Kidney Disease and Its Leading Causes: Diabetes and Hypertension

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Kidney Disease and Its Leading Causes Diabetes
and Hypertension

• A Brown-Bag Presentation by
• Robert Beallo, M.D.
• Sponsored by
• LBNL Health Care Facilitator Program
• March 31, 2005
• Perseverance Hall

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The Real Epidemics in Our Community
Hypertension, Diabetes, and Obesity

• Epidemic a disease or condition which is highly
  prevalent in a community or large geographical
  area.
• High blood pressure affects approximately 25 of
  people in the United States.
• Obesity affects approximately 30 of people in
  the United States.
• Diabetes affects approximately 8 of people in
  the United States.

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High Blood Pressure/Hypertension

• What is hypertension (HTN)
• a blood pressure reading more than 140/90
• about 25 of U.S. residents are affected
• once it develops, it usually lasts a lifetime
• it can be treated and controlled very well
• Hypertension is a silent killer
• may be present for years without symptoms
• if not diagnosed at an early stage, people will
  not find out it is present until they experience
  trouble with their heart, brain, kidney, or blood
  vessels

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Consequences of untreated or inadequately treated
hypertension

• Enlargement of the heart leading to heart
  failure.
• Bulges in large blood vessels (aneurysms) of the
  brain, intestine, legs, and aorta (main artery in
  the chest and abdomen) can develop. These bulges
  can rupture leading to severe consequences
  including death.
• Arteries throughout the body can become narrowed
  (arteriosclerosis) leading to reduced blood
  supply to the heart (heart attack),
• or the brain (stroke),
• or the kidney (dialysis),
  or the legs
  (gangrene and amputation.

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What is blood pressure ?

• Blood pressure is recorded as these 2 numbers
  systolic and diastolic, e.g. 120/80.
• When the heart beats, blood is propelled out of
  the heart into blood vessels called arteries.
• Blood pressure is the force of blood pushing
  against the wall of arteries.
• Systolic pressure blood pressure is highest when
  the heart beats and blood is pumped out of the
  heart into the arteries.
• Diastolic pressure blood pressure is lowest
  in-between heart beats when the heart is at rest.

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Variations in blood pressure

• Normal variations blood pressure
• lowest when sleeping
• slightly higher early in the day
• increases with vigorous exercise
• increases with sudden events that provoke
  anxiety or anger
• High blood pressure / HTN
• normal 120/80
• prehypertension 120-130/80-90
• HTN greater than 130/90

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What causes hypertension?

• Essential hypertension
• most people with HTN are in this category
• an identifiable cause cannot be found
• the exact scientific explanation for this
  category remains unknown
• Secondary hypertension
• when HTN is caused by another medical condition
  or drug
• screening for a secondary cause is done routinely
  by most physicians

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Risk factors for developing hypertension

• Obesity
• Family history
• Excess dietary salt and alcohol intake
• Older age over 50 of Americans over 60 have HTN
• African Americans
• develop HTN at an earlier age
• have more severe HTN
• increased risk of heart attack, stroke, and
  kidney failure
• Tobacco use
• Diabetes

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Prevention of high blood pressure life style
modifications

• Exercise regularly e.g. walk briskly for 40
  minutes, 5 times a week.
• Maintain a healthy body weight.
• Avoid excess dietary salt see a dietician, NIH
  web site, or one of many diet manuals.
• Avoid excess alcohol less than 2 drinks / day,
  e.g. 24 oz. of beer, 10 oz. of wine, 3 oz. of
  whiskey in most men and less in women.
• Stop tobacco use.

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Recent important clinical studies on drug
treatment of HTN ALLHAT

• Published in 2002 in JAMA
• ALLHAT Antihypertensive and Lipid Lowering
  Treatment to Prevent Heart Attack Trial
• 8 year study of 33,000 pts. With HTN randomly
  selected to receive a diuretic or ace inhibitor
  or calcium channel blocker
• The incidence of stroke, CHF, heart attack and
  all cause mortality was measured for each group.
• Diuretic drug treatment was equal or superior to
  the other drug types.

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Seventh report of the Joint National Commission
of Hypertension Treatment

• Commonly referred to as JNC 7
• Systolic BP is a more important indicator of risk
  than diastolic.
• Risk of CV disease doubles with each 20mm/Hg
  increase in systolic pressure starting at 115.
• Thiazide diuretics should be used alone or in
  combination with other drugs to reach target BP.
• Most pts. will require 2 or more drugs to achieve
  target BP of lt 140/90 or 130/80 if diabetes or
  kidney disease is present.

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How many different blood pressure lowering drugs
are required to reach target goal ?
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Increasing Prevalence of Diabetes from 1990 to
2000
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Diabetes what is it?

• A disease in which blood glucose levels are
  higher than normal.
• After a meal, some of the food is broken down
  into a sugar called glucose.
• Glucose is carried by the blood to cells in the
  body.
• The amount of glucose entering the cells is
  controlled by insulin, a hormone secreted by the
  pancreas. When more insulin is secreted, cells
  take up more glucose and blood sugar levels
  decrease.

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Diabetes how blood glucose levels become
abnormally high

• Diabetes develops when cells do not take up
  glucose normally and blood glucose levels rise.
• Inadequate secretion of insulin by the pancreas
  will cause elevation of blood glucose levels.
• Cells of the body become less responsive to
  usually adequate levels of insulin. This
  situation is called insulin resistance.

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Types of diabetes modern terminology

• Type 1 diabetes
• formally called juvenile diabetes
• develops in children and young adults
• insulin producing cells in the pancreas become
  damaged by the bodys immune system so insulin
  production is impaired
• affects almost I million people in the U.S.
  

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Types of diabetes modern terminology

• Type 2 diabetes
• formally called adult onset diabetes
• most common form affects 8 to 9 million people
  in the U.S.
• develops at any age including childhood
• begins with insulin resistance muscle, liver,
  and fat cells do not use insulin properly
• at first the pancreas responds by making more
  insulin, but eventually its ability to keep up is
  also impaired and blood glucose levels become
  poorly controlled.

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Types of diabetes modern terminology

• Pre-diabetes - blood glucose levels are
  higher than normal but not high enough to be
  characterized as diabetes. - many people
  with pre-diabetes develop diabetes within 10
  years. - an increased risk of stroke and heart
  disease has been noted. - life style
  changes e.g., exercise and weight loss can delay
  or prevent full blown
• diabetes.

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Diabetes diagnosis

• Fasting blood glucose - measures your blood
  glucose levels after not eating for 8
  hours. - a positive test should be confirmed
  by a repeat fasting glucose on another day
• How to interpret the fasting glucose result -
  less than 100 normal - 100 to 125
  pre-diabetes - more than 125 diabetes

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Risk factors for developing diabetes

• Age 45 years or older
• Obesity body mass index greater than 25
• Family history parent or sibling with diabetes
• Physical inactivity
• Abnormal values for blood lipid levels - low
  HDL cholesterol less than 35 - high
  triglyceride levels more than 250
• Family background African American,
  Hispanic, American Indian, or Asian American
• Presence of high blood pressure

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Complications of diabetes

• Hypertension 25 of diabetics have HTN
• Heart disease
• leading cause of death
• accounts for 65 of deaths
• risk is 2x higher than those without diabetes
• Blindness
• leading cause of severe visual loss
• approximately 12,000 new cases per year
• Stroke 2 to 4x the risk compared to non-diabetic

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Complications of diabetes

• Kidney disease approximately 45 of people
  starting dialysis are diabetics.
• Nerve injury
• referred to as neuropathy
• about 60 of diabetics are affected
• slow digestion of food
• reduced sensation or pain in arms and legs
• foot infection from reduced sensation and
  reduced immune response. This can lead
  to amputation.

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Complications of diabetes

• Ketoacidosis and hyperosmolar states
• when blood levels become very high
• occurs when glucose levels are poorly
  controlled or another stressful illness occurs
• Dental problems increased risk of periodontal
  disease.
• Cost estimates of all the above complications
• direct medical care costs 82 billion / year
• loss of work/early retirement costs 40 billion /
  year

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Causes of death associated with diabetes
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Treatment of diabetes life style modifications

• Regular exercise 40 to 60 minutes at least 5
  times per week unless contraindicated by some
  other medical condition.
• Maintenance of proper weight even small amounts
  of weight loss can markedly improve glucose
  control.
• Stop smoking to reduce risk of cardiovascular
  events.
• Follow a proper diet ask your doctor and
  dietician what is most appropriate for you.

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Drug treatment of diabetes

• Type I insulin is required
• short acting insulins given before meals
• long acting insulins given once or twice a day.
  Glargine (Lantus), a new long acting insulin
  reduces the incidence of hypoglycemic (low blood
  sugar) reactions.
• Type 2 try oral medications first
• start with metformin or glyburide
• add a thizolidinedione, e.g. rosiglitazone-Actos
• add insulin to the above if needed

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Measuring adequacy of diabetic control
Hemoglobin A1C (hgb A1C)

• Hgb A1C measures the amount of glucose attached
  to red blood cells and reflects the overall blood
  glucose control over the preceding 2-3 months.
  Normal value is less than 6.
• United Kingdom Prospective Diabetes Study
  (UKPDS) a ten year study of 3,867 people with
  newly diagnosed diabetes randomly assigned to
  diet plus drugs to maintain either conventional
  or tight control of blood glucose.

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Results of UKPDS

• Each 1 decrease in HGB A1c led to a decline of
• 21 in any diabetic end point
• 21 in diabetes related death
• 14 in heart attack
• 37 in retinopathy and neuropathy
• Effect of blood pressure control
• tight control -145/80 vs. less intense control
  -156/85
• Tight control resulted in a decrease of
• 24 in any diabetic death
• 15 in heart attack
• 34 in retinopathy and neuropathy

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Diabetes Prevention StudyNEJM.2002

• A randomized study of 3,234 non-diabetic people
  who had mild elevations in blood glucose.
• They were randomly assigned to receive a placebo
  or metformin or life style modifications, i.e.,7
  weight loss plus 150 minutes of exercise per
  week.
• After a 3-year average follow up
• placebo 11 developed diabetes
• metformin 31 reduction in diabetes
• life style modification 58 reduction in
  diabetes

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Target blood pressure and initial
antihypertensive agent in diabetes
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Kidney Disease Basic Functions of the Kidney

• Two kidneys are normally present.
• Urinary excretion of waste products resulting
  from normal tissue breakdown and metabolism of
  food stuffs.
• Maintenance of fluid balance by urinary excretion
  of water, salt, and other ingested substances
  according amount ingested and environmental
  conditions.
• Endocrine functions including secretion of
  hormones which prevent anemia (erythropoietin),
  maintain bone integrity (vitamin D), and regulate
  blood pressure (renin-angiotensin).

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Kidney Disease Risk Factors

• Clinical
• hypertension
• diabetes
• severe arteriosclerosis
• urinary tract obstruction
• family history
• autoimmune diseases Lupus, polyarteritis
• infection hepatitis B and C, AIDS
• nephrotoxin exposure NSAIDS, Chinese herbs

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Kidney Disease Risk Factors

• Age gt 60
• African Americans, American Indians, Hispanic,
  Asian
• Low income/education
• Illicit drug use cocaine, heroine

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Clinical Assessment of Kidney Injury

• Symptoms do not occur unless kidney is
  mechanically obstructed or infected or until
  greater than 70 of kidney function has been
  lost.
• Serum creatinine and blood urea nitrogen (BUN)
• commonly measured with routine blood tests
• asses overall ability of the kidney to excrete
  waste products
• become abnormally elevated when kidneys are
  damaged

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Clinical Assessment of Kidney Injury

• Proteinuria the appearance of abnormally large
  amounts of protein in the urine may indicate
  kidney injury. Methods of assessment include
• dipstick test of urine
• ratio of urinary albumin to urinary creatinine
  ratio in spot specimen (lt3.0 is normal)
• 24-hr protein excretion (lt 150mg./day is normal)

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Chronic Kidney Disease Slowing the Rate of
Progression

• Control of hypertension
• numerous large clinical studies have documented a
  protective effect of good HTN control on slowing
  decline of kidney function
• two related classes of drugs are recommended for
  initial therapy angiotensin converting enzyme
  inhibitors (ACE) and angiotensin receptor
  blockers (ARB)
• statins may also be effective
• Diabetes good control of blood glucose level
• Stop smoking
• Life style modifications diet, weight control

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Control of Hypertension in Kidney Disease Menon
AJKD 2005
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Kidney Disease Cardiovascular Risk Menon AJKD
2005
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What is obesity ?

• A life log, progressive, life threatening,
  costly, multifactorial disease of excess fat
  storage.
• Prevalence has increased dramatically in the past
  10-15 years.
• Has contributed markedly to the increase in
  diabetes and high blood pressure.

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Increasing Prevalence of Obesity from 1990 to 2000
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The Thrifty Gene Hypothesis

• Evolutionary pressure has selected people who can
  survive caloric deprivation.
• In the past, people have been subjected to
  circumstances in which periods of poor
  nutritional intake were likely. Starvation was a
  real threat to individual and species survival.
• Metabolic compensation for excess caloric intake
  apparently did not develop in humans.
• Increase in obesity no recent genetic changes
  but rather increase in caloric intake and less
  compensatory physical activity.

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Basic principles in caloric balance

• If more calories are consumed than expended, body
  weight will increase.
• If less calories are consumed than expended, body
  weight will decrease.
• If caloric intake equals caloric expenditure,
  body weight stays the same.
• Total caloric intake determines weight gain or
  loss, not the relative amounts of protein, fat,
  and carbohydrates in a diet.

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What are the numbers?

• Energy expenditure to maintain ideal body weight
  ( average values ) 62 calories/ lb.
• men 2100 2400 cal/day
• women 1600-1800 cal/day
• Energy expenditure with exercise
• walking 1 mile 100 calories
• running 1 mile 100 calories
• An expenditure of 3500 calories is required to
  lose a pound of body weight.
• We are very thrifty in terms of calories!

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Caloric content of common foods

• 20 oz. bottle of coke 240 cal.
• Slice of cheese pizza 250 cal.
• Big mac, large fries, large coke 1,450 cal.
• Sausage and cheese bisquet sandwich 450 cal.
• Turkey breast sandwich, bag of chips, and water
  460 cal.
• 1 dozen buffalo wings 850 cal.
• 1 cup of Haggen Dazs ice cream 560 cal.
• Krispy Kreme donut 300 cal.

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Health risk associated with obesity
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Body Mass Index Table
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Strategies for treatment of obesity

• Dietary control of total caloric intake
• self awareness about eating habits
• failure to change may indicate latent emotional
  or psychological issues
• Regular exercise concrete strategies
• Drugs used for obesity
• sibutramine (Meridia)
• orlistat (Xenical)

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Low-Carbohydrate versus Conventional Weight Loss
Diets in Severely Obese Adults Annals of
Internal Med. May, 2004

• A one year study of 132 patients randomly
  assigned to either a low carbohydrate or
  conventional diet.
• Weight loss was similar in both groups.
• More patients in the low carb. diet lost weight
  because the drop out rate was higher in the
  conventional group.
• Lipid changes were more favorable in conventional
  group.
• HGB AiC declined more in the low carb. group.

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Obesity treatment

• Surgery
• Consider if obesity is severe and not responsive
  to other treatment
• Morbid obesity when other severe medical
  problems occur as a direct result of obesity.
  When one is gt 100 lb. overweight or BMI is gt 40.
• May be done by open technique or laprascopically.

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Present nomenclature for obesity according to
Body Mass Index (BMI)
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