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Renal Physiology Final Project HAPS Institute August 3, 2008 Robert E. Martin Associate Professor of Biology Department of Biology Dyersburg State Community College 1510 Lake Road Dyersburg, Tennessee 38024 [email protected] Phone 731-413-7405 Project Name: Estimation of Glomerular Filtration Rate (GFR) Using Creatinine Clearance Key Words: Creatinine clearance, glomerular filtration, kidney, urinary system Abstract: Glomerular filtration rate (GFR) is the term used to describe the volume of fluid filtered from the glomerular capillaries into the Bowman’s capsules per unit of time, and is the standard indicator of renal function. Various methods are used to approximate GFR, including the calculation of creatinine clearance. Creatinine is a natural by-product of muscle metabolism, and so is normally found in constant levels within the blood plasma. In addition, creatinine is freely filtered by the glomerulus, but not readily reabsorbed or secreted by the kidney tubule at a significant level. The calculation of creatinine clearance can therefore be used as an estimate of GFR. The following exercise demonstrates the calculation of GFR using a creatinine clearance equation, and the calculated values are then used in the diagnosis of three fictitious renal patients. Description: This lab exercise requires students to use their understanding of basic renal function to calculate Glomerular Filtration Rate (GFR), using a formula for creatinine clearance. The GFR values are then used to answer a few questions about each patient and to attempt to make a preliminary diagnosis based on the available information. The exercise requires students to use their basic understanding of renal physiology for simple clinical applications, with the goal of deepening and reinforcing their understanding of renal function. Subject: Using creatinine clearance to estimate glomerular filtration rate. Time Required: Approximately 1 hour. Level of Difficulty: This exercise is designed for community college students taking a 2-semester Human Anatomy and Physiology course. Low level of difficulty. Equipment Required: No equipment required other than paper, pen, calculator, and textbook for reference if needed. Special Supplies: None needed. Special skills/background: Basic understanding of human anatomy & physiology and of the urinary system. Estimation of Glomerular Filtration Rate (GFR) Using Creatinine Clearance Urine formation begins when water and dissolved substances are filtered out of the blood plasma in the glomerular capillary and into the Bowman’s capsules. Glomerular filtration rate (GFR) is the term used to describe the volume of fluid filtered from the glomerular capillaries into the Bowman’s capsules per unit of time, and is the standard indicator of renal function. Normal values for young adults are in the range of 120-130 mls/min and GFR levels generally decline somewhat with increasing age so that an average-sized person at age 75 may have a normal GFR of 75 ml/min. Various methods are used to approximate GFR, including the calculation of creatinine clearance. As discussed in the muscular system, creatinine is a natural by product of muscle metabolism, and so is normally found in constant levels within the blood plasma. In addition, creatinine is freely filtered by the glomerulus, but not readily reabsorbed or secreted by the kidney tubule at a significant level. The calculation of creatinine clearance, can therefore be used as an estimate of GFR. The following exercise demonstrates the calculation of GFR using the equation for the clearance of creatinine. The goal of the exercise is to promote a better understanding of glomerular filtration and renal function. The equation for calculation of creatinine clearance (Ccr) is: Ccr = Ucr X V Pcr Where: Ucr = creatinine’s urine concentration V = urine flow rate Pcr = creatinine’s plasma concentration Commonly, two 1-hour urine collections are taken, with a comparative blood test then taken. For the 3 following cases, calculate each patient’s Ccr, and then answer the following questions. 1. Patient 1, a 140-lb 30-year old female is found to have high blood pressure at 175/105 mm Hg, and has a family history of kidney disease. Her doctor orders a creatinine clearance test as part of a comprehensive physical exam. The results show her to have a creatinine plasma concentration of 0.01 mg/ml and in 1 hour she produces 60 ml of urine with a creatinine concentration of 1.25 mg/ml. Calculate creatinine clearance for this person (show your equation). What does the Ccr value tell us about this person’s GFR? What does this person’s GFR tell us about their kidney function? What other tests might be ordered by this person’s doctor and what diagnosis might be expected in regard to kidney function? 2. Patient 2, a 160-lb 45-year old male, has recently undergone chemotherapy with a potentially nephrotoxic drug. As part of his followup examination, the doctor orders a creatinine clearance test. The results produced the following values: a creatinine plasma concentration of 0.008 mg/ml, and in 1 hour the production of 50 ml of urine with a creatinine concentration of 0.45 mg/ml. Calculate creatinine clearance for this person (show your equation). What does the Ccr value tell us about this person’s GFR? What does this person’s GFR tell us about their kidney function? What other tests might be ordered by this person’s doctor and what diagnosis might be expected? 3. Patient 3, a very slim 120-lb 85-year old male, is suffering from chronic dehydration, and undergoes a creatinine clearance test as part of a comprehensive physical exam. The results show him to have a creatinine plasma concentration of 0.008 mg/ml and in 1 hour produces 40 ml of urine with a creatinine concentration of 0.92 mg/ml. Calculate creatinine clearance for this person (show your equation). What does the Ccr value tell us about this person’s GFR? What does this person’s GFR tell us about their kidney function? What other tests might be ordered by this person’s doctor and what diagnosis might be expected? Answers for Patient 1 1. Calculate the creatinine clearance value for this person (show your equation). Ccr = 1.25 mg/ml X 60ml/60 min = 1.25 mg/ml X 1 ml/min = 1.25 mg/min =125 ml/min 0.01 mg/ml 0.01 mg/ml 0.01 mg/ml 2. What does the Ccr value tell us about this person’s GFR? This Ccr value would indicate this person to have a GFR of approximately 125 ml/min. 3. What does this person’s GFR tell us about their kidney function? This GFR value is in a very normal range and would indicate healthy kidney function. 4. What other tests might be ordered by this person’s doctor and what diagnosis might be expected? Kidney damage is not indicated by the creatinine clearance value, but a complete physical exam and medical history would likely be used for further evaluation. Blood pressure measurements at other times would likely be taken to confirm the blood pressure values. Weight loss, exercise, and dietary changes might be recommended if warranted, and appropriate medications might be prescribed to help the patient manage her blood pressure. Answers for Patient 2 1. Calculate the creatinine clearance value for this person (show your equation). Ccr =0.45 mg/ml X 50ml/60 min=0.45 mg/ml X 0.83 ml/min= 0.37 mg/min=46.9 ml/min 0.008 mg/ml 0.008 mg/ml 0.008 mg/ml 2. What does the Ccr value tell us about this person’s GFR? The Ccr value indicates GFR significantly below normal values. 3. What does this person’s GFR tell us about their kidney function? This GFR value indicates significantly reduced kidney function and likely kidney impairment. 4. What other tests might be ordered by this person’s doctor and what diagnosis might be expected? Significant kidney impairment may have resulted due to the chemotherapy drugs. Additional blood testing and urinalysis might be used for more in depth analysis of kidney function. A reexamination of the chemotherapy drug regimen might be made to consider other less nephrotoxic options. Answers for Patient 3 1. Calculate the creatinine clearance value for this person (show your equation). Ccr = 0.92 mg/ml X 40ml/60 min=0.92 mg/ml X 0.67 ml/min=0.61 mg/min =77 ml/min 0.008 mg/ml 0.008 mg/ml 0.008 mg/ml 2. What does the Ccr value tell us about this person’s GFR? The Ccr value indicates a GFR of approximately 77 ml/min. 3. What does this person’s GFR tell us about their kidney function? Considering the age and small stature of this patient, a lower GFR value would be expected, due to normal decline in GFR with age, as well as the small muscle mass (source of creatinine) of this individual. This GFR value would fall within a normal range for this individual, indicating healthy kidney function. 4. What other tests might be ordered by this person’s doctor and what diagnosis might be expected? Blood tests could be used to check electrolyte levels and to evaluate the severity of the dehydration problem. Other laboratory tests could be ordered to determine any other underlying condition such as diabetes or an adrenal gland disorder. At the same time, however, dehydration is very common in elderly persons and if no pathological cause is determined, a stricter regimen of fluids may need to be enforced to insure adequate hydration. References: 1. Hole’s Human Anatomy & Physiology, 11th Edition. Shier, Butler, and Lewis. 2. National Kidney Foundation: Glomerular Filtration Rate, http://www.kidney.org/kidney disease/ckd/knowGFR.cfm 3. Renal Blood Flow – Glomerular Filtration Rate, http://www.uhmc.sunysb.edu/internalmed/nephro/webpages/Part_A.htm 4. Renal function – Wikipedia, the free encyclopedia, http://en.wikipedia.org/wiki/Renal_function 5. Vander’s Renal Physiology, 6th Edition, Eaton and Pooler. 5 Stages of Chronic Kidney Disease Stage At increased risk Description Glomerular Filtration Rate GFR) Risk factors for kidney disease (e.g., diabetes, high blood pressure, family history, older age, ethnic group) More than 90 1 Kidney damage (protein in the urine) and normal GFR More than 90 2 Kidney damage and mild decrease in GFR 60 to 89 3 Moderate decrease in GFR 30 to 59 4 Severe decrease in GFR 15 to 29 5 Kidney failure (dialysis or kidney transplant needed) Less than 15