1. End-Stage Renal Disease  By  Jason Klein  BMB Seminar  May 3, 1999

2. Outline  I. Kidney: Basic structure and function  II. Scope of the Problem  III. Causes of End-Stage Renal Disease  IV. Metabolic consequences of End-Stage Renal Disease  V. Treatment of End-Stage Renal Disease

3. Kidney: Basic Functions  Each kidney contains about 1 million nephrons which filter about 100 quarts of fluid every day  Juxtaglomerular apparatus: produces renin which raises angiotensin II and aldosterone levels

4. Scope of the Problem  End-stage renal disease is the result of years of chronic renal disease and is defined as the condition where the kidney’s are only able to function at 5-10% of normal capacity  Approximately 310,00 people in the U.S. are currently being treated for end-stage renal disease with 70,000 new cases reported each year  In 1995, the cost of treatment for these patients reached a total of 13.1 billion dollars

5. Causes of End-Stage Renal Disease  Over 50% of the cases of renal failure are either due to diabetes mellitus(30%) or hypertension(25%)  1. Glomerulopathies(glomerulonephritis)  2. Tubulointerstitial nephritis(drugs,heavy metals)  3. Hereditary Diseases(Polycystic kidney disease)  4. Obstructive nephropathies  5. Vascular diseases  Progressive deterioration of glomeruli or renal tubules leads to decreased GFR and End-Stage Renal Disease

6. Metabolic Consequences of ESRD  1. “Uremia”-fatigue, nausea, dizziness, coma, death  2. Acid/Base disorders-pH of blood is lowered(7.33-7.37)  3. Renal Osteodystrophy-bony pain, spontaneous fractures that heal slowly  4. Anemia

7. Treatment of ESRD  Hemodialysis-remove metabolic wastes by diffusion as blood is pumped through dialysis machine  Fistula: Joined artery and vein that allows vascular access to patient’s blood  3-4 hr sessions, 3 times/week, $46,000/yr

8. Dialysis(cont.)  Peritoneal Dialysis-peritoneal membrane is “dialyzer”, patient’s blood is cleaned within the body  More liberating for the patient and better for the heart than hemodialysis  $41,000/yr

9. Transplantation  20,000 people currently living with kidney transplants-more cost effective and preferred over dialysis  In the U.S. in 1996-12,198 kidneys were transplanted and 34,550 people were on the waiting list  Immunosuppressive drugs-cyclosporine, prednisone, azathioprine

10. Tissue Engineering  Harvest renal cells, expand them in culture, seed them on biodegradable polymers, implant scaffold into host  Experiments in mice: Renal cells replicated and organized into nephron segments  Goal: Produce 3-dimensional renal units that could eventually lead to full replacement of kidney function

11. Bibliography  1. Amiel, Gilad(1999) Current and Future Modalities For Functional Renal Replacement. Urol Clin North Am 26(1): 235-45.  2. Andreucci, M. et al.(1999) Diuretics in Renal Failure. Miner Electrolyte Metab25(1-2): 32-38  3. Brest, Albert. Renal Failure. J.B. Lippincott Company, 1967.  4. Krupp, Marcus. Physician’s Handbook. 21st Ed. Lange Medical Publications: Los Altos, 1985.  5. Larson, David Ed. Mayo Clinic Family Health Book. William Morrow and Company Inc.: New York, 1990.  6. Marieb, Elaine. Human Anatomy & Physiology. 4th Ed. Addison Wesley Longman Inc., 1998.  7. Martin-Mateo, MC et. al.(1999) Oxidative Stress in Chronic Renal Failure. Ren Fail 21(2): 155-67.  8. McCarthy, JT(1999) A practical approach to the management of patients with chronic renal failure. Mayo Clinic Proc 74(3): 269-73.