End-Stage Renal Disease

End-Stage Renal Disease

End-Stage Renal Disease By Jason Klein BMB Seminar May 3, 1999 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 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 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 kidneys 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 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. 2. 3. 4. 5. Glomerulopathies(glomerulonephritis) Tubulointerstitial nephritis(drugs,heavy metals) Hereditary Diseases(Polycystic kidney disease)

Obstructive nephropathies Vascular diseases Progressive deterioration of glomeruli or renal tubules leads to decreased GFR and End-Stage Renal Disease 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 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 patients blood 3-4 hr sessions, 3 times/week , $46,000/yr Dialysis(cont.)

Peritoneal Dialysis-peritoneal membrane is dialyzer, patients blood is cleaned within the body More liberating for the patient and better for the heart than hemodialysis $41,000/yr 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 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

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. Physicians 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.

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