End-Stage Renal DiseaseOutlineKidney: Basic FunctionsScope of the ProblemCauses of End-Stage Renal DiseaseMetabolic Consequences of ESRDTreatment of ESRDDialysis(cont.)TransplantationTissue EngineeringBibliographyEnd-Stage Renal Disease ByJason KleinBMB SeminarMay 3, 1999Outline 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 DiseaseKidney: 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 levelsScope 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 dollarsCauses 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 DiseaseMetabolic 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. AnemiaTreatment 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/yrDialysis(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/yrTransplantation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, azathioprineTissue 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 functionBibliography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):