To “Pee” or not to “Pee”—the KIDNEY in health and disease

1. To “Pee” or not to “Pee”—the KIDNEY in health and disease “It is no exaggeration to say that the composition of the blood is determined not by what the mouth takes in but by what the kidneys keep.” Homer W. Smith (1895-1962)

2. Some numbers… • Renal diseases are responsible for a great deal of morbidity but are not major causes of mortality. • Approximately 45,000 deaths are attributed to renal disease per year (as compared to 650,000 deaths due to heart disease, 560,000 due to cancer, and 145,000 due to stroke) (National Center for Health Statistics, 2002)

3. Some numbers… • Millions of persons are affected annually by nonfatal kidney diseases, most notably infections of the kidney or lower urinary tract, kidney stones, and renal obstruction. • Twenty percent of all women have a urinary tract infection or kidney infection at some time in their lives • 20% of all women and 10% of all men 65 and older have bacteriuria; double those #’s in nursing homes (25-50% of women, and 15%-40%) in men

4. Some numbers… • 10% of men and 5 % of women will have a kidney stone by the age of 70; about one million Americans are treated each year for a kidney stone • BPH is a major cause of bladder outlet obstruction • Kidney cancer, bladder cancer, prostate cancer are major urologic cancers (especially as the population ages)

5. Some numbers… • Urinary incontinence is estimated to affect between 15% and 30% of independent adults ages 65 and older • Costs the US about $20 billion per year to be incontinent

6. Kidney failure • Bones can break, muscles can atrophy, glands can loaf, even the brain can go to sleep, without immediately endangering our survival; but should the kidneys fail…neither bone, muscle, gland nor brain could carry on. --Idem

7. CKD and renal failure… • From 1988 to 2004 the rates of chronic kidney disease climbed from 10 percent to 13 percent of the US population • Contributing factors? Diabetes, hypertension, obesity, and the aging U.S. population (JAMA 2007; 298:2038) • Chronic kidney disease affects 16.8% of the U.S. population over 20 • Only about 1 in 8 men and 1 in 16 women with moderate (stage 3) kidney disease know they have it—YIKES! If we can pick it up, we can slow it down or reverse it!

8. Renal failure and renal dialysis • If renal failure is left untreated it will cause death within two to three weeks • Dialysis—from the Greek word for “separation”—Willem Kolff, M.D. devoted his entire medical career to the treatment of renal failure after watching the death of a 22-year old patient die from the disease. He invented the first dialysis machine in 1941 (using materials from a local factory) and in 1945 he successfully treated the first patient, a 67 year-old woman who lived another 7 years on dialysis

9. Renal failure and renal dialysis • 1960—Scribner and colleagues at the University of Washington developed a blood-access device using Teflon-coated plastic tubes, which facilitated the use of repeated hemodialysis as a life-sustaining treatment for patients with uremia • It was called the Scribner shunt…led to the development of AV fistulas and grafts and to long-term renal replacement therapy and the era of the “artificial kidney”

10. A little more history… • Gustav Simon, in 1869, performed the first successful removal of a human kidney, the patient survived and the remaining kidney “picked up the slack” so to speak • FACT: The healthy kidney can grow enough to handle 80% of the load that 2 kidneys used to handle

11. Dr. Joseph Murray, Boston • During WWII Murray treated burn patients and wondered why skin rejection occurred when grafts were donated by other people. He and another colleague surmised that the closer the genetic relationship the longer the graft would last • December 23, 1954 the first transplanted kidney from a 23 year-old man to his identical twin; the recipient lived another 8 years; Murray won the Nobel Prize in 1990

12. Looking for a kidney somewhere else because the waiting list in the U.S. is too long? • India for $15,000; China? $62,000 • U.S.? $262,900 • Organ harvesting rings around the world; latest one from Kosovo (2008) • China—convicts on death row are routinely tested, typed, and held for on-demand “donations” • Pakistan, India, and Indonesia—slum dwellers sell their body parts (Scott C, The Red Market, Wired, 2011) • ARE YOU AT RISK FOR CKD?

13. The SCORED questionnaire—to identify patients at high risk for kidney disease • I am between 50 and 59 years of age—2 • I am between 60 and 69 years of age—3 • I am 70 years or older – 4 • I am a woman – 1 • I had or have anemia – 1 • I have high blood pressure – 1 • I am diabetic – 1 • I have a history or heart attack or stroke--1

14. The SCORED questionnaire—to identify patients at high risk for kidney disease • I have a history of CHF or HF – 1 • I have circulation disease in my legs – 1 • I have protein in my urine – 1 • If you score 4 or higher on the test you have a 1 in 5 risk of chance of having chronic kidney disease • Get it checked out! (88-95% accuracy in identifying kidney disease) • Arch of Intern Med 2008 (Feb 29)

15. Let’s start at the very beginning… • How much embryology did you get in nursing school? • The sperm meets the egg and then…

16. Embryologic development • Kidneys appear during the 3rd week of fetal development; Three sets of kidneys develop; first two are discarded and the third time is the charm • By the 3rd month the fetus is excreting urine into the amniotic fluid; urine becomes the main component of amniotic fluid

17. Embryology—the development of the kidney • The kidneys and the ears from the same mesenchymal tissse • The otorenal axis • Nephrotoxic drugs and ototoxc drugs

18. Location, location, location… • Kidneys located in the retroperitoneal space between T12 and L3 • Right lower than the left

19. Kidney size is NOT affected by body build • The kidneys grow at the same rate that the entire body grows, until ~25-26. This is the age that internal organs reach their final dimensions. • The mean dimensions of the kidneys upon maturation are: length~12cm (~4.7 inches), width~6 cm (~2.4 inches) and thickness~ 3 cm (~1.2 inches). • The weight of one kidney averages about 120-150 g (4.5-5 oz).

20. PEARL: • The kidney makes up less than 0.5% of the body’s weight, yet takes in 20-25% of the resting body’s cardiac output and uses 20-25% of the body’s oxygen • It’s busy…

21. Kidney size • Any decrease in size (atrophy) is not normal. An enlarged kidney is normal only in cases when one kidney is removed and the remaining kidney enlarges to compensate for the functional absence of the first. • THE MOST IMPORTANT NON-INVASIVE TEST FOR RENAL DISEASE is a renal ULTRASOUND to determine renal size

22. The kidney…retroperitoneal space • CVA tenderness • Acute pyelonephritis • Glomerulonephritis • Palpation? Can you palpate the kidney in an adult? • Not unless the kidney is HUGE…(tumor) • Polycystic kidney disease (PKD)

23. The kidney…retroperitoneal space • Palpation? Can you palpate the kidney in an adult? • Not unless the kidney is HUGE…(tumor) • Polycystic kidney disease (PKD)

24. Polycystic kidney disease • Autosomal dominant polycystic kidney disease (ADPKD) • 1/1000; C>AA; 4-10% of patients w/ kidney failure on dialysis or needing transplant • 50% by age 50 have renal failure • Kidneys can be the size of a football

25. Associated structures • Ureters • Bladder • Urethra

26. Ureters • 10 – 12 inches (25 – 30 cm) and about 0.04 to 0.4 inches (1 – 10 cm) in diameter • When the bladder fills, the distal end of the ureter closes to prevent urine from backing up into the kidney • If this mechanism is not working properly bacteria can reflux into the ureters and up to the kidneys—vesicoureteral reflux • Muscularis layer of the ureter propels urine via peristalsis to bladder—1 to 5 contractions per minute

27. Ureters • Pregnancy--progesterone slows down peristalsis • Kidney stones—the pain?? On a scale from 1 to 1,000? • The incidence of kidney stones increases with age and it’s higher in Caucasians than African-Americans. There is a significant regional variation in kidney stone formation with the highest prevalence in the Southeastern part of the United States.

28. Digression…kidney stones • Does fluid intake make a difference? YES • This approach increases urine flow rate and decreases the urine solute concentration—both mechanisms prevent kidney stones. In warmer climates, inadequate fluid intake causes dehydration, which increases the acidity of urine and stone formation. (Southeastern U.S.= hot=increased kidney stones) • This time-honored recommendation for reducing the risk of kidney stones is to take two or more liters of fluids per day. And, not just any fluids…

29. Fluids and kidney stones… • Certain fluids have been associated with a high risk of kidney stones—these include soft drinks and tea. (Southeastern U.S.=lots of tea) Grapefruit juice has also been linked to an increased risk of kidney stones but the mechanism is unknown.

30. The good news… • Alcohol, especially wine, and coffee consumption have been negativelyassociated with kidney stones. YES!! there is a God.

31. Kidney stones • Foods that are high in potassium decrease urinary calcium and increase urinary citrate excretion. • Some vegetables, such as spinach and rhubarb, as well as peanuts, cashews, and almonds, have high oxalate content and should be avoided.

32. Bladder • Medium-full bladder holds about 1 pint (500 mL) of urine and measures 5 inches (12.5 cm) in length • Fully expanded, the bladder can hold 1 quart (1 L) or more and YES, it can burst • Newborns void 5-to 40 times a day • At 2 months a baby voids 400 mL (14 fl oz) per day • Adolscents and adults—1.5 quarts (1500 ml) per day

33. Urination • Awareness of urination starts at about 15 months • Control of nighttime urination sometimes takes until age four • Girls vs. boys and potty training

34. Urethra • 1.5 inches (4 cm) in women • MEN? Depends on who you ask…hahaha… • 6-8 inches (15-20 cm)

35. Cystitis • Lower urinary tract infections • Lots of reasons—back to front wiping (E. coli and the rectum), pH changes, lack of estrogen, vesicoureteral reflux • Young girls? Old girls?

36. The importance of estrogen and the maintenance of urinary tract health • Estrogen receptors and the urethra • Prepuberty , perimenopause, and postmenopause • E.Coli and the rectum

37. Treatment of urinary tract infections • TMP-SFX—Bactrim/Septra—watch out for K+ levels in patients on ACE inhibitors or patients with CKD and ESRD • Fluoroquinolones – the “floxacins” – used when greater than 20% resistance to TMP-SFX • Side effects: C. difficile, tendonitis with acute ruptured Achilles’ tendons in high-risk patients (elderly and patients on Prednisone)

38. The antibiotics—the fluoroquinolones, the “floxacins”… • Ciprofloxacin (Cipro)*(2) (↑ INR) • Lomefloxacin (Maxaquin)(2) • Norfloxacin (Noroxin)*(2) • Ofloxacin (Floxin)(2)* *uncomplicated UTI if resistance to TMP/SMX is ≥20% • Levofloxacin (Levaquin) (3)—too broad spectrum for UTI

39. Gross anatomy • Renal capsule • Renal cortex (glomeruli—80-85% of nephrons lie in cortex) • Renal medulla (collecting ducts and some Loops of Henle) • renal papillae • the renal interstitium (columns) • renal pelvis (pyelo)/calyces

40. The anatomy of a nephron—greater detail • The basic functioning unit of the kidney • The nephron—1.5 million per kidney in normal birth weight individuals**

41. Premature babies/LBW babies • LBW babies are much more likely to develop hypertension later on in life and it may be due to the fact that they have less nephrons to start with • Autopsies on patients between 35-59 • 10 kidneys w/ known hypertension; 10 w/ normal BP • Average number of nephrons in people w/ HBP was fewer than ½ that of people w/ normal BP

42. Premature babies/LBW babies • Couldn’t find damaged nephrons or nephrons that had dropped out—suggesting inherited # of nephrons • Good prenatal nutrition and the # of nephrons—restricting proteins ↓ # of developing nephrons • (N Engl J Med 9 Jan 2003)

43. Premature babies/LBW babies • Another implication • Screening kidney donors for LBW may be important when deciding who might be a candidate as an appropriate donor • The donor loses 50% of nephrons—if remaining kidney has fewer #’s due to LBW, this increases the risk of hypertension in the donor—overworked and underpaid triggering the release of renin-angiotensin-aldosterone

45. The anatomy of a nephron—greater detail • Afferent arteriole → glomerulus → basement membrane → Bowman’s capsule → tubular system (proximal convoluted tubule (PCT), Loop of Henle, distal convoluted tubule (DCT), collecting duct) • Peritubular capillaries (the vasa recta)

46. The nephron and the filtration membrane • The filtration membrane—3 layers 1) the endothelial cells of the glomerulus 2) the basement membrane between the glomerulus and the, 3) epithelial cells of Bowman’s capsule • Diseases—1) Lupus nephritis 2) “sugar” diabetes 3) nephrotic syndrome

47. 1.The glomerular capillary wall (lined with endothelial cells) 2. The basement membrane (a glycoprotein layer) 3. The fenestrated wall (epithelial) cells of Bowman’s capsule into the first part of the tubule (the proximal tubule)(epithelial cells) Lupus nephritis 2) diabetic nephropathy 3) nephrotic syndrome Glom BM BC PCT The glomerular filtration membrane 3 2 3 1

48. A note on the tubules of the kidney… • The tubules of Bowman’s capsule and the PCT—proximal convoluted tubule) are lined with epithelial cells • The epithelial cells are extremely vulnerable to hypoxia • Without oxygen, the epithelial cells become necrotic and slough into the tubule; clogging the works resulting in • Acute tubular necrosis (ATN)

49. Ethylene glycol nephrosis results in acute tubular necrosis • Dogs and cats love the sweet taste of antifreeze • Crystals precipitate in the tubular lumen resulting in intrarenal obstruction, degeneration and necrosis of the lining of the tubular epithelium • Irreversible renal failure

50. Kidney disease • Traditional approach is to divide the kidney into 4 basic morphologic components • 1) Glomeruli--glomerulonephritis • 2 + 3) Tubules—tubulointerstitial diseases including pyelonephritis) • 3) Interstitium • 4) Blood vessels