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Diabetic Nephropathy-Causes, Symptoms and Treatment 2020

What is Diabetic Nephropathy-


Diabetic nephropathy, or more commonly known by the name Diabetic Kidney Disease, is a chronic disease of kidney function. Chronic disease cannot be cured permanently and thus its progression can be delayed.

The kidney gradually loses its functionality. Kidneys filter excess and waste fluids from the blood, which is then excreted through the urine. Diabetic nephropathy occurs in those with diabetes mellitus (commonly known as diabetes).



When the body starts losing protein in the urine due to deterioration and damage to the Glomeruli and this may become massive and frequent, this causes low serum albumin (also known by the name blood albumin) with generalized body swelling(Edema) and may result in nephrotic syndrome.

The collection of symptoms due to kidney damage is called Nephrotic syndrome. The symptoms may include protein in the urine (proteinuria), low levels of blood albumin, swelling in body parts and high blood lipids.

Weight gain, feeling tired and foamy urine can be some of the symptoms. Likewise, the estimated glomerular filtration rate (eGFR) can fall from a normal range of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage kidney disease (ESKD).

It is also known by the name of Chronic kidney disease (CKD).  It usually progresses over the years.

When the body has long-standing poorly controlled blood glucose levels and there is an imbalance of Glucose levels in the blood, Pathophysiologic abnormalities in DN begin.

The kidney then suffers multiple changes in the filtration units, the nephrons. In the human body, there are normally about 750,000-1.5 million nephrons in each kidney of an adult.

Initially, the efferent arterioles may become narrower and suffers constriction and afferent arterioles may become broader and suffers dilation. This results in glomerular capillary hypertension and hyperfiltration. Over a period of time, this gradually changes to hyperfiltration.

Concurrently, the glomerulus experience changes within itself: these include an increased width of the slit membranes of the podocytes, increased thickness of the basement membrane, an increase in the mesangial matrix and a rise in the number of the mesangial matrix.

The matrix covers the glomerulus capillaries and produces layers of deposits called Kimmelstiel-Wilson nodules. The mesangial matrix and cells can progressively expand and consume the entire glomerulus, shutting off filtration.

To know the type or stage of Diabetic Nephropathy, it can be checked by measuring two values: the levels of protein present in the urine (known as proteinuria) and a prescribed blood test called the serum creatinine.

The body produces Creatinineat a constant rate. Muscle mass is an important factor in considering the production of creatinine. Creatinine is considered important as it is a byproduct of metabolized muscle that is excreted unchanged by the kidneys.

The serum creatinine value can be used to analyze the estimated glomerular filtration rate (eGFR). eGFR reflects the percentage of glomeruli which are no longer filtering the blood.

Levels of the proteinuria tell the degree of damage to any still functioning glomeruli. For slowing down (not stopping) the progression of the disease, treating the glomerulus with the angiotensin-converting enzyme inhibitor (ACEI) is practiced.

Angiotensin receptor blocker (ARB) also dilates the arteriole exiting the glomerulus, thus reducing the blood pressure within the glomerular capillaries, which may slow (but not stop) progression of the disease.

Some diabetes medications such as – SGLT2 inhibitors, GLP-1 agonists and DPP-4 inhibitors – are also sought to slow the progressing diabetic nephropathy.

One serious complication is that Diabetic Nephropathy affects approximately one-quarter of diabetic individuals in the United States and it is commonly caused by ESKD.

Patients suffering from ESKD often require hemodialysis and eventually kidney transplantation to replace the gradually failing/failed kidney function. Diabetic nephropathy often increases the risk of death, particularly from cardiovascular disease.


Signs and Symptoms




The disease is not easy to identify and the symptoms are visible 5-10 years after the disease begins. A usual first symptom is an increased number of urination desires at night. Other symptoms include:

Tiredness

Headaches

Vomiting

Nausea

A general feeling of illness 

Lack of appetite

Itchy skin

Leg swelling

Frequent daytime urination


Risk Factors


It is usually advised to do a lot of exercises, to burn glucose accumulating in the body. Diabetic people are more prone to Diabetic Nephropathy and may have one of the following conditions:

Family history or the ancestors having diabetic nephropathy

Cigarette Smoking (can be recent or past use)

Blood pressure is unstable, high and it is not controlled

A person having Type 1 diabetes mellitus, before achieving age 20

Blood Glucose is poorly controlled in the body



Pathophysiology


One can understand the pathophysiology of the glomerulus by considering the three involved cells: the mesangial cell, the endothelial cell, and the podocyte.

A diabetic person suffering from DN has abnormal cells. These cells are in physical contact and are chemically active towards each other and communicate with each other at various locations within the glomerulus.

Diabetes alone can cause a series of changes to the body’s blood circulation and metabolism. They likely combine to produce excess reactive oxygen species. Reactive Oxygen Species means chemically reactive molecules containing oxygen.

These changes can damage the kidney’s glomeruli which are networks of tiny blood vessels. This leads to albumin in the urine. As diabetic nephropathy advances, a structure in the glomeruli by the name GFB (glomerular filtration barrier) is increasingly damaged.

This barrier is made up of three-layer basement membrane, podocytes, and endothelium. The GFB is responsible for the filtrated blood entering the kidney’s glomeruli. Small molecules, Small proteins and the passage of water are only allowed.

Damage to the basement membrane allows proteins in the blood to leak through, leading to excess protein in the urine. This phenomenon is called proteinuria.

High blood sugar and cytokines also cause Diabetic Nephropathy.



Diagnosis:




The measurement of abnormal levels of albumin in the urine indicated in the blood test report in a diabetic patient coupled with the exclusion of other causes of albuminuria. Levels of Albumin measurements are defined as follows:

Normal/Perfect albuminuria: albumin excretion in urine found at <30 mg/24h;

Microalbuminuria: albumin excretion in urine found at 30–299 mg/24h;

Macroalbuminuria: albumin excretion in urine found at ≥300 mg/24h.

In Albuminuria, protein albumin is abnormally present in the urine and It is a type of proteinuria. 

Albumin represents major plasma protein. In a healthy adult body, only trace/minute amounts of it are present in urine, whereas larger amounts occur in the patient’s urine with kidney disease.

Microalbuminuria(now also known as increased a moderate increase in the level of urine albumin. It occurs when an abnormally high permeability for albumin in the glomerulus of the kidney occurs.

In simple words, it means when the kidney leaks a small amount of albumin into the urine. Normally albumin is filtered by kidneys, so if albumin is found in the urine, it is a symptom of the disease.

Severely increased urinary albumin/creatinine ratio greater than 300 mg/g or greater than 30 mg/mmol is called Macroalbuminuria. Protein amount lost in the urine can be calculated by collecting the urine for 24 hours, measuring and extrapolating to the collected volume. 

A dipstick test for proteinuria is also available for a user to test. It can give a rough estimate for albuminuria in the urine. Specific agent Bromophenol blue, specific to albumin is used in the dipstick. 

According to a belief, red meat intake can be helpful in lowering albuminuria levels. 

Type 2 Diabetes patients are recommended to have their albumin levels checked annually, beginning immediately after the diagnosis of diabetes disease.

Type 1 Diabetes patients are recommended for the test once in a 5-year span.

Ultrasonography is recommended by the physician for medical imaging of the kidneys if there is a suspicion of kidney stones, polycystic kidney disease, urinary tract obstruction, and urinary tract infection.


Staging:



The severity and degree of the damage to the kidney in kidney diseases can be determined by the serum creatinine. It can be used to calculate the estimated glomerular filtration rate (eGFR). Normal/ideal eGFR values can be equal to greater than 90ml/min/1.73 m2

Stage 1 value is >= 90

Stage 2 value is 60-89

Stage 3 value is 30-59

Stage 4 value is 15-29

Stage 5 value is <15


Treatment:


Treatment for kidney diseases usually involves slowing down the progress of kidney damage and control related complications.

The main treatment, once proteinuria is established, is ACE inhibitor medications, which slow the progression of diabetic nephropathy and reduce the levels of proteinuria. In the management of this condition, other issues include control of high blood pressure and blood sugar levels.

One may also have to reduce the consumption for dietary salt intake.

Diabetes Management:


The purpose of managing diabetes is to balance the carbohydrate levels in the body to a normal state. 

To achieve this aim, individuals with absolute insulin deficiency may often require insulin replacement therapy, which is given through an insulin pump.

Injections can also be used instead of the insulin pumps. Insulin resistance can be corrected by dietary modifications and exercise.

Other aims of managing diabetes are to prevent or treat the many complications arising due to the disease itself and from its treatment.


Prognosis:


Type 2 diabetes in Diabetic nephropathy can be more difficult to predict as the symptoms are usually shown after 5-10 years.

The onset of diabetes is usually not well established. Without the use of medication or slowdown agents, 20-40 percent of patients with Type 2 diabetes /microalbuminuria, will evolve to macroalbuminuria.

For end-stage kidney diseases, diabetic nephropathy is the most common cause and treatment may require hemodialysis or even kidney transplantation.

The chances of death usually go high in general, particularly from cardiovascular disease.

Epidemiology


The number of people suffering from diabetic nephropathy is expected to rise even more.

Diabetic Diet:


In order to minimize and reduce the dangerous consequences of diabetes, a diabetic patient can introduce changes to his/her diet to minimize symptoms (most probably high blood glucose).

A diabetic person can follow a diabetic diet. If diabetes is left unchecked, it results in a high concentration of a sugar called glucose in the blood.

When the pancreas cannot produce sufficient insulin hormone in significant amounts, it results in Diabetes mellitus type 1. Diabetes type 2, is now believed to occur from the pancreas when there is an autoimmune attack on the pancreas and/or resistance of the insulin.

Type 2 diabetic person pancreas may be producing normal or even abnormally large amounts of insulin.

The main goal of the diabetes diet as far as possible is to maintain carbohydrate metabolism to a normal state.  For overweight and obese people with Type 2 diabetes, any weight-loss diet that the person will adhere to and achieve weight loss is partly effective.

The most agreed-upon recommendation by the nephrologists for the diet is to be low in sugar and refined carbohydrates, while relatively high in dietary fiber, especially soluble fiber.

People with diabetes are usually encouraged to eat small frequent meals a day.

Diabetic people are also recommended to reduce their intake of food that have a high glycemic index (GI). The glycemic index (GI) is a number from 0 to 100 assigned to food, with pure glucose value being 100, which represents the relative rise in sugar levels after consuming the food after 2 hours. Specific food GI values primarily depend on the type of carbohydrate it contains and its quantity. It is also affected by the amount of entrapment of carbohydrate molecules within the food, the fat content, protein content and the number of organic acids in the food. Food is known to have a low GI if its value is 55 or less. Mid-range values vary from 56 to 69 and if the GI is 70 or more, it is considered as high GI.

In hypoglycemia cases, diabetics are advised to have quick food items or sports drink that can raise blood sugar, such as sports drink used by athletes or any sugary drink, followed by carbohydrate diet to prevent the risk of further hypoglycemia

People with Type 1 diabetes who use insulin can eat whatever they want, preferably a healthy diet with some carbohydrates to make sugar management easier.





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