Kidney Disease and Its Leading Causes: Diabetes and Hypertension

1. 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

2. 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.

3. 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

4. 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.

5. 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.

6. 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

7. 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

8. 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

9. 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.

11. 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.

12. 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 < 140/90 or 130/80 if diabetes or kidney disease is present.

13. How many different blood pressure lowering drugs are required to reach target goal ?

14. Increasing Prevalence of Diabetes from 1990 to 2000

15. 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.

16. 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.

17. 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 body’s immune system so insulin production is impaired • affects almost I million people in the U.S.

18. 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.

19. 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.

20. 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

21. 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

22. 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

23. 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.

24. 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

25. Causes of death associated with diabetes

26. 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.

27. 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

28. 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.

29. 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

30. Diabetes Prevention Study:NEJM.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

31. Target blood pressure and initial antihypertensive agent in diabetes

32. 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).

33. 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

34. Kidney Disease: Risk Factors • Age > 60 • African Americans, American Indians, Hispanic, Asian • Low income/education • Illicit drug use: cocaine, heroine

36. 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

37. 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 (<3.0 is normal) • 24-hr protein excretion (< 150mg./day is normal)

38. 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

39. Control of Hypertension in Kidney Disease: Menon AJKD 2005

40. Kidney Disease: Cardiovascular Risk Menon AJKD 2005

41. 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.

42. Increasing Prevalence of Obesity from 1990 to 2000

43. 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.

44. 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.

45. 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!

46. 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.

47. Health risk associated with obesity

48. Body Mass Index Table

49. 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)

50. 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.