Excerpt for Diabetic Nephropathy, A Simple Guide To The Condition, Diagnosis, Treatment And Related Conditions by , available in its entirety at Smashwords

Diabetic Nephropathy,





The Condition,




Related Conditions


Dr Kenneth Kee

M.B.,B.S. (Singapore)

Ph.D (Healthcare Administration)

Copyright Kenneth Kee 2017 Smashwords Edition

Published by Kenneth Kee at


This book is dedicated

To my wife Dorothy

And my children

Carolyn, Grace

And Kelvin

This book describes Diabetic Nephropathy, Diagnosis and Treatment and Related Diseases which is seen in some of my patients in my Family Clinic.

(What The patient Need to Treat Diabetic Nephropathy)

This eBook is licensed for your personal enjoyment only. This eBook may not be re-sold or given away to other people. If the patient would like to share this book with another person, please purchase an additional copy for each reader.

If you’re reading this book and did not purchase it, or it was not purchased for your use only, then please return to and purchase your own copy.

Thank you for respecting the hard work of this author.


I have been writing medical articles for my blog (A Simple Guide to Medical Disorder) for the benefit of my patients since 2007.

My purpose in writing these simple guides was for the health education of my patients.

Health Education was also my dissertation for my Ph.D (Healthcare Administration).

I then wrote an autobiolographical account of his journey as a medical student to family doctor on his other blog

This autobiolographical account “A Family Doctor’s Tale” was combined with my early “A Simple Guide to Medical Disorders” into a new Wordpress Blog “A Family Doctor’s Tale” on

From which many free articles from the blog was taken and put together into 800 amazon kindle books and 200 into eBooks.

Some people have complained that the simple guides are too simple.

For their information they are made simple in order to educate the patients.

The later books go into more details of medical disorders.

The first chapter is always from my earlier blogs which unfortunately tends to have typos and spelling mistakes.

Since 2013, I have tried to improve my spelling and writing.

As I tried to bring the patient the latest information about a disorder or illness by reading the latest journals both online and offline, I find that I am learning more and improving on my own medical knowledge in diagnosis and treatment for my patients.

Just by writing all these simple guides I find that I have learned a lot from your reviews (good or bad), criticism and advice.

I am sorry for the repetitions in these simple guides as the second chapters onwards have new information as compared to my first chapter taken from my blog.

I also find repetition definitely help me and maybe some readers to remember the facts in the books more easily.

I apologize if these repetitions are irritating to some readers.

Chapter 1

Diabetic Nephropathy

What is Diabetic Nephropathy?

Diabetic nephropathy is a form of kidney damage that often happens over time in people with diabetes.

People with diabetes are at higher risk of renal atherosclerosis, urinary tract infections, papillary necrosis and glomerular lesions (e.g., from basement membrane thickening and glomerulosclerosis)

Diabetic nephropathy may be diffuse or nodular (Kimmelstiel-Wilson lesion).

The early stages produce a raised glomerular filtration rate with enlarged kidneys but the principal feature of diabetic nephropathy is proteinuria.

This forms insidiously, beginning as intermittent micro-albuminuria before going on to constant proteinuria and occasionally nephrotic syndrome.


1. Micro-albuminuria:

The albumin:creatinine ratio (ACR) is greater than or equal to 2.5 mg/mmol (men) or 3.5 mg/mmol (women), or albumin concentration is greater than or equal to 20 mg/L.

2. Proteinuria:

The ACR is greater than or equal to 30 mg/mmol or albumin concentration is greater than or equal to 200 mg/L.

What are the causes of Diabetic Nephropathy?


Each kidney is made of hundreds of thousands of small entities called nephrons.

These nephrons:

1. Filter the blood,

2. Help remove waste from the body, and

3. Control fluid balance.

In people with diabetes, the nephrons slowly become thickened and scarred over time.

The nephrons start to leak and protein (albumin) escapes into the urine.

This injury can occur years before any symptoms start.

Kidney injury tends more likely if the patient can:

1. Have uncontrolled blood sugar

2. Have high blood pressure

3. Have type 1 diabetes that started before the patient was 20 years old

4. Have family members who also have diabetes and kidney problems

5. Smoke

6. Be African American, Mexican American, or Native American


Kidney injury in type 1 diabetes is the biggest cause of chronic kidney disease in the working age group

Kidney disease in people with type 2 diabetes is rising because of the rising incidence of people with diabetes, improved cardiovascular survival and the trend to younger start of type 2 diabetes.

The incidence of micro-albuminuria in patients with type 1 diabetes at 30 years' disease duration is about 40%.

The incidence of micro-albuminuria in patients with type 2 diabetes at 10 years' disease duration is about 20-25%.

What are the symptoms of Diabetic Nephropathy?


Frequently, there are no symptoms as the kidney damage begins and slowly becomes worse.

Kidney injury can start 5 to 10 years before symptoms begin.

People who have serious and prolonged (chronic) kidney disease may have symptoms such as:

1. Fatigue most of the time

2. General ill feeling

3. Headache

4. Nausea and vomiting

5. Poor appetite

6. Swelling of the legs

7. Itchy skin

8. Easily develop infections

How is Diabetic Nephropathy diagnosed?


The doctor will require tests to detect signs of kidney disorders.

A urine test looks for a protein called albumin leaking into the urine.

Too much albumin in the urine is frequently a sign of kidney injury.

This test is also called a microalbuminuria test because it measures small amounts of albumin.

The doctor will also examine the blood pressure.

High blood pressure injures the kidneys and is difficult to control when the patient have kidney damage.

A kidney biopsy may be required to confirm the diagnosis or look for other causes of kidney damage.

If the patient has diabetes, the doctor will also examine the kidneys by using these blood tests every year:

1. Blood urea nitrogen (BUN)

2. Serum creatinine

Detection and surveillance of kidney disorders

Medical features are normally absent until the advanced chronic kidney disease forms.

There may be features of poor diabetes control (e.g., thirst, lethargy) and it is necessary to evaluate for other possible complications of diabetes.

The annual review is advised for all people with type 1 and type 2 diabetes.

The monitoring of children with type 1 diabetes should start at age 12 years.

The reviewing should start at the time of diagnosis for adults with type 1 or type 2 diabetes and for children with type 2 diabetes.

The urinary ACR or albumin concentration is measured annually.

A first morning urine sample is taken when possible.

The test is repeated if an abnormal ACR is found (in the absence of proteinuria or a urinary tract infection) at each of the next two clinic visits but within a maximum of 3-4 months.

The serum creatinine is measured and glomerular filtration rate (eGFR) estimated annually.

Other early investigations to evaluate cause of proteinuria are:

1. Urinalysis,

2. Urine culture and microscopy and

3. Renal ultrasound.

Renal biopsy may sometimes be necessary.

Other investigations for monitoring of diabetes are:

1. Glycosylated hemoglobin (HbA1c) and

2. Serum lipids.

Any increased albumin excretion rate in type 2 diabetes is often an indication of general vascular damage rather than specific renal damage.

It is a helpful arterial risk marker.

Abnormal serum creatinine in type 2 diabetes is often because of renal arterial disease and diuretic treatment for cardiac failure rather than for diabetic nephropathy.

The detection and surveillance of specific kidney disorders therefore is dependent on identifying the progression of albumin excretion rate and serum creatinine, in the absence of other causes.

A non-diabetes-related cause of renal disease should be considered (full history and examination, urinalysis, renal ultrasound and other investigations done if required).

Other renal disease should be determined:

1. In the absence of progressive retinopathy.

2. If blood pressure is particularly high or resistant to treatment.

3. If proteinuria forms suddenly.

4. If they had a reported normal ACR and heavy proteinuria (ACR >100 mg/mmol) is present.

5. If significant hematuria is present.

6. In the presence of systemic ill health.

What is the treatment of Diabetic Nephropathy?


When kidney damage is identified in its early stages, it can be slowed down with treatment.

Once bigger quantities of protein appear in the urine, kidney injury will slowly get worse.

The patient should follow the doctor’s advice to keep the disorder from getting worse.

Control the blood Pressure

Maintaining the blood pressure under control (below 130/80 mm Hg) is one of the best methods to slow kidney damage.

The doctor may give medicines to lower the blood pressure and protect the kidneys from more damage.

These medicines, even when the blood pressure is in a healthy range, assist slowing kidney damage.

Control the Blood Sugar Level

The patient can also slow kidney damage by regulating the blood sugar level through:

1. Eating healthy foods

2. Getting regular exercise

3. Consuming medicine or having the insulin injection as instructed by the doctor

Reviewing the blood sugar level as often as instructed and maintaining a record of the blood sugar numbers so that the patient knows how food in meals and activities affect the sugar level

Other ways to protect the Kidneys

Contrast dye that occasionally given with an MRI, CT scan, or other imaging test can induce more damage to the kidneys.

The patient should inform the doctor who is ordering the test that the patient has diabetes.

The NSAID pain medicine, such as ibuprofen or naproxen, should be avoided.

The patient should ask the doctor if there is another medicine that the patient can take instead.

NSAIDs can injure the kidneys, more so when the patient uses them every day.

The doctor may want to stop or change other medicines that can injure the kidneys.

The patient should know the signs of urinary tract infections and get them treated right away.

Primary prevention

The best control of blood glucose and blood pressure is by:

1. The doctors found that a decrease in mean HbA1c from 75 mmol/mol to 56 mmol/mol in people with type 1 diabetes was linked with a 39% decrease in micro-albuminuria and 54% decrease in proteinuria over 6.5 years.

There is no clear advantage seen in the treatment of established micro-albuminuria in people with type 1 diabetes.

2. The doctors also showed that a decrease in blood pressure from 154/87 mm Hg to 144/82 mm Hg was linked with an absolute risk decrease of developing micro-albuminuria of 8% over six years in patients with type 2 diabetes.

For type 2 diabetes, this also means early diagnosis and therefore treatment before complications have already started.

3. Smoking cessation.

3. Microalbuminuria and proteinuria

Good blood glucose control must be done (HbA1c below 48-59 mmol/mol based on the patient's target).

Any cardiovascular risk factors must be measured, assessed and treated aggressively (smoking, glucose, raised lipids, high blood pressure).

Angiotensin-converting enzyme (ACE) inhibitors should be begun and titrated to full dose in all adults with confirmed nephropathy (such as those with micro-albuminuria alone) and type 1 diabetes.

ACE inhibitors considerably decrease the risk of all-cause mortality for patients with diabetic kidney disease.

If ACE inhibitors are not accepted because of adverse effects, angiotensin-ll receptor antagonists should be replaced but combination therapy with both ACE inhibitors and angiotensin-ll receptor antagonists is not advised at present.

ACE inhibitor therapy (and angiotensin-II receptor antagonists) should be given with caution in those with:

1. Peripheral arterial disease or known renovascular disease.

2. Reduced glomerular filtration rate.

Blood pressure should be kept below 130/80 mm Hg by addition of other antihypertensive drugs if required.

Adults with type 1 diabetes and nephropathy should be advised about the benefits of not taking a high-protein diet.

Dietary protein restrictions are not advised.

Any referral criteria for tertiary care should be determined between local diabetes specialists and nephrologists.

Patients with an eGFR that is less than 30 ml/min/1.73 m2 should be referred to a specialist.

Urine albumin and serum creatinine levels should be measured more often (e.g., six-monthly for micro-albuminuria but normal serum creatinine).

The frequency will be dependent on the personal situation of the patient.

What is the prognosis of Diabetic Nephropathy?


Diabetic kidney disease is a main cause of sickness and death in people with diabetes.

It can result in the need for dialysis or a kidney transplant.

Type 1 Diabetes

About 19% to 24% of patients with micro-albuminuria form diabetic nephropathy.

Systolic blood pressure, glycated hemoglobin and triglycerides are considerably higher in people with type 1 diabetes who go on to diabetic nephropathy than for those who do not

Kidney disease is responsible for 21% of deaths in people with type 1 diabetes

With intensive antihypertensive therapy, proteinuric type 1 diabetic patients lose glomerular filtration rate at about 4 ml/min/year

When proteinuria and hypertension are present, the standardized death rate ratio is raised 11-fold in men and 18-fold in women

Type 2 Diabetes

20% of micro-albuminuric type 2 patients who live for 10 years form proteinuria

Patients with microalbuminuria have a 2 to 4-fold rise in cardiovascular morbidity and death.

When proteinuria and hypertension are present, the standardized mortality ratio is raised 5-fold in men and 8-fold in women with type 2 diabetes.

Chapter 2


Diabetic nephropathy is a medical syndrome typically featured by:

1. Persistent albuminuria (>300 mg/d or >200 μg/min) that is confirmed on at least 2 occasions 3-6 months apart

2. Progressive decline in the glomerular filtration rate (GFR)

3. Elevated arterial blood pressure

Kidney disease was clearly identified as a frequent complication of diabetes, with as many as 50% of patients with diabetes of more than 20 years having this complication.

Presently, diabetic nephropathy is the main cause of chronic kidney disease in the USA and other Western societies.

It is also one of the most important long-term complications in terms of morbidity and death for individual patients with diabetes.

Diabetes accounts for 30-40% of all end-stage renal disease (ESRD) cases in the USA.

Normally, diabetic nephropathy is identified after a routine urinalysis and screening for micro-albuminuria in the setting of diabetes.

Patients may have physical findings linked with long-standing diabetes mellitus.

The evidence indicates that early treatment slows or stops the onset of diabetic nephropathy or diabetic kidney disease.

This has constantly been proven in both type1 and type 2 diabetes mellitus.

Regular outpatient follow-up is the main factor for treating diabetic nephropathy successfully.

Recently, there is attention to atypical presentations of diabetic nephropathy with dissociation of proteinuria from decreased kidney function.

It has been observed that microalbuminuria is not always predictive of diabetic nephropathy.

A majority of the cases of diabetic nephropathy still presents with proteinuria, which progressively becomes worse as the disease progresses, and is almost uniformly linked with hypertension.


3 major histological changes happen in the glomeruli of persons with diabetic nephropathy.

1. First, mesangial expansion is directly caused by hyperglycemia, perhaps by increased matrix production or glycation of matrix proteins.

2. Second, thickening of the glomerular basement membrane (GBM) happens.

3. Third, glomerular sclerosis is produced by intraglomerular hypertension (caused by dilatation of the afferent renal artery or from ischemic injury induced by hyaline narrowing of the vessels supplying the glomeruli).

These different histological patterns seem to have similar prognostic significance.

The main change in diabetic glomerulopathy is increase of the extra-cellular matrix.

The earliest morphologic anomaly in diabetic nephropathy is the thickening of the GBM and expansion of the mesangium because of accumulation of extra-cellular matrix.

The pathogenesis of diabetic nephropathy

Metabolic abnormalities

1. Glucose

2. AGE (Advanced Glycation End products)

3. Polyols

Hemodynamic abnormalities

1. RAS (renin–angiotensin system)

2. ET

It tends to be likely that the metabolic and hemodynamic abnormalities seen in diabetes interact with each other and pathways linked to reactive oxygen species (ROS) generation.

Gene regulation and activation of transcription factors are affected by interactions among metabolic stimuli, hemodynamic factors and various ROS in diabetes.

The results of molecular activation and inhibition of the various pathways result in functional and structural changes (such as increased vascular permeability and extra-cellular matrix accumulation) characterized by higher albuminuria and decreasing renal function.

This medically become manifest as diabetic nephropathy.

Light microscopy findings indicate a rise in the solid spaces of the tuft, most often observed as coarse branching of solid (positive periodic-acid Schiff reaction) material (diffuse diabetic glomerulopathy).

Large acellular accumulations also may be seen within these areas.

These are circular on section and are termed the Kimmelstiel-Wilson lesions/nodules.

Immunofluorescence microscopy may show deposition of albumin, immunoglobulins, fibrin, and other plasma proteins along the GBM in a linear pattern, most often as an effect of exudation from the blood vessels.

This is not immunopathogenetic or diagnostic and does not suggest an immunologic pathophysiology.

The renal vasculature normally reveals evidence of atherosclerosis, normally due to concomitant hype-rlipidemia and hypertensive arteriosclerosis.

Electron microscopy gives a more detailed definition of the structures affected.

In advanced disease, the mesangial regions hold a large proportion of the tuft, with prominent matrix content.

More, the basement membrane in the capillary walls (i.e., the peripheral basement membrane) is thicker than normal.

The seriousness of diabetic glomerulopathy is measured by the thickness of the peripheral basement membrane and mesangium and matrix expressed as a fraction of suitable spaces (e.g., volume fraction of mesangium/glomerulus, matrix/mesangium, or matrix/glomerulus).

The glomeruli and kidneys are usually normal or larger in size initially, thus differentiating diabetic nephropathy from most other forms of chronic renal insufficiency, where the renal size is decreased (except renal amyloidosis and polycystic kidney disease).

Besides the renal hemodynamic alterations, patients with overt diabetic nephropathy (dipstick-positive proteinuria and reducing glomerular filtration rate [GFR]) normally form systemic hypertension.

Hypertension is a risk factor in all progressive renal diseases and appears particularly so in diabetic nephropathy.

The dangerous effects of hypertension are likely directed at the vasculature and microvasculature.

The evidence indicates that hypertension linked with obesity, metabolic syndrome, and diabetes may play an important part in the pathogenesis of diabetic nephropathy.

Central obesity, metabolic syndrome, and diabetes result in higher blood pressure.

Central obesity causes hypertension initially by raising renal tubular reabsorption of sodium and causing a hypertensive shift of renal-pressure natriuresis through multiple mechanisms, such as:

1. Activation of the sympathetic nervous system and renin-angiotensin-aldosterone system, and

2. Physical compression of the kidneys.

Hypertension, along with rises in intraglomerular capillary pressure and the metabolic anomalies (e.g., dyslipidemia, hyperglycemia) likely interact to speed up renal injury.

In the same way, obesity-linked glomerular hyper-filtration, renal vasodilation, rises in the glomerular filtration rate and intra-glomerular capillary pressure, and raised blood pressure also are typical of diabetic nephropathy.

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