1. Matthew R. Weir, MD Professor and Director Division of Nephrology University of Maryland School of Medicine Baltimore, Maryland Kidney Disease and Dialysis

2. 2 Outline  What are the kidneys’ jobs?  Causes of kidney failure  Why is chronic kidney disease important?  Dialysis  Kidney Transplantation

3. 3 Kidney Jobs  Fluid  Cleanse the blood  Metabolize medications  Produce hormones

4. 4 Causes of Kidney Failure  Pre-renal  Renal  Post-renal

5. 5 Urogenital Overview

6. 6 Normal Kidney Anatomy Renal artery Renal vein Renal pelvis Perirenal fat in renal sinus Ureter Cortex Capsule Medulla Renal columns (of Bertin) Papillae Renal pyramid Corticomedullary junction Calyces Arcuate artery

7. 7 The Nephron Is the Functional Unit of the Kidney – Loss of Nephrons Translates to Loss of Function Peritubular capillaries Distal convoluted tube Thick ascending limb Collecting duct Peritubular venules Proximal tubule Afferent arteriole Glomerulus Bowman’s capsule Efferent arteriole Proximal convoluted tubule

8. 8 Pre-Renal  History  Physical Exam  Lab tests  Causes

9. 9 Renal  History  Physical Exam  Lab tests  Causes

10. 10 Post-Renal  History  Physical Exam  Lab tests  Causes

11. 11 Why is chronic kidney disease important?  It is associated with stroke and heart attack!  Kidney function or proteinuria are the barometer of blood vessel disease in the body  Only objective measures of vascular disease!

12. 12 Relationship Between CKD and CVD 1 CKD = chronic kidney disease; CVD = cardiovascular disease; CV = cardiovascular. 1. Menon V et al. Am J Kidney Dis. 2005;45:223–232. CVD CKD Traditional CV risk factors Non-traditional CV risk factors CKD is a risk factor for CVD, and CVD may be a risk factor for the progression of CKD

13. 13 CKD Prevalence by Stage GFR = glomerular filtration rate. Adapted from Sarnak MJ et al. Hypertension. 2003;42(5):1050–1065. StageDescription GFR, ml/min/1.73 m 2 U.S. Prevalence, Thousands U.S. Prevalence, % 1 Kidney damage with normal or increased GFR ≥9059003.3 2 Kidney damage with mildly decreased GFR 60-8953003.0 3Moderately decreased GFR30-5976004.3 4Severely decreased GFR15-294000.2 5Kidney failure <15 or dialysis 3000.1

14. 14 200 180 160 140 120 100 80 60 40 20 0 Estimated GFR (mL/min/1.73m 2 ) Age (years) 020406080100 Inulin (Davies and Shock, 1950) NHANES III Estimated GFR (median, 5th, 95th percentiles) Uremia, Ca-PO 4 imbalance, volume overload, oxidative stress, inflammation, anemia incident CVD, CVD death Estimated Glomerular Filtration and Normal Aging

15. 15 Traditional and Nontraditional Risk Factors Increase CVD Event Risk in Patients With CKD 1 CVD = cardiovascular disease; CKD = chronic kidney disease; LDL-C = low-density lipoprotein cholesterol; HDL-C = high-density lipoprotein cholesterol; Apo = apolipoprotein. 1. Shastri S et al. Am J Kidney Dis. 2010;56:399-417. Traditional Risk Factors Older age Male sex Hypertension High LDL-C Low HDL-C Diabetes Smoking Physical inactivity Menopause Family history of heart disease Left ventricular hypertrophy White race Non-Traditional Risk Factors Anemia Volume overload Abnormal mineral metabolism Electrolyte imbalances Albuminuria Lipoprotein(a) and Apo(A) isoforms and lipoprotein remnants Homocysteine Oxidative stress/inflammation Malnutrition Thrombogenic factors Sleep disturbances High sympathetic tone Altered nitric oxide/endothelin balance Particular to individuals with CKD

16. 16 Graded and Independent Relationship Between Estimated Glomerular Filtration Rate (GFR) and CVD Outcomes* *Adjusted for baseline age, sex, income, education, coronary disease, chronic heart failure, stroke or transient ischemic attack, peripheral artery disease, diabetes, hypertension, dyslipidemia, cancer, hypoalbuminemia, dementia, liver disease, proteinuria, prior hospitalizations, and subsequent dialysis requirement. Shastri S et al. Am J Kidney Dis. 2010 Jul 2. [Epub ahead of print].

17. 17 Patients Diagnosed with CKD Have a Greater Likelihood of Death than ESRD Status in the entry period DM/CKDDM/Non-CKD NDM/CKD NDM/Non-CKD 19,335 188,596 33,586 N=1,045,263 0.07 0.31 2.25 5.85 Percent of Patients Event Free ESRD Death 5% Medicare sample, 1996-1997 cohort, 2 year follow-up 9.40 14.65 29.04 85.04 73.18 65.12 24.57 90.53 0 20 40 60 80 100 Collins et al. Kid Int. 64 (Suppl 87)S24-S31, 2003

18. 18 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0123456 0 Years Mortality N = 6,252 *Adjusted for age, high BP, diabetes, history of angina, previous MI, current smoker, anterior acute MI, ventricular fibrillation, CHF, wall motion index, and thrombolytic therapy. Creatinine clearance <70 mL/min predicted significantly worse outcome after adjustment for co- variables* Sorensen CR et al. Eur Heart J. 2002;23:948-952. Renal Dysfunction Predicts Increased Mortality After Acute MI <40 mL/min 40-55 56-70 71-85 >85

19. 19 Renal Dysfunction Predicts Increased Mortality After Acute Stroke 0 0.2 0.4 0.6 0.8 1.0 01234567 Time to death (yrs) Cumulative survival CrCl <51 mL/min predicted significantly worse outcome, even after adjustment for confounders* *Adjusted for age, neurologic score, high BP, ischemic heart disease, smoking, and diuretic use; Kaplan-Meier survival analysis (log-rank test, P<.0001) MacWalter et al. Stroke. 2002;33:1630-1635. >66 mL/min 51-66 mL/min 39-51 mL/min <39 mL/min N=2,042

20. 20 Decreased GFR has consistently been found to be an independent risk factor for CVD outcomes and all cause mortality!

21. 21 Dialysis 2 Types: Hemodialysis Peritoneal Dialysis

22. 22 Hemodialysis  12 hours/week, kidneys work 168 hours/week  4 hours 3x/week  Need access to the blood stream: pump 400 cc blood out of the body per minute through the “artificial kidney”

23. 23 Hemodialysis BUN Creatine Na + K + Cl - HCO - 3 Ca ++ BLOOD 4m 2 membrane

24. 24 Solute Clearance on Hemodialysis HD 100 50 BUN

25. 25 Hemodialysis Access  Arteriovenous fistula  Arteriovenous graft  Catheter

26. 26 Peritoneal Dialysis Catheter in Peritoneal Cavity

27. 27 Peritoneal Dialysis  Peritoneal membrane: 3-4 m 2  2 L of dialysate, 4-5 exchanges/day  Increasing glucose concentrations to pull of fluid: 1.5%2200 ccRemoval 2.5%2400 ccRemoval 4.25%2800 ccRemoval

28. 28 Cardiovascular Mortality Is Higher in Patients With ESRD Adapted from Foley RN et al. Am J Kidney Dis. 1998;32(5 Suppl 3):S112–S119. GP Male GP Female GP Black GP White Dialysis Male Dialysis Female Dialysis Black Dialysis White Transplant Age (years) Annual mortality (%) Cardiovascular mortality in the general population (NCHS) and in kidney failure treated by dialysis or transplant (USRDS) 25-3435-4445-5455-6465-7475-84≥85 0.001 0.01 0.1 1 10 100

29. 29 Kidney Transplantation  Improved Vitality  Improved longevity

30. 30 Outline: Summary  What are the kidneys’ jobs?  Causes of kidney failure  Why is chronic kidney disease important?  Dialysis  Kidney Transplantation