albumin, tissue-type plasminogen activator, immunoglobulin G, fibrinogen, α2-macroglobulin, immunoglobulin M) in insulin-dependent diabetic patients with and without diabetic nephropathy.Design: Cross-sectional study.Setting: Outpatient diabetic clinic in a tertiary hospital.Subjects: Insulin-dependent diabetic patients without diabetic nephropathy (normoalbuminuria, n = 17), patients with incipient diabetic nephropathy (n = 19), and patients with diabetic nephropathy (n = 13). Non-diabetic subjects served as a control group (n = 14).Results: For plasminogen activator inhibitor type 1 and fibronectin we found a smaller increase in protein concentration after venous occlusion in diabetic patients...