Research Project for Dialysis Patients with a Hgb >13 for 2005 Researched, Edited, and Presented by Mindy Huttu, Anatole Besarab, and Stan Frinak

Why are dialysis patients anemic? – Anemia is measured as a reduction in hemoglobin (Hgb), the substance in red blood cells that carries oxygen. – Chronic Kidney Disease (CKD) patients become anemic as they loose kidney function. – This results from the loss of the Kidneys’ ability to produce the red blood cell stimulating hormone Erythropoietin (EPO). – To prevent Anemia, replace EPO produced in the kidney with “artificial” (genetically engineered) EPO. – Maintaining a near constant Hgb is not easy for doctors and patients to do. Why are dialysis patients anemic? – Anemia is measured as a reduction in hemoglobin (Hgb), the substance in red blood cells that carries oxygen. – Chronic Kidney Disease (CKD) patients become anemic as they loose kidney function. – This results from the loss of the Kidneys’ ability to produce the red blood cell stimulating hormone Erythropoietin (EPO). – To prevent Anemia, replace EPO produced in the kidney with “artificial” (genetically engineered) EPO. – Maintaining a near constant Hgb is not easy for doctors and patients to do. Introduction

What is Dialysis? Type of therapy used to provide an artificial replacement for lost kidney function due to kidney failure. It is a life maintaining treatment. Dialysis may be used for very sick patients who have suddenly lost their kidney function or for quite stable patients who, over time, have permanently lost their kidney function. Type of therapy used to provide an artificial replacement for lost kidney function due to kidney failure. It is a life maintaining treatment. Dialysis may be used for very sick patients who have suddenly lost their kidney function or for quite stable patients who, over time, have permanently lost their kidney function.

What is Hemoglobin, (Hgb)? Hemoglobin is the oxygen-carrying protein in the red blood cells. In vertebrates, it transports oxygen from the lungs to the rest of the body. It also transports carbon dioxide to the lungs for removal.

What is EPO? Erythropoietin (EPO) is a glycoprotein hormone that is a growth factor for red blood cell precursors in the bone marrow. It is produced by the kidney, and is the hormone regulating red blood cell production. It is used in treating anemia resulting from chronic kidney disease or from cancer chemotherapy. EPO is generally injected under the skin of the patient. Several injections weekly are required for the original forms, but newer long-acting forms (Darbepoetin) may require injections only once every two to four weeks. EPO can also be injected into the blood stream directly. This route of administration is the preferred mode in dialysis patients. Erythropoietin (EPO) is a glycoprotein hormone that is a growth factor for red blood cell precursors in the bone marrow. It is produced by the kidney, and is the hormone regulating red blood cell production. It is used in treating anemia resulting from chronic kidney disease or from cancer chemotherapy. EPO is generally injected under the skin of the patient. Several injections weekly are required for the original forms, but newer long-acting forms (Darbepoetin) may require injections only once every two to four weeks. EPO can also be injected into the blood stream directly. This route of administration is the preferred mode in dialysis patients.

When and how was EPO developed? First postulated in 1906 based on transfusion experiments in rabbits. In 1950, the still unidentified erythropoietic factor was found to be stimulated in rats breathing a low-oxygen atmosphere. In the 1960s its source was identified as the kidneys. Human EPO was first purified from human urine by T. Miyake, C. K. Kung and E. Goldwasser at the University of Chicago in EPO has now been identified with a molecular mass of about 30,000 Daltons. It has a 165 amino acid chain with four oligosaccharide side chains and circulates in the blood plasma at about 5 pmol/L. First postulated in 1906 based on transfusion experiments in rabbits. In 1950, the still unidentified erythropoietic factor was found to be stimulated in rats breathing a low-oxygen atmosphere. In the 1960s its source was identified as the kidneys. Human EPO was first purified from human urine by T. Miyake, C. K. Kung and E. Goldwasser at the University of Chicago in EPO has now been identified with a molecular mass of about 30,000 Daltons. It has a 165 amino acid chain with four oligosaccharide side chains and circulates in the blood plasma at about 5 pmol/L.

What is Chronic Kidney Disease? Chronic kidney disease (CKD) is a slowly progressive loss of kidney function over a period of months or years and quantitated as low glomerular filtration rate. CKD that leads to severe illness and requires some form of renal replacement therapy (such as dialysis) is called end-stage renal (kidney) disease (ESRD). Chronic kidney disease (CKD) is a slowly progressive loss of kidney function over a period of months or years and quantitated as low glomerular filtration rate. CKD that leads to severe illness and requires some form of renal replacement therapy (such as dialysis) is called end-stage renal (kidney) disease (ESRD).

What is Anemia? Anemia is the diminution of red blood cells that contain hemoglobin. This reduces the ability of blood to carry oxygen to the tissues. Severity of anemia is measured as a decreased Hgb level below the normal range Male: gm/dL Female: gm/dL Anemia is the diminution of red blood cells that contain hemoglobin. This reduces the ability of blood to carry oxygen to the tissues. Severity of anemia is measured as a decreased Hgb level below the normal range Male: gm/dL Female: gm/dL

Aims of Study Question: How well do doctors regulate the Hgb of dialysis patient’s? Method: Examine the trends between EPO dose and Hgb in dialysis patients. Goal: Can the data teach us how to do a better job of managing anemia? Question: How well do doctors regulate the Hgb of dialysis patient’s? Method: Examine the trends between EPO dose and Hgb in dialysis patients. Goal: Can the data teach us how to do a better job of managing anemia?

A good correlation between EPO and HGB level Hgb and EPO vs Time Reducing EPO reduces Hgb three months later

Hgb and EPO vs Time Reducing EPO reduces Hgb three months later

Problems of using EPO The effect of a given EPO dose can persist for up to 3 months. Therefore, a change in EPO dosage may not alter the Hgb level to the desired level for up to several months. The effect of a given EPO dose can persist for up to 3 months. Therefore, a change in EPO dosage may not alter the Hgb level to the desired level for up to several months.

Defining the Project Physicians respond to Hgb levels only when limits are exceeded. Low Hgb occur for many reasons, most of which are not under the control of the physician. High Hgb, however, result from dosing by doctors and medical staff and are potentially modifiable. Physicians respond to Hgb levels only when limits are exceeded. Low Hgb occur for many reasons, most of which are not under the control of the physician. High Hgb, however, result from dosing by doctors and medical staff and are potentially modifiable.

Methods Extract Data from data base Sort with Access Calculate in Excel Analyze in StatView and develop graphs and study trends Suggest Improvements in dosing strategies Extract Data from data base Sort with Access Calculate in Excel Analyze in StatView and develop graphs and study trends Suggest Improvements in dosing strategies

Data 2005 Descriptive StatisticsMeanStd. Dev.NMinMax Hgb Roll Average EPO Dose Corr FESAT FERR CHR delta Hgb delta time (days) slope Time to reach Time Hgb >13 g total duration Hgb > EPO Increased EPO Decreased Hgb Increase Hgb Decrease Hgb Slope Inc (per mo) Hgb Slope dec (per mo) MeanSDNMinMax Rolling Average (Hgb) EPO Increase EPO decrease Hgb increase Hgb decrease Hgb Slope Inc mo Hgb Slope Dec mo MeanSDNMinMax Rolling Average (Hgb) EPO Increase EPO decrease Hgb increase Hgb decrease Hgb Slope Inc mo Hgb Slope Dec mo Average number of times a patient Hgb exceeded 13 = 1.8 times per year

Percent Hgb (g/dL) Hgb Distribution for Patients with a Hgb Value >13 (g/dL) 13≤ Hgb <15 (24%) Hgb <11 (23%) Hgb ≥15 (3%) N = ≤ Hgb <13 (50%)

Mean Hgb Time (mo) Mean Hgb measurements for all dialysis patients with a Hgb >13 for 2005 (time in months) (684) N=(4878) (445) (467) (442) (313) (541) (355) (222) (492) (336) (279) (291)

Percent N = 4644 Mean = 0.0 ±1.1 Change Hgb (g/dL) Change in Hgb Between Measurements 2005 Data Std. Deviation (±1.12)

Patient Data for Hgb ≤ 13 vs. Hgb > 13 P <.0003 EPO Dose Mean Diff: Hgb > 13 Hgb ≤ Hgb ≤ 13 Hgb > P <.0001 Hgb

Patient Data for Hgb ≤ 13 vs. Hgb > 13 FESAT Hgb > 13Hgb ≤13 P <.0001 FERR Hgb ≤ 13Hgb > 13 P <.0154 CHR Hgb > 13 P <.0065 Hgb ≤ 13

Hgb (g/dL) Hgb (g/dL) Time (in Days) Hgb Values for an Individual Dialysis Patient EPO units EPO units 42 days above Hgb days to increase above Hgb days above Hgb 13

Suggest Improvements in dosing strategies A patients EPO dose should not be changed every month, because EPO effects can last up to 3 months or more. A trend analysis (graph) of the patient’s data may be very useful in making dosing decisions. A patients EPO dose should not be changed every month, because EPO effects can last up to 3 months or more. A trend analysis (graph) of the patient’s data may be very useful in making dosing decisions. A computerized anemia management system that recommends dosing change according to a set protocol could improve results. Reducing EPO reduces Hgb three months later

Hemoglobin Distribution EPO vs. Darbepoetin Using Computerized Anemia Management Program Pre Dialysis Patients on Darbepoetin Last Monthly HGB N = Percent Hgb (g/dL) 63%

The study showed that an individual patients Hgb can change over a wide range and the Hgb level did not always correspond to the patients EPO dose. There are many things other than just the Hgb in which the doctors must look at to decide the amount of EPO which might be right for the patient. The current Hgb level, the current EPO dose and the patients iron status measure by FERR, TSAT, and CHR levels. A trend analysis (graph) of the patient’s data may be very useful in making decisions. A computerized anemia management program that uses a database to track changes in Hgb and EPO dose may help regulate Hgb levels in dialysis patients. The study showed that an individual patients Hgb can change over a wide range and the Hgb level did not always correspond to the patients EPO dose. There are many things other than just the Hgb in which the doctors must look at to decide the amount of EPO which might be right for the patient. The current Hgb level, the current EPO dose and the patients iron status measure by FERR, TSAT, and CHR levels. A trend analysis (graph) of the patient’s data may be very useful in making decisions. A computerized anemia management program that uses a database to track changes in Hgb and EPO dose may help regulate Hgb levels in dialysis patients. Conclusions

References Introduction.htm ch.yahoo.com%2Fsearch%2Fimages%3Fp%3Dkidney%2Bdialysis%26rs%3D0%26ei%3D UTF-8%26fr%3DFP-tab-img-t- t400%26vf%3D&w=427&h=331&imgurl= %2F jpg&rurl=http%3A%2F%2Fwww.ahealthyme.com%2Ftopic%2Fdialysis&siz e=24.3kB&name= jpg&p=kidney+dialysis&type=jpeg&no=5&tt=12,773&ei=UTF-8 ase.tufts.edu/biology/.../ index.asp?PP=kidneys MedicalGlossary/images?D=D Introduction.htm ch.yahoo.com%2Fsearch%2Fimages%3Fp%3Dkidney%2Bdialysis%26rs%3D0%26ei%3D UTF-8%26fr%3DFP-tab-img-t- t400%26vf%3D&w=427&h=331&imgurl= %2F jpg&rurl=http%3A%2F%2Fwww.ahealthyme.com%2Ftopic%2Fdialysis&siz e=24.3kB&name= jpg&p=kidney+dialysis&type=jpeg&no=5&tt=12,773&ei=UTF-8 ase.tufts.edu/biology/.../ index.asp?PP=kidneys MedicalGlossary/images?D=D

Data 2005 Descriptive StatisticsMeanStd. Dev.NMinMax Hgb Roll Average EPO Dose Corr FESAT FERR CHR delta Hgb delta time (days) slope Time to reach Time Hgb >13 g total duration Hgb > EPO Increased EPO Decreased Hgb Increase Hgb Decrease Hgb Slope Inc (per mo) Hgb Slope dec (per mo) MeanSDNMinMax Rolling Average (Hgb) EPO Increase EPO decrease Hgb increase Hgb decrease Hgb Slope Inc mo Hgb Slope Dec mo MeanSDNMinMax Rolling Average (Hgb) EPO Increase EPO decrease Hgb increase Hgb decrease Hgb Slope Inc mo Hgb Slope Dec mo Average number of times a patient Hgb exceeded 13 = 1.8 times per year